Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172

Pharmacology and Pharmacotherapeutics in Advanced Nursing Practice NGR6172 Chapter 1: Prescriptive Authority and Role Implementation: Tradition vs Change o 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 community." • Prevention, Diagnosis, Prescription, Treatment ▪ Assess health status. ▪ Promote healthy lifestyles. ▪ Identifying/diagnosing normal/abnormal conditions. ▪ Determining the causes of abnormal conditions, providing referral to health care specialists. ▪ Selecting appropriate therapeutic measures. ▪ Implementing treatment. ▪ Supervising/monitoring the patient on an ongoing basis. • 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 practice. • Most Prescribed by PCP--antidepressants, NSAIDs, antihistamines/bronchodilators, antihypertensives, antilipidemic. • Rate of Adoption by Prescribers--innovators, early adopters, early majority, late majority, and laggards. o Problems in the Prescribing Practice of Physicians • Prescriptions are not the most up to date--"new research findings diffuse slowly into practice." • Pharmaceutical company influence--FDA intervention and PhRMA guidelines. • Lack of time--short consultation, incorrect H&P, problem is left undefined, over-reliance on drug therapy. • 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 alerts. Rising use of OTC and herbal products. Chapter 2: Historical View of Prescriptive Authority (Nurses vs. PA) o 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 community." o "Delegable authority -- "Delegable prescriptive authority" without it, an APN can only suggest OTC medications. o Nursing Legislation • Dependent authority--the physician retains ultimate authority through co-signature. • Independent authority--the APN prescribes alone--can still be restrictive. • 1993--Definition and Registration of MLPs--can obtain DEA# beginning with M ▪ NPs • DEA number and prescriptive authority differ by state. • May dispense pharmaceutical samples in all states. • Across-state-line prescribing ▪ CNMs ▪ CRNAs--do not "prescribe" under law. ▪ 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 Chapter 9: Establishing the Therapeutic Relationship • "How scientific principles are introduced in the relationship with the patient has everything to do with therapeutic success." 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." o 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 solution. • Factors of a Therapeutic Relationship o Time--investment--particularly with the elderly--initial investment to obtain thorough H&P--cost-effective--follow up call strengthen the relationship o Attitude--how time is spent and what is said--"Who owns the problem?" o Information--it may take several visits to obtain a full history o Communication--effective two-way communication between patient and provider requires consistent commitment to respect the others' role in the relationship. • 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 reassurance. • 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) measurable. • Be flexible, accept occasional lapses in compliance, attempt to understand the patient's point of view. o Therapeutic Relationship Fails • Skepticism in the medical profession. ▪ Provider main goal is pharmacoadherence. ▪ Over or under utilization. ▪ Therapeutic failure and increase in disease severity. ▪ Gender, race, education, occupation, income, marital status--are not factors in compliance. • 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 benefit. ▪ 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 Chapter 10: Practical Tips on Writing Prescriptions • DEA--state-controlled substance license--federally issued DEA# o Drugs are scheduled by potential for abuse. • Components of a Traditional Prescription o Name of prescriber--credentials, address, phone number o Date o Name of patient--address, age, and weight o Superscription--Rx--"take" o Inscription--drug ingredients, quantity, strength, and/or concentration • Drug--full name of medication--no abbreviations • Strength/concentration o Signature o The better the instructions, the better the medication compliance and patient understanding. o Refills • No refills on Schedule II drugs • Only 6 months/5 refills allowed • "NO REFILLS" o DEA#--should not be printed on Rx or used for ID purposes o Generic Substitutions Okay? • Dispense as Written • Brand Medically Necessary • Electronic Signatures in Global and National Commerce Act: 2000 o E-Sign • No need to paper or hard copy. • Schedule II--need to fax/present hard copy. • Specifically, and emphatically prohibit the reimposition of tangible/paper requirements. o Prescription Etiquette • Cannot prescribe narcotics to self or family--can prescribe non-narcotic Schedule IIs but it is considered poor judgement. ▪ The DEA may start an investigation. ▪ Frequent prescribing for self/family may not be covered by HMOs. ▪ Prescriptions that are refilled without a Provider visit. ▪ Drug sampling--on the margin of legality. ▪ The prescriber is always responsible for what happens to the individual receiving the medication. • 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 analgesics. ▪ 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. • 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 executed. • Critical Thinking in Nursing o 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 option. • Clarify personal values or preferences of the patient. ▪ Joint decision making. 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 art. • Brenner 1984--described the process of skill acquisition by nurses. o Begins with decision-making analysis, then hypothetical deductive reasoning, and the eventual emergence of the expert that functions at an intuitive level. • 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 o 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 • Critical Decision Making Regarding Pharmacologic Therapy o 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. • Evidence-Based Medicine o 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 treatment. • 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 treatment. • Content experience and clinical expertise form a sufficient base from which valid guidelines for clinical practice can be derived. • Evidence-Based Health Care o 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 exposure. • 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 o Official statements that outline how to prevent, diagnose, and treat specific medical conditions or how to perform certain clinical procedures. 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 elimination. o Absorption--how the drug leaves its site of administration • Drug characteristics ▪ Formulation of the drug • 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 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 o Bioavailability--how much of the drug that is administered reaches its site of action o F-value--the fraction of the drug that reaches the systematic circulation o 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 o Chemical name--chemical composition and molecular structure o Generic name--non-proprietary name--official name assigned by the manufacturer with the approval of the US Adopted Name Council o Trade Name--patent name given to the medicine by the company marketing the drug Chapter 33: Male Urinary Agents • Overview o 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 therapy. • Finasteride—reduces size of prostate gland by blocking the conversion of testosterone—6-12 months for effect. o 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% o Finasteride is teratogenic even through semen • Saw Palmetto herbal treatment—acts as a 5-Alpha reductase inhibitor. • 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 cGMP. 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 o Anticholinergics • Oxybutynin chloride • Fesoterodine • Tolterodine • Trospium • OnabotulinumtoxinA • Bladder Related Anticholinergics • Darifenacin • Solifenacin (Vesicare) o Antispasmodics o Cholinergic Agonists o Posterior Pituitary Hormones o Urinary Tract Analgesia • Phenazopyridine (Pyridium) • Urinary Incontinence—unintentional leakage of urine—stress, urge, mixes, and overflow • Mechanism of Action o 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 contractions. o Antispasmodics—direct smooth muscle relaxant—can also have anesthetic and analgesic properties. o Cholinergic Agonists—release acetylcholine to increase detrusor muscle tone—starts a contraction and bladder emptying—used for overflow incontinence. o Biologic Toxin—blocks muscle contraction—used for detrusor muscle over activity in patients with an inadequate response or intolerance to anticholinergic medication. o Desmopressin—synthetic vasopressin that acts as an antidiuretic—decreases urine output for 6 hours. o Urinary Tract Analgesia—azo dye excreted in urine—only useful as analgesic—used for short-term, 2 weeks. • Treatment o 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 Chapter 15: Upper Respiratory Agents • Overview o 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 o OTC combination medications may be confusing and counterproductive o Nighttime formulations contain alcohol and acetaminophen--cannot be taken together • 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 o Oral--for nasal congestion caused by the common cold, hay fever other respiratory allergies, sinusitis, and Eustachian tube congestion. • 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 incontinence. o 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 relaxation. • Sympathomimetic drugs mimic the action of norepinephrine on sympathetic effector organs and affect adrenergic receptors o Use with caution for patients with HTN, PVD, hyperthyroidism, DM, prostatic hypertrophy, urinary retention, and increased intraocular pressure--sympathomimetic effects. o Contraindicated for mitral valve prolapse and palpitations o 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 o 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 o Symptomatic relief for perennial/seasonal allergic rhinitis, vasomotor rhinitis, allergic conjunctivitis, temporary relief of runny now/sneezing caused by common cold. o Skin--allergic/non-allergic pruritic symptoms, mild and uncomplicated urticaria and angioedema. o 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 o 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 itch. • Must be used daily, maximum effects are seen after days to weeks. o 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 allergies. o 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). o Prevention/treatment of allergic rhinitis. • 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 o 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 o Treatment of allergic/perennial allergic rhinitis. • Montelukast Sodium -- Singulair • Antitussives--adjunctive therapy in URI and lower respiratory conditions o Narcotic--codeine for suppression of cough induced by chemical/mechanical respiratory tract infection. • Codeine Phosphate o 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. o Acts centrally on the cough center in the medulla to suppress a cough • Expectorants--adjunctive therapy in URI and lower respiratory conditions o 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 secretions. • Non-productive coughs become productive, less frequent, and less irritating. • Time-release OTC requires FDA approval. • 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 component. 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 swallowed. ▪ 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 headache. • 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 dysfunction. • 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 cough. ▪ 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 decongestant. ▪ Severe symptoms--treat with or without a decongestant--possibly oral steroid for 5 days and oxymetazoline, no longer than 3 days. 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 Chapter 16: Asthma and COPD Medications • Overview o 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 o Respiratory bronchioles = smooth muscle • Sympathetic stimulation through catecholamines—epinephrine on B2 adrenergic receptors = bronchodilation • Parasympathetic stimulation through the Vagus nerve and cholinergic receptors = bronchoconstriction. • Pathophysiology o 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 medication. • 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 heliox. • 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 o 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 QOL. • 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 sputum. • 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 o 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 relaxation. • 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 o Methylxanthines—promote bronchodilation by inhibiting phosphodiesterase and slowing down the breakdown of cAMP—also positive inotrope, diuretic—beneficial as add-on therapy. • 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 heartbeat. o 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. o Mast Cell Stabilizers—prevent and reduce inflammatory response—antiasthmatic and antiallergic. o Corticosteroids—modify the body’s immune responses. o Leukotriene Modifiers—act on inflammatory mediators of asthma—leukotriene receptor antagonists. Chapter 66: Antitubercular Agents • Overview o 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 o Mycobacterium tuberculosis--thick-walled bacterium. o Primary route--inhalation--bacilli are spread to the lymphatic system, may lodge in bone, bladder, of CNS. o Cell-mediated immune response results in tubercle formation. o Non-immunocompromised exposed to TB and testing positive to skin test has 10% chance of developing active TB-- HIV patients have 30-50% o Most common site--pulmonary system--can also cause bone pain and UTI (rural areas) o Reactivation Disease--occurs when a previously infected patient becomes immunocompromised--COPDers using prednisone o 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 Rifapentine. 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 later. ▪ 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 repeated. ▪ Measure induration (not erythema) crosswise to the axis of the forearms--record in millimeters-- not negative or positive. ▪ Close contacts of those with infectious TB with a negative PPD should be retested 10 weeks later. ▪ Previous vaccination of BCG does not change the need for treatment or testing. ▪ 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 used. • 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 vaccinations. ▪ 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 bronchoscopy. • 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 o Isoniazid--prevents TB in high-risk patients without HIV--6-12 months--possible hepatotoxicity • Metabolized by acetylation and dehydrazination o First-Line: Isoniazid (INH), Rifampin (RIF), Ethambutol (EMB), Pyrazinamide (PZA). • Newly diagnosed pulmonary TB--6-month course of chemo with at least 2 drugs. ▪ Initial Phase--3-4 drugs given x 6-8 weeks ▪ Continuation Phase--2 drugs given x 18 weeks. o Second-Line: Cycloserine, Ethionamide, Streptomycin, Amikacin/Kanamycin, Capreomycin, P-Aminosalicylic Acid (PAS), Levofloxacin, Moxifloxacin, Gatifloxacin • Aminoglycosides--end in cin, Fluoroqionolones--end in xacin. o Dispense 1-month supply and monitor patient monthly. • 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 ▪ 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 o Latent Infection • Isoniazid + Rifapentine x 3 months ▪ HIV--treatment begins when TB is suspected. ▪ Non-HIV--treatment starts after definitive diagnosis. o Active Infection • Report all cases to local and state health authorities--within 24 hours--maintain respiratory isolation • Test and treat all close contacts. • Monitor for compliance and response to treatment. • Direct Observed Therapy (DOT) is more successful. • 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 treatment. o Health Care Provider should assess for--history of hepatitis, heavy alcohol ingestion, liver disease, or age older than 35 years--monitor LFTs--adjust therapy. o 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 therapy. • Never add single drugs to a failing regimen Chapter 67: Antifungals • Overview o 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 o 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 hyphae. • Mycosis—presence of parasitic fungi in or on the body. • Disease Process o Topical Fungi • Tinea capitis—caused by Trichophyton tonsurans--requires systemic treatment. • Tinea corporis—caused by T. rubrum—may respond to topical or need systemic treatment. • Tinea versicolor—caused by Malassexia furfur—requires systemic treatment. • Mucosal candidiasis—caused by candida albicans. ▪ Invasive candidiasis—neutropenia, recent surgery, broad-spectrum antibiotic therapy, indwelling catheters, and immunodeficiency—suspect HIV. o Endemic Mycoses—in rural and regional populations—maintain suspicion—skin scrape smears. • 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 plaques. • 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 o Azoles—more fungistatic instead of fungicidal—inhibit ergosterol synthesis—inhibition of cell growth and replication. o Terbinafine—blocks synthesis of ergosterol—collapsing the fungal cell membrane. o Griseofulvin—penicillium derivative—deposits into keratin of diseased tissue and creates resistance to fungal infection. • Treatment o Topical fungi are often resistant to PO treatment—terbinafine, itraconazole, fluconazole. o Endemic fungal infections—itraconazole, fluconazole. o Unclear duration of treatment o Griseofulvin—tinea capitis of skin, hair, and nails that are unresponsive to topical therapy. • Monitoring o Initial cultures. o Signs/symptoms of hepatitis—fatigue, anorexia, nausea, vomiting, jaundice, dark urine, or pale stools. o LFTs for baseline and periodically—q4-6 weeks in healthy patients, q2 weeks in immunocompromised. o High doses of itraconazole—adrenal suppression, hypokalemia, and secondary v-fib. o Terbinafine—monitor CBC for treatment 6 weeks. o Griseofulvin—baseline and periodic renal, liver, and hematopoietic function. • 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 alcohol. o Geriatrics—greater risk for hepatotoxicity—use renal dosages. o Children • Fluconazole 6 months old. • Itraconazole 6 months – 12 years. • Griseofulvin—2 years old—estrogen-like effects—enlarged breasts, hyperpigmentation or areolae, nipples, and external genitalia. o Griseofulvin and Ketoconazole may cause photosensitivity. o Women of childbearing are should use back up contraception when taking -azoles. Chapter 69: Antivirals and Antiprotozoal Agents • Overview o 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 hours. • 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 ineffective. • 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 o 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 o Malaria • Chloroquine (raises internal pH of parasites—given weekly 1 week prior to travel). o Amebiasis o Giardiasis o Trichomoniasis • Monitoring o Antivirals—monitor for toxicity and adverse effects—especially with renal impairment. • Decrease dose for geriatrics o Antiprotozoals—monitor for muscular weakness—knee and ankle reflexes. • 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 insufficiency. • Anatomy and Physiology o 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 retention. • Androgen (sex steroid) • Mechanism of Action o 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 extremities. • 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 lymphokines. • 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 deposition. • 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 activation. • 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 medication. ▪ Increase hemoglobin concentration, RBCs, and platelets. ▪ 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. o Mineralocorticoids--activity is needed in adrenal insufficiency but not in inflammation. • Hydrocortisone and Cortisone both have Glucocorticoid and Mineralocorticoid properties. • 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 o Short-term--2 weeks or less--do not titrate off o Long-term--very gradual dosage reduction o 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 recovery. • Consider short-acting or QOD therapy for long-term therapy--double dose every other morning--causes less HPA axis and child growth suppression. • 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 food. • 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 o 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 exacerbation. ▪ During titration, monitor for steroid withdrawal and adrenal insufficiency o 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 hypoadrenalism. • Cold, clammy skin, tachycardia, tachypnea, weakness, irritability, poor feeding, dehydration. • Prednisone/Prednisolone 20mg/day • Methylprednisone 8mg/day ▪ Wait 3-4 hours to breastfeed o Avoid live-virus vaccines o Do not use in the presence of systemic fungal infection Chapter 52: Thyroid Medications • Overview o 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 o 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 gland. ▪ TSH secretion is influenced by TRH released from the hypothalamus. ▪ 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 thyrotoxicosis. ▪ 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 thyrotoxicosis. • Secondary hypothyroidism--lack of TSH secretion from pituitary gland. • Tertiary hypothyroidism--lack of TRH secretion from the hypothalamus. • 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 maturity. • Treatment o 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 aging. ▪ 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. o History of thyroid cancer with partial or total thyroidectomy must take thyroid hormone supplements to suppress endogenous levels of TSH and to regulate metabolism. • High levels of TSH allows for radioiodine imaging to detect remnant thyroid tissue or metastasis. ▪ Thyrogen instead of discontinuing thyroid hormones prior to imaging study o Pregnancy--category A--minimal in breast milk--may need dosage adjustment to meet increased energy demands-- monitor TSH closely. • Thyroid Suppressants o 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 transient. • 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 symptom