NR Pharmacology, INTRODUCTION TO PHARMACOTHERAPEUTICS

INTRO TO PHARMACOTHERAPEUTICS Prescription Writing Need at least 2 patient identifiers: Name, DOB, Address, Date of Rx, Prescriber name, address, license number, DEA number if applicable, Info for supervising MD, Drug: ...

INTRO TO PHARMACOTHERAPEUTICS Prescription Writing Need at least 2 patient identifiers: Name, DOB, Address, Date of Rx, Prescriber name, address, license number, DEA number if applicable, Info for supervising MD, Drug: name/strength/dose/route/QTY/refills, Signature JC “Do Not Use” List • U: write out “unit” • IU: write out “international units” • Q.D., Q.O.D.: write out daily or every other day • Trailing/leading zeros • MS, MSO4, MgSO4: write morphine sulfate or magnesium sulfate • µg: write mcg • H.S.: write half-strength or at bedtime • T.I.W.: write three times weekly or 3 times weekly • S.C. or S.Q.: write Sub-Q or subQ or subcutaneously • D/C: write discharge • c.c.: write mL • AS, AD, AU, OS, OD, OU: write out, e.g., both eyes or left ear ANTIBIOTICS Class Drug MOA Uses/Coverage ADR/DDI Education/Other PCN: 1 st Gen Pen G (IV) Inhibit cell wall synthesis, Bactericidal Pneumococcal pneumonia Benzathine penicillin (IM) Syphilis, strep throat Pen VK (PO) Gram + coverage and Treponema pallidum PCN: 2 nd Gen Nafcillin (IM/IV) Cloxacillin (PO) Antistaphylococcal, MSSA Dicloxacillin (PO) PCN: 3 rd Gen Ampicillin (PO) Extended-spectrum: G(+) PLUS some G(-); Amoxicillin (PO) OM, URI Augmentin (amox + clavulanate) Diarrhea, Good for beta-lactamase: H.Flu, M.Cat PCN: 4 th Gen Zosyn (piperacillin + tazobactam) (IV) Broad spectrum, covers Pseudomonas, many G(-) Cephalosporin: 1 st Gen Cefazolin (IM, IV) Inhibit cell wall synthesis good Gram + coverage, NO MRSA coverage Cross-sensitivity with PCNs Cephalexin (PO) Cephalosporins: 2 nd Gen Cefaclor Not as good G+ but some G(-); OM, Strep Cefuroxime (IM, IV, PO) pharyngitis Cephalosporins: 3 rd Gen Ceftriaxone (IM, IV) better G- but lower G+ coverage, High risk w/ some for ESBL resistance Ceftriaxone good for gonorrhea d/t single dose Cefotaxime (IM, IV) Cefixime (PO) Cephalosporins: 4 th Gen Cefepime (IM/IV) Good G+ and G- coverage, Covers Pseudomonas Cephalosporins: 5 th Gen Ceftaroline (IV) G- as 3rd-gen plus MRSA coverage Carbapenems Doripenem Inhibit cell wall synthesis Broader than other BL-abx All IV, IM, saved for very broad coverage May have cross-sensitivity to PCNs Ertapenem Ertapenem: not good Pseudomonas coverage Imipenem & cilastatin Meropenem Monobactam Aztreonam: IM, IV, inhale Inhibit cell wall G- ONLY, Covers Pseudomonas Never use for empiric tx, synthesis Good for PCN-allergic Vancomycin IV Inhibit cell wall synthesis Mainly for G+ and MRSA IV ADR: dose-related ototoxicity & nephrotoxicity; Red man (infusion NOT allergy) Dose for renal fxn, monitor serum levels Vancomycin PO For C. diff. colitis Telavancin Inhibit cell wall synthesis Alternative to vancomycin Covers G+ and MRSA ADR: Teratogenic and QT prolongation No drug monitoring Macrolides Erythromycin Inhibit protein synthesis, bind to 50s ribosomal subunit G+, G-, and atypicals, Often used to treat G+ in pen-allergic patients; Enzyme inhibitor: E > C >> A Must watch with: CBZ, warfarin, statins, etc. Allergic reactions are rare! Clarithromycin ADR: n/v, metallic taste Improved H.Flu vs. E-mycin Azithromycin Long 1/2 life, good for Chlamydia, other atypicals Tetracyclines Doxycycline Inhibit protein synthesis, bind to 30s ribosomal subunit Coverage very broad: G+, G-,aerobic and anaerobic, spirochetes, mycoplasmas, rickettsiae, chlamydiae, some protozoa, MRSA PO High levels of resistance CI: Avoid with chelating agents (MVI, antacid, milk, iron), Avoid in pregnancy and small children (<8) – Binds Ca and will stain teeth ADR: n/v, liver disease, phototoxicity Minocycline Tigecycline IV Derivative of minocycline MRSA, MDRSp, VRE, ESBL-producing G-, many anaerobes, NOT for Pseudomonas; for Complicated SSTIs, intraabdominal ifxn, CAP Aminoglycoside Amikacin Inhibit protein synthesis, bind to 30s ribosomal subunit G- including Pseudomonas Monitor renal function and serum drug levels! ADR: ototoxicity, nephrotoxicity Gentamicin Tobramycin Clindamycin Inhibit protein synthesis, bind to 50s ribosomal subunit Mainly for anaerobic coverage PO or IV and in some topicals, MRSA PO ADR: rashes and high rate of C.diff. Linezolid (Zyvox) Inhibit protein synthesis, bind to 50s ribosomal subunit PO & IV Use for resistant organisms: MRSA, VRSA, VRE, penicillin-resistant Strep. pneumo Caution for Serotonin Syndrome Might offer benefit when transitioning to outpatient Fluoroquinolones Ciprofloxacin Inhibit nucleic acid synthesis – inhibit topoisomerase UTI, GI, Pseudomonas broad G-, respiratory FQs with improved G+ coverage ADR: C.diff colitis!! CNS: seizure, dizziness; Cardiac: QT prolong; MS: tendon, cartilage; Endo: glycemic control; Skin: photosensitivity, rash DDI: antacids, Fe, Ca, Zn Levofloxacin UTI, GI, LRI, URI, skin Moxifloxacin LRI, URI, GI, skin (no UTI!!) Others PO, otic, ophthalmic Folate Antagonist TMP-SMX (Bactrim, Septra) Broad with G+ and G-, NO Pseudomonas Common for UTI, MRSA PO ADRs: rash (simple to SJS), photosensitivity, crystalluria (need to counsel) Dose based on TMP (more important in PO liquid) Miscellaneous Metronidazole Covers protozoa, anaerobes **DOC: C.diff. colitis Trichomoniasis; Various infections of: skin, bone, CNS, GYN, GI, LRI, endocarditis ADR: Avoid with EtOH. Metallic taste Nitrofurantoin unclear, thought to inhibit several enzyme pathways and possibly Use in simple UTI treatment and prophylaxis NOT pyelonephritis or complicated cystitis CI: ClCr <60 mL/min; Do not use in renal impairment Warnings/Caution: Hepatic disease, Elderly HARM FALL 2013 BLOCK I: DERM & EENT INTRODUCTION TO DERMATOLOGIC PRODUCTS Determinant of Pharmacologic Response 1. Permeability and penetration – hydrated > dehydrated, thin > thick, trauma > no trauma 2. Concentration gradient – greater concentration  greater amount per unit time (threshold may exist) 3. Dosing – time left on skin, frequency, quantity; dermis acts as barrier and can effect duration 4. Vehicle – cream, ointment, liquid, solution 5. Occlusion – maximizes efficacy, increases absorption, protection Drug Delivery Systems  Emulsions – drug particle contained w/in vehicle/base; Indication for different types of products (dry/wet, sensitivity/pain, size, location, acute/chronic)  Creams – most common vehicle, no occlusion  Ointments – common, good for dry lesions due to occlusive properties; NOT for intertriginous areas; can be cosmetically unpleasing  Gels – clear, non-greasy, non-staining, non-occlusive, quick drying; can sting on application and be drying (due to EtOH)  Solutions – evaporate quickly (drying), used in acute/weeping/oozing wounds o Tinctures – alcohol-based solution, used for extreme drying properties  Aerosols – advantage for painful skin, but expensive and not efficient dosage form  Lotions – good for tender areas, spreads easily, evaporates quickly, good for large areas  Powders – used to absorb moisture/friction; caution w/ very wet lesions due to crusting Choosing Which Drug Delivery System to Use DRY wet lesions and WET dry lesions **more liquid agents dry better  Acute inflammation (oozing/weeping/vesication/edema/pruritis)  aqueous vehicles, powders, lotions, sprays, aerosols  Subacute inflammation (crusting/oozing/pruritis)  creams, gels  Chronic inflammation (lichenification/dryness/erythema/pruritis/scaling)  ointments ANDROGENIC ALOPECIA Tx goal: reduce loss and maintain existing hair **If you stop therapy, hair loss WILL return! Drug MOA Indication ADRs/DDI/CI Specific Education/Other Minoxidil Changes follicle size & growth cycle of hair to  f hair & thicker/longer shaft Topical formulation only to limit and contain ADR (BP); OTC, 1st line M & F ADR: local irritation, undesirable growth if inappropriately use **well- tolerated Wash hands after application, treatment must be continuous Finasteride Type II 5-alpha-reductase inhibitor, PO (tablet) formation that only grows *CI: pregnancy Caution in women of child-bearing 4inhibits conversion of testosterone to dihydrotestosterone (reverse loss) hair at vertex/frontal scalp; first line for men, second line for women ADR: libido, erectile dysfunction, ejaculation disorder, ejaculation vol age, wash hands/gloves, treatment must be continuous SYSTEMIC ANTIFUNGALS Class Drug MOA Indication ADRs/DDI/CI Specific Education/Other Amphotericin B (“Amphoterrible”) binds to ergosterol and alters permeability; large spectrum of activity IV; only used in infectious disease with high resistance *lipid formations are less toxic, but still not good ADRs: EXTREMELY TOXIC (nephrotoxicity, infusion- related toxicity) Azoles Fluconazole (Diflucan) inhibit synthesis of ergosterol by blocking demethylation of lanosterol IV and PO; Important treatment for infections due to Candida; drug of choice for vaginal yeast infections Itraconazole IV and PO *bioavailability varies, PO solution achieves higher serum concentrations; Used for fungal nail infections Can cause liver problems – must get liver enzymes checked every 4- 6 weeks Voriconazole IV and PO; Broad spectrum triazole used for serious infections, first line for aspergillosis ADR: visual abnormality Posaconazol e PO suspension Broad-spectrum triazole, but can cause many DDIs *Enhanced w/ high-fat meal, splitting dose in fasting Echinocandins disrupts cell wall structure formation by inhibiting β- glucan synthase IV only; used to treat significant fungal infection – integral component of Aspergillus and Candida cell wall Generally well tolerated (but expensive) *more common/better tolerated/less DDIs than azole Flucytosine disrupts cell wall formation via pyrimidine analog PO only, rarely used as monotherapy due to rapid resistance development Spectrum: Cryptococcus spp, Candida spp; used to treat cryptococcal meningitis in combination w/ AmB Key Points of Systemic Antifungals  Always consider hepatic function (liver disease, heavy EtOH use, etc.)  Review patient’s medical history to avoid DDIs  Systemic –azole agents in primary care are mainly used for skin/nail disorders, vaginal yeast infections (fluconazole) TOPICAL ANTIFUNGALS Class Drug MOA Indication Specific Education/Other Topical Azoles Block biosynthesis of ergosterol Tinea pedis/cruris/corporis, tinea versicolor, cutaneous candidiasis, vaginal candidiasis *Most effective topical antifungal for treatment of dermatophytes Topical Allylamines, Butylamine Naftifine inhibit squalene epoxidase (key enzyme in ergosterol biosynthesis pathway) Tinea pedis/cruris/corporis, tinea versicolor Terbinafine (Lamisil) **Terbinafine = tx for nail fungus Butenafine Topical Polyene Nystatin Bind to ergosterol in fungal cell membrane, changes membrane permeability cutaneous infections caused by Candida albicans, other Candida spp *not useful against dermatophytes *highly toxic systemically Other Selenium exerts a cytostatic effect of cell of epidermis tinea versicolor Lotion, Shampoo formulations OTC (well- Sulfide and follicular epithelium tolerated) Tolnaftate Distorts the hyphae and stunts mycelial growth of fungal species Tinea pedis/cruris/corporis, tinea versicolor (Tinactin) *tough-actin tinactin; Cream, solution, powder, spray, gel forumations OTC Ciclopirox alters integrity of fungal cell membrane skin, superficial nail infections; tinea pedis/cruris/corporis, tinea versicolor *activity against Candida Cream, lotion, nail laquer (Penlac) formulations Systemic Agents for Superficial Infections *Fluconazole Itraconazole Ketoconazole Terbinafine Griseofulvin Indicated for candidiasis *yeast/vaginal infections Single dose is used for treatment Indicated for candidiasis, dermatophytes (tineas), onychomycosis (nail fungus) Multiple DDIs – Inhibited CYP3A4 Indicated for candidiasis, dermatophytes Multiple DDIs, potential hepatotoxicity *only last line in life-threatening infection PO and topical available Indicated for candidiasis, dermatophytes, onychomycosis Potential hepatotoxicity – monitor liver enzymes Inhibits mitosis, rarely used Indicated for dermatophytes and onychomycosis *Pulse Therapy (Terbinafine and Itraconazole): Used in onychomycosis treatment, has some evidence for less toxicity (dosed daily 1 week, off 3 weeks) to decrease ADRs, DDIs DRUG ERUPTIONS Types of Drug Eruptions  Mild rash, itching, dry skin  severe, potentially life-threatening conditions)  SJS, TEN, Angioedema, Vasculitis, Coagulent-induced skin necrosis General Approach to Drug Reactions (1) Recognize that problem may be drug-related Identify agent (2) STOP OFFENDING AGENT (3) Determine severity (i.e. triage situation) (4) Treat sequelae **Don’t forget to EDUCATE PATIENT Reaction Characteristics Common Offenders Acneiform Reactions Differ from true acne: no comedone, uniform appearance of lesions, location, age, recent drug exposure glucocorticoids, oral contraceptives, lithium, anabolic steroid Photosensitivity Reactions Phototoxic reactions – exaggerated sunburn or increased sensitivity to light; UVA causes alteration of drug to toxic form (>common) Photoallergic reactions – manifests in bullae, urticaria, sunburn; UVA alters drug to antigen and leads to allergic response ( 2weeks!! Topical Corticosteroids Inflammatory skin diseases  1% hydrocortisone ointment +/- occlusive dressing, minimal systemic absorption  Systemic administration for widespread/severe exacerbations (prednisone, prednisolone)  Many preparations – betamethasone (most potent), triamcinolone, clobetasol  Fluorinated steroids should NOT be used on face (dexamethasone, triamcinolone, betamethasone, “flu-sone,lone,rone) * DOC for skin inflammation and pruritus but avoid use in infectious etiologies (except when combined w/ antifungal) Ocular Inflammation  Dexamethasone eye drops or ointment **should always be used under Aoid overuse, use lowest potency *educate patient not to exceed recommended dosing Don’t forget systemic effects: children, elderly, liver disease, thin skin, use of occlusion/high potency agents (ointments) ADRs *fewer than systemic Local – with chronic, repeated use Systemic – adrenal suppression can occur with high dose, long-term treatment