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117 Cards in this Set
- Front
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Acyclovir
1) tx 2) MOA&selectivity 3) MOR 4) kin 5) tox&CI |
G-Analog
1) HSV 2) converted to Acyclo-GMP by VIRAL THYMIDINE KINASE (TK) => converted to Acyclo-GDP/GTP by cellular kinases => ACYCLO-GTP INHIBITS VIRAL DNA POL & CHAIN TERMINATES - highly selective (x3000 viral pol) 3) mutations in viral TK or DNA pol 4) oral, topical, and i.v. POORLY WATER SOLUBLE => poor bioavailabilty short 1/2life, RENAL ELIMINATION 5) crystaluria if pt not well hydrated - hypersensitivity |
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1) Valacyclovir
2) Penciclovir 3) Famciclovir |
1) acyclovir ester (derivative) with IMPROVED ORAL BIOAVAILABILITY
2) HIGHER INTRACELLULAR STABILITY (longer 1/2life) NOT A CHAIN TERMINATOR 3) penciclovir derivative with IMPROVED SOLUBILITY => IMPROVED ORAL BIOAVAILABILITY (along with longer 1/2life) NOT A CHAIN TERMINATOR |
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Vidarabine
1) tx/use 2) MOA 3) MOR |
1) HSV - topical only due to RAPID METABOLIC INACTIVATION & HIGH GENETIC TOXICITY
2) Activated by viral TK & inhibits viral DNA pol NOT A CHAIN TERMINATOR 3) mutation in viral DNA pol |
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1) Idoxuridine
2) Trifluridine |
**SAME AS VIDARABINE** (treats HSV)
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Ganciclovir
1) tx 2) MOA 3) MOR 4) kin 5) tox&CI |
1) CMV
2) activated by CMV KINASE UL97 => converted to cyclo-GDP/GTP by cellular kinases => CYCLO-GTP INHIBITS VIRAL DNA POL & CHAIN TERMINATES 3) mutation in UL97 or DNA pol 4) poor oral bioavailability renal elimination 5) myelosupression => neutropenis - if used with AZT in AIDS pts => SEVERE neutropenia; cross hypersensitivity w/ acyclovir |
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Valganciclovir
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***SAME AS GANCICLOVIR***
IMPROVED WATER SOLUBILITY => increased bioavailability |
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Cidofovir
1) tx/use 2) MOA 3) MOR 4) kin 5) tox&CI |
1) HSV/VZV - with ACYCLOVIR RESISTANCE; or just straight up CMV
2) Cyclovir-MP analog (no need of TK) => already active (bypasses acyclovir resistance) => DNA pol inhibition and chain termination 3) mutation in viral DNA pol 4) IV, MAJOR RENAL EXCRETION 5) MASSIVE RENAL TOXICITY IS DOSE LIMITING; thus pt is prehydrated (saline) and given PROBENECID - hypersensitivity |
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Foscarnet
1) tx/use 2) MOA 3) MOR 4) kin 5) tox&CI |
1) HSV/VZV - with ACYCLOVIR RESISTANCE; or just straight up CMV
2) blocks phosphate binding site on viral DNA pol 3) mutation in viral DNA pol 4) IV, MAJOR RENAL EXCRETION 5) RENAL IMPAIRMENT, pt must be hydrated well |
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Lamivudine
1) tx 2) MOA 3) MOR 4) kin 5) tox&CI |
1) HBV
2) NRTI (also used in HIV) => CHAIN TERMINATOR & INHIBITS REVERSE TRANSCRIPTASE 3) RAPID resistance (mutation in RT, occurs in 20% of cases w/in a year) 4) oral; renal excretion 5) non-toxic for HBV - hypersensitivity |
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Adefovir
1) tx 2) MOA 3) MOR 4) kin 5) tox |
1) HBV
2) NRTI => CHAIN TERMINATOR & INHIBITS REVERSE TRANSCRIPTASE 3) SLOW resistance (no resistance for up to 1 year) 4) oral; renal excretion 5) MASSIVE RENAL TOXICITY IS DOSE LIMITING (like cidofovir) |
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IFN-alpha
1) tx/use 2) MOA 3) kin 4) tox&CI |
1) HCV (&HBV); both prophylaxis (PREVENTIVE) and for actual tx
2) cytokine (non specific) - binds to cell membrane receptors => induces gene expression in infected cells => interferes with viral replication cycle by degradation of viral RNA & apoptosis - stimulates systemic immune responses => mac's and NK cells 3) subcut or IM, once a wk; degraded in kidneys 4) pyogen = fever and flu-like symptoms; injection site tissue damage; at high doses = bone marrow suppression => leucopenia & granulocytopenia - CI = hypersensitivity; autoimmune disease; hepatic decompensation |
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Ribavirin
1) tx 2) MOA 3) kin 4) tox&CI |
1) HCV; used with IFN-alpha
2) G&A analog => inhibits RNA replication by HYPERMUTATION of genes ("GENETIC MELTDOWN") NOT A CHAIN TERMINATOR 3) oral; degraded & renal elimination RBCs store phosphorylated ribavirin for LIFETIME of cells (120days) 4) DOSE LIMITING HEMOLYTIC ANEMIA - CI = pregnancy (teratogen from hypermutation!) |
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Amantadine & Rimantadine
1) tx 2) MOA 3) resistance? 4) kin (amantadine & rimantadine) 5) tox&CI |
1) Influenzae A, useful only for prophylaxis and treatment of SUSPECTED influenzae A infection
crosses BBB and is dopaminergic => useful for parkinsons 2) M2 BLOCKER 3) YES! resistance so bad it is barely used anymore... 4) oral amantidine = renal elimination rimantidine = liver metabolized and renal elimination 5) GI and CNS side effects (such as nauseea and diziness); amantadine is more CNS-toxic; amantadine overdose = AGITATION, HALLUCINATIONS, cardiac arrythmia, death - CI = hypersensitivity |
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Oseltamivir & Zanamivir
1) tx 2) MOA 3) kin (Oseltamivir & Zanamivir) 4) tox&CI (Oseltamivir & Zanamivir) |
1) Influenae BOTH A&B; prophylaxis and early treatment (48h)
2) NEURAMINIDASE BLOCKER (SIALIC ACID ANALOG) 3) oral (oseltamivir) & intranasally (zanamivir) renal elimination for both 4) GI irritation (oseltamivir) & bronchospasm (zanamivir) |
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CLASS - NRTI ############ 1) tx/use 2) MOA 3) MOR (#codon substitutions? cross resistance?) 4) what are the NRTIs? |
1) 1st line of HIV drugs
- ONLY affects newly infected cells - given to mother&child to prevent transmission of HIV during birth 2) Substrates for RT => inhibits RT by incorporating false nucleic acids into newly made proviral DNA => these NA's lack 3'-OH grp, and CHAIN TERMINATES 3) 3-4 CODON (AA) sustitutions required - cross-resistance with drugs having similar chemical structures (all NRTIs) 4) Zidovudine (AZT), Lamivudine (3TC), Stavudine (d4T), Didanosine (ddI), Abacavir (ABC), Emtricitabine (FTC), Tenafavir |
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NRTIs - Facts
1) what is RT? 2) what is significant about their half-life? 3) high plasma protein binding? 4) common adverse effects? |
1) converts viral RNA into proviral DNA and inserts it into host cell's genetic material
2) IC 1/2life is longer than serum 1/2life. 3) no, less than 50%, and only 5% for some. 4) inhibits cellular DNA pol => mitochondrial DNA synthesis dysfunction => HEPATIC STEATOSIS & LACTIC ACIDOSIS (n/v, abd. pain, sob, ext.fatigue, myalgias) |
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Zidovudine (AZT) unique side effects?
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- BONE MARROW SUPPRESSION
- GI (n/v) - headaches - insomnia - asthenia - myopathies |
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Lamivudine (3TC) unique side effects?
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- MINIMAL TOXICITY
- GI - Headache |
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Stavudine (d4T) unique side effects?
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- PERIPHERAL NEUROPATHY (20-30%)
- LIPODYSTROPHY (redistribution of fat & become a pear => from face&extremities to the belly&fanny) - pancreatitis |
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Didanosine (ddI) unique side effects? avoid foods?
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- PERIPHERAL NEUROPATHY (35%)
- PANCREATITIS (5%) - nausea - diarrhea - acidic pH increases degradation of medication => take 1 hr before or 2 hrs after meals - buffered formulation |
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Abcavir (ABC) unique side effects?
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- (3%) develop FATAL HYPERSENSITVITY (RASH) = stop drug and do not rechallenge
- nausea - headache |
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Emtricitabine (FTC) unique side effects?
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- MINIMAL TOXICITY
- diarrhea - headache |
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Tenafovir unique side effects?
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- neprhotoxicity
- asthenia - headache - diarrhea |
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CLASS - NNRTI ############ 1) tx/use 2) MOA 3) MOR (#codon substitutions? cross resistance? how long for mutations to occur? high or low genetic barrier?) 4) what are the NNRTIs? |
1) ONLY HIV-1
- ONLY newly infected cells 2) inhibits RT by binding to peripheral site on HIV-1 RT enzyme and inducing conformational changes 3) does not require intracellular activation => SINGLE CODON substitution decreases susceptibility by MANY FOLDS - cross resistance to OTHER CLASS AGENTS is common - can occur within days or weeks - low genetic barrier to resistance 4) Nevirapine, Delavirdine, Efavirenz, Etravirine |
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NNRTI - Facts
1) what is significant about their half-life? 2) plasma protein binding? 3) liver metabolism? 4) common adverse effects? |
1) they don't need to be activated inside the cell (so no "intracellular 1/2life"); serum 1/2life is it
2) HIGH, close to 100% for all but Nevirapine. 3) HIGH, mostly metabolized in liver. 4) RASH, HEPATOTOXICITY (3-5 fold increase in transaminase lvls, asymptomatic, possible hepatitis), common resistance which occurs quickly |
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Nevirapine unique side effects?
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- symptomatic hepatitis
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Delavirdine unique side effects?
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- hepatotoxicity
- headaches |
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Elfavirenz unique side effects? CI? avoid type of food?
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- CNS symptoms (vivid dreams) >50% pts
- hepatotoxicity - CI IN PREGNANCY - AVOID HIGH FAT FOODS |
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Etravirine unique side effects?
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- rash that is SEVERE AND LIFE THREATENING w/in first 6 weeks of therapy
- hepatic failure |
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CLASS - Protease Inhibitors (PI) ############ 1) tx/use (do they protect already infected cells?) 2) MOA 3) MOR (#codon substitutions? active or distant sites? how long for mutations to occur? high or low genetic barrier?) 4) what are the PIs? |
1) ANY HIV INFECTED CELL (YES!)
2) bind irreversibly to the active site of HIV protease => viral particles become immature and noninfectious 3) minimum of 4-5 CODON substitutions - mutations of BOTH the protease active or distant sites - can take up to months for mutations to occur - high genetic barrier 4) "navirs" = Saquinavir, Indinavir, Ritonavir, Nelfinavir, Tipranavir, Lopinavir, Atazanavir, Fosamprenavir |
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PI - Facts
1) what is the HIV protease? 2) half-life? 3) plasma protein binding? 4) liver metabolism? 5) common adverse effects? 6) what about hepatotoxicity and hyperbilirubinemia? |
1) essential enzyme that allows protein to be chopped up
2) short 1/2life, but since given with other drugs, DON'T need multiple doses per day. also, like NNRTIs, they don't need to be activated inside the cell (so no "intracellular 1/2life") 3) HIGH, most close to 100% 4) HIGH, mostly metabolized in liver 5) GI (N/D), ENDOCRINE distubances (HDL = Hyperglycemia, Dyslipidemia, Lipodystrophy), osteoporosis 6) HEPATOTOXICITY in all except those beginning with vowels (Indinavir & Atazanavir = HYPERBILIRUBINEMIA) |
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Saquinavir unique side effects?
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- hepatotoxicity
- headache |
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Indinavir unique side effects?
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- KIDNEY STONES
- HYPERBILIRUBINEMIA - alopecia |
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Ritonavir unique side effects?
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- greatest cyp3A4 enzyme inhibitor of the class (DECR. METABOLISM) => INCR. TG's
- dry mouth - hepatitis |
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Nelfinavir unique side effects?
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- hepatotoxicity
- adominal pain - asthenia |
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Tipranavir unique side effects?
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- INTRACRANIAL HEMORRHAGE
- hepatotoxicity |
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Lopinavir unique side effects?
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- hepatotoxicity
- asthenia |
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Atazanavir unique side effects?
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- HYPERBILIRUBINEMIA
- PROLONGED PR INTERVAL - nephrolithiasis |
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Fosamprenavir unique side effects?
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- hepatotoxicity
- CNS - rash |
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CLASS - Fusion Inhibitors (FI) ############ 1) tx/use/HIV-1 or HIV-2?/injected or orally? 2) MOA 3) what are the FIs? 4) kin/(1/2life and protein binding) 5) adverse reactions? |
1) given as LAST DITCH EFFORT for HIV (and ONLY HIV-1)
- injected 2) inhibits fusion to the cell membrane by preventing necessary conformational changes by the virus transmembrane glycoprotein to the CD4+ cells 3) enfurviritide, maraviroc 4) metabolized via proteolytic hydrolysis (not an inhibitor of CYP450) - short 1/2life, highly protein binding 5) injection site reactions, diarrhea, nausea, fatigue |
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Maraviroc
1) tx/use 2) side effects? |
1) treats MULTIDRUG RESISTANT HIV
- CCR5 receptor antagonist (CCR5 = viral protein) => used only in CCR5-tropic HIV-1 infection patients only 2) hepatotoxicity |
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Raltegravir
1) what does it treat? what is it? 2) side effects? |
1) treats MULTIDRUG RESISTANT HIV
- integrase inhibitor => prevents integration of viral DNA into host nucleus 2) headache, GI, myopathy |
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How do you monitor HIV?
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Measure:
- CD4+ count, q3months - HIV RNA levels |
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Amphotericin B
1) tx/use 2) MOA 3) kin (CNS penetration? protein binding? 1/2life?) 4) tox (dose dependent? renal, rbcs, infusion, clotting?) |
1) fungal infection = the ONLY fungiCIDAL
- IV only (no GI absorption) - broad spectrum - improved formulations (w/ higher cost) are complexed with lipids to decrease nephrotoxicity & allow for larger doses 2) binds to ergosterol (w/ greater affinity than cholesterol) => disrupts membrane permiability (ter's holes) 3) poor CNS penetration - high protein binding - long 1/2life 4) amphoterrible/awfultericin = severe & dose dependent - renal = reversible, K+ wasting (monitor BUN/creatinine) - anemia = suppresses erythropoietin of kidneys (monitor CBC) - infusion related = fever/chill, myalgia, arthralgia, headaches (premedicate w/ acetaminophen/NSAIDS/steroids) - thrombophlebitis = clotting at injection site (give heparin) |
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Nystatin
1) tx/use 2) MOA 3) kin 4) tox |
1) fungal infection
- topical: vaginal, GI, skin - mucous membrane (mouth swish&swallow) = oral/esophageal Candida 2) binds ergosterol and tears holes in cell membrane 3) not absorbed orally => only used topically or for esophagus 4) minimal toxicity, possible allergies |
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Flucytosine
(pyrimidine) 1) tx/use 2) MOA 3) kin (absorption? renal excr? 1/2life?) 4) tox |
1) fungal infection
- oral - always in combination w/ Amphotericin B against cryptococcal meningitis (or resistance develops) 2) metabolized by cytosine deaminase (fungal enzyme) => 5-fluorouridylic acid => 2 moa's (1) 5-fluo incorporates into RNA => STOP TRANSLATION or (2) 5-fluo metabolized further to 5-fluoroDEOXYuridylic => inhibits thymidylate synthetase => IMPAIRS DNA SYNTHESIS 3) good absorption (oral) - high renal excretion - medium 1/2life 4) similar to cancer drugs => bone marrow suprression, GI (n/v/d), hepatotoxicity (must ^LiverFunctionTests, reversible) |
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Azoles
1) tx? 2) MOA 3) what are the two subclasses? what are the drugs in each subclass? use? |
1) fungal infection
2) inhibits ergosterol biosynthesis by inhibiting sterol 14-alpha-demethylase (part of cyp450 system) => leads to lots of DRUG INTERACTIONS! 3) - IMIDAZOLES = clotrimiazole, miconazole, ketoconazole, econazole, butoconazole, oxiconazole - TRIAZOLES = terconazole, itraconazole, fluconazole, voriconazole, posconazole - only KETOCONAZOLE is systemic use from imidazole class - only TERCONAZOLE is topical in triazoles class - topical ones used in superficial infections: ringworm, candidiases, tinea versicolor/nigra, fungal keratitis - for nail/hair mycoses = systemic must be used |
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Ketoconazole
1) tx/use 2) MOA 3) kin (how is it absorbed? cyp450?) 4) tox |
1) candida, but not aspergillus
- oral 2) azoles = inhibits ergosterol biosynthesis by inhibiting sterol 14-alpha-demethylase (cyp450 system) 3) absorption = acid needed for dissolution & absorption (histamine2 & H+pump inhibitors decr. bioavailability) - cyp450 enzyme inhibitor => incr. plasma levels of other drugs (DRUG INTERACTIONS!) 4) GI (dose dependent), allergy (rash), hepatotoxicity (incr.LFTs) - HORMONAL (cyp450 needed for testosterone) = menstrual irregularities, gynecomastia, decr.libido/potency |
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Itraconazole
1) tx/use 2) MOA 3) kin (how is it absorbed? 1/2life? protein bound? enzyme inhibitor?) 4) tox |
1) candida, aspergillus
- oral, IV 2) azoles = inhibits ergosterol biosynthesis by inhibiting sterol 14-alpha-demethylase (cyp450 system) 3) GI absorption = empty stomach & acid (drinks) - long 1/2life, protein bound parent/metabolite - potent enzyme inhibitor of cyp3A4 => incr. plasma levels of other drugs (DRUG INTERACTIONS!) 4) GI, rash, hepatotoxicity (incr.LFTs), CARDIAC effects (fatal arrhythmias w/ cisapride/quinidine = drug interactions) |
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Fluconazole
1) tx/use 2) MOA 3) kin (how is it absorbed? excr? 1/2life? protein bound?) 4) tox&CI |
1) candida (very effective)
- oral, IV 2) azoles = inhibits ergosterol biosynthesis by inhibiting sterol 14-alpha-demethylase (cyp450 system) 3) GI absorption not affected by food - kidney excretion - long 1/2life, not extensively protein bound 4) GI, rash, hepatotoxicity (incr.LFTs), REVERSIBLE ALOPECIA - CI = NEVER USED DURING PREGNANCY (skeletal&cardiac muscle deformities in infants) |
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Voriconazole
1) tx/use 2) MOA 3) kin (linear kinetics? 1/2life? enzyme inhibitor?) 4) tox |
1) candida, aspergillus
- oral, IV 2) azoles = inhibits ergosterol biosynthesis by inhibiting sterol 14-alpha-demethylase (cyp450 system) 3) NON-LINEAR kinetics (1/2life dependent on dose) - potent enzyme inhibitor of cyp3A4 => incr. plasma levels of other drugs (DRUG INTERACTIONS!) 4) rash, LFTs - VISUAL CHANGES = photophobia, color changes, blurred vision - CARDIOVASCULAR = HTN, tachycardia, edema - CNS = fever, headache, dizziness, hallucinations |
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Posaconazole
1) tx/use 2) MOA 3) kin (excr? 1/2life? protein bound? enzyme inhibitor?) 4) tox |
1) broad spectrum = candida, aspergillus, zygomycetes
- oral (w/ full meals) 2) 3) excretion via hepatic metabolism & feces - long 1/2life, high protein binding - moderate inhibitor of cyp3A4 4) GI, LFTs - CARDIOVASCULAR = HTN, hypokalemia - CNS = headache, dizziness |
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Echinocandins
1) tx/use 2) MOA 3) kin (1/2life? protein binding? CNS?) 4) what are the echinocandins? 5) tox |
1) systemic infections of candida, aspergillus
- IV 2) inhibits synthesis of B-1,3-glucan on fungal cell walls 3) long 1/2life, high protein binding - minimal CNS penetration 4) caspofungin, micafungin, anidulfungin 5) "3-Hs" = headache, hepatotoxicity (LFTs), histamine related reactions at injection site (rash, swelling, warmth) - cyclosporine increases caspofungin levels |
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Griseofulvin
Echinocandins 1) tx/use 2) MOA 3) kin (excr? 1/2life?) 4) tox |
1) mycoses of hair, skin, nails (keratin regions only)
- oral 2) binds human keratin to prevent invasion & inhibits fungal cell mitosis (keratin takes time to grow..) 3) renal excretion - long 1/2life 4) "3-Hs" (different) = headache, hepatotoxicity (LFTs), hematologic (leucopenia, neutropenia, basophilia) & photosensitivity - enzyme inducer = griseofulvin increases metabolism of warfarin & oral contraceptives |
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Terbinafine
1) tx/use 2) MOA 3) kin (1/2life? protein binding?) 4) tox |
1) mycoses of nail (drug accumulates in nail beds)
- oral 2) blocks ergosterol synthesis by inhibiting SQUALENE EPOXIDASE 3) extremely high half life (due to nail accumulation), high protein binding 4) well tolerated uncommon = GI, hepatotoxicity, possible Stevens-Johnson syndrome (hypersensitive rash) not many drug interactions, but cimetidine may increase its levels in plasma |
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Direct Acting Muscarinic Agonist
MOA? |
- agonist activity at muscarinic receptors
(+)PARASYMPATHETICS (+)SWEAT-GLANDS |
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Direct Acting Muscarinic Agonist
Effects/Use? (GI, Heart, Vasculature, Bladder, Eye, Airway, Secretions) |
- GI: incr. motility, incr. secretions (Bethenachol = tx GI motility probs)
- Heart: decr. rate => decr. b.p - Vasculature: NO-mediated vasodilation => decr. b.p - Bladder: contract bladder, relax sphincter (Bethanechol = tx urinary retention) - Eye: miosis & decr. intraocular pressure (Ach, Carbachol, Pilocarpine = tx glaucoma) - Airway: bronchoconstriction (Methacholine = dx pulm.fx.) - Secretions: incr. saliva, lacrimal, GI, sweating, etc. (Pilocarpine = tx salivary gland probs) |
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Direct Acting Muscarinic Agonist
Toxicity? |
- unwanted/excess muscarinic stimulation (diarrhea, drooling, bradycardia, hypotension, etc.)
- NEVER GIVE I.V. |
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Direct Acting Muscarinic Agonist
CI? |
- asthma
- bradycardia, hypotension, coronary artery disease - peptic ulcer disease - hyperthyroidism => life threatening arrhythmias - weak SM of bladder/GIT - urinary/GI obstruction |
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Direct Acting Muscarinic Agonist
Name them. |
Acetylcholine, Carbachol, Methacholine, Bethanechol, Pilocarpine
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Direct Acting Muscarinic Agonist
Acetylcholine (kin? use?) |
- if given systemically, rapidly hydrolyzed by pseudocholinesterase in plasma
- ONLY TOPICALLY FOR GLAUCOMA |
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Direct Acting Muscarinic Agonist
Carbachol (kin? action? use?) |
- resistant to hydrolysis by cholinesterases
- can stimulate BOTH muscarinic AND NICTONIC receptors - TOPICALLY USED FOR GLAUCOMA |
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Direct Acting Muscarinic Agonist
Methacholine (action? use?) |
- mostly stimulates muscarinic receptors
- pulm. fx. testing in asthma |
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Direct Acting Muscarinic Agonist
Bethanechol (action? use?) |
- mostly stimulates muscarinic receptors
- stimulates GI MOTILITY and treats URINARY RETENTION (beth = bathroom) |
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Direct Acting Muscarinic Agonist
Pilocarpine (action? use?) |
- muscarinic receptors
- GLAUCOMA and XEROSTOMIA |
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Cholinesterase Inhibitors
MOA? |
- competitively bind AchE and prevents breakdown of Ach at synapse => INCREASED Ach action
- NON-QUATERNARY SALTS CAN CROSS BBB (+)PARASYMPATHETIC (+)SKELETAL MUSCLE EFFECTS |
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Cholinesterase Inhibitors
Effects/Use? (GI, Heart & Vasculature, Bladder, Eye, Airway, Secretions) |
- GI: incr. motility/secretion (tx paralytic ileus)
- Heart: bradycardia, hypotension (via both heart & vasculature) Bladder: contracts bladder & relaxes sphincter (tx urine retention) Eye: decr. intraocular pressure (Echothiophate = tx glaucoma, backup drug to cholinergic agonists) Airway: bronchoconstriction Stimulate secretion (saliva, lacrimal, GI, sweating, etc) Skeletal muscle: stimulation of muscle (edrophonium, neostigmine, pyridostigmine = tx myasthenia gravis) Paralysis of muscle (toxic dose – dose response curve of nicotinic receptors) CNS: reverse cholinergic deficit in brain (rivstigmine, donepezil = tx Alzheimer’s) |
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Cholinesterase Inhibitors
Toxicity? |
- SLUDGE = salivation, lacrimation, urination, defecation, GI distress, emesis)
- skeletal muscle fasciculations => paralysis - CNS stimulation => seizures & coma |
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Cholinesterase Inhibitors
Tx from AchE-inhibitor overdose? |
- ATROPINE & PRALIDOXIME/2-PAM
- pyridostigmine for nerve gas prophylaxis |
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Cholinesterase Inhibitors
Name them. |
- Edrophonium
- Physostigmine - Neostigmine - Pyridostigmine - Rivastigmine - Donepezil - Carbamate insecticides IRReversible: - DFP/diisopropylfurophosphate/isoflurophate/echothiophate - organophosphate insecticides (Parathion, Malathion) - nerve gases (SARIN) |
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Cholinesterase Inhibitors
Edrophonium (kin? use?) |
- short acting, used for diagnosis
- Tensilon test: dx myasthenia gravis & dx muscle weakness from excess AchE-in - MYASTHENIA CRISIS = edrophonium BETTERS the situation - CHOLINERGIC CRISIS = edrophonium WORSENS the situation |
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Cholinesterase Inhibitors
Neostigmine & Pyridostigmine (kin? use?) |
- long lasting
- treatment for myasthenia gravis (&neuromusc. blockers) |
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Cholinesterase Inhibitors
Physostigmine (kin? use?) |
- non-quaternary => no CNS effects
- treat poisoning from atropine or other anti-muscarinics |
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Cholinesterase Inhibitors
Parathion & Malathion (use? kin? sx? tx?) |
- organophosphate insecticides
- IRRev. AchE-in, absorbed thru skin - typical AchE-in effects - atropine & pralidoxime |
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Cholinesterase Inhibitors
Carbaryl (use? kin? sx? tx?) |
- carbamate insecticide
- IRRev. AchE-in, NOT absorbed thru skin - typical AchE-in effects - atropine (NO pralidoxime) |
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Cholinesterase Inhibitors
DFP/Sarin (use? kin? sx? tx?) |
- very potent toxic chemical warfare agent
- IRRev. AchE-in - tx: atropine & pralidoxime |
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PDE-5 Inhibitors
Name them. |
- Sildenafil
- Vardenafil - Tadalafil |
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PDE-5 Inhibitors
MOA? |
- inhibits PDE-5, enhancing vasodilation => reflex tachycardia
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PDE-5 Inhibitors
Use? |
- E.D., Pulm. HTN
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PDE-5 Inhibitors
Toxicity? CI? |
- hypotension => reflex tachycardia
- CI: PRE-EXISTING CARDIOVASCULAR DISEASE |
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PDE-5 Inhibitors
Kinetics? (+metabolized by?) |
- oral administration, peak lvls w/in 1 hour
- Sildenafil/Vardenafil = 4 hrs - Tadalafil = 36 hrs - metabolized by CYP3A4 => dose adjustment with renal or hepatic disease |
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PDE-5 Inhibitors
Drug Interaction? |
- other drugs metabolized by CYP3A4 = erythromycin, ketoconazole, cimetidine, etc.
- Vasodilators (nitrites, etc.) - Sympathetomimetics (which stimulate the heart) |
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Botulinium Toxin
MOA? Tx? Use? |
- prevents release of Ach from nerve endings (anti-cholinergic effects)
- aggressive sxatic support (resp. fx), Ab's to toxin - BOTOX |
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Muscarinic Antagonists
MOA? |
- competitive antagonists at muscarinic receptors (muscarinic blockers)
(-)PARASYMPATHETICS (-)SWEAT GLANDS |
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Muscarinic Antagonists
Effects/Use? (GI, Heart, Bladder, Eye, Airway, Secretions, Temp., CNS) |
- GI: decr. tone/motility (tx cramping, diarrhea, IBS)
- Heart: tachycardia; slight transient bradycardia with atropine only (cardiac stimulation) - Bladder: relax bladder & constrict sphincter - Eye: mydriasis, cycloplegia, incr. intraocular pressure - Airway: bronchodilation - Drying of secretions (saliva, lacrimal, GI, sweat, etc) - Temp: rise in temperature due to sweat inhibition - CNS: sedation/amnesia (low doses) & excitation/seizures (toxic doses) - CNS effects only if the drug is non-quaternary |
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Muscarinic Antagonists
Toxicity? CI? |
- excessive Ach action (dry mouth, dry/hot skin, constipation, urine retention, visual disturbances, lose accommodation, photophobia, CNS effects)
- CI: GLAUCOMA!!!, BPH, CV instability, severe ulcerative colitis |
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Muscarinic Antagonists
If acutely poisoned with a Muscarinic Antagonist, tx? |
- Physostigmine, or other AchE-in
- Benzodiazepines (for seizures) - ice bath, dark/quiet area |
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Muscarinic Antagonists
Atropine (use?) |
- PROTOTYPE antimuscarine agent
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Muscarinic Antagonists
Scopolamine (use?) |
- orally for prevention of motion-sickness and vertigo (crosses BBB)
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Muscarinic Antagonists
Dicyclomine (use?) |
- GI (tx IBS)
- non-quaternary, penetrates CNS |
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Muscarinic Antagonists
Propantheline (use?) |
- GI (tx IBS)
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Muscarinic Antagonists
Glycopyrrolate (use?) |
- dry resp. secretions & inhibit vagal reflexes
- general purpose (like atropine) |
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Muscarinic Antagonists
Ipratropium & Tiatropium (use?) |
- inhalation for tx of asthma (few systemic effects)
Tiatropium lasts longer |
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Muscarinic Antagonists
Bentropoine & Trihexyphenidyl (use?) |
- Parkinson's
- non-quaternary, penetrates CNS (duh.. parkinson's) |
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Muscarinic Antagonists
Tolterodine, Oxybutynin, Solfenacin (use?) |
- urinary incontinence due to over active bladder
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Muscarinic Antagonists
Tropicamide & Cyclopentolate (use?) |
- dilate pupil for ophthalmologic exam
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Neuromuscular Blocking Drugs
General MOA? Name them. |
- act at neuromuscular junction to cause relaxation or paralysis of skeletal muscle
- Pancuronium, Succinylcholine |
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Neuromuscular Blocking Drugs
MOA (for each)? |
- Pancuronium: COMPETITIVE Ach antagonist (tx overdose w/ AchE)
- Succinylcholine: stimulates receptors and acts like Ach (fasciculations), but then STAYS BOUND and muscles STAY DEPOLARIZED (tx overdose w/ TIME... can't use AchE, lol) |
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Direct Acting Sympathomimetics
Epinephrine |
- a1 = a2 = b1 = b2
- low dose => decr. DP, incr. SP => incr. HR - high dose => incr. everything |
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Direct Acting Sympathomimetics
Norepinephrine |
- a1 = a2 = b1 >> b2
- low dose => incr. SP, incr. DP => decr. HR - high dose => incr. SP&DP, incr. HR (but not so much due to reflexive decr.) |
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Direct Acting Sympathomimetics
Isoproterenol |
- b1 = b2 >> all
- low dose => decr. SP, decr. DP, incr. HR - high dose => (even more) decr. SP, decr. DP, incr. HR |
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Direct Acting Sympathomimetics
Dopamine |
- D > b1 > a1 > all others
- low dose: incr. RBF&GIBF - intermediate dose: incr. HR & cardiac contractility - high dose: vasoconstriction => incr. MAP => decr. HR => decr. RBF&GIBF |
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Direct Acting Sympathomimetics
Dobutamine (selectivity? use? kin?) |
- b1 > b2 > all others (selective b1 agonist)
- used in CHF and shock (cardiogenic & late phase septic) |
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Direct Acting Sympathomimetics
Albuterol (selectivity? use? other drugs in class?) |
- b2 > b1 > all others (selective b2 agonist)
- bronchodilators (asthma... you used this fool) - albuterol, metaproterenol, pirbuterol, salmeterol, terbutaline (terbutal-INE used to prevent premature labor by uterINE relaxation) |
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Direct Acting Sympathomimetics
Phenyephrine & Midodrine (selectivity? effects on bp? use?) |
- a1 >> all others (selective a1 agonist)
- raise BP, but with more reflex bradycardia - hemorrhoids, nasal congestion, SUPRAVENTRICULAR TACHYCARDIAS |
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Indirect Acting Sympathomimetic Agents
Cocaine (moa? use? why not used more?) |
- inhibits reuptake of NE (incr. NE)
- local anesthetic (exerts its own local vasoconstrictor to prevent its own loss from site of injection) - local only... also, IT'S FUCKING COKE!!!! |
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Alpha Blockers (General)
MOA? Tox? |
- inhibition of PERIPHERAL alpha-adrenergic receptors
- COMPETETIVE => short acting, reversible (all except Phenoxybenzamine) - decreased BP - nasal congestion, difficulty ejaculating, reflex tachycardia, systemic fluid retention, orthostatic hypotension |
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NonSelective Alpha Blockers
Name them. MOA? |
- Phenoxybenzamine (only NON-COMPETETIVE alpha blocker, long lasting, irreversible), Phentolamine
- block both a1&a2 |
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NonSelective Alpha Blockers
Phentolamine (Use? Tox? CI?) |
- in case of accidental alpha-agonist injection => PREVENTS LOCAL DERMAL TISSUE NECROSIS
- reverses oral soft-tissue anesthesia - GI problems: n/v/d, incr. GI motility (CI in ulcers!) |
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Selective Alpha Blockers
Name them. |
- Prazosin, Terazosin, Doxazosin, Tamulosin, Alfuzosin, Silodosin
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Selective Alpha Blockers
Prazosin (moa? use?) |
- selective for a1
- relaxes SM => tx obstructive urinary symptoms (BPH) |
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Selective Alpha Blockers
Doxazosin & Terazosin (moa? use?) |
- same as Prazosin BUT LONGER 1/2LIFE
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Selective Alpha Blockers
Tamsulosin (moa? use?) |
- selective for a1A (subtype in smooth muscle of bladder neck and prostate; less toxic b/c of selectivity)
- DRUG OF CHOICE FOR BPH |
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Selective Alpha Blockers
Alfuzosin (moa? use?) |
- unclear MOA... but "uroselective"
- TX BPH |
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NonSelective Alpha Blockers
Phenoxybenzamine (Use?) |
- prevent hypertensive episodes in pt's with pheochromocytoma during preop (and long term HTN for untxable pts)
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Beta Blockers
Name them (selective & non-selective) |
- selective: Acebutolol, Atenolol, Esmolol, Metoprolol (b1)
- nonselective: Nadolol, Pindolol, Propranolol, Timolol |
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Labetalol
use? |
- combination beta blocker and a1 blocker used to treat moderate-severe primary HTN (oral) and emergency HTN crisis (IV).
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