Pharm Notes Exam 3 PDF

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Textbook: Pharmacology for the Primary Care Provider, 4th ed. (2013), Edmunds & Mayhew. Mosby Elsevier....

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Chapter 15 – Upper Respiratory Agents

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Decongestants are used as 1st line drugs for URIs. Antihistamines are 1st line drugs for allergic rhinitis. Intranasal steroids and Cromolyn are generally considered 2 nd line treatment for URIs. Antitussives and expectorants are used as adjunct therapy in upper and lower respiratory conditions.

Pathophysiology • •

URIs are often viral in origin, and allergic rhinitis is from allergic reaction and nothing to do from infection. Secondary bacterial infections is common in both URIs and allergic rhinitis is undertreated. • Acute sinusitis and otitis media are the most common complications of URIs. • Pneumonia in susceptible patients.

URI •

Diagnosis is based observation, after absence of signs bacterial infection is noted – purulent nasal discharge or high fever.

Allergic Rhinitis • •

Symptoms similar to URI symptoms, but more persistent Sneezing, injected conjunctiva, watery itchy eyes, red edematous eyelids, watery rhinorrhea, pale turbinates

MOAs Decongestants – sympathomimetics amines that act to stimulate alpha adrenergic receptor of vascular smooth muscle and cause vaconstriction. Results in nasal decongestion.

Antihistamines – compete for histamine at the H1 receptor sites and are used to treat immunoglobin (Ig) E-mediated allergy.

Intranasal corticosteroids – inhibit immune cells and exert local anti-inflammatory effects with minimal systemic effects

Intranasal Mast Cell Stabilizers – anti-inflammatory agent that has no intrinsic bronchodilator, antihistaminic, vasoconstrictor, glucocorticoid activity.

Leukotriene Receptor Antagonists – causes inhibition of airway cysteinyl leukotriene receptors (CysTLs), which are released from the nasal mucosa after allergen exposure and are associated with allergic rhinitis.

Antitussives – act centrally on the cough center of the medulla to suppress cough Expectorants – increases respiratory tract fluid secretions and helps to loosen bronchial secretions by reducing adhesiveness and tissue surface tension

Cardinal Points of Treatment

**Hand washing** • • • • •

Upper and lower airway obstruction and headache need to be promptly evaluated No aspirin containing products for younger than age 21 No cold and cough meds for children younger than 6 yrs No Tylenol for liver dysfunction No medical literature supporting use of echinacea

Allergic Rhinitis • •

Allergy testing is rarely helpful in diagnosing allergic rhinitis, but may help patients with multiple allergen sensitivities Patients with moderate to severe perennial allergies may benefit most from immunotherapy

Cough • • •

Associated with viral infection- can be treated with 1stgeneration antihistamine/decongestant combo Cough d/t URI – ipratropium bromide Chronic broncholitis – codeine

Rhinosinusitis •

Amoxicillin/clavulanate as 1stline therapy

Nonpharmacologic Treatment • • • • •

Rest, hydration Teaspoon of honey for reducing cough in small children HEPA filters NS sprays or nasal irrigation – 2x day Ask patients if they are using complimentary or alternative meds – many interact (see table 15.1, p190)

Pharm Treatment •

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Decongestants • Should be used in caution in patients with HTN, CV disease, hyperthyroidism, diabetes, prostatic hypertrophy, urinary retention, and increased intraocular pressure d/t sympathomimetic effects • Contraindicated with mitral valve prolapse and cardiac palpitations • Topical decongestants have little systemic effect because of rebound congestion they should be used only in acute conditions for no longer than 3 consecutive days. Antihistamines • Best used to relieve allergic rhinitis symptoms • In general, not recommended to treat lower respiratory tract symptoms, including asthma • 1stgeneration agents are usually available OTC • 2ndgeneration antihistamines favored by clinicians for safety and efficacy. • Sedating antihistamines preferred if sleep is an issue Intranasal Corticosteroids • Used for at least 1 month before it is decided whether they are effective • Warn patients improvement usually does not occur until 1-2 weeks after therapy starts Intranasal Mast Cell Stabilizers • Usually available OTC and should start 3-4 weeks prior to peak allergy season Leukotriene Receptor Antagonist • Used in treatment of allergic rhinitis, especially asthma Antitussives • Determine the underlying disorder that is causing the cough • Not given in situations where retention of secretions would be harmful Expectorants • Relief of DRY cough • Thins thick secretions to promote drainage

Monitoring • •

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Antihihistamines • Relief of symptoms and excessive drowsiness Intranasal Corticosteroids • Development of infection in nose or sinus • Long term use – changes in mucosa or polyps in nose Antitussives • Narcotic antitussives for effectiveness and excessive side effects • Constipation in elderly

Patient Variables •

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Decongestants • Sustained release should not be used in nursing mothers or children under 12yo • No cough or cold meds for children oral medication preferred o Good tissue penetration --> effective for skin, bone, genital infections o Poor CNS penetration o NOT first-line abx for mild infection o Agent of choice for UTIs, pyelonephritis, complicated sinusitis, severe diarrhea, prostatitis o Alternative tx for: dog bite, acute or severe sinusitis, chlamydia Contraindications: o Hx of myasthenia gravis, may cause severe muscle weakening, including respiratory muscles o Ciprofloxacin: pts receiving QT-prolonging drugs or drugs that cause torsades Precautions: o Risk of tendon rupture < 18 years or > 60 years; taking steroids; kidney, heart, and lung transplant recipients. D/C drug if pt has tendon pain or inflammation Monitoring: o Renal, liver, hematopoietic function (leukopenia, thrombocytopenia, anemia) at baseline & q6 weeks o Pts on warfarin should be monitored for PT, INR at baseline —daily during week 1, weekly thereafter o Theophylline product levels Side effects: o Risk of tendonitis and tendon rupture o Headache, dizziness, drowsiness, weakness, confusion, shaking o Photosensitivity Patient variables: o Geriatrics ▪ If reduced renal function, reduce dosage ▪ Caution in CNS disorders (seizure, stroke) and cerebrovascular dz (atherosclerosis) d/t increased risk of seizures

Pediatrics ▪ Only Ciprofloxacin is FDA approved for UTI and pyelonephritis in pediatric pts d/t risk of tendon rupture o Pregnancy and lactation ▪ Pregnancy category C; use only if other options not available ▪ Quinolones enter breast milk and should not be used in breastfeeding Patient teaching: o Caution when driving, operating machinery, hazardous activity d/t risk of dizziness and drowsiness o Avoid taking with milk, sucralfate, antacids, iron preparations, or any products containing aluminum, mg, calcium, iron, or zinc o Avoid 2 hours before OR 6 hours after chelation. Absorption can be reduced by chelation. o Drink lots of fluids o May cause photosensitivity o

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Ch. 64 – Aminoglycosides • Pharmacotherapeutics: o Contain “mycin” or “micin” suffix o Serious gram negative infections (that are resistant to other abx) o Effective against: M. catarrhalis, H. influenzae, Legionella, Chlamydia, mycobacteria (except Mycobacteria avium intracellulare complex), Klebsiella, E. coli, Enterobacteriacea o Weak against: S. pneumoniae o Narrow therapeutic window o NOT absorbed from GI tract. ORAL aminoglycosides are not absorbed. o Neomycin (neosporin) can be used only as bowel prep prior to surgery or topically for skin infection o Does NOT cross blood-brain barrier o Tx: ▪ Oral: suppression of GI bacterial flora and in the treatment of patients with hepatic coma ▪ Topical: irrigation of infected wounds ▪ Parenteral: resistant or complicated UTIs, respiratory infections, skin/bone/soft tissue infections, CNS infection, GI infections (peritonitis) • Mechanism of action: o Bactericidal o Create fissures in outer cell membrane, resulting in leakage of intracellular contents & enhanced antibiotic uptake o Inhibit bacterial DNA replication • Treatment principles: o Poor CNS penetration o Avoid prolonged use (no more than 10-14 days) • Monitoring: o Peak concentration

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▪ 30-45 min after IV dose ▪ 60 min after IM dose o Trough ▪ Drawn immediately before administering dose o Serum calcium, magnesium, sodium (levels may be decreased – electrolyte imbalance) o BUN and creatinine, creatinine clearance o Test cranial nerve 8 (vestibulocochlear) with audiometry. Hearing loss may occur. Adverse Effects: o Allergy, anaphylaxis, Stevens-Johnson syndrome o Nephrotoxicity (reversible if detected early and drug stopped) o Ototoxicity (usually irreversible) o Neuromuscular blockade --> can result in respiratory paralysis o Superinfection, esp. By fungi o Hypomagnesemia Patient teaching: o Regular monitoring of blood levels needed o Maintain hydration (esp for children and elderly) o Report tinnitus, change in hearing, vertigo o Report muscle weakness, difficulty breathing Patient variables: o Geriatrics: ▪ Diminished GFR may prolong half-life and increase toxicity, nephrotoxicity, renal failure o Pediatrics: ▪ Immature renal function in neonates, results in prolonged half-life --> reduced drug clearance & risk of toxicity o Pregnancy & lactation: ▪ Category C: gentamicin, tobramycin, amikacin ▪ Category D: neomycin, streptomycin, kanamycin Drug Interactions: Beta-lactam antibiotics --> renders both abx inactive Caution: impaired renal function at increased risk for toxicity

Ch. 65 – Sulfonamides • Contains “sulf” in the name • Most commonly used sulfa = Trimethoprim/Sulfamethoxazole (TMP/SMX) • 4 classes: o Topical antibiotics – short-acting ▪ Rapidly absorbed, rapidly eliminated o Topical antibiotics – long-acting ▪ Rapidly absorbed, excreted slowly o Topical infections ▪ Not absorbed systemically, used in eye and ear o Bowel problems ▪ Poorly absorbed

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Sulfa allergies are common Indications: o UTIs (most common use) o Acute exacerbation of COPD o Pneumonia o Traveler’s diarrhea o Diverticulitis o Sinusitis Broad spectrum o Gram-positive o Gram-negative o NOT against anaerobes o May be effective against: Streptococcus pneumoniae, Moraxella cararrhalis, E. coli, Klebsiella spp, Enterobacter, Legionella Mechanism of action: o Bacteriostatic Treatment principles: o Resistance is a problem that limits the usefulness of sulfonamides o Sulfonamide allergy is common o Advantage: low-cost o Trimethoprim/Sulfamethoxazole (TMP/SMX) is 1st line treatment for acute bacterial exacerbation of COPD and diverticulitis. o TMP/SMX is alternative tx for dog and human bites, acute sinusitis, diarrhea, UTIs, and pyelonephritis. Monitoring: o Blood levels in pts with serious infection o Severe adverse effects o Symptomatic evaluation Patient variables: o Geriatrics: ▪ Skin reactions, bone marrow depression, decreased platelets, wit or without purpura ▪ Thiazides + sulfa may have increased incidence of thrombocytopenia with purpura ▪ TMP/SMX in elderly results in increased risk of severe reactions, esp. In conjunction with other drugs or those with impaired renal or liver function o Pediatrics: ▪ Not for use in kids < 2 months d/t allergies o Pregnancy and lactation: ▪ Category C/D ▪ Do not use at term ▪ TMP/SMX can interfere with folic acid metabolism --> use only if benefits outweigh risk to fetus ▪ TMP/SMX can be used during 2nd trimester

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▪ Excreted in breast milk Patient education: o Drink 8oz glass of water with each dose and multiple times a day to prevent crystalluria o Take on empty stomach with water o Avoid prolonged exposure to sunlight d/t photosensitivity o Notify provider if hematuria, rash, tinnitus, dyspnea, fever, chills, or sore throat develops o Oral suspension: shake well and refrigerate Adverse Effects: o Photosensitivity Drug interactions: o Thiazides, indomethacin, methenamine, probenecid, salicylates

CH. 66: Antitubercular Agents

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focus is on treatment of latent TB TB → high contagious, reportable dx whose treatment should be initiated by an ID specialist High risk → HIV/AIDS

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Pathophysiology • Caused by Mycobacterium tuberculosis • Primary route on infection → inhalation of infectious particles • Bacilli are also spread to the lymphatic system and may lodge in bone or other organs Disease Process • According to the CDC, the number of TB cases in the US continues to DROP • CDC found that TB rates were 12 times higher among foreign born people (esp in Mexico, Philippines, India, China and Vietnam) • Nonimmunocompromised adult exposed has a 10 % risk of developing TB • Higher risk for HIV/AID: 30-50% • “cluster” cases seen in → low SES, inadequate housing and high rates of drug abuse, poverty & crime • “unclustered” cases → reactivation of old infection • most common site of TB infection → pulmonary system • Pulmonary TB → predominately in urban areas • Urinary and bone TB → rural areas • Reactivation disease → occurs in a patient who was infected in the past • Ex: aging/ immunocompromised pts; ex in COPD pt taking prednisone • Box 66-1 (p.706) Patients at Risk for TB • HIV infection • foreign born from areas where TB is common • Close contact w/ infectious TB pt

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Certain medical conditions (DM, lymphoma, certain GI surgeries, chronic renal failure, CA, silicosis and immunosuppressive therapy Persons who inject drugs

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medically underserved, low SES residents/ employees of long term care facilities (nursing homes; jails) migrant worker/ homeless health care workers

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Assessment • Clinical symptoms: fever, cough, pain in chest when breathing/ coughing, cough productive of sputum/ blood, fatigue, malaise, weight loss • Children often present asymptomatic or with systemic infection

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Testing for Exposure to TB • A pt w/ a positive test is considered to have a latent TB infection • Mantoux TB skins test is the preferred test for TB bc it is most accurate • 0.1ml of PPD tuberculin containing 5 TU is injected intradermally to make a wheel of 6-10 mm in diameter • read test 48-72 hours after • only the induration (hardness) is measured; not erythema • * previous vaccination with BCG usually should not influence the need for TB skin testing

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Diagnosis of TB • CXR no longer a good screening tool for TB dx in low risk people • In high risk, may be a useful tool • CXR should be obtained on all pts who have a positive PPD • Obtain PA and lateral views • Apical lordotic view if the hx is suggestive of TB and initial films are normal • Biopsy showing caseation granulomas would confirm the diagnosis • Culturing of TB organism takes 6 weeks • AFB smear, much quicker → sputum sample observed under lights • Gastric aspiration → best way to obtain specimens from infants and young kids ; should be done in AM, before pt gets out of bed or eats • Positive results → pt should immediately be placed in isolation in hospital • Pts w/ positive smear are considered contagious • Presumptive diagnosis of active TB is made when the pt has any of the following: • Recent conversion to positive PPD associated with s/s • Positive sputum smear • Characteristic CXR

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Initial Phase Continuation Phase

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HIV/AIDS th Confirmed diagnosis of act positive TB is made by a positive culture from any body fluid or biopsy specimen

Daily INH, RIF, PZA and EMB Daily INH and RIF for 126 doses (18 weeks) or Twice weekly INH and RIF for 36 doses (18 weeks)

TB is treated with ANTIBIOTICS Evidence Based Recommendations: • To prevent TB in high risk people w/o HIV, isoniazid is given 6-12 months (careful, can cause hepatotoxicity) • 1st line: INH, RIF, EMB and PZA • pts newly dx w/ pulmonary RB ➔ 6 month course of chemotherapy with at lest 2 drugs is recommended • several available regimens, all do: • initial phase → 3 or 4 drugs for 6-8 weeks • continuation phase → 2 drugs given for 18 weeks

CARDINAL POINTS • • •

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dispense 1 month supply at a time treatment of latent infection • isoniazid is the treatment of choice; given for 3 months with rifapentine treatment of active infection • report all cases to local/state health care authorities • test and treat close contacts • monitor closely for compliance; DOT has highest success rate • add at least 2 new antitubercular agents when treatment failure is suspected treatment of latent TB • first line: • isoniazid, rifampin, rifabutin, rifapentine, pyrazinamide, ethambutol • second line: • cyclosporine, ethionamide, streptomycin, amikacin’ kanamycin, capreomycin, PAS, levofloxacin, moxifloxacin, gatifloxacin

treatment of active disease • report all cases within 24 hours to health department • maintain respiratory isolation • pt assumed to be contagious if any of the following: • cough is present

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pt undergoing a cough inducing procedures (sputum smear is positive and until 3 negative smears are obtained) been on therapy for at least 1 week

How to Monitor •

Isoniazid prophylaxis • see pts on a monthly basis • ask about s/s of liver damage ➔ anorexia, n/v, fatigue, weakness, new and persistent paresthesias of hands/feet, persistent dark urine, icterus rash or elevated temps • obtain routine LFTs monthly for pts high risk for developing INH hepatitis (> 35 yrs, daily drinkers, concomitant med toxic to liver, hx of liver dx) • discontinue INH immediately if pt develops s/s toxicity

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Patients with Active TB • Obtain CXR at baseline and at 6 months • Collect sputum smear and culture at baseline and monthly until negative • Measure levels of hepatic enzymes, bili, Cr, CBC & platelets and uric acid at baseline in monthly in pts taking INH, RIF and EMB • At each monthly visit patients who are taking EMG should be questioned regarding possible visual disturbances (blurred vision or scotomata); monthly testing of visual acuity and color discrimination is recommended • Pts taking INH ➔ obtain periodic ophthalmologic exam • Pyrazinamide ➔ collect blood glucose levels (may be hard to regulate in DM) • Ethambutol ➔ monitor color vision for red-green at baseline and at 2 and 3 months • Streptomycin ➔ obtain audiogram before beginning the drug and at 2 and 3 months; also, monitor drug serum levels • Cycloserine ➔ monitor blood levels weekly in pts w/ reduced renal fxn

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Geriatrics • At increased risk for toxic effects, esp of liver and CNS Pediatrics • Treatment similar to adults • Except don’t give ethambutol unless routine eye exams can be performed • Streptomycin is not recommended for use in children Pregnancy/ Lactation • Treatment with 3 meds is recommended: isoniazid, rifampin, and ethambutol

Patient Education

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compliance • take all meds • keep all appts • adequate testing • maintain resp isolation while contagious • avoid intimate contact w/ other • cough into tissue, dispose in closed plastic bag • don’t share utensil or drinks • good hand washing • adhere to proper hydration/ rest/ diet/ exercise

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Isoniazid (INH) • CI ➔ known contact w/ isoniazid resistant TB case; liver dx • Warnings ➔ watch for hypersensitivity rxn; INH induces tumors in mice; ophthalmic exam recommended annually or with any visual symptoms • Pharmacokinetics ➔ INH metabolized primarily by acetylation and dehydrazination • MOA ➔ bacteriostatic for r...