Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

 Chapter 1: Prescriptive Authority and Role Implementation: Tradition vs Change

• Primary Care is provided by clinicians who address “personal health care needs, developing a sustained partnership with patient, and practicing in the context of family and “

• Prevention, Diagnosis, Prescription, Treatment

• Assess health
• Promote healthy
• Identifying/diagnosing normal/abnormal
• Determining the causes of abnormal conditions, providing referral to health care
• Selecting appropriate therapeutic
• Implementing
• Supervising/monitoring the patient on an ongoing

• Traditional Primary Care–physicians as the only providers with diagnostic and treatment authority–an intention to

protect the public.

• Prescriptive practices should not be compared to those of physicians–all providers should be held to a standard of approved therapeutic

• Most Prescribed by PCP–antidepressants, NSAIDs, antihistamines/bronchodilators, antihypertensives,

antilipidemic.

• Rate of Adoption by Prescribers–innovators, early adopters, early majority, late majority, and

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o                      Problems in the Prescribing Practice of Physicians

• Prescriptions are not the most up to date–“new research findings diffuse slowly into “
• Pharmaceutical company influence–FDA intervention and PhRMA
• Lack of time–short consultation, incorrect H&P, problem is left undefined, over-reliance on drug
• Consumers’ pressure for prescribed medications–“Do something!”–lifetime of medications, overused antibiotics, and direct-to-consumer advertising.
• Ineligible prescriptions –> Medication errors. Current federal mandate for e-prescribing. TJC Do Not Use

Abbreviations.

• Undetected/anticipating drug interactions–liver cytochrome P450 enzymes = drug-to-drug interactions may render medication ineffective–prescription warning system Rising use of OTC and herbal products.

Chapter 2: Historical View of Prescriptive Authority (Nurses vs. PA)

• Primary Care is provided by clinicians who address “personal health care needs, developing a sustained partnership with patient, and practicing in the context of family and “
• “Delegable authority –> “Delegable prescriptive authority” without it, an APN can only suggest OTC
• Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

o                      Nursing Legislation

• Dependent authority–the physician retains ultimate authority through co-signature.
• Independent authority–the APN prescribes alone–can still be
• 1993–Definition and Registration of MLPs–can obtain DEA# beginning with M
  • NPs
    • DEA number and prescriptive authority differ by
    • May dispense pharmaceutical samples in all
    • Across-state-line prescribing
  • CNMs
  • CRNAs–do not “prescribe” under
  • CNSs

o                      Barriers to Practice for Nurses in the Diagnosing and Prescribing Role

• Regulatory irregularity among states
• Increased antagonism from organized medical groups competing with APNs for patients
• Growing number of NP graduates without prior nursing experience
• Inequity in data collection on physician prescribing patterns among pharmaceutical companies

 

• Difficulty in obtaining prescribing data from Prescription Drug Marketing Act

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

Chapter 9: Establishing the Therapeutic Relationship

• “How scientific principles are introduced in the relationship with the patient has everything to do with therapeutic ” The balance of art and science in healthcare.
• “A continuing relationship with the healthcare provider is essential in making adjustments to discover the proper therapy for

the individual.”

• Identify a problem, assess it adequately, identify various potential solutions, examine he variables needed to judge the risk/benefit ratio of the solutions, choose the most appropriate solution, and identify the effects (beneficial and adverse) that may result from implementation of the chosen

• Factors of a Therapeutic Relationship

• Time–investment–particularly with the elderly–initial investment to obtain thorough H&P–cost-effective–follow up call strengthen the relationship
• Attitude–how time is spent and what is said–“Who owns the problem?”
• Information–it may take several visits to obtain a full history
• Communication–effective two-way communication between patient and provider requires consistent commitment to respect the others’ role in the
  • Transference
  • Focus on patient, environment, and lastly, self.
  • Find a balance between creating uncontrolled and unfounded anxieties vs creating a false sense of equally grounding security and
  • It is implicitly understood that once a problem is presented, the provider will do their utmost to provide

the best therapy.

• The therapeutic objective must be clearly stated–1) must be realistic and attainable, 2) clearly related to the problem as defined and assessed, 3)
• Be flexible, accept occasional lapses in compliance, attempt to understand the patient’s point of

o                                   Therapeutic Relationship Fails

• Skepticism in the medical
  • Provider main goal is pharmacoadherence.
  • Over or under
  • Therapeutic failure and increase in disease
  • Gender, race, education, occupation, income, marital status–are not factors in
    • Blame the economy!
  • Compliance vs adherence–both suggest patient fault
  • Concordance–suggests a therapeutic alliance between prescriber and patient–a negotiated agreement

that may even be an agreement to disagree.

• Patient–actively participates in consultation process regarding treatment, risk, and
• Provider–communicates evidence to enable the patient to make informed choices, accepts

patient’s choices regarding their care, continues to negotiate treatment and part of the ongoing process.

• Risk Factors

• Increases with preventive care
• Increases with duration of therapy
• Greatest for regimens with significant behavioral change
• Poor understanding of instructions
• Complex treatment regimen
• Unpleasant side effects
• Increases in drug costs

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

Chapter 10: Practical Tips on Writing Prescriptions

• DEA–state-controlled substance license–federally issued DEA#
  • Drugs are scheduled by potential for

 

• Components of a Traditional Prescription

• Name of prescriber–credentials, address, phone number
• Date
• Name of patient–address, age, and weight
• Superscription–Rx–“take”
• Inscription–drug ingredients, quantity, strength, and/or concentration
  • Drug–full name of medication–no abbreviations
  • Strength/concentration
• Signature
• The better the instructions, the better the medication compliance and patient
• Refills
  • No refills on Schedule II drugs
  • Only 6 months/5 refills allowed
  • “NO REFILLS”
• DEA#–should not be printed on Rx or used for ID purposes
• Generic Substitutions Okay?
  • Dispense as Written
  • Brand Medically Necessary

• Electronic Signatures in Global and National Commerce Act: 2000

• E-Sign
  • No need to paper or hard
  • Schedule II–need to fax/present hard
  • Specifically, and emphatically prohibit the reimposition of tangible/paper

o                                   Prescription Etiquette

• Cannot prescribe narcotics to self or family–can prescribe non-narcotic Schedule IIs but it is considered poor
  • The DEA may start an
  • Frequent prescribing for self/family may not be covered by
  • Prescriptions that are refilled without a Provider
  • Drug sampling–on the margin of
  • The prescriber is always responsible for what happens to the individual receiving the

• Avoiding Mistakes

• Write clearly
• Stay up-to-date
  • Drug-drug interactions
  • Renal dosing of medications
  • Direct-to-consumer advertising–patients ask for medications PCP’s may not normally prescribe
  • Medication errors are inversely correlated to PCP’s years of practice
• With disclosed suicidal ideation: Write for no more than a 7-day supply of a medication a patient could overdose on if taken all at once
• Discuss side effects
• Discontinue a medication when it causes a cautioned side effect
• Get informed consent when a drug can cause permanent side effects and a less risky alternative is

available

• If prescribing “off-label”: Document the rationale for deviating from the package insert instructions, and be prepared to prove that the standard of care supports the alternative prescribing regimen
• If a drug is known to cause adverse effects after long-term use, avoid using the drug for long-term

therapy or monitor carefully for the onset of potential problems

• Ask, Listen, and Alter the Plan

• Administrative Concerns

 

• Formularies–cost-saving measure that can be restrictive, are slow to integrate new and effective drugs.
• Medicaid–joint Federal and State program–provider must be a Medicaid subscriber–states have

their own Medicaid formularies which omit new medications, expensive trade name medications, and

medications deemed “less than effective” by the FDA–payment is not made for non-formulary drugs unless a waiver stating medical necessity or life-sustaining measures will be obtained from the medication.

• Out-of-State Prescriptions–may or may not be filled–can also cause problems with telehealth

prescriptions–counterfeit medications purchased online.

• Telephone Orders–no Schedule I or II
• Emergency Dispensing of Medications–usually antibiotics or narcotic
• Generic Substitutions–some states automatically allow–if brand name is required, write “Do Not Substitute.”

• Preventing Problems in Drug Use

• The Abusing Patient–asks for narcotics by name, carries proof of pain, calls requesting refills early due to lost or stolen medications, altering prescriptions, using multiple
  • Providers who feel they cannot continue to meet the needs of the patient have a

responsibility to help that patient find another provider.

• The Abusing Provider

• The Financially Needy Patient

 

Chapter 11: Evidence-Based Decision Making and Treatment Guidelines

• Quality of healthcare relies upon 1) decisions that determine what actions are taken, 2) the quality of the actions

• Critical Thinking in Nursing

• Made up of knowledge and an attitude of inquiry–a critical appraisal of knowledge
  • Collecting and analyzing whatever evidence exists regarding the benefits, harms, and costs of each
  • Clarify personal values or preferences of the
    • Joint decision

Knowledge –> Judgements –>  Estimate –> Patient/provider preferences –> Decision Evidence Critical analyses. Outcomes Critical thinking

Benefits vs Harm                                  Judgements

Costs                                      Important patient outcomes

Marginal benefits Estimated patient outcomes Patient preferences

• Evidence-based medicine is the science–no single correct answer and no obligation that everyone must agree–is the
• Brenner 1984–described the process of skill acquisition by

o             Begins with decision-making analysis, then hypothetical deductive reasoning, and the eventual emergence of the

· § The effects of intuition on an expert nurse’s ability to make clinical decisions… Pattern recognition–recognizing relationships § § § § § Similarity recognition–recognizing relationships despite obvious differences Commonsense understanding–having a deep understanding of a given entity Skilled know-how–ability to visualize a situation Sense a salience–ability to recognize what is important Deliberative rationality-ability to anticipate events Diagnostic errors can be classified into: · · · · § § § § Faulty hypothesis triggering Failure to pick right hypothesis or revise hypothesis Faulty context formulation Occurs when clinician and patient have different goals Faulty information gathering process Failure to order appropriate tests or misinterprets information Faulty verification of diagnoses Failure to collect enough data to confirm a diagnosis or to completely rule out others

expert that functions at an intuitive level.

• Critical Decision Making Regarding Pharmacologic Therapy

• Confirm the diagnosis

· ·	§	Try non-pharmacologic first How aggressive will the therapy be? Palliative, curative, symptom-reduction, prevention
	§	Define patient and drug variables–age, smoker, allergies, comorbidities (renal, hepatic,
·		immunologic), other medications taken, severity of disease, risk vs benefit ratio, cost of product Select the drug and start it
·	§	Determine drug effectiveness after start of treatment Patient reaction determines… ·                        Whether to continue the medication because it is doing what it should or because it is

partially working and should be given more time

• Whether the regimen should be modified
• Whether the medication should be discontinued because the therapeutic objective has

been reached and the medication is no longer needed or because the medication was a failure and

should be stopped. Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

• Evidence-Based Medicine

• Train for uncertainty–incomplete mastery of available knowledge and from limitations in current medical

knowledge

o                     Traditional Decision-Making Paradigm

• Unsystematic observations from clinical experience leads to building and maintaining one’s knowledge about patient prognosis, the value of diagnostic tests, and the efficacy of
• The study and understanding of basic mechanisms of disease and pathophysiologic principles are sufficient

guides for clinical practice.

• The combination of thorough medical training and common sense is sufficient to allow one to evaluate new tests and
• Content experience and clinical expertise form a sufficient base from which valid guidelines for clinical

practice can be derived.

• Evidence-Based Health Care

• EBM focuses primarily on the development of research skills and use of the critical appraisal exercise
  • Defining an answerable and structured question about the target population, outcomes, and intervention or

· · ·	§	Searching the published literature for sources of data that might answer the question Appraising or evaluating the data for methodologic rigor and relevance to the question Describing and analyzing study data to answer the question posed Understanding the underlying pathophysiology is necessary to interpret and apply the results of
·	§	clinical research Barriers to Implementation of Evidence-Based Decision Making EBM ignores clinical experience and intuition, basic investigation and pathophysiology, and

standard aspects of clinical training.

• Five factors influence medical decision making
  • The patient’s situation
  • The patient’s desires and values
  • The health care provider’s values
  • The health care provider’s experience
  • Evidence from research

• Clinical Guidelines

• Official statements that outline how to prevent, diagnose, and treat specific medical conditions or how to perform certain clinical

 

Chapter 3: General Pharmacokinetic and Pharmacodynamic Principles

• Pharmacokinetics–the study of the action of drug sin the body, including the processes of absorption, distribution, metabolism, and
  • Absorption–how the drug leaves its site of administration

 

• Drug characteristics

· Influences dissolution rate of solid form of drug § Concentration of the drug · The higher the concentration, the more quickly the drug is absorbed § Lipophilic drug formulations are more readily absorbable · Non-ionized drugs are more lipid soluble an may readily diffuse across cell membranes ·                            Ionized drugs are lipid insoluble and non-diffusible § Acidic drugs become non-ionized in the acidity of the stomach and then diffuse across

• Formulation of the drug membranes

• Basic (alkaloid) drugs tend to ionize and are not well absorbed by the stomach, but may be better absorbed by the small intestine–a changed in pH in the stomach will affects the absorption of many drugs.
• Route of administration

• Blood flow
• Cell membrane characteristics

• Bioavailability–how much of the drug that is administered reaches its site of action
• F-value–the fraction of the drug that reaches the systematic circulation
• Bioequivalence–two drug products contain the same active ingredients and are identical in strength or concentration, dosage form, and route of administration, and have essentially the same rate and extent of bioavailability.
  • Generics must be 20% + or – the proprietary drug–variance in bioavailability
• Pharmacodynamics–the study of the biochemical and physiologic effects of drugs on the function of living organisms and of

their component parts.

• Drug Nomenclature

• Chemical name–chemical composition and molecular structure
• Generic name–non-proprietary name–official name assigned by the manufacturer with the approval of the US Adopted Name Council
• Trade Name–patent name given to the medicine by the company marketing the drug

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

Chapter 33: Male Urinary Agents

• Overview

• Benign Prostatic Hyperplasia—complications of obstructive uropathy
  • Alpha-1 Adrenergic Agonists—reduce sympathetic tone and relax urethral structure—can lower blood pressure.
    • Alpha-1A Selective—FIRST LINE without HTN
      • Prazosin
    • Long-Acting Alpha-1—SECOND LINE with HTN
      • Cardura

• Short-Acting Alpha-1

• Finasteride

• 5-Alpha Reductase Inhibitors—can be used in combination

• Finasteride—reduces size of prostate gland by blocking the conversion of testosterone—6-12

months for effect.

• Erectile Dysfunction—inability to maintain an erect penis with sufficient rigidity to allow sexual intercourse— causes can be organic or psychological
  • PDE5 Inhibitors—FIRST LINE
• Sildenafil (Viagra)
• Tadalafil (Cialis)
• Vardenafil (Levitra)

• Other

• Tests for renal function—UA, serum Cr, BUN, PSA, uroflowmetry, postvoid residual, pressure flow studies
• Finasteride and Doxazosin shown to lower the risk of the clinical progression of BPH by 66%
  • Finasteride is teratogenic even through semen
• Saw Palmetto herbal treatment—acts as a 5-Alpha reductase

 

• Mechanism of Action for Erectile Dysfunction—erection involves release of NO in response to stimulation—NO increases cGMP and allows penile blood flow—PDE5 degrades

o           Pharmacologic treatment

• Hormone replacement
• PDE5 inhibitors
• Intraurethral prostaglandin

• Yohimbine

o           Nonpharmacologic treatment

• Vascular reconstruction
• Vacuum constriction devices

• Implanted penile prostheses

Chapter 34: Agents for Urinary Incontinence and Urinary Analgesia

• Overview

• Anticholinergics

• Oxybutynin chloride
• Fesoterodine
• Tolterodine
• Trospium
• OnabotulinumtoxinA

• Bladder Related Anticholinergics

• Darifenacin
• Solifenacin (Vesicare)

o           Antispasmodics

• Cholinergic Agonists
• Posterior Pituitary Hormones
• Urinary Tract Analgesia
  • Phenazopyridine (Pyridium)
• Urinary Incontinence—unintentional leakage of urine—stress, urge, mixes, and overflow

• Mechanism of Action

• Anticholinergics—block muscarinic actions—adverse effects: blurred vision, urinary retention, constipation, dry mouth, tachycardia, and confusion—used to treat urge incontinence along with TCAs and dicyclomine—blocks contraction of the bladder and decreases the urodynamic response of detrusor overactivity—leads to increased bladder capacity, delayed desire to void, and decreased frequency of involuntary bladder
• Antispasmodics—direct smooth muscle relaxant—can also have anesthetic and analgesic
• Cholinergic Agonists—release acetylcholine to increase detrusor muscle tone—starts a contraction and bladder emptying—used for overflow
• Biologic Toxin—blocks muscle contraction—used for detrusor muscle over activity in patients with an inadequate response or intolerance to anticholinergic
• Desmopressin—synthetic vasopressin that acts as an antidiuretic—decreases urine output for 6
• Urinary Tract Analgesia—azo dye excreted in urine—only useful as analgesic—used for short-term, 2

• Treatment

• Stress incontinence
  • Beneficial: SSIs (duloxetine), estrogen cream, ring, imipramine, pseudoephedrine
  • Likely to be beneficial: Pelvic floor electrical stimulation, pelvic floor muscle exercises, vaginal cones
• Tradeoff between benefits and harms: Estrogen supplements

o                       Urge incontinence

• First line: Oxybutynin, darifenacin, Solifenacin, tolterodine, Trospium
• Second line: TCAs

• Third line: Flavoxate, propantheline, dicyclomine

o                       Nonpharmacologic treatment

• Mainstay of treatment
  • Fluid management
  • Bladder training
  • Bladder retraining
  • Pelvic floor muscle rehabilitation

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

Chapter 15: Upper Respiratory Agents

• Overview

• Decongestants

• Oral
  • Pseudoephedrine
  • Phenylephrine
• Topical Nasal
  • Phenylephrine
  • Oxymetazoline

o           Antihistamines

• Sedating Antihistamines
  • Ethanolamine
    • Diphenhydramine
    • Clemastine Fumarate
  • Alkylamine
    • Chlorpheniramine Maleate
  • Piperazine
    • Hydroxyzine
  • Low-Sedating Antihistamines
    • Piperidine
      • Cetirizine (possible

s crisis)

• Non-Sedating Antihistamines
  • Fexofenadine
• Miscellaneous Antihistamines
  • Loratadine
  • Desloratadine
• Intranasal Antihistamines
  • Azelastine

o           Intranasal Corticosteroids

• Nasal
  • Beclomethasone Diproprionate
  • Fluticasone Propionate

o           Intranasal Mast Cell Stabilizer

• Cromolyn Sodium

o           Leukotriene Receptor Antagonist

• Montelukast Sodium

o           Antitussives

• Narcotic Antitussives
  • Codeine Phosphate
• Non-Narcotic Antitussives
  • Dextromethorphan HBr

o           Expectorants

• Benzonatate
• Guaifenesin
• Most Common Conditions in PCP–URI and allergic rhinitis
  • OTC combination medications may be confusing and counterproductive
  • Nighttime formulations contain alcohol and acetaminophen–cannot be taken together

 

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

• Upper air passages–conducting portion–nasal passages –> paranasal sinuses –> pharynx –> larynx
  • Epithelial tissue, mucous glands, goblet cells–synthesize and secrete mucous
• Lower air passages–respiratory portion–trachea –> bronchi –> lungs
• Epithelial cells, cilia

• Decongestants–first line for URI
  • Oral–for nasal congestion caused by the common cold, hay fever other respiratory allergies, sinusitis, and Eustachian tube
    • Pseudoephedrine, Phenylephrine (orally and topically) —adrenergic receptor agonists = sympathomimetic
      • Not for patients with HTN, glaucoma, and urinary retention
      • Off-Label–for treatment of mild-moderate urinary stress
    • Topical (no systemic effects) –symptomatic relief of nasal and nasopharyngeal mucosal congestion caused by the

common cold, sinusitis, hay fever, other upper respiratory allergies–adjunctive therapy for otitis media (decreases congestion in eustachian ostia), relief of ear block, pressure, and pain during travel.

·		Phenyl ephedrine, Oxymetazoline
o	MOA
·	§	Sympathomimetic amines, stimulate alpha receptors of vascular smooth tissue and cause vasoconstriction Causes nasal decongestion, contraction of GI and urinary sphincters, pupil dilation, and decreased

pancreatic beta call secretion.

• Pseudo epinephrine has beta adrenergic properties that cause relaxation of the bronchi.
• SNS

• Adrenergic effector cells
  • Alpha receptors–adrenergic activities: vasoconstriction of arterioles (increased

BP), dilation of pupils, intestinal relaxation, bladder sphincter contraction.

• Beta-receptors
  • Beta 1–cardio acceleration and increased myocardial contractility
  • Beta 2–vasodilation of skeletal muscle, bronchodilation, uterine relaxation, and bladder
• Sympathomimetic drugs mimic the action of norepinephrine on sympathetic effector

organs and affect adrenergic receptors

• Use with caution for patients with HTN, PVD, hyperthyroidism, DM, prostatic hypertrophy, urinary retention, and increased intraocular pressure–sympathomimetic

 

• Contraindicated for mitral valve prolapse and palpitations
• Systemic effects–nervousness, dizziness, and difficulty sleeping–tachycardia, headache, irritability
  • Sustained-release decreases symptoms but can interfere with anti-hypertensives
• Antihistamines–first line for allergic rhinitis
  • Compete for histamine and the H1-receptor sites and treat 1gE-mediated immunoglobulin–antagonize effects of

histamine–do not block, inactivate, or decrease release.

• Cause anticholinergic drying, antipruritic, and sedative effects

• Symptomatic relief for perennial/seasonal allergic rhinitis, vasomotor rhinitis, allergic conjunctivitis, temporary relief of runny now/sneezing caused by common
• Skin–allergic/non-allergic pruritic symptoms, mild and uncomplicated urticaria and
• Amelioration of allergic reactions to blood/plasma, dermatographism, and adjunctive therapy in anaphylactic reactions.

·		Sedating Antihistamines
	§	Ethanolamine –> Diphenhydramine, Clemastine Fumarate (Tavist)
	§	Alkylamine –> Chlorpheniramine Maleate (Chlor-Trimenton)
	§	Piperazine –> Hydroxyzine
·		Low-Sedating Antihistamines
	§	Piperidine –> Cetirizine
·		Non-Sedating Antihistamines
	§	Fexofenadine –> Allegra
·		Miscellaneous Antihistamines
	§	Loratadine –> Claritin
	§	Desloratadine –> Clarinex
·		Intranasal Antihistamines
	§	Azelastine –> Astelin–topical antihistamine nasal spray for allergic and vasomotor rhinitis with

few adverse effects.

• Triamcinolone Acetonide –> Nasacort AQ

• Intranasal Corticosteroids–second line for URI
  • Potent glucocorticoids (inhibit mast cells, eosinophils, neutrophils, macrophages, lymphocytes, ad mediators like

histamine, leukotrienes, and cytokines) and weak mineralocorticoid

• Control rhinorrhea, congestion, sneezing, and nasal
• Must be used daily, maximum effects are seen after days to

• Vasomotor rhinitis and relief of symptoms of seasonal/perennial rhinitis when effectiveness of antihistamines or

tolerance to treatment develops.

• Beclomethasone Diproprionate –> Beconase, Vancenase

• Fluticasone Propionate

• Intranasal Mast Cell Stabilizers–second line for URI—effective for intermittent
  • Preventative treatment taken prior to allergen exposure–anti-inflammatory agent that inhibits sensitized and mast cell degranulation that occurs after exposure, inhibits the release of mediators, histamine, and slow-reacting substance of anaphylaxis (SRS-A) from the mast cell–inhibits calcium from entering the mast cell and prevents mediator release and mast cell degranulation–reduces rhinorrhea, sneezing, and nasal itch (no effect on nasal congestion).
  • Prevention/treatment of allergic

• Cromolyn Sodium –> NasalCrom

• Nebulized aerosol inhaled through the mouth or swallowed orally four to six times/day and

effects are seen within 4-6 weeks to months.

• Leukotriene Receptor Antagonists–prescribed when other treatments fail to relieve symptoms
  • Leukotriene receptor agonist that inhibits airway cysteinyl leukotriene receptors (CysTLs) (products of arachidonic

acid metabolism that are released from mast cells and eosinophils)

• CysTLs type 1 receptor is found in airway smooth muscle cells, airway macrophages, and proinflammatory cells like eosinophils and myeloid stem cells–released from the nasal mucosa after allergen exposure

• Treatment of allergic/perennial allergic

• Montelukast Sodium –> Singulair

• Antitussives–adjunctive therapy in URI and lower respiratory conditions
  • Narcotic–codeine for suppression of cough induced by chemical/mechanical respiratory tract

 

• Codeine Phosphate

• Non-narcotic–Dextromethorphan for suppression of non-productive cough–Benzonatate for symptomatic relief of

cough.
·		Dextromethorphan –> Delsym, Robitussin
	§	D-isomer of codeine without analgesic and addictive properties.
·		Benzonatate –> Tessalon Perles
	§	Anesthetizes stretch receptors in respiratory passages to reduce the cough reflex at its source.

• Acts centrally on the cough center in the medulla to suppress a cough

• Expectorants–adjunctive therapy in URI and lower respiratory conditions
  • Guaifenesin may provide symptomatic relief of respiratory conditions characterized by productive/non-productive

cough.

• Guaifenesin

• Increases respiratory tract fluid secretions and loosens bronchial secretions by reducing adhesiveness and tissue surface tension so mucociliary mechanism can remove accumulated
  • Non-productive coughs become productive, less frequent, and less
    • Time-release OTC requires FDA
  • URI (viral) and Allergic Rhinitis (allergic rxn)–secondary bacterial infection if left untreated–usually, acute sinusitis and otitis media–pneumonia may develop in susceptible patients–clinical decision is whether it is viral or bacterial and whether there is an allergic

o                          URI

• Increase in mucous production, mucous thickens with dehydration and fever, mucociliary mechanism is inhibited and cilia become sticky and unable to move, mucous is coughed and
  • Rhinovirus, adenovirus
    • Rhinosinusitis–Amoxicillin/Clavulanate
  • Nasal congestion, watery rhinorrhea, and sneezing in 50-70% of patients within the first 3 days,

sore throat in 50% within the first 2 days

• Examination–nasal mucosa is reddened, edematous, with watery discharge–bacterial is purulent discharge, red tympanic membrane, change in discharge color, or high fever

• Enforce handwashing!
• S/s of serious illness–upper/lower airway obstruction and severe
• No aspirin-containing products <21 years, no cold/cough medications <6 years (use caution with <12

years), no decongestants <6 years

• No acetaminophen with liver
• Zinc Gluconate may decrease the duration of a cold if started within 24 hours of onset–only for adults–

conflicting studies–adverse side effects of nausea, bad taste, loss of smell.

• Associated cough–treat with first generation antihistamine/decongestant combination preparation and naproxen to suppress cough–non-sedating antihistamines do not suppress

	§	Ipratropium bromide, codeine
·		Non-Pharmacologic Treatment
	§	Bronchial toilet–adequate hydration.
	§	Teaspoon of honey to suppress cough in children.
	§	Normal saline irrigation BID.
·		Pharmacologic Treatment
	§	Decongestants, antihistamines or a combination
	§	Antitussives and expectorants
	§	Not antibiotics
	§	Mild, intermittent symptoms–antihistamine and decongestant
		·                        Nasal antihistamine, intranasal cromolyn, or leukotriene receptor antagonist
	§	Moderate, frequent symptoms–regular-to-high-dose intranasal corticosteroid–add oral or nasal

antihistamine and decongestant

• Moderate, persistent symptoms–require a combination regimen–intranasal corticosteroids, antihistamine, and

 

• Severe symptoms–treat with or without a decongestant–possibly oral steroid for 5 days and oxymetazoline, no longer than 3

o                          Allergic Rhinitis

• Seasonal–irritants: pollen, trees in spring, grass in summer, ragweed in fall
• Perennial–dust, mold, mites
• Symptoms are similar to URI except more persistent, may fluctuate, and related to exposure to allergens– sneezing, injected conjunctiva, watery itchy eyes, red edematous eyelids, watery rhinorrhea, turbinates may be

pale or violaceous due to venous engorgement (instead of red and erythematous).

• Oral antihistamines prescribed first but do not alleviate ocular symptoms–nasal corticosteroids are indicated for patients who do not respond–most potent

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

Chapter 16: Asthma and COPD Medications

• Overview

• Short-acting Relatively Selective B2 Adrenergic Agonist Bronchodilators
  • Albuterol

o           Long- acting Relatively Selective B2 Adrenergic Agonist Bronchodilators

• Salmeterol xinafoate

o           Methylxanthines

• Theophylline

o           Anticholinergics

• Ipratropium bromide

o           Mast Cell Stabilizers

• Cromolyn sodium

o           Corticosteroids

• Aerosols
• Oral Solutions/Tablets

o           Leukotriene Modifiers

• Leukotriene Receptor Antagonist

• Montelukast (Singulair)

• 5-lipoxygenase Inhibitor

o           Combination Products

• Combivent
• Advair
• Symbicort

• Anatomy and Physiology

• Respiratory bronchioles = smooth muscle
  • Sympathetic stimulation through catecholamines—epinephrine on B2 adrenergic receptors = bronchodilation
  • Parasympathetic stimulation through the Vagus nerve and cholinergic receptors =

• Pathophysiology

• Asthma
  • Airway hyperresponsiveness—reaction to triggers
  • Airway inflammation—inflammatory mediators released
  • Airway obstruction—usually reversible—decline of the forced expiratory volume in 1 second
  • Classified on symptomatology, function, risk for exacerbation, and pulmonary function—FEV1 and forced

vital capacity—peak expiratory flow monitoring at home.

• Only mild intermittent asthma requires no daily

• Treatment

• Adult and Children
  • Persistent asthma with a low-dose ICS—an LM or mast cell stabilizer as an alternative to

long-term control.

• Moderate asthma with a LABA and a corticosteroid—never use LABA alone
• Severe asthma—a course of oral steroids—omalizumab new monoclonal antibody

directed at igE is the first biologic therapy for this use in >12 years.

• Urgent medical interventions—supplemental oxygen, mechanical ventilation, and

 

• Pharmacologic Treatment

• Long-term control
  • Corticosteroids (inhaled, occasionally systemic)
  • Mast cell stabilizers
  • Leukotriene modifiers
  • Long-acting beta2 agonists
  • Methylxanthines

• Quick relief

• Short-acting beta2 agonists
• Anticholinergics

• Systemic corticosteroids

• COPD—goals of treatment: to alleviate symptoms, enhance lung function, improve physical activity, reduce long- term decline, prevent and treat exacerbations, reduce hospitalizations and mortality, relieve disabling dyspnea, and improve tolerance and
  • Airway inflammation, edema, fibrosis of bronchial wall, hypertrophy of submucosal glands, hypersecretion

of mucus, loss of elastic lung recoil, destruction of alveolar tissue.

• Earliest symptoms—morning cough with clear or yellow

• Pharmacologic Treatment

• Maintenance
  • Anticholinergics
  • Beta-2 adrenergic agonists
  • Methylxanthines
  • Corticosteroids (inhaled and occasionally oral)
  • Expectorants

• Severe Exacerbation

• Anticholinergics
• Beta-2 agonists
• Methylxanthines

• Corticosteroids (oral)
• Mechanism of Action

• Beta Adrenergic Agonist Bronchodilators—sympathomimetics that activate the enzyme adenyl cyclase to increase production of cyclic adenosine monophosphate to inhibit phosphorylation of myosin and lowers intracellular concentrations of calcium = smooth muscle
  • Short-acting is used for relief of bronchospasm during asthma exacerbation or prior to exercise

• Using one inhaler per month is inadequate control

• Long-acting are first line in asthma and COPD

• Methylxanthines—promote bronchodilation by inhibiting phosphodiesterase and slowing down the breakdown of cAMP—also positive inotrope, diuretic—beneficial as add-on
  • Theophylline peak levels measured 8 hours after ingestion or 1 hour after quick release—no dose changes

x 3 days—5-15mcg/mL—do not exceed 400mg/day—discontinue breastfeeding.

• Possible toxicity—nausea, vomiting, insomnia, jitteriness, headache, rash, severe GI pain, restlessness, convulsions, or irregular

• Anticholinergics—nonselective competitive antagonists of muscarinic receptors in the airways and other organs— blocks acetylcholine -induced stimulation of cyclic guanyl cyclase and reduce its production—reduces airway secretions and resistance—more effective in COPD than asthma—used as first-line.
• Mast Cell Stabilizers—prevent and reduce inflammatory response—antiasthmatic and
• Corticosteroids—modify the body’s immune
• Leukotriene Modifiers—act on inflammatory mediators of asthma—leukotriene receptor

 

Chapter 66: Antitubercular Agents

• Overview

• Antituberculars
  • Isoniazid (INH)
  • Rifampin (RIF)
  • Rifabutin
  • Rifapentine

 

• Pyrazinamide (PZA)
• Ethambutol (EMB)
• Streptomycin (SM)
• Cycloserine
• Ethionamide
• P-Aminosalicylic Acid (PAS)

o           Aminoglycosides

• Amikacin/Kanamycin
• Capreomycin

o           Fluoroquinolones

• Levofloxacin
• Moxifloxacin
• Gatifloxacin

• Tuberculosis

• Mycobacterium tuberculosis–thick-walled
• Primary route–inhalation–bacilli are spread to the lymphatic system, may lodge in bone, bladder, of
• Cell-mediated immune response results in tubercle
• Non-immunocompromised exposed to TB and testing positive to skin test has 10% chance of developing active TB– HIV patients have 30-50%
• Most common site–pulmonary system–can also cause bone pain and UTI (rural areas)
• Reactivation Disease–occurs when a previously infected patient becomes immunocompromised–COPDers using prednisone
• Latent TB Infection–occurs when a patient in infected with TB bacteria but does not have symptom and cannot transmit the bacteria. Latent TB –> Active TB
  • 9-month treatment–many do not start it or do not end it
  • New treatment–12 weekly doses of Isoniazid and

o                          Clinical Symptoms

• Primary Pulmonary TB
  • Fever (70%)
  • Cough
  • Pain in chest when breathing/coughing
  • Productive cough with sputum or blood

• General Symptoms–Pulmonary or Disseminated

• Weight loss
• Malaise
• Fever
• Night sweats
• Children are usually asymptomatic or present with pulmonary symptoms

o                          Testing

• Mantoux Tuberculin Skin Test–0.1mL of protein purified derivative (PPD) with 5 tuberculin units injected intradermally to produce a discrete, pale elevation of skin 6-10mm in diameter

 

• Read 48-72 hours
• Positive results can be read up to 1 week after–are considered to have a latent tuberculosis infection.
• Negative test after 3 days–needs to be
• Measure induration (not erythema) crosswise to the axis of the forearms–record in millimeters– not negative or
• Close contacts of those with infectious TB with a negative PPD should be retested 10 weeks
• Previous vaccination of BCG does not change the need for treatment or
• Immunocompromised patients–evaluate for anergy prior to receiving PPD–FDA approved–

Mantoux-method tests (Mumps and Candida) –cutoff of 5mm of induration.

• Mumps Skin Test Antigen (MSTA) and tetanus toxoid (fluid) may be
  • Give 0.1mL of antigen intradermally and read 48-72 hours later–induration >

2mm is positive and PPD testing can proceed.

• False-Negative–HIV, lymphoma, and recent live

• Two-step method for patients with diminished skin test reactivity such as geriatric patients–give

PPD and a follow up 1-3 weeks later if the first is negative–then resume yearly testing.

• If the first test is negative and the second is positive–the patient is considered to have a positive PPD–reaction is called “boosted.”

o                          Diagnosis

• CXR is no longer a good screening tool among low-risk populations–should be obtained for all who have a positive PPD–PA and Lateral views first, Apical Lordotic views next if history is suggestive of TB and first CXR is

negative.

• X-rays indicate lung abnormalities that indicate active disease–films do not confirm that TB causes detected abnormalities–need a biopsy confirming caseation granulomas–yearly CXRs for those

who test positive are not needed, once you have a clear CXR you do not need another one unless you present signs/symptoms of TB.

• Sputum culture takes 6 weeks–diagnosis and severity relies on acid-fast bacilli smear (AFB)–sputum is

inspected under a light microscope for presence of bacteria—5,000-10,000 bacteria per mL.

• Persons with negative smear and positive sputum cultures cause a significant number of infections
  • Gastric aspiration is more cost-effective than
    • Used for infants and young children–should be performed in the morning before getting out of bed or eating.
  • Positive results = isolation
  • Mycobacterium Tuberculosis Direct Test gives results in 4-5 hours–but misses 5% of cases so culture is still required

o                          Presumptive Diagnosis of Active TB

• Recent conversion to positive PPD and signs/symptoms
• Positive sputum smear
• Characteristic CXR
• Biopsy with caseating granulomas
• HIV/AIDS

o                          Confirmed diagnosis of active TB is made by a positive culture from any body fluid or biopsy specimen.

 

• Medications
  • Isoniazid–prevents TB in high-risk patients without HIV–6-12 months–possible hepatotoxicity
    • Metabolized by acetylation and dehydrazination
  • First-Line: Isoniazid (INH), Rifampin (RIF), Ethambutol (EMB), Pyrazinamide (PZA).
    • Newly diagnosed pulmonary TB–6-month course of chemo with at least 2
      • Initial Phase–3-4 drugs given x 6-8 weeks
      • Continuation Phase–2 drugs given x 18

o                          Second-Line: Cycloserine, Ethionamide, Streptomycin, Amikacin/Kanamycin, Capreomycin, P-Aminosalicylic Acid

(PAS), Levofloxacin, Moxifloxacin, Gatifloxacin

• Aminoglycosides–end in cin, Fluoroqionolones–end in

• Dispense 1-month supply and monitor patient

• Isoniazid Prophylaxis

• Ask about signs of liver damage:
  • Anorexia, nausea, vomiting, fatigue, weakness, new and persistent paresthesia of the

hands/feet persistent dark urine, icterus, rash, elevated temp

• INH Hepatitis–over 35, daily drinkers, concomitant hepatotoxic medications, and history of liver disease

• Inhibits the metabolism of Phenytoin and Carbamazepine§                          Pregnancy and Lactation

• Category C–three-drug regimen–INH, RIF, EMB–cross the placenta–not teratogenic
• Category D–aminoglycosides–Ethionamide–teratogenic
• Do not discourage breastfeeding

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• Rifampin induces cytochrome P450–decreases the half-life
•                        Active TB

• CXR at baseline and 6 months
• Sputum culture and smear at baseline and monthly until negative
• If patient has baseline abnormality or is at increased risk for hepatotoxicity–LFTs, bilirubin, creatinine,

CBC, platelets, and serum uric acid at baseline and monthly–for those taking INH, RIF, and EMB.

• If on EMB–ask about blurry vision or scotomata–monthly visual testing for visual acuity and color discrimination for doses > 1mg/kg or therapy > 2 months–monitor color vision for red-green at baseline and 2-3 months
  • Drug is not recommended for children/teens unless routine eye exam is done–not for

children younger than 13 unless benefit outweighs risk.

• If on INH–periodic ophthalmologic exams
• If on Pyrazinamide–obtain glucose levels
• If on Streptomycin–obtain audiogram at baseline at 2-3 months–monitor blood serum concentrations
  • Not recommended for use in children
• If on Cycloserine–monitor blood levels if renal patient
  • Not for pediatric use–or Ethionamide

 

• Treatment

• Latent Infection
  • Isoniazid + Rifapentine x 3 months
    • HIV–treatment begins when TB is
    • Non-HIV–treatment starts after definitive

o                          Active Infection

• Report all cases to local and state health authorities–within 24 hours–maintain respiratory isolation
• Test and treat all close
• Monitor for compliance and response to
• Direct Observed Therapy (DOT) is more
• Administer multiple drugs to which the organisms are susceptible–add 2 new anti-tubercular agents when

treatment failure is suspected.

• Incidence of resistance is high–patterns of resistance determine local

• Health Care Provider should assess for–history of hepatitis, heavy alcohol ingestion, liver disease, or age older

than 35 years–monitor LFTs–adjust therapy.

 

• Assume patient is contagious if–cough is present, cough-inducing procedures are ordered, patient is on therapy x 1 week, patient is not responding to
  • Never add single drugs to a failing regimen

Chapter 67: Antifungals

• Overview

• Azoles
  • Imidazoles
    • Clotrimazole
    • Econazole
    • Ketoconazole
    • Miconazole
    • Oxiconazole

• Triazoles

• Fluconazole
• Itraconazole
• Voriconazole
• Posaconazole

• Allylamines

• Terbinafine
• Naftiline

• Benzylamine Derivatives

• Butenafine

• Polyenes

• Nystatin
• Amphotericin B

• Echinocandins

• Caspofungin
• Micafungin
• Anidulafungin

• Hydroxy pyridines
• Ciclopirox
• Other
• Griseofulvin Microsize and Ultramicrosize

 

 

• Anatomy and Physiology

• Fungi
  • Mold—multicellular colonies of tubular structures (hyphae)—grow by branching and longitudinal extension.
  • Yeasts—unicellular fungi, round or oval, reproduce by budding—long chains—pseudo
  • Mycosis—presence of parasitic fungi in or on the

• Disease Process

• Topical Fungi
  • Tinea capitis—caused by Trichophyton tonsurans–requires systemic
  • Tinea corporis—caused by rubrum—may respond to topical or need systemic treatment.
  • Tinea versicolor—caused by Malassexia furfur—requires systemic
  • Mucosal candidiasis—caused by candida
    • Invasive candidiasis—neutropenia, recent surgery, broad-spectrum antibiotic therapy, indwelling

catheters, and immunodeficiency—suspect HIV.

• Endemic Mycoses—in rural and regional populations—maintain suspicion—skin scrape
  • Caused by inhalation during the mold phase—presents as atypical pulmonary infection
  • Histoplasmosis—caused by histoplasma capsulatum—bird droppings and bat exposure—severe infections

show marked prostration, fever, dyspnea, and loss of weight.

• Blastomycosis—caused by Blastomyces dermatidis—occupational and recreational contact with soil— severe infection can cause lesions on the lungs, skin, bones, and in the urogenital system—primarily cutaneous symptoms via papules, nodules, or
• Pneumocystosis—caused by pneumocystis jiroveci—found in the lungs of domesticated and wild

mammals—causes acute pneumonia—cause of dead with AIDS.

• Cryptococcosis—caused by Cryptococcus neoformans—yeast in soil and pigeon droppings—inhaled.
• Aspergillosis—caused by aspergillus fumigatus—found in soil and decaying vegetation—may invade food

and water—colonized in burn eschar and detritus in the external ear canal—bronchospasm and

pulmonary infiltrates.

• Mechanism of Action

• Azoles—more fungistatic instead of fungicidal—inhibit ergosterol synthesis—inhibition of cell growth and

replication.

• Terbinafine—blocks synthesis of ergosterol—collapsing the fungal cell
• Griseofulvin—penicillium derivative—deposits into keratin of diseased tissue and creates resistance to fungal infection.

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• Treatment

• Topical fungi are often resistant to PO treatment—terbinafine, itraconazole,
• Endemic fungal infections—itraconazole,

o         Unclear duration of treatment

• Griseofulvin—tinea capitis of skin, hair, and nails that are unresponsive to topical

• Monitoring

• Initial
• Signs/symptoms of hepatitis—fatigue, anorexia, nausea, vomiting, jaundice, dark urine, or pale
• LFTs for baseline and periodically—q4-6 weeks in healthy patients, q2 weeks in
• High doses of itraconazole—adrenal suppression, hypokalemia, and secondary v-fib.
• Terbinafine—monitor CBC for treatment >6
• Griseofulvin—baseline and periodic renal, liver, and hematopoietic
  • Bioavailability improves with food—may cause headaches, disappear with continued therapy or food— notify provider of skin rash or sore throat—may potentiate effects of
• Geriatrics—greater risk for hepatotoxicity—use renal

o         Children

• Fluconazole >6 months
• Itraconazole 6 months – 12
• Griseofulvin—>2 years old—estrogen-like effects—enlarged breasts, hyperpigmentation or areolae,

nipples, and external genitalia.

• Griseofulvin and Ketoconazole may cause
• Women of childbearing are should use back up contraception when taking -azoles.

 

Chapter 69: Antivirals and Antiprotozoal Agents

• Overview

 

• Antivirals
  • Antiherpes
    • Acyclovir
    • Famciclovir
    • Valacyclovir
    • Penciclovir
    • Antiinfluenza
      • Amantadine
      • Rimantadine
    • Neuraminidase Inhibitors
      • Oseltamivir
      • Zanamivir

• Antiprotozoals

• Metronidazole
• Tinidazole
• Chloroquine

• Virus—single or double stranded DNA or RNA molecule enclosed in a protein—some have lipoprotein envelope—may

contain proteins that cause antigenic reactions or enzymes that initiate viral replication—lacks metabolism or synthesis and

relies on host—do not produce waste, do not reproduce independently.

o         DNA Viruses

• Herpesvirus—Acyclovir, Famciclovir, Valacyclovir—all used for short, long, and breakthrough use—

Penciclovir

• Chickenpox
• Shingles—start treatment within 48
• Herpes 1 and 2
• Epstein-Bass

• The peak of viral activity and reproduction occur prior to the appearance of symptoms—therapy is always

prescribed late in disease process—viral agents inhibit reproduction but do not eradicate latent viruses

• Adenovirus

• Conjunctivitis
• Pharyngitis

• Hepadna virus

• Hepatitis B

• Papillomaviruses

• Warts

o         RNA Viruses

• Rubella

• German measles

• Rhabdoviruses

• Rabies

• Picornaviruses

• Poliomyelitis
• Meningitis
• Colds

• Arboviruses

• Yellow fever

• Orthomyxoviruses

• Influenza A and B
  • Amantadine, Rimantadine—recently developed resistance—largely
  • Zanamavir—inhaled, generally unavailable, Oseltamivir—cuts the length of symptoms

but does not prevent against pneumonia—neuropsychiatric symptoms have been

reported.

• Paramyxoviruses

• Measles and Mumps
  • Antivirals—narrow spectrum of activity inhibiting replication but not killing the virus—target a specific viral protein

—an enzyme involved in viral nucleic acid synthesis.

 

• Protozoa—Helminths—Arthropods—small unicellular, categorized by locomotion—Metronidazole (cytotoxic agent—

damages DNA synthesis—can be used for bacterial, trichomoniasis, amebiasis, giardiasis, and C. diff—vancomycin still used

for severe cases—effective on gram negative and positive anaerobes—reaches high concentrations in tissues—also for H. pylori with bismuth, a PPI, an antihistamine, and an antibiotic), Tinidazole

• Malaria
  • Chloroquine (raises internal pH of parasites—given weekly 1 week prior to travel).
• Amebiasis
• Giardiasis
• Trichomoniasis

• Monitoring

• Antivirals—monitor for toxicity and adverse effects—especially with renal
  • Decrease dose for geriatrics
• Antiprotozoals—monitor for muscular weakness—knee and ankle
  • Metronidazole—CBC with diff before and after
  • Chloroquine—baseline and periodic ophthalmic examinations

 

Chapter 51: Glucocorticoids

• Overview

• Glucocorticoids
  • Short Acting
    • Hydrocortisone
    • Cortisone

• Medium Acting

• Prednisone
• Prednisolone
• Methylprednisolone

• Long Acting

• Dexamethasone
• Betamethasone
• Used for inflammatory and immunosuppressive actions–replacement therapy for adrenal                                       Anatomy and Physiology

• Adrenal Cortex
  • Cortisol (Glucocorticoid)–anti-inflammatory effect, modifies immune response, influences metabolic processes–production controlled by negative feedback loop involving the hypothalamus-anterior-pituitary-

adrenal cortex (HPA) axis.

• Low Cortisol –> anterior pituitary produces ACTH –> adrenal cortex increases cortisol secretion

 

• Released naturally in uneven pattern over 24 hours–10mg/day–highest in AM 2a-7a, and lowest in evenings 6p-12a.

• Aldosterone (Mineralocorticoid)–renin-angiotensin system–regulates Na, K, and water
• Androgen (sex steroid)

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• Mechanism of Action

• Glucocorticoids
  • Affect the Metabolism of Carbs, Proteins, and Fats
    • Maintains adequate level of serum glucose–stimulates gluconeogenesis in the liver and inhibits

peripheral glucose use–stimulate protein breakdown.

• Stimulate protein breakdown to increase amino acid levels–these enhance enzymatic activity and supports increased glycogen deposition and decreased glycolysis–maintains homeostasis but can result in

diabetogenic state when large doses of exogenous glucocorticoids are used–latent diabetes or glucose intolerance while on steroid therapy.

• Increase protein breakdown = muscle atrophy, osteoporosis, impaired wound healing,

and thinning of skin–growth impairment in children.

• Mobilization of fats from area of deposition–buffalo hump, moon faces, and loss of subcutaneous fat in

• Direct/Indirect Effects on Immune Response

• Mask the manifestations of immunity:
  • Cellular–primarily mediated by T-lymphocytes–block several steps in the cascade of T-

cell activation and impede the ability to mount an effective cellular immune response–used after

transplantation.

• Humoral–interaction of B-lymphocytes with macrophages and helper T-lymphocytes to create antibodies–do not decrease the number of antibodies but inhibit antibody production by interfering with macrophage function and activation of

• Steroid administration affects circulating WBCs–decrease in lymphocytes, monocytes,

and eosinophils, increase in neutrophils–lymphocytes are sequestered to lymph tissue, T-cell

numbers fall below B-cell–neutrophils are released from bone marrow in greater numbers and are removed from circulation slowly under the influence of exogenous Glucocorticoids = redistribution of WBC types rather than a true leukopenia.

 

• Modulate Inflammatory Response

• Inhibit early manifestations of inflammation–local edema, capillary dilation, migration and activation of WBCs, and phagocytosis–and later effects proliferation of capillaries and collagen
  • Simultaneous inhibition of inflammation and immune response = effectiveness in acute

asthma and allergic reactions.

• Monitor suppression–serious infection or illness may be masked by absence of characteristic signs of inflammation/immune system

• Plays a Role in the Body’s Response to Stressful Stimuli

• Surgery, fright, starvation, and abrupt physiologic change
  • Release of glucocorticoids from adrenal cortex and release of epi/norepi from adrenal

medulla

• Potentiate the effects of catecholamines–raise HR, BP, and glucose in “fight or flight”

• Other Effects

• Changes in mood, sleep pattern, and motor activity–upregulation and euphoria–or anxiety and depression–rarely causes steroid psychosis–discontinue
• Increase hemoglobin concentration, RBCs, and
• Impede child growth–brain, lung, liver, skin, and epiphysis of long bones–osteonecrosis.
• When taken orally–increases an enzyme that inactivates vitamin D, causing deficiency–

osteomalacia, Rickets, clinical myopathy, drug-induced osteoporosis–vitamin D deficiency is not seen

through inhaled route.

• Mineralocorticoids–activity is needed in adrenal insufficiency but not in
  • Hydrocortisone and Cortisone both have Glucocorticoid and Mineralocorticoid
  • Prednisone, Prednisolone, and Methylprednisolone–synthetic analogs–also have Glucocorticoid and

Mineralocorticoid properties–predominately Glucocorticoid.

• Triamcinolone, Dexamethasone, and Betamethasone–exclusively Glucocorticoid anti-inflammatory response.

 

• Treatment–length of therapy and how it is stopped
  • Short-term–2 weeks or less–do not titrate off
  • Long-term–very gradual dosage reduction
  • Steroid administration suppresses the hypothalamic-pituitary axis (HPA)–leaves the body compromised during periods of physiologic stress due to complete/partial dependence on exogenous Glucocorticoids–HPA suppression requires 12-month

 

• Consider short-acting or QOD therapy for long-term therapy–double dose every other morning–causes less HPA axis and child growth
• Daily therapy required for acute exacerbations and limited number of conditions–temporal arteritis,

pemphigus vulgaris.

• Minimize steroid injections in older women and those at risk for osteoporosis
• Give medication along with natural peak time activity–before 9a–divide large doses–oral glucocorticoids with
• Drug of choice–Prednisone–medium duration, minimal mineralocorticoid effect, and low cost–4x anti-

inflammatory–initial dosage may be high to achieve control of symptoms, titrate dose to point of worsening

symptoms.

• Monitor

• Long-Term Therapy
  • Baseline weight, blood pressure, serum glucose, serum potassium, vitamin D level, bone mineral density
  • Monitor for edema, weight gain, negative nitrogen balance, electrolyte imbalance, increased BP…signs and symptoms of disease
    • During titration, monitor for steroid withdrawal and adrenal insufficiency
  • Pregnancy–cross the placenta and appear in breast milk–long-term therapy in 1st trimester = 1% increase in cleft palate–discourage breastfeeding, monitor baby for

·		Cold, clammy skin, tachycardia, tachypnea, weakness, irritability, poor feeding, dehydration.
·		Prednisone/Prednisolone <20mg/day
·		Methylprednisone <8mg/day
	§	Wait 3-4 hours to breastfeed

• Avoid live-virus vaccines
• Do not use in the presence of systemic fungal infection

 

Chapter 52: Thyroid Medications

• Overview

• Thyroid Supplements
  • Levothyroxine Sodium (Synthetic T4)
  • Liothyronine (Synthetic T3)
  • Liotrix (T4:T3 = 4:1)

o           Thyroid Suppressants

• Methimazole
• Propyllthiouracil (PTU)

o           Adjunctive

• Thyrotropin

• Anatomy and Physiology

• Hypothalamic-Pituitary-Thyroid Feedback Control System–regulates basal metabolism
  • T4 (thyroxine) and T3 (triiodothyronine) are released by thyroid in response to circulating TSH released by pituitary
    • TSH secretion is influenced by TRH released from the
    • Inverse relationship–T3 T4 and TSH TRH
    • Elevated TSH with low levels of circulating free and unbound T3 and T4–diagnostic of primary hypothyroidism.
      • Primary hypothyroidism–failure within the thyroid gland

• Causes

• Iatrogenic–the result of thyrotoxicosis treatment or other medications

(Lithium).

• Idiopathic thyroid atrophy, autoimmune destruction of thyroid (Hashimoto’s thyroiditis), or post-partum thyroid disease
• Thyrogen–recombinant DNA source of human TSH for management

and treatment of thyroid cancer.

• Pituitary thyroid-stimulating hormone (TSH) Suppression–treatment of euthyroid goiters and management of thyroid cancer

• Low TSH with high levels of circulating free and unbound T3 and T4–diagnostic of
• Low TSH with low T3 and T4 OR high TSH with high T3 and T4–diagnostic for central cause (secondary or tertiary) of hypothyroidism or
  • Secondary hypothyroidism–lack of TSH secretion from pituitary
  • Tertiary hypothyroidism–lack of TRH secretion from the
• Thyroid gland releases T4 (90%), T3 (10%), and reverse T3 (rT3) <1%–elevated rT3 is diagnostic for euthyroid sick

syndrome.

• T3 and T4 are mostly protein bound–unbound portion is metabolically active–T4 has higher protein affinity and longer half-life
• T4 is converted to T3 in the peripheral tissues through removal of iodine–administered T4 and the body

will make T3.

• Physiologic effects of thyroid hormones are due to peripheral T3–basal metabolic rate, O2 consumption, respiratory rate, body temp, HR, SV, enzyme system activity, metabolism, growth, and

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• Treatment

• Levothyroxine (T4) for hypothyroidism–individualized dosage–labs + patient response–small therapeutic range

·		T3 can rapidly correct a hypothyroid state–radioisotope scanning or thyroid cancer.
·		T3 + T4 rarely used for patients that cannot metabolize T4 into T3.
·		In event of toxicity–discontinue x 5-7 days and resume at a lower dose
·		Dosage
	§	1.6mcg/kg/day–reassess and titrate every 4-6 weeks–until a normal TSH level is obtained–

maintenance dose of 75-150mcg–single daily dose before breakfast

• Adults 50-100mcg/day
• Elderly and history of CAD 25mcg–may exacerbate CAD and angina–CHF is atypical presentation–absorption increases with

• Bioequivalence based on T4 measurement–not TSH–bioequivalence is not the same as

therapeutic equivalence–keep the same brand throughout treatment.

	§	Do not use as replacement therapy: desiccated thyroid hormone, combination thyroid hormone,
·	§	triiodothyronine Monitor T4, free T4–only T4 must be measured
	§	Thyroid-binding globulin–TBG (proteins to which thyroid hormones are bound) –measured by
		TBG test
§ §		· ·	Resin T3 uptake–no longer used If patient has abnormal TBG, evaluate free T4 Check TSH 4-6 weeks–3-6 weeks for full therapeutic effectiveness. TSH and symptom review monitored monthly until stable
		·	Check annual once at maintenance dose and if patient has signs/symptoms of
§		·	over/underdosage. Children < 3 years Keep at upper end of T4 therapeutic range with a normal TSH–monitor every 1-2

months x 1 year old, every 2-3 months x 1-3 years old, and every 3-12 months thereafter.

• Congenital hypothyroidism–may discontinue 2-8 weeks after age 3–discontinue permanently if TSH levels remain normal.

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• History of thyroid cancer with partial or total thyroidectomy must take thyroid hormone supplements to suppress endogenous levels of TSH and to regulate
  • High levels of TSH allows for radioiodine imaging to detect remnant thyroid tissue or
    • Thyrogen instead of discontinuing thyroid hormones prior to imaging study
  • Pregnancy–category A–minimal in breast milk–may need dosage adjustment to meet increased energy demands–

monitor TSH closely.

• Thyroid Suppressants

• Thyrotoxicosis–primary hyperthyroidism–Graves’ Disease (autoimmune–diffuse toxic goiter), toxic nodular goiter (hyperfunctioning of uninodular or multinodular goiter), and iodide-induced hyperthyroidism (iodide is iatrogenic), thyroid inflammatory diseases (postpartum thyroiditis and subacute thyroiditis).
  • In thyroiditis, thyrotoxicosis is usually
  • Excessive synthesis of thyroid hormone increases basal metabolism to potentially fatal levels–results in

systemic collapse

· ·	§ § §	TSH will be suppressed and T3 and T4 will be elevated Geriatrics may have atypical presentation–lassitude, anorexia, and palpitations (a-fib). Mechanism of Action Diversion of iodine causes inhibition of thyroid hormone synthesis. ·                        PTU also inhibits the T4 to T3 conversion Suppressants do not affect stored or circulating levels of T3 and T4–also do not affect oral and
·	§ §	parenteral thyroid supplements ·                                                                                                     Methimazole is longer acting and requires a less frequent dosage schedule Treatment First-line for Graves’ and toxic multinodular goiter–Radioactive iodine ·                                                                                                     Geriatric/CAD–pre-treat with antithyroid medication Second-line–surgical intervention
	§ §	Third-line–anti-thyroid drugs–Methimazole > PTU except in first trimester of pregnancy Rest, adequate diet, and avoidance of stress. ·                        Antithyroid drugs are prescribed to achieve remission of symptoms–remission rates are

variable and relapse rates are frequent–half of patient experience full remission–temporary hypothyroidism occurs with over treatment.

• Symptoms improvement in 1-2 weeks–euthyroid in 4-8 weeks. Patient should be

euthyroid before surgery.

• Therapy duration is 12-18 months–patient should be euthyroid 6-12 months before decreasing medication to determine if remission was

• Beta-adrenergic blocking drugs–Propranolol or Atenolol can be used to control

signs/symptoms of thyrotoxicosis related to sensitization of the sympathetic nervous system

• Use Beta-adrenergic blocking drugs cautiously with patients with asthma or HF.
• Monitor

• T3 and T4 levels are monitored initially and after every 3-6 weeks until euthyroid state–then

every 3-5 months.

• When clinical thyrotoxicosis has resolved, an elevated TSH levels indicates the need to lower the dosage.
• WBC initially, with signs/symptoms of infection, and routinely for the first 3-5 months of

treatment.

• PTT during therapy and before procedures
• Possible hepatotoxicity–AST, ALT alkaline phosphatase, LDH, bilirubin, and PT
• Every visit–monitor for signs/symptoms of infection, correction of hypermetabolic state– evaluate for hepatitis, agranulocytosis (assess bone marrow function), and GI
• Pregnancy–category D–crosses placenta and can induce goiter or cretinism–PTU is preferred–

thyrotoxicosis in pregnancy diminishes as it progresses.

• Do not take while breastfeeding.

• Avoid ingesting iodine containing
• Notify signs and symptoms of fever, sore throat, malaise, unusual bleeding or bruising, headache, skin rash, or enlargement of cervical lymph

 

Chapter 53: Endocrine Agents

• Overview

• Insulin
  • Rapid Acting
    • Insulin Lispro (Humalog)
    • Insulin Aspart (Novolog)
    • Insulin Glulisine

• Short Acting

• Regular Insulin

• Intermediate Acting

• NPH Insulin

• Long Acting

• Insulin Glargine (Lantus)
• Insulin Detemir (Levemir)

• Mixtures

• Oral Medications
  • Second-Generation Sulfonylureas
• Glyburide
• Glipizide
• Glimepiride

• Biguanides

• Metformin

• Thiazolidinediones

• Rosiglitazone
• Pioglitazone (Actos)

• Non-Sulfonylureas Secretagogues (Meglitinides)

• Nateglinide
• Repaglinide

• Alpha-Glucosidase Inhibitors

• Acarbose
• Miglitol

• Incretin Agents

• Amylin Analogs
  • Pramlintinde
• Glucagon-like Peptides
  • Liraglutide (Victoza)
• Incretin Mimetics
  • Exenatide (Byetta)
• Dipeptidyl Peptidase-4
  • Linagliptin
  • Saxagliptin
  • Sitagliptin Phosphate (Januvia)

• Bile Acid Sequestrants

• Colesevelam

• Bromocriptines

• Bromocriptine

• Combination Therapies

• Sitaglipin/Metformin (Janumet)

 

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

• Anatomy and Physiology

• Pancreas (gland)

• Exogenous

• Endogenous
  • Isle of Langerhans–1-2% area–1 million cells–80% beta cells produce and secrete insulin–alpha cells produce glucagon (glycogenolysis [converts glycogen into glucose] and gluconeogenesis [converts

lactate and amino acids to glucose])

• Elevated blood glucose–beta cells stimulated to produce and secrete insulin—insulin allows muscles and liver to use glucose and to store it as glycogen in the liver–also facilitates fat

storage in adipose tissue and uptake/conversion of amino acids to protein.

• Pathophysiology

 

• Diabetes--a relative or absolute lack of insulin and/or insulin resistance and impaired or insufficient target cell receptors = lack of glucose for cell metabolism = glycogenolysis, lipolysis, and
  • Glucose uptake by the liver is impaired and results in increased circulating glucagon–protein storage is

decreased = overproduction of free fatty acids = increase hepatic glucose production by stimulating

gluconeogenesis.

• DM2–insulin resistance and beta cell dysfunction–at diagnosis, 50% beta cell function is 1
  • Insulin secretion is biphasic–rapid secretion 3-5 minutes after glucose rises and duration is 10

minutes, if glucose remains elevated, a slower release is triggered.

• DM2 loses the first phase, post-prandial hyperglycemia is the first sign–causes glucotoxicity and beta cells become more dysfunctional–the lack of insulin increases

gluconeogenesis and glycogenolysis, causing further hyperglycemia–causes elevated fasting glucose levels.

• DM1 autoimmune destruction of beta cells–onset may occur suddenly with DKA or slowly with latent

autoimmune diabetes of adults (LANA).

• Test all adults with BMI >25 and have one or more risk factors–without risk factors, test all adults > 45
  • Risk Factors–inactivity, first-degree relatives with DM, high risk race/ethnicity, A1C > 5.7% or impaired glucose tolerance test, history of gestational DM or giving birth to baby > 9lbs, HTN, HDL <35 or Triglycerides > 250, PCOS, obesity, conditions associated with insulin resistance, and
    • A1C of < 7% delays complications
      • Advise patients to lose 5-10% weight and increase physical activity to 150 mins/week– 50-70% max HR, and resistance training 3x/week (if no contraindications).
      • Metformin therapy–for patients who hit several risk factors and are < 60
      • Target A1C goal for non-pregnant women is <7%.
      • Titrate medications and augment therapy over time (especially as glucotoxicity and beta

cell destruction occur).

• Goals–maintain optimal control and lessen vascular and neurologic complications of the disease.

• Assessment–obtain a thorough H&P
  • Skin changes, visual problems, thyroid function, cardiac arrhythmias, HTN, lipid abnormalities, history of CAD or CHF, and review of
  • Physical Examination–height, weight, BMI, BP, vitals, eye, mouth, thyroid, heart, lungs abdomen (hepatic enlargement), bruit, pulses, hands, feet, skin (acanthosis nigricans, inflammation, infection) and nervous system (reflexes, sensory examination of feet).
  • Laboratory Evaluation–CBC, CMP, BUN, TSH, Hgb, and HbA1c (8-12 weeks of glycemia), fasting lipid profile, UA, microalbuminuria, and ECG in adults.

• Mechanism of Action

• Insulin–proteins that bind to cell wall receptors to allow cellular utilization of glucose–lowers blood glucose levels

· Using synthetic human insulin decreases the chances of antibodies and lipodystrophy at injection site. · If glycemic control is not reached with an oral antidiabetic agent–add insulin! § Indications: ·                        New DM and severe hyperglycemia (>300) ·                        Pregnancy ·                        Intercurrent illness/surgery ·                        Renal or hepatic disease ·                        Allergies or intolerance ·                        Maxed out on 2 oral antidiabetics ·                        Increased hyperglycemic symptoms, weight loss ·                        Low C-Peptide. · Types § Rapid: Lispro (Humalog) § Short: Regular (Humulin R, Novolin R) § Intermediate: NPH (Humulin N, Novolin N) § Long-acting: Glargine (Lantus) § Combinations

by stimulating peripheral glucose uptake, and inhibits hepatic glucose production.

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

• 70% NPH/30% regular: Novolin 70/30
• 70% Aspart protamine/30% Aspart: Humulin 70/30, NovoLog 70/30

• DM2 Regimens

• Basal Therapy with Oral Agents
  • Glargine (Lantus) or detemir (Levemir) 10 units or 2 units/kg q HS–increase 2-4 units every

3-5 days until goal.

• NPH insulin 10 units at dinner or HS–increase 1-2 units every 3-5 days

• Pre-Mixed Insulin Regimens

• 70/30 or NPH/Regular insulin at dinner–good for elevated bedtime and fasting glucose levels
• 70/30 at breakfast and dinner–good for elevated glucose throughout the day and patient is

not a candidate for additional oral agents.

• NPH/Regular Insulin Before Breakfast and Dinner

• 2 units/kg–total daily dose–give 2/3 in AM and 1/3 before dinner–divide doses into 2/3

NPH and 1/3 Regular.

• Basal-Bolus Regimen–long-acting insulin with pre-meal rapid insulin

• Monitor blood sugars frequently
• Add pre-meal rapid or short acting insulin to the largest meal–prandial boluses of rapid-acting insulin can be added to other mealtimes–rapid and short-acting insulin

can be added as standing doses or on a sliding scale based of glucose readings.

• Twice daily premixed insulin is given before breakfast and dinner–for patients unwilling to take multiple daily injections.

• Stresses–fever, infection, trauma, surgery–may cause temporary loss of glycemic control–

induces activation of glucagon, cortisol, growth hormone, and catecholamines.

• DM1 Regimens

• Long-acting or intermediate-acting insulin for basal coverage–second phase
• Rapid-acting or regular insulin for bolus coverage before meals–first phase
  • 1-2 units per 10g-15g CHO
• Open-loop insulin pumps, continuous subcutaneous
  • Help mimic physiologic
  • Dosage is determined by blood glucose

o           Monitoring

• Weekly x 1 month–then monthly, or PRN
• Teaching–hypoglycemia, build rapport with patient
• Pre and post prandial sugars
• A1C at baseline and q 3 months
• Microalbuminuria yearly–start an ACE or ARB if
• Monitor lipids
• Long-acting Degludec Insulin can raise 10% risk of unstable anginal non-fatal stroke, non-fatal MI, and CV
• Pediatric–no Sulfonylureas, Meglitinides, and Alpha-Glucosidase Inhibitors—Biguanides (10-16) 500mg BID total

dose 2,000mg

• DO NOT TAKE–bitter melon, fenugreek, and St. John’s wort

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

• Sulfonylureas–second-generation are used–Chlorpropamide (still available but rarely used) –enhance insulin secretion by binding to receptor sites on beta cells–decreased potassium permeability and membrane depolarization–increases intracellular calcium ions–causes exocytosis of insulin into the portal vein and increased muscle glucose uptake via elevated insulin
  • Previously first-line for DM2–now second-line treatment for
  • Work best in early DM2 where patient still has pancreatic function–lose effect with disease
  • Beneficial in patients with normal or slightly increased
  • Glyburide (Micronase) is more potent than Glipizide and more likely to cause

• Start with long-acting Glipizide (Glucotrol XL).

• Glimepiride may cause less weight gain and

• Max doses reduce A1C by 1.1%-1.9% and lower blood sugar by 20%.

• Do not control fasting glucose–use Acarbose–combination can also diminish insulinotropic and weight-

increase side effects.

• Monitor–renal function annually and CBCs

• Biguanides—Metformin decreases hepatic glucose production–has minor effects on insulin sensitivity in liver and

peripheral tissues–has no direct effect on the pancreas and does not enhance insulin secretion–can also decrease triglycerides and LDLs and increase HDLs.

• First-line for DM2

• Antihyperglycemic–not
• Combined with a Sulfonylureas.
• Improves insulin action in muscle tissue and lowers free fatty acids but to a lesser degree than Thiazolidinediones.
• May suppress appetite = slight weight loss
• Helpful in obese patients–improves fasting, postprandial glucose, and triglycerides

• Decreases A1C by 0.9-1.4%.

 

• Patients on Metformin have less risk for mood disorders–especially when combined with a
• Monitor–lactic acidosis (nausea, abdominal pain, tachycardia, hypotension, tachypnea (if severe) –electrolytes, ketones, blood glucose, blood pH, lactate, pyruvate, metformin levels, serum Cr–avoid with renal and hepatic

impairment

• Contraindicated for Cr >1.4 in women and >1.5 in men

• Geriatric–accumulation with renal insufficiency and increased risk of Metformin Associated Lactic Acidosis

• Withhold therapy of procedure with iodinated contrast media–resume no sooner than 48 hours afterward or when

renal function returns to baseline.

• Thiazolidinediones—Rosiglitazone and Pioglitazone increase muscle and liver sensitivity by improving control of glycemic utilization–this reduces circulating insulin levels–must have functioning beta cells–agonists for peroxisome proliferator-activated receptors (PPAR) found in adipose tissue, skeletal muscle, and liver activation regulates the insulin–responsive genes involved in the control of glucose production, transport, and utilization and facilitates the regulation of fatty acid
  • Rosiglitazone (Avandia)–undergoes risk evaluation and mitigation strategy to restrict access and distribution due

to increased risk for heart attacks.

• Pioglitazone (Actos)–comes with warning about possible risk of bladder cancer if used > 1
• Monitor–LFTs (contraindicated if AST > 5 the upper limit of normal) –monitor every 2 months x 1 year–hepatic dysfunction–unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, and dark urine.
  • “Black Box Warning”–may increase risk for ischemic event–monitor for CHF, edema, dyspnea–do not use

for CHF or recent MI patients–monitor for fluid retention and fat accumulation.

• Rosiglitazone + Insulin + Nitrates = NO!

• Meglitinides—Repaglinide and Nateglinide lower blood sugar by stimulating the release of insulin from the pancreas

in short bursts, must have functioning beta cells–they bind receptor cells to close ATP-dependent potassium channels in the beta membrane–this opens calcium channels for influx of calcium and insulin secretion

• Second-line treatment for
• Short-acting secretagogues–only taken with meals–low risk of
• For patients with low fasting glucose but high postprandial glucose
• Rather weak, used as an adjunct for mild DM,
  • Repaglinide has longer duration than Nateglinide.

• Max doses reduce A1C by 0.5-1.3%.

• Alpha-Glucosidase Inhibitors—Acarbose and Miglitol inhibit pancreatic alpha-amylase and membrane-bound intestinal

alpha-glucoside hydrolase enzymes (brush border of the small intestine) –these enzymes metabolize complex starches into oligosaccharides and break down saccharides to glucose and other monosaccharides–enzyme inhibition delays glucose absorption and lowers post prandial hyperglycemia–insulin secretions is not enhanced.

• Second-line treatment for
• Short-acting–taken with meals
• GI SIDE EFFECTS–flatulence, diarrhea, abdominal pain–work in gut!
• Prevent the absorption of sucrose–treat hypoglycemia with glucose or lactose–not table sugar!
• Acarbose has fewer problems with systemic absorption than Miglitol.
• Max doses reduce A1C by 3-0.8%.
• Monitor–LFTs q 3 months x 1 year

• Incretin Agents–hormones released from gut post prandially–stimulate insulin secretion in pancreatic beta cells and restore the biphasic release of
  • Amylin Replacement—Pramlintide is an analog of amylin–endogenous peptide that is secreted with insulin from

the beta cells–produces the same effect as Amylin and stable enough to be used as medication.

• Suppress glucagon production (especially in post prandial state), reduce post prandial hepatic glucose production, delay gastric emptying, centrally mediate induction of satiety, reduce post prandial glucose

levels.

• Indicated for patients with DMI and insulin-dependent
• Given subcutaneously TID immediately AC (meals >200 kcals or 30g CHO) –administer as a separate

injection and with insulin–works in the presence of glucose–skip a dose if forgotten

• Pramlintide and Insulin have reduced A1C an additional 4-0.7% in DM1 and DM2 (with or without Metformin and a Sulfonylurea)
• Helpful for wide glycemic swings–weight neutral or loss–monitor blood glucose and adjust

frequently.

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

• Adverse reactions–nausea, vomiting, headache, anorexia, early satiety, and vomiting-– subside over 4 weeks.
  • Severe hypoglycemia with DM1, lower insulin dosage by 50% prior to
  • Contraindicated for patients with hypoglycemia unawareness and
• Glucagon-Like Peptide 1 (GLP1) –regulates glucose homeostasis via complementary actions–stimulate glucose- dependent endogenous insulin secretion (and perhaps insulin sensitivity), inhibit endogenous glucagon

secretion, suppress appetite/induce satiety, reduce rate of gastric emptying, and protect beta-cells from cytokine and free fatty acid-mediated injury.

• Exenatide (Incretin mimetics) (Byetta and Bydureon)–synthetic version of naturally occurring hormone–derived

from a component of Gila monster saliva–Exenatide binds to GLP1 and stimulates secretion when glucose levels

are high–first drug to restore the first phase of insulin secretion (usually does not occur with DM2)–increases insulin release, restores first-phase insulin secretion, suppresses glucagon secretion, and slows gastric emptying–stimulates beta-cell replication and neogenesis, increase beta-cell mass and improve glucose tolerance.

• Byetta reduced A1C by 1% in 30 weeks–patients receiving max doses of Metformin, a Thiazolidinedione,

or a combination of Metformin and Sulfonylurea.

• 5kg weight loss, 3kg weight loss with Metformin.

• Injection 1 hour before morning and evening meals–associated with weight loss–do not use with insulin– long-acting release version given
  • Adverse reactions–hypoglycemia (with Sulfonylurea) –reduce dose, nausea, vomiting, diarrhea,

and upper respiratory symptoms–may cause a reduction in food intake and necessitates

adjustment of medications.

• Hypoglycemia is not a risk with Metformin–but it is a risk with Sulfonylureas.

• DPP-4 Inhibitors–inhibits the enzyme that breaks down endogenous GLP1 and prolongs its activity–Sitagliptin

(Januvia) was the first FDA approved on 10/2006 as a daily PO medication–Saxagliptin, Linagliptin (does not

require renal/hepatic dosing–may have less effects with CAD) –can be used alone or combined with Metformin

or Thiazolidinedione.

• Second-line treatment for
• Reduces fasting and post prandial hyperglycemia in DM2, does not cause weight gain or
• Hypersensitivity is the only
• Sitagliptin (Januvia) as monotherapy reduces A1C by 6-1.5% with A1C <8% and <9% after 24 weeks–

Linagliptin reduces A1C by 0.4-0.7%–no renal or hepatic dose adjustment required–Saxagliptin reduces

A1C by 1.1-1.6%

• Sitagliptin (Januvia) + Metformin reduced A1C by 0.6%

• Side effects–headache and diarrhea

• May cause pancreatitis and thyroid cancer.

• Bile Acid Sequestrants—Colesevelam is an add-on medication for DM2 that lowers cholesterol and fasting glucose

levels by binding bile acids and cholesterol for excretion–lowers A1C modestly 0.5%–not first line agent for

hyperglycemia–does not cause hypoglycemia or weight gain, useful for patients that cannot tolerate statins.

• Side effects–constipation, triglyceride elevation, and may interfere with oral agent

• Dopamine-2 Agonists—Bromocriptine Mesylate is a dopamine receptor agonist used for Parkinson’s disease and

approved for DM2–alters hypothalamic metabolism and increases insulin sensitivity–centrally acting–lowers

post prandial glucose levels, hepatic glucose production, triglyceride and free fatty acid levels, and A1C by 0.5- 0.7%.

• Side effects–dizziness, nausea, fatigue,

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

• Evidence-Based Recommendations

• Use educational interventions
• Metformin is more effective than diet alone
• Sulfonylureas reduce A1C better than placebo or diet
  • Second generation are better than first in contributing to hypoglycemia

• Non-Pharmacologic Treatment

• Establish glycemic goals.
• DM2 utilize referrals and collaborations with other specialties–DM1 may need an endocrinologist or Diabetes Specialist
• Diet, exercise, nutritional counseling, physical
  • Bariatric surgery for morbidly obese HTN Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

Chapter 35: Acetaminophen

• APAP–similar to aspirin for fever and pain–weak anti-inflammatory, no GI side effects, no platelet interference–metabolite of Phenacetin–taken off-market due to nephropathy–3,000mg max dose (4,000mg if monitored) –difficult to dose for children (not for <2 years old).

• Pathophysiology

 

• Fever–hypothalamus temperature regulation–monocyte-macrophages release pyretic cytokines interleukin-1– decreased heat loss via shivering and peripheral
  • Fever of unknown origin–> 38.3C x 3 weeks without neutropenia or
  • Replace fluids and electrolytes

• Mechanism of Action

• Antipyretic–inhibits the action of pyrogenic cytokines on the hypothalamus–increases sweating and
• Analgesic–centrally acting–possible inhibition of prostaglandin synthetase in the
  • APAP vs ASA–no inhibition of peripheral prostaglandin synthesis–poor anti-inflammatory and platelet inhibitor

• Pharmacologic Treatment

• Fever
  • Use Aspirin, NSAIDs, or APAP
    • APAP for children to prevent Reye’s
  • APAP is every 4-6 hours–give routinely to prevent swings in temperature

o                          Acute mild to moderate pain

• Useful for non-inflammatory pain–headache, muscle ache, malaise of viral infection, teething in
  • Pain effectiveness is improved if given routinely vs
  • Also given IV as an adjunct to

o                          Chronic pain

• Malignant or non-malignant origin
  • First choice for mild OA pain in elderly who cannot tolerate NSAIDs
  • When given in combination with codeine or other opioids–monitor APAP intake

o                          DPT vaccination

• Every 4-6 hours post vaccine x 48-72 hours–for fever and injection site pain

• Monitoring

• Evaluate for overdose via serum acetaminophen concentration–4 hours after infusion–plot of Rumack-Matthew

nomogram–if above treatment line–start acetylcysteine (also activated charcoal) –report to Poison Control.

• Hepatotoxicity–>7.5g in 8 hours, >250mg/kg in a single dose, or >12g within 24
  • Nausea, vomiting, lethargy, malaise, and confusion–increase in LFTs within 24 hours is indicative of permanent injury
• Monitor for hepatotoxicity or hepatic insufficiency–taking other hepatotoxic drugs, alcoholics, and
• <5 days of therapy for children–infant drops are more potent

(80mg/0.8mL) than regular elixir/solution (160mg/5 mL) –may                             increase asthma prevalence in children.

• 10-15mg/kg dosage–2.6g/day

• Crosses the placenta and is excreted in breast milk–category
• Known G6PD problems

Chapter 36: Aspirin and NSAIDs

• Overview

• Salicylate

• Acetylsalicylic Acid

o                          NSAIDs

• Propionic Acids
  • Ibuprofen
  • Fenoprofen
  • Flurbiprofen
  • Ketoprofen
  • Naproxen
  • Oxaprozin

• Acetic Acids

• Indole and Indene acetic acids
  • Indomethacin
  • Etodolac

 

• Sulindac

• Heteroaryl Acetic Acids

• Diclofenac Sodium
• Ketorolac
• Tolmentin Sodium

• Alkanones

• Nabumetone

• Fenamates

• Meclofenamate
• Mefenamic Acid

• Oxicams

• Piroxicam
• Meloxicam

• COX-2 inhibitors—not for patients with sulfonamide allergy
  • Celecoxib (Celebrex)

 

• Anatomy and Physiology

• Synovium—lines the capsule that

holds bone joints—cartilage and bone

• Inflammation—

prostaglandins

(produced from mast cells from arachidonic acid by the action of the COX enzyme— prostaglandins E1 and E2 are active in the inflammatory response.) increase vascular permeability and neutrophil chemotaxis,

causing pain—inflammatory molecules enter the cell and into the site of inflammation.

• NSAIDs and Aspirins block COX (cyclooxigenase) enzyme from producing prostaglandins— inhibiting inflammation—inhibits production of prostaglandins, prostacyclin, and

thromboxanes in CNS and peripheral tissue.

• COX1 = blood vessels, stomach, kidney

• COX1 prostaglandins protect the gastric mucosa—encourage blood flow and elaboration of bicarbonate to produce a neutral/less acidic layer—also produce

a layer of mucus that blocks acid—blocking them causes GI effects.

• Prostaglandins maintain normal renal and mental function, and temperature

• COX2 = brain, kidneys, and bone—inhibition is necessary to prevent inflammatory action.

• With inflammatory process, synovium becomes lumpy and grows into cartilage and tendon

sheath becomes inflamed—motion of joint is painful—denuded ends and bone grinds on bone–

joint is destroyed.

• Signs and symptoms of inflammatory response—erythema, edema, tenderness,

• Pathophysiology

• OA—low level of inflammation, cartilage degeneration, bone hypertrophy of the articular margins, spur formation,

and lipping at the joint surface.

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Essay Assignment

• Characteristic of pain with movement and weight bearing and relief with rest, morning stiffness, no systemic manifestations—normal ESR.
• Knee OA—topical NSAIDs, acupuncture, and tramadol
  • Glucosamine and chondroitin are not effective for OA but is for knee trauma/overuse.
• Mild OA—start with acetaminophen, then NSAIDs (more effective for knee of hip)—some can be

managed long-term with Acetaminophen and NSAIDs can be used for flare-ups—COX-2 inhibitors for

long-term management in the elderly.

• RA and other rheumatological diseases—2 weeks of therapy for relief
• Acute mild to moderate pain—start NSAIDs immediately, for large muscle injury and risk of continued bleeding wait 24 hours due to NSAIDs effect on platelets—given for a limited
  • Lower back pain, bursitis, tendinitis
• Dysmenorrhea—24-72 hours prior to bleeding x 2-3 days—do not use with pregnancy
• Reduction of cardiovascular risks—enteric coated Aspirin 81mg to prevent GI toxicity—Aspirin + NSAIDs decreases the cardioprotective

 

• Mechanism of Action

• Pain—blocking prostaglandin production results in decreased inflammation—salicylates may also cause pain

reduction centrally at subcortical sites.

• Antipyretic—ASA blocks the effects of interleukin-1 on the hypothalamus, peripherally, causes vasodilation of peripheral
• Platelet Effects—thromboxane stimulates platelet activation, resulting in aggregation and clotting cascade— blocking of COX1 enzymes = no
  • Aspirin causes irreversible inactivation of COX,

allowing decreased production of thromboxane

for the life of the platelet (8-10 days), NSAIDs exhibit reversible inactivation of COX that lasts only the duration of drug activity.

• Adverse Effects

• GI bleeding, ulcers
  • Use PPis, high-dose H2-receptor agonists, and misoprostol (only one that prevents both gastric

and duodenal ulcers—200mcg QID—if patient experiences diarrhea, change to 200mcg BID or 100mcg QID—abortifacient).

• Impaired kidneys rely on prostaglandins to cause vasodilation—NSAIDs can decrease renal

• Contraindications

• Impaired renal/liver function
• HF
• Elderly patients
• Patients on: diuretics, ACE inhibitors, and angiotensin-II agonists

• Non-Pharmacologic Treatment—exercise, rest, walking program, weight loss—patient must be realistic about expectations

of medications.

 

• Monitoring

o      Salicylates—vertigo, tinnitus, or impaired hearing.

• Measure serum concentration

o           NSAIDs

• Long-term—CBC with diff, Cr, UA, K, and LFTs—q3 months until stable, then q3-6 months—follow patients
• GI bleeding can occur at any time—CBC, PT, UA, and Occult Blood in

stool.

• Elderly—can have GI, CNS, and renal effects—confusion, decreased renal clearance—monitor when used with antihypertensive agents (especially diclofenac)—monitor for edema and signs of
  • ASA has been found to be ineffective as in primary prevention of MI or

strokes in women.

• Can use ASA with naproxen

• Pediatrics—juvenile arthritis—ibuprofen, naproxen, and indomethacin
• Stop ASAs 5-10 days before surgery
• Stop NSAIDs 3 days before surgery

 

Chapter 38: Gout Medications

• Overview

• NSAIDs
  • Indomethacin
  • Naproxen
  • Sulindac

o           Colchicine

• Uricosuric Agents

• Probenecid

o           Interleukin-1 Inhibitor

• Rilonacept

o           Xanthine Oxidase Inhibitors

• Allopurinol
• Febuxostat
• Gout—deposition of monosodium urate crystals in body tissue
• Primary—inborn error of purine metabolism resulting in overproduction/underexcretion of uric acid—males affected 10x more than females

• 24-hour urine collection to determine overproduction or underexcretion

• Secondary—hyperuricemia from other diseases/medications that interfere with uric acid secretion
  • Endocrine disorders
  • Lead poisoning
  • High-dose salicylates (>3g/day)
  • Myeloproliferation disorders
  • Chronic renal disease
  • Obesity—early onset

o           Disease Process

• Asymptomatic hyperuricemia (>6 in men, >7 in women)—acute gouty arthritis (painful monoarthropathy, any synovial joint can be affected but mostly the metatarsophalangeal joint of the great toe)—intercritical

period (between acute attacks—usually 6 months to 2 years after the first attack)—chronic tophaceous gout can occur.

• Tophi—sodium urate crystals deposited in soft tissues—occurs in 50% of patients with gout—

appear 2-3 years to 10 years after onset—tophi in synovium, prepatellar, olecranon bursae,

Achilles tendon, and helix of the ear.

• Risk Factors

• HTN
• Thiazide and loop diuretics
• Obesity
• Alcoholism (not wine)

• >60 years
• Family history
• Lead exposure (or moonshine consumption)
• Certain medications
• Diet (dairy = lower risk)

• 90% of patients with gout are underexcreters—kidney produce 700mg/dl of uric acid, 10% is excreted—

any factor that interferes with glomerular and renal tubular reabsorption or uric acid = increased serum

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• Overproduction is less common—the result of another disease, frequently ne with excessive rates of cell turnover—hemolytic anemias, myeloproliferative and lymphoproliferative diseases, and psoriasis
  • Gout vs Septic joint—synovial fluid aspiration and examination to confirm diagnosis—WBC and

diff, crystal analysis, and Gram stain with culture.

• Gout and infection can coexist in a joint—presence of birefringent crystals is insufficient for a

• Mechanism of Action

• Increase the excretion of uric acid (Uricosurics—Probenecid—tubular blocking agents that decrease uric acid level by increase excretion by inhibition of tubular reabsorption of urate—this leaves high levels of uric acid in the proximal renal tubules and may precipitate kidney stones—increase fluid intake and alkalinize the urine—also inhibits tubular secretion of PCN and cephalosporins—increases )
• Decrease the synthesis of uric acid (Allopurinol and Febuxostat—inhibit xanthase oxidase which converts xanthine to uric acid—xanthase more easily excreted)
• Decrease/stop the inflammatory response (NSAIDs and Colchicine—affects leukocyte function to reduce lactic acid—no effect on uric acid metabolism and not an analgesic)

• Treatment—Colchicine, Corticosteroids, and NSAIDs

• Xanthine oxidase inhibitors—then add a uricosuric agent if serum levels are still not decreased—treatment should achieve <6 serum urate level, <5 to control signs and symptoms.

o           Acute flares—NSAIDs and Glucocorticoids

• Prevention of acute attacks (recurrence)—first line: Colchicine, second line: Uricosuric drug if underexcretor, allopurinol if overproducer, febuxostat if unable to tolerate allopurinol.
  • Urate lowering drug for long-term treatment
• Asymptomatic hyperuricemia—non-pharmacologic treatment—hydration, weight loss, blood pressure control, decreased alcohol consumption, and reduced purine diet (no meats, alcohol, liver, kidney, sweetbreads, dried beans/peas, mushrooms, lentils, spinach, anchovies, sardines, whole grain and bran breads and cereals).
• Acute gouty arthritis—stop inflammatory response—NSAIDs (indomethacin—high risk of adverse effects, Naproxen, and Sulindac—COX2 is at risk for GI bleed)—treat hyperuricemia after attack subsides—bedrest x 24
  • Colchicine is second line due to causing nausea and vomiting before causing

pain relief

• Corticosteroids—for patients who cannot take NSAIDs or Colchicine—intraarticular injection if the gout if monoarticular—new interleukin1 trap drug—rilonacept.

• Prevention of recurrence—increasing excretion/ decreasing the synthesis of uric acid reduces attacks and minimizes urate deposition in tissues (cause of chronic tophaceous arthritis)—treat during intercritical period based off of likelihood of additional attacks—high risk patients who cannot make lifestyle changes need
  • Colchicine—prophylaxis for patients with normal renal
    • Increase dosage or add NSAID if attack occurs on prophylactic therapy
    • Narrow therapeutic window—side effects: nausea, vomiting, diarrhea, abdominal pain
  • Reduction in uric acid level–uricosurics (Probenecid) + Colchicine—do not give Probenecid within 2-3

weeks of acute attack due to possible prolongation of inflammation—increased frequency of attacks is

common during the first 6-12 months of Probenecid.

• Allopurinol also lowers uric acid level 2-3 after initiation—in both underexcreters and overproducers, patients with tophaceous gout, unresponsive patients, and patients with uric acid

• Monitor

renal stones—do not start during the acute phase—can also cause increased frequency of attacks during the first few months—concurrent therapy with colchicine.

 

• Baseline serum uric acid level, monitor q3-4 months—ideal serum urate is 5-6mg/dl.
• NSAIDs—baseline renal/hepatic function tests, short-term
  • Dizziness may occur at start of therapy—watch for signs and symptoms of GI bleed—lethargy-fatigue associated with anemia—sign of small
• Colchicine—initially, monitor weekly for signs of toxicity—weakness, nausea, vomiting, diarrhea, anorexia—CBC, LFTs, and B12 q 3-6
  • Notify of skin rash, sore throat, fever, unusual bleeding, bruising, tiredness weakness, numbness, or

tingling.

• Uricosuric agents—avoid Aspirin and Salicylates as it can cancel efficacy—notify if rash
• Xanthine oxidase inhibitors—baseline CBC and serum levels q2-3 months for allopurinol—serum uric acid evaluates efficacy—BUN, Cr, creatinine clearance should be monitored with patients with decreased renal
  • Allopurinol sensitivity syndrome—dose-dependent—signs and symptoms: fever, eosinophilia, dermatitis,

hepatic dysfunction, renal failure, and vasculitis—start low.

• Notify of rash, painful urination, blood in urine, irritation of the eyes, or swelling of lips and mouth.
• 6 weeks for optimal

 

Chapter 40: Muscle Relaxants

• Overview

• Antispasmodics
  • CNS Depressants
    • Metaxalone
    • Methocarbamol
    • Chlorzoxazone
    • Carisoprodol

• TCA Relatives

• Cyclobenzaprine

o           Antispasmodic + Antispasticity

• Benzodiazepines
  • Diazepam

• Beta-Adrenergic

• Tizanidine

o           Antispasticity

• GABA Receptor Stimulants
  • Baclofen

• Mechanism of Action

• CNS depressants
  • Action unknown—do not work on skeletal muscle of the neuromuscular junction—effective in localized muscle spasms by producing sedation—decreased facilitative and inhibitory
    • Methocarbamol—CNS
    • Chlorzoxazone—acts at the spinal cord and subcortical levels inhibiting multi-synaptic reflex
    • Carisoprodol—blocks interneuronal activity in the descending reticular formation and spinal cord

—metabolized to meprobamate—similar to barbiturates—potential for abuse.

o           TCA Relatives

• Cyclobenzaprine—structurally related to TCAs—acts in CNS to reduce tonic somatic motor activity— causes reserpine antagonism, norepinephrine potentiation, substantial anticholinergic effects and

sedation—also effective for non-CNS muscle spasms (TMJ)—works at the brainstem—aids in sleep.

o           Benzodiazepines

• Diazepam—direct skeletal muscle relaxant action on the brainstem and spinal cord level, enhancing GABA- mediated presynaptic inhibition—can be used for skeletal muscle strain and spasticity caused by upper motor neuron

o           Alpha 2-adrenergic receptor agonists-

 

• Tizanidine—imidazoline derivative, related to clonidine—centrally mediated myospasmlytic action— muscle relaxant, antinociceptive, and gastroprotective properties—effective for CNS and non-CNS

o           GABA receptor stimulants

• Baclofen—only effective for muscle spasms caused by CNS disease—inhibits monosynaptic and polysynaptic reflexes at the spinal level and structural analog of GABA the inhibitory

• Treatment

• Analgesics—first line: NSAIDs, Acetaminophen, second line: muscle relaxant, Tramadol, opioids if severe or debilitating
• Muscle relaxants—first line: Cyclobenzaprine, centrally acting sedatives—usually for 7
• Nonpharmacologic—rest, ice x 24-48hrs, heat/ice alternating, physical therapy, good alignment

o               Pharmacologic

• Non-specific lower back pain—muscle relaxants—break the cycle of pain and muscle
• Acute lower back pain—analgesics x 1-2 weeks—add skeletal muscle relaxants if spasms are source of

pain—if no improvement, order diagnostic tests.

• Simple radiculopathy—sciatica—6 weeks of care
  • Order CT or MRI with neurological deficit
  • Metaxalone and Methocarbamol are most commonly used—have limited effectiveness

—Cyclobenzaprine is also frequently used.

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Chapter 43: Analgesia and Pain Management

• Overview

• Opioid Agonists
  • Phenanthrenes
• Morphine Sulfate ER
• Morphine
• Codeine w/wo Acetaminophen
• Hydrocodone with Acetaminophen
• Hydrocodone with Ibuprofen
• Oxycodone (Oxycontin)
• Oxycodone with Aspirin
• Oxycodone with Acetaminophen
• Hydromorphone

• Phenylpiperidines

• Meperidine
• Fentanyl

• Diphenylheptanes
• Methadone
• Miscellaneous

• Mu-receptor agonist and NE reuptake inhibitors
  • Tapentadol
  • Tapentadol ER

• Mixed agonist-antagonists
• Pentazocine
• Partial agonists

• Tramadol—not scheduled
• Tramadol with Acetaminophen

• Pathophysiology

• Pain—an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of damage—always
  • Four processes required for pain to occur—transduction, transmission, modulation, and perception.
    • Sensory receptors (nociceptors) sensitive to painful (tissue-damaging—noxious) stimuli are

present in the skin, bone, muscle, connective tissue, thoracic, abdominal, and pelvic viscera.

• Transduction occurs when a noxious stimulus depolarizes peripheral nerve endings and sets off electrical
  • Nerve endings that transduce the noxious stimuli conduct electrical signals to the spinal

cord through:

 

• A Delta Fibers—myelinated—sharp, stinging
• C Fibers—unmyelinated—vaguely localized pain, dull or

• Transmission electrical impulses are carried throughout the peripheral and
• Modulation is the central neural activity that controls the transmission of pain
• Perception the neural activities involved in transmission and modulation result in a subjective

correlate of pain that includes behavioral, psychologic, and emotional factors.

• Tolerance—pharmacologic phenomenon—decreasing drug effect over
• Dependence—physiologic development of withdrawal symptoms wen a drug is discontinued or an

antagonist is given.

• Addiction—psychologic dependence—overwhelming obsession with obtaining and using a drug for a non- medical
  • Pseudoaddiction—watch the clock, demand pain medication, may resort to illegal means to get

drugs—behavior ceases when patient attains adequate pain control.

• Classifications of Pain

• Nociceptive—direct stimulation of afferent nerves in cutaneous or deep musculoskeletal tissues
  • Somatic—well-localized in skin and subcutaneous tissues—not bone, muscle, blood

vessels, and connective tissues—typically dull and aching.

• Visceral—poorly localized—continual aching, deep, crampy, sharp, squeezing pain— occurs in response to stretching, distention, compression, or infiltration of

• Neuropathic—injury to peripheral nerves or CNS—shooting, stabbing pain superimposed over a

background of aching and burning—originates from peripheral nerves, spinal cord, or brain—

poorly localized and associated with paresthesias and dysesthesias.

• Assessment—characterize pathophysiology of pain, identify its cause, determine its intensity, and evaluate the impact on the patient ability to
• Acute Pain—facial grimacing, tachycardia, hypertension, pallor, diaphoresis, mydriasis, and
• Chronic Pain—fatigue, depression, sleep disturbance, decreased appetite, increased irritability, and decreased libido.
• Follow-Up Assessment—assess the effectiveness of

• Mechanism of Action

• Opioid Agonists—inhibit painful stimuli in the substantia gelatinosa of the spinal cord, brainstem, reticular activating system, thalamus, and limbic system—analgesia, sedation, euphoria, mental clouding, respiratory depression, miosis, decreased peristaltic motility, depression of the cough reflex, and orthostatic

• Receptors

• Mu
• Kappa
• Delta

• Mixed Agonist-Antagonists—Tramadol–stimulate kappa receptors and block the mi receptors—less likely to be abused.
• Norepinephrine Reuptake Inhibitor—Tapentadol—centrally acting, activates mu-receptor and inhibits norepinephrine synaptic reuptake (additive analgesia).

• Treatment

• Identify cause of pain—maximize referrals to specialists—use non-pharmacological
• Start with Acetaminophen and/or NSAIDs.
• Opioids can be given w/wo Acetaminophen—prophylactically treat constipation
• Adjuvant drugs—Gabapentin, anticonvulsants, SNRI (Duloxetine)

• Monitoring

• See patient on opioids weekly until pain is
• Assess for side
• Monitor for misuse or abuse—unsanctioned dose escalations and resistance to changing medication
  • Geriatrics—no propoxyphene, tramadol, methadone
• Pediatrics—no oxycodone, propoxyphene, methadone, or pentazocine—hydromorphone safety has not

been established.

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Chapter 44: Migraine Medications

• Overview

 

• Abortive Agents
  • Serotonin 5-HT1D Receptor Agonists
    • Sumatriptan

(Imitrex)

• Frovatriptan
• Naratriptan
• Rizatriptan

(Maxalt)

• Zolmitriptan (Zomig)

• 5-HT1B/1D

• Eletriptan

(Relpax)

• Ergotamine Derivatives

• Ergotamine Tartrate (Cafergot)
• Dihydroergotamine
• Isometheptenemucate

o           Prophylactic Agent

• Cyproheptadine

• Common Drug Classes for Prophylaxis—analgesics, beta blockers, calcium channel blockers, antidepressants,

anticonvulsants.

• Pathophysiology

o      Underlying physiologic problem is a dysfunction of an ion channel in brainstem neurons that normally modulate sensory input and exert neural influence on cranial vessels—cerebral vasodilation and trigeminal nerve activation are believed to be precursors to migraine pain.

o           Migraines

• Ophthalmoplegic—affect 3^rd, 4^th, or 6^th crania nerve—permanent damage to the 3^rd.
• Hemiplegic—motor/sensory symptoms, unilateral, may last longer than the headache—rare.
• Basilar-type—combination of vertigo, diplopia, dysarthria, tinnitus, decreased hearing, ataxia,

simultaneous bilateral paresthesias, and altered consciousness.

• Transformed—rebound headache from medications—caffeine, acetaminophen, NSAIDs, barbiturates, sedatives, narcotics, ergots, and

• Mechanism of Action

• Abortive Agents
  • Serotonin 5-HT1D Receptor Agonists
    • (Triptans) engage in cranial vessel constriction, inhibition of neuropeptide release, and reduced

transmission in trigeminal pain pathways.

• Ergotamine Derivatives

• Depress central vasomotor centers, constrict peripheral and cranial blood vessels, and reduce

intracranial blood flow and decrease hyper perfusion of the basilar artery area.

• Ergotamine Tartrate

• Alpha-adrenergic-blocking agent—direct stimulating effects on smooth muscle of peripheral and

cranial vessels—stronger venoconstrictor and weaker arterial vasoconstrictor than ergotamine.

o           Prophylactic Agents

• Beta Blockers—stabilize vascular
• Calcium Channel Blockers—regulate vascular smooth muscle contraction, neurotransmission, and

hormone secretion enzyme activity—may also impede vascular inflammation and prevent hypoxia of

cerebral neurons.

• Tricyclic Antidepressants—increase the availability of synaptic norepinephrine—increased threshold for precipitation of a migraine
• SSRIs—reduce frequency and intensity—prevent venoconstrictive effect of decreased serotonin level

during headaches.

• Anticonvulsants—influence cerebral arteries and circadian rhythms—regulate secretion of hormones from the anterior pituitary gland that help to relax vascular

• Treatment—Evidence-Based

• Acute Treatment

• Beneficial—Salicylates, Ibuprofen, Almotriptan, Eletriptan, Frovatriptan, Naratriptan, Rizatriptan, Sumatriptan (nasal spray is effective), Zolmitriptan.

▪                           Treat attacks rapidly and consistently

• First line—Triptans.
• Second line—DHE (ergotamine derivatives).
• Third line—combination analgesics of NSAIDs, ASA, and
• Emergency rescue drugs—Prochlorpemazine (prochlorperazine?) PR/IM/IV, Opiates,

Corticosteroids.

• Likely to be Beneficial—Diclofenac, Ergotamine, Naproxen, Flufenamic Acid.

• Children—Ibuprofen, probably Acetaminophen—Sumatriptan use in >5 years but does not have FDA

approval—Cyproheptadine is often used as prophylaxis—contraindicated in children <2 years.

• Combination products with ASA, Acetaminophen, NSAIDs, and Caffeine.

o               Preventative Treatment

• Adults—Propranolol, Timolol, Divalproex, Sodium, and Topiramate.
• Children—insufficient evidence.

• Pharmacologic Treatment

o      Abortive Treatment (For Those Having an Acute Migraine)—do not administer more than 2 days/week.

• Triptans, Ergotamine Derivatives

o           Mild to Moderate Migraines

• Aspirin, NSAIDs (Naproxen, Ibuprofen, Indomethacin), or combination product

o           Nausea and Vomiting

• Triptan migraine medication in nasal spray or injection if patient cannot tolerate PO
• Prochlorperazine (Compazine), Trimethobenzamide (Tigan), Metoclopramide (Reglan)—may have adverse

reactions.

o           Moderate to Severe Migraine

• Triptans, DHE (if Triptans are ineffective).

o           Migraine Recurrence

• Consider a long-acting Triptan such as

o           Severe Migraine

• Triptan or DHE injection
• Corticosteroids, Opioids

o           Prophylactic Medications

• Used when patients experience 2-3 attacks/month—or when headaches do not respond to abortive medication.
• Decrease the frequency, intensity, and duration—Propranolol, Timolol, Amitriptyline, Valproate, and

Topiramate.

 

·	Monitor
	o	Keep a log
	o	Triptans and Ergots—periodic EKGs and cardiac enzymes
	o	Cyproheptadine—LFTs regularly—effectiveness within 3 weeks
	o	Monitor weight
	o	Anticholinergic side effects
	o	Migraines in the elderly—suspect intracranial lesion—new headaches require evaluation

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Chapter 39: Osteoporosis Treatment

• Overview

• Bisphosphonates
  • Alendronate Sodium (Fosamax)
  • Risedronate (Actonel)
  • Ibandronate Sodium (Boniva)
  • Zoledronic Acid (Reclast)

o           Endocrine and Metabolic Agents

• Calcitonin
• Parathyroid Hormone Analog
  • Teriparatide

o           Estrogen Derivatives

• Hormone Replacement Therapy
  • Conjugated Estrogens
  • Estradiol
  • Norethindrone/Ethinylestradiol
  • Conjugated Estrogens/Medroxyprogesterne Acetate
  • Estradiol/Norethindrone

o           Selective Estrogen Receptor Modulators

• Raloxifene (Evista)

o           Biologic and Immunologic Agents

• Monoclonal Antibody
  • Denosumab

o           Vitamins and Calcium Salts

• Calcium Citrate + Vitamin D
• Calcium Carbonate

• Anatomy and Physiology

• Bone remodeling—resorption and formation—osteoclasts scoop away bone over 2 weeks and are replaced by osteoblasts—calcium in broken down tissue goes into circulation for other functions—new bone fills in the spaces from which old bone was removed—after age 30, bine is removed faster than it is
  • Osteoporosis—bone is at an increased risk of fracture because newly produced bone is less densely

mineralized, the resorption sites are temporarily unfilled, and maturation and isomerization of collagen are impaired.

• Bone homeostasis is maintained by Calcium, Vitamin D, and

• Mechanism of Action

• Bisphosphonates
  • Non-hormonal agents with affinity for bone—Alendronate (treatment and prevention), Risedronate (treatment), Ibandronate (monthly dosage)—inhibit activity of osteoclasts and increase bone mineral
    • Drug Holiday—after 4-5 years of

treatment, if fracture risk is low             —

holiday of 1-2 years after 10       years

of treatment.

• Routine oral examinations.

• SERMs

• Raloxifene (only one for osteoporosis—exerts

estrogenic effect on bone only, does not prevent against hip fractures, helps decrease endometrial cancer, does not help with vasomotor symptoms of menopause, can lower LDL increases risk of VTE, protects against breast cancer), Tamoxifen.

• Raloxifene Side Effects—hot flashes, leg cramps 3x risk for VTE—greatest risk within first

4 months of use—women should be fully ambulatory.

• Hormones

• Calcitonin made from c-cells in the thyroid gland—blocks bone resorption by inhibiting

osteoclasts in number and function—protein that is inactivated by the PO route—can also serve

as analgesic via release of endorphins, beneficial after vertebral facture—200IU daily intranasal— for osteoporotic women after the first 5 years of menopause—observe patient’s nose.

• Teriparatide is synthetic human PTH—first treatment of osteoporosis that stimulates bone

formation—once daily subcutaneous injections stimulate osteoblastic activity vs osteoclastic—

not for patients at risk for osteosarcoma, not approved for >2 years of use.

o      Drugs that can contribute to bone loss or increased fracture risk…  

• Medications either stimulate bone formation or reduce bone absorption—combination therapy is not recommended—take on empty stomach—remain upright and do not drink anything 30-60 mins after administration

• Treatment

• First-line: Bisphosphonates—Alendronate, Ibandronate, Risedronate
• Second-line: Teriparatide
• Calcitonin (for patients who cannot tolerate other treatments—not as ) Allergy to salmon is contraindication.
• All therapies should be given with Calcium and Vitamin D
  • Calcium 1,000mg for post-menopausal women and older men, 1,200mg for premenopausal
  • Vitamin D3 400-800 IU minimum
• Weight-bearing exercises
• Avoid tobacco and alcohol intake
• Bone density testing

• Denosumab—humanized monoclonal antibody directed against receptor activator of nuclear factor-kappa B ligand— mediator in the absorptive phase of bone modeling—inhibits osteoclast activity—indicated for patients with post- menopausal
• HRT—no longer for osteoporosis treatment—adverse outcomes associated with combined estrogen and progesterone

therapy—breast cancer, MI, stroke, and VTE.

• Monitor

• Baseline Cr, serum Ca and Phos levels at start and a year after
• Dexa at start of treatment and 2 years after
• Monitor bone turnover markers n patients taking bisphosphonates to check for suppression—urine test NTx at start of therapy, 3 months later, and 1 year later of when therapy is changed—measures urine levels of a compound linked to bone breakdown—collect second urine of the day–<38,

successful therapy should yield lower numbers, 30% is optimal

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Chapter 54: Contraceptives

• Overview

• Combination Estrogen and Progestin
  • Contraceptive Patch
  • Intravaginal Ring

o           Progestin Only

• Emergency Contraception
• Progestin Only Contraceptive
• Progestin Only Injection
• Progestin Subdermal Implants

 

• Intrauterine Device (Mirena)

o           Progestin Receptor Modulators

• Emergency Contraception

o           Non-Hormonal

• Intrauterine Device
• Menstrual Cycle

• 28-day negative feedback loop involving the hypothalamus, anterior pituitary gland, and
  • Estrogen and progesterone level decline, endometrium
  • Follicular phase, Luteal phase
  • Hypothalamus responds to lowered levels of estrogen and progesterone and releases gonadotropin-

releasing hormone (GnRH) which stimulates the anterior pituitary gland to secreted follicular stimulating

hormone (FSH) and luteinizing hormone (LH).

• Hormones
  • Progestins
  • Androgens
  • Estrogens
    • Estradiol
    • Estrone
    • Estriol

• Mechanism of Action

• OCPs
  • Interfere with the hypothalamic-pituitary-ovarian negative feedback loop to inhibit ovulation—also thickening of cervical mucus to prevent

passage of sperm, creating an endometrial environment that is not conducive to implantation, slow fallopian tube peristalsis and decrease secretions).

• Monophasic and multiphasic
• Post-pregnancy—natural birth can resume OCPs in 3 weeks, C-

section in 6 weeks—due to hypercoagulable state.

• Decreased Effects—anticonvulsants (except Valproic), Rifampin, Griseofulvin, Modafinil, Protease Inhibitors,

John’s Wort, Antibiotics (decreased gut flora = decreased absorption), PPI, Gastric Bypass.

o           Emergency Contraceptive

• Interfere with ovulation, disrupt implantation in endometrium, and alter the tubal transport of sperm/ova to prevent

• Treatment

• OCPs—quick start method is preferred—first-day start, Sunday start—take at the same time every
  • Can ease symptoms of
• Extended Cycle Pills—84/7 days vs 21/7
• Transdermal System—bypasses the liver and the first-pass effect, decreased dose—steady rate of ethinyl estradiol increases the chances of VTE
  • Can switch from pill to patch—start when it is time to apply new patch or start new

o      Vaginal Ring

• Can switch from pill to ring within 7 days of the last active OCP—bypasses the liver and the first-pass effect, decreased dose.

• Emergency Contraceptives—progestin only—taken within 72 hours of unprotected sex, decreases chances of pregnancy by 75%.
• Progestin Only Pills—no estrogen side effects—can be started immediately post-partum—safe while breastfeeding

—no increased risk for VTE—report prolonged episodes of bleeding, amenorrhea, or severe abdominal pain.

• COPs to POPs, start the POP after the last active pill is
• If a pill Is taken more than 3 hours late—backup birth control is needed x 48
• Increases quality and quantity of breast

• Subdermal Implants—progestin only device, single-rod implant containing etonogestrel—insertion and removal take 5 minutes—offers protection for 3-5 years—good option for cigarette smokers >35 years, DM, history of stroke, MI, or

 

• Side Effects: headache, acne, breast tenderness, weight and mod changes, ovarian cyst formation, and galactorrhea.

• Depomedroxyprogesterone Injection—long-acting injectable—for patients with history of anemia, dysmenorrhea, menstrual migraines, SZs, sickle cell, and those with increased risk for endometrial/cervical cancer—also used for fibroid tumors because of its potential to suppress
  • Give first injection during the first 5 days of menses, every 3 months—remains in blood stream for 6-9

months.

• Should be used as last resort due to increased weight gain and decreased

• Intrauterine Device—hormonal is good for 5 years; non-hormonal is good for 10 years and can be used as emergency contraception within 7 days of unprotected

• Absolute Contraindications

• Hypersensitivity
• Thrombophlebitis, thromboembolic disorders
• History of deep vein thrombophlebitis
• Cerebrovascular disease
• Myocardial infarction, coronary artery disease
• Known or suspected breast carcinoma or estrogen-dependent neoplasms
• Carcinoma of endometrium
• Hepatic adenomas/carcinomas
• Acute liver disease
• Undiagnosed abnormal genital bleeding
• Known or suspected pregnancy
• Cholestatic jaundice of pregnancy/jaundice with prior pill use
• Hypersensitivity

• STOP MEDICATIONS–ACHES

• Abdominal pain
• Chest pain, SOB
• Headache, dizziness, weakness
• Eye problems, speech problems
• Severe leg/calf pain

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Chapter 55: Hormone Replacement Therapy

• Overview

• Replacement Therapy for Women—relief of menopausal symptoms, uterine bleeding, secondary amenorrhea, primary ovarian failure—palliative for breast and prostate cancers, endometrial hyperplasia—unlabeled use: diminished libido in

• Estrogens

• Conjugated Estrogens
• Synthesized Estrogens
• Bioidentical

• Progestogens

• Synthesized
• Bioidentical

• Combination Agents

• Replacement Therapy for Men–hypogonadism
  • Androgens—Schedule III
    • Synthesized
    • Bioidentical
  • Menopause—identified by symptoms, menstrual changes, and
  • Perimenopause—8-10 years prior—change in levels of estrogen and progesterone—ages 42-55.
  • Menopause—natural cessation of menses x 12 months (ovarian production of estrogen ceases—loss of negative feedback loop—FSH and LH accumulate)—average is age
    • Starting HT near the onset of menopause reduces the risk of
  • Postmenopause—5-year period following menopause—hot flashes, sleep interruptions, vulvovaginal changes—not a disease process, a normal

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• Signs/Symptoms—vasomotor tone instability causes hot flashes (dizziness, nausea, headache, palpitations, sweating, night sweats, sleep interruptions w/ subsequent cognitive functional decline), vaginal atrophy (increase in pH and susceptibility to infections, decreased muscle tone can lead to UTI and incontinence), cardiovascular onset of atherosclerosis and increased LDL and decreased HDL production from lack of estrogen, breasts decrease in size and density (breast cancer risk increases), decreased BMD, structural effects on

• Treatment
• Menopausal symptoms
• Colorectal cancer
• Osteoporosis
• Prevention of endometrial hyperplasia and cancer—unopposed estrogen causes rapid cell division, all menopausal women with an intact uterus need progesterone to turn the endometrium into