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 amount of drug in body/_______ = Vd plasma drug concentration (Vd is Volume of Distribution) rate of elimination of drug/[plasma drug] = ? CL (Clearance) (.7)(Vd)/CL = ? T 1/2 A drug infused at a constant rate reaches about 94% of steady state after _______ t 1/2s. 4 A loading dose is calculated using this formula. (Cp)(Vd)/F (note: Cp = target plasma concentration, and F = bioavailability) A maintenance dose is calculated using this formula. (Cp)(CL)/F Rate of elimination is proportional to _______ ______ in 1st order elimination. drug concentration In the case of EtOH, which is elimated by _____ order elimination, a constant amount of drug is eliminated per unit time. zero Phase ____ (I or II) reactions yield slightly polar metabolites that are often _____ (active or inactive) I, active Phase ____ (I or II) reactions yield very polar metabolites that are often _____ (active or inactive) and are excreted by the _______. II, inactive, kidney Phase II reactions are often of this type. conjugation Cytochrome P-450 is involved in _____ phase (I or II) reactions. I A drug patent lasts for _____ years after filing for application. 20 How many phases are there in drug development? 4 Drugs are first tested in patients in phase _____ of clinical testing, pharmacokinetic safety is determined in phase ______ of clinical testing, double blind tests are done in phase ____ and post-market surveillance is done in phase _____. 2,1,3,4 In a dose response curve, a competitive antagonist shifts the curve _____, while a non-competitive antagonist shifts the curve ______. right, down What pharmacologic relationship would determine the existence of spare receptors? EC50 is lower then Kd (EC50 is more to the left) What does it mean if EC50 and Kd are equal? The system does not have spare receptors A partial agonist acts on the same receptor system as a full agonist? T/F TRUE What's the main difference between a partial agonist and a full agonist? A partial agonist has a lower maximal efficacy. Is a partial agonist less potent than a full agonist? Not necessarily. It can be less, more or equally potent as a full agonist. The penicillin type drugs work by blocking ------ synthesis, specifically by inhibiting this molecule from cross-linking? blocks bacterial cell wall synthesis by inhibition of peptidoglycan synthesis. Which other drugs have the same mechanism of action as penicillin? (3) - Cephalosporins - Imipenem - Aztreonam Bacitracin, vancomycin and cycloserine block the synthesis of this molecule, preventing cell wall synthesis peptidoglycans These drugs block the 50s ribosomal subunit (4) clindamycin "buy at 30 CELL @ 50" - Chloramphenicol - Erythromycin - Linezolid - cLindamycin These drugs block the 30s ribosomal subunit (2) "buy AT 30, cell @ 50" - Aminoglycosides - Tetracyclines These drugs block nucleotide synthesis by interfering with the folate pathway Sulfonamides (e.g. Bactrim), trimethoprim These drugs block DNA topoisomerases Quinolones (e.g. Cipro) Which drug blocks mRNA synthesis rifampin Which are the bacteriacidal Abx Penicillin, cephalosporin, vancomycin, aminoglycosides, fluoroquinolones, metronidazole These drugs disrupt the bacterial/fungal cell membranes polymyxins These specific disrupt fungal cell membranes (3) FAN the fungal cell: - Fluconazole/azoles - Amphotericin B - Nystatin What is the mechanism of action of Pentamidine Unknown Which is the IV form and which is the oral form of Penicillin? G = IV V = oral Which of these is not a mechanism of penicillin action: (1) binds penicillin-binding protein, (2) blocks peptidoglycan synthesis, (3) blocks transpeptidase catalyzed cross-linking of cell wall and (4) activates autolytic enzymes Penicillin does not block peptioglycan synthesis, bacitracin, vancomycin and cycloserine do that T or F: penicillin is effective against gram pos and gram neg rods False: penicillin is used to treat common streptococci (but not staph), meningococci, gram pos bacilli and spirochetes (i.e. syphilis, treponema). Not used to treat gram neg rods. What should you watch out for when giving penicillin? Hypersensitivity rxn (urticaria,severe pruritus) and hemolytic anemia Methicillin, nafcillin, and dicloxacillin are used mainly for what type of infection? Staphlococcal infection (hence very narrow spectrum) T or F: Methicillin, nafcillin, and dicloxacillin have the same mechanism of action as penicillin TRUE Are Methicillin, nafcillin, and dicloxacillin penicillinase resistant? If so why? Bulkier R group makes these drugs resistant to penicillinase What should you watch out for when giving Methicillin, nafcillin, or dicloxacillin? Hypersensitivity rxn (urticaria,severe pruritus); methicillin can cuase interstitial nephritis T or F: Ampicillin/amoxicillin have the same mechanism of action as penicillin TRUE Which has greater oral bioavailability: Ampicillin or Amoxicillin? amOxicillin (O for Oral) What do you use Ampicillin/amoxicillin for? Ampicillin/amoxicillin HELPS to kill enterococci (H. influenzae, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella) Can penicillinase effect Ampicillin/amoxicillin efficacy? Yes, they are penicillinase sensitive since Ampicillin/amoxicillin are penicillinase sensitive, what inhibitor is used w/ them? clavulanic acid What should you watch out for when giving Ampicillin/amoxicillin? (2) Hypersensitivity rxn (ampicillin rash) Pseudomembranous colitis Why are Carbenicillin, piperacillin, and ticarcillin considered to have an extended spectrum? Because they are effective against pseudomonas and other gram neg rods (enterobacter and some species of klebsiella) What should you watch out for when giving Carbenicillin, piperacillin, and ticarcillin? Hypersensitivity rxn Why does concomitant administration with clavulanic acid increase the efficacy of piperacillin and ticarcillin? Because they are penicillinase sensitive What is the mechanism of action of Cephalosporins? inhibit cell wall synthesis How are Cephalosporins similar/different from penicillin? both have a beta-lactam ring structure but cephalosporins are less susceptible to penicillinases What are the main similarities/difference between 1st and 2nd generation cephalosporins? 2nd gen has extensive gram neg coverage but weaker gram pos coverage 1st gen covers what bugs? gram positives (staph and strep), Proteus mirabilis, E. coli, Klebsiella (PEcK) 2nd gen Cephalosporins cover what bugs? gram positives (staph and strep) though less, H. influenzae, Enterobacter aerogenes, Neisseria, Proteus mirabilis, E. coli, Klebsiella (HEN PEcK) What can 3rd generation Cephalosporin drugs do that 1st and 2nd generation can't? Cross the blood brain barrier What are some other benefits of 3rd gen Cephalosporins? better activity against gram neg bugs; resistant to beta-lactam drugs; Ceftazidime for Pseudomonas; Ceftriaxone for N. gonorrhea What are the benefits of 4th gen Cephalosporins (e.g. Cefipime)? increased activity against Pseudomonas, gram pos organisms and more beta-lactamase resistant (i.e. 4th gen combines 1st gen and 3rd gen characteristics into super drug) What drugs should you avoid taking with cephalosporins? Aminoglycosides (increases nephrotoxicity) and ethanol (causes a disulfiram-like rxn -- headache, nausea, flushing, hypotension) When would you use aztreonam? (3) Only to treat: Klebsiella, Pseudomonas, Serratia spp. Is Aztreonam beta-lactamase resistant? Yes, this is one of the huge benefits of the drug, and it is not cross-reactive with PCN! Which population of pt. is Aztreonam good for? The PCN-allergic patient that can't take aminoglycosides b/c of renal insufficiency Are there any toxicity issues with Aztreonam? Not really. Generally well tolerated with occasional GI upset. Vertigo, Headache and rare hepatotoxicity have been reported. What is imipenem? broad spectrum beta-lactamase-resistant abx What do you always administer Imipenem with and why? cilastatin -- it decreases inactivation of imipenem in renal tubules What do you use Imipenem for? Gram pos cocci, gram neg rods and anaerobes (broad spectrum) What bug is Imipenem the drug of choice for? Enterobacter What are its side-effects of Imipenem? GI distress, skin rash, seizures at high conc. Is Vancomycin bactericidal or bacteriastatic and why? Bactericidal because it blocks cross linkage and elongation of peptidoglycan by binding D-ala D-ala protion of cell wall. How does resistance to Vanco occur? D-ala D-ala is replaced with D-ala D-lactate which vanco does not block What is Vancomycin used for? Used for serious infection that is resistant to other drugs (e.g. gram pos multi-drug resistant organisms like S. aureus and C. difficile, methicillin resistant staph (MRSA)) What are the important toxicities of vanco? generally NOT many problems except, Nephrotoxicity, Ototoxicity and Thrombophlebitis What can happen with rapid infusion of Vancomycin? Red man's syndrome. Diffuse flushing which can be controlled by pretreatment with anti-histamines and with slow infusion rate Which drugs target bacterial protein synthesis by blocking the 30S unit vs 50S unit? Buy AT 30, CELL at 50 What does AT stand for? A = Aminoglycosides (streptomycin, gentamicin, tobramycin and damikacin) T = Tetracyclines What does CELL stand for? C = Chloramphenicol, E= Erythromycin, L= Lincomycin, L= cLindamycin Which of the protein synthesis inhibitors are bactericidal? Only the aminoglycosides are, the rest are bacteriostatic Name some aminoglycosides? Gentamicin, neomycin, amikacin, tobramycin and streptomycin How do Aminoglycosides work? They inhibit formation of the initiation complex in mRNA translation Why are Aminoglycosides ineffective against anaerobes? They require oxygen for uptake into bacteria When would you use aminoglycosides? against severe gram-negative rod infections What drugs can you use aminoglycosides with for synergy? the drugs that inhibit cell wall synthesis (e.g. penicillin and cephalosporins -- the beta-lactam antibiotics). Presumably this allows the drug to get in with out reliance on oxygen transport What drug in the Aminoglycosides class is commonly used for bowel surgery? Neomycin What are the two major Aminoglycoside toxicities? Nephrotoxicity (esp. when used with cephalosporins) and Ototoxicity (esp. when used with loop diuretics). amiNOglycosides Name some tetracylcines Tetracycline, doxycycline, demeclocycline, minocycline How do Tetracyclines work? Blocks t-RNA attachment to 30S subunit Which tetracycline can you use in patients with renal failure and why? Doxycycline because its elimination is fecal What drug class should you not take with a glass of milk? Tetracyclines What are tetracyclines used for? VACUUM your Bed Room -- Vibrio cholerae, Acne, Chlamydia, Ureaplasma, Urealyticum, Mycoplasma pneumoniae, Borrelia burgdorferi, Rickettsia, tularemia What are the common toxicities of Tetracyclines? (4) Teeth discoloration, inhibition of bone growth in children; Fanconi's syndrome; photosensitivity Name (3) macrolides? Erythromycin, Azithromycin, Clarithromycin How do Macrolides work? inhibit protein synthesis What are Macrolides used for? URIs, pneumonias, STDs -- gram pos cocci in patients that are allergic to PNC --- Mycoplasm, Legionella, Chlamydia, Neisseria. Pneumonic for Macrolide use? (4)* Eryc's Nipple is at his Mid Clavicular Line: Erythromycin tx: Neisseria, Mycoplasm, Chlamydia, Legionella Eryc's Nipple is at his Mid Clavicular Line What are the major toxicities of Macrolides? (4)* Macros make you GASE: GI discomfort, Acute cholestatic hepatitis, Skin rashes, Eosinophilia Macros make you GASE What is the most common cause for non-compliance to macrolides? GI discomfort How does Chloramphenicol work? inhibits 50S peptidyltransferase Main use of Chloramphenicol? Meningitis (H. influenzae, N. meningitides, S. pneumo) Used conservatively b/c of toxicity What are the main toxicities of Chloramphenicol? Anemia and aplastic anemia (both dose dependent), Gray baby syndrome (in premes b/c they lack UDP-glucoronyl transferase) How does Clindamycin work? blocks peptide bond formation at 50S When do you use Clindamycin? Anaerobic infections (e.g. Bacteroides fragilis and C. Perfringens) Toxicities of Clindamycin? (3) Pseudomembranous colitis, fever, diarrhea MC sulfonamide Sulfamethoxazole (SMX) How do Sulfonamides work? Inhibits bacterial folic acid synthesis from PABA (by blocking dihydropteroate synthase) What are its uses? (4) Gram-positive, Gram-negative, Nocardia, Chlamydia (simple UTIs) Toxicities of Sulfonamides? (5) hypersensitivity rxn, hemolysis if G6PD deficient, nephorotoxicity (tubulointerstitial nephritis), kernicterus in infants, displaces other drugs from albumin (e.g. warfarin) How does Trimethoprim work? inhibits folic acid pathway by blocking dihydrofolate reductase What are Trimethoprim's uses? (4) used in combo with Sulfamethoxazole (TMP-SMX) for recurrent UTIs, Shigella, Salmonella, prophylaxis for PCP in AIDS patients Toxicities of Trimethoprim? (2) Megaloblastic anemia, Pancytopenia (may be alleviated with supplemental folic acid) What the most famous floroquinolone? Ciprfloxacin (treatment for Anthrax) How do Fluoroquinolones work? inhibits DNA gyrase (topoisomerase II) What are Fluoroquinolones uses? (3) Gram neg, First line for Pseudomonas UTI, Neisseria What population is contraindicated for Fluoroquinolone use? (2) pregnancy and children What are Fluoroquinolone toxicities? (2) FluoroquinoLONES hurt attachment to BONES: Cartilage damage; Tendonitis and tendon rupture in adults How does Metronidazole work? forms toxic metabolites in the bacteria (Bactericidal) What are Metronidazole uses? (6) anti-protozoal: Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes: Bacteroides, Clostridium What is the role of Metronidazole in H. pylori infection? Used as part of triple therapy: Bismuth, Amoxicillin and Metronidazole Main toxicity of Metronidazole? disulfiram-like (antabuse) reaction to alcohol and headache Which drug do you use to treat anaerobic infections above the diaphram and below the diaphram? Anaerobes above diaphram: Clindamycin Anaerobes below diaphram: Metronidazole How do Polymyxins work? disrupts osmotic properties of bacteria, acts like a detergent What are Polymyxins used for? resistant gram negative infections Toxicities of Polymyxins? (2) Neurotoxicity, ATN Isoniazid p. 296 How does it work? decreases synthesis of mycolic acid What is it used for? MTB (mycobacterium tuberculosis). The only agent used as solo prophylaxis against TB Toxicities? Hemolysis if G6PD deficient, neurotoxicity, hepatotoxicitiy, drug induced SLE. INH, Injures Neurons and Hepatocytes What vitamin prevents neurotoxicity Vitamin B6 (pyridoxine) Why are toxicities particularly important to monitor in patients taking INH? INH half-lives are different in fast versus slow acetylators! Rifampin P. 296 How does it work? inhibits DNA-dependent RNA polymerase What is it used for? MTB, meningococcal prophylaxis Toxicities? Minor hepatotoxicity and increases P-450 How can it be used for leprosy? rifampin delays resistance to dapsone when used for leprosy What would happen if you used rifampin alone? get rapid resistance What does it do to bodily fluids? makes them red/orange in color What are the 4 R's of Rifampin RNA polymerase inhibitor, Revs up microsomal p-450, Red/Orange body fluids, Resistance is rapid Anti-TB Drugs p. 296 What are the anti-TB drugs? Rifampin, Ethambutol, Streptomycin, Pyrazinamide, Isoniazid (INH) -- RESPIre What do you use for TB prophylaxis? INH What toxicity is common to all? hepatotoxicity arachadonic acid products pg 150 name the enzyme that liberates AA from the cell membrane phospholipase A2 what does the lipoxygenase pathway yield leukotrienes (L for Lipoxygenase and Leukotrienes) LTB4 is a____ neutrophil chemotactic agent which leukotrienes are involved in bronchoconstriction, vasoconstriction, smooth muscle contraction, and increased vascular permeability LT C4, D4, E4 (SRS-A) what are the 3 products of the cyclooxygenase pathway? thromboxane, prostacyclin, prostaglandin what are the 2 functions of TxA2 platelet aggregation, vasoconstricion what are the 2 functions of PGI2 inhibition of platelet aggregation; vasodilation (Platelet Gathering Inhibitor) microtubule pg 150 what are the shape and dimensions of a microtubule? cylindrical, 24 nm in diameter, variable length. what are the components of a microtubule polymerized dimers of alpha and beta tubulin (+2 GTPs per dimer) where are microtubules found cilia, flagella, mitotic spindles, neuronal axons (slow axoplasmic transport) antihelminthic drug that acts on microtubules mebendazole/thiabendazole anti breast cancer drug that acts on microtubules (prevent disassembly) taxol antifungal drug that acts on microtubules griseofluvin anti cancer drug that acts on microtubules (prevent assembly) vincristine/vinblastine anti gout drug that acts on microtubules cholchicine Resistance mechanisms for various antibiotics p297 Most common resistance mechanism for penicillins / cephalosporins. Beta-lactamase cleavage of beta-lactam ring. Most common resistance mechanism for aminoglycosides. Modification via acetylation, adenylation, or phosphorylation. Most common resistance mechanism for vancomycin. Terminal D-ala of cell wall component replaced with D-lac; decrease affinity. Most common resistance mechanism for Chlorampenicol. Modification via acetylation. Most common resistance mechanism for macrolides. Methylation of rRNA near erythromycin's ribosome-binding site. Most common resistance mechanism for tetracycline. Decrease uptake or increase transport out of cell. Most common resistance mechanism for sulfonamides. Altered enzyme (bacterial dihydropteroate synthetase), decrease uptake, or increase PABA synthesis. Nonsurgical antimicrobial prophylaxis p297 Drug of choice for meningococcal infection. Rifampin (drug of choice), minocycline. Drug of choice for gonorrhea. Cefriaxone. Drug of choice for syphilis. Benzathine penicillin G. Drug of choice for history of recurrent UTIs. TMP-SMX. Drug of choice for Pneumocystis carinii pneumonia. TMP-SMX (drug of choice), aerosolized pentamindine. Anti-fungal therapy p297 Mechanism of action of the anti-fungal therapy polyenes. Form artificial pores in the cytoplasmic membrane. Mechanism of action of the anti-fungal therapies terbinafine and azoles. Terbinafine blocks the conversion of squalene to lanosterol. Azoles block the conversion of lanosterol to ergosterol. Mechanism of action of the anti-fungal therapy flucytosine. Blocks the production of purines from the precurors. Mechanism of action of the anti-fungal therapy griseofulvin. Disrupts microtubles. Amphotericin B p298 Mechanism of action of Amphotericin B. Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes and disrupt homeostasis. "Amphotericin 'tears' holes in the fungal membrane by forming pores." Clinical uses of Amphotericin B. Used for a wide spectrum of sytemic mycoses. Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor (systemic mycoses). Intrathecally for fungal meningitis; does not cross blood-brain barrier. Symptoms of Amphotericin B toxicity. Fever/chills ("shake and bake"), hypotension, nephrotoxicity, arrhythmias ("amphoterrible"). Nystatin p298 Mechanism of action of Nystatin. Binds to ergosterol, disrupting fungal membranes. Clinical use of Nystatin. "Swish and swallow" for oral candidiasis (thrush). Fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole. p298 Mechanism of action for fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole. Inhibits fungal steroid (ergosterol) synthesis. Clinical uses of fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole. Systemic mycoses. Fluconazole for cryptococcal meningitis in AIDS patients and candidal infections of all types (i.e., yeast infections). Ketoconazole for Blastomyces, coccidioides, Histoplasma, Candida albicans; hypercortisolism. Symptoms of fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole toxicity. Hormone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), fever, chills. Flucytosine p298 Mechanism of action of Flucytosine. Inhibits DNA synthesis byconversion to fluorouracil, which competes with uracil. Clinical uses of Flucytosine. Used in sytemic fungal infections (e.g. Candida, Cryptococcus). Symptoms of Flucytosine toxicity. Nausea, vomitting, diarrhea, bone marrow suppression. Caspofungin p298 Mechanism of action for Caspofungin. Inhibits cell wall synthesis. Clinical use of Caspofungin. Invasive aepergillosis. Symptoms of Caspofungin toxicity. GI upset, flushing. Terbinafine p298 Mechanism of action of Terbinafine. Inhibits the fungal enzyme squalene epoxidase. Clinical use of Terbinafinel. Used to treat dermatophytoses (especially onychomycosis). Griseofulvin p298 Mechanism of action of Griseofulvin. Interfers with microtubule function; disrupts mitosis. Deposits in keratin-contianing tissues (e.g. nails). Clinical use of Griseofulvin. Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm). Symptoms of Griseofulvin toxicity. Teratogenic, carcinogenic, confusion, headaches, increase warfarin metabolism. Antiviral chemotherapy p299 Viral adsorption and penetration into the cell is blocked by ---------. Gama-globulins (non-specific). Uncoating of the virus after its penetration into the cell is blocked by --------. Amantadine (influenza A). Early viral protein synthesis is blocked by --------. Fomivirsen (CMV). Viral nuclei acid synthesis is blocked by --------. Purine, pyrimidine analogs; reverse transcriptase inhibitors. Late viral protein synthesis and processing is blocked by --------. Methimazole (variola); protease inhibitors. Packaging and assembly of new viron is blocked by --------. Rifampin (vaccinia). Amantadine p299 Mechanism of action of Amantadine. Blocks viral penetration/uncoating; may buffer pH of endosome. Also causes the release of dopamine from intact nerve terminals. "Amantadine blocks influenza A and rubellA and causes problems with the cerebellA." Clinical uses of Amantadine. Prophylaxis for influenza A; Parkinson's disease. Symptoms of Amantadine toxicity. Ataxia, dizziness, slurred speech. (Rimantidine is a derivative with fewer CNS side effects.) Zanamivir p299 Mechanism of action of Zanamivir. Inhibits influenza neuraminidase. Clinical use of Zanamivir. Both influenza A and B. Ribavirin p299 Mechanism of action of Ribavirin. Inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase. Clinical use of Ribavirin. RSV (respiratory syncytial virus). Symptoms of Ribavirin toxicity. Hemolytic anemia. Severe teratogen. Acyclovir p299 Mechanism of aciton of Acyclovir. Perferentially inhibits viral DNA polymerase when phosphorylated by viral thymidine kinase. Clinical use of Acyclovir. HSV, VZV, EBV. Mucocutaneous and genital herpes lesions. Prophylaxis in immunocompromised patients. Symptoms of Acyclovir toxicity. Delirium, tremor, nephrotoxicity. Ganciclovir (DHPG dihydroxy-2-propoxymethyl guanine) p300 Mechanism of action of Ganciclovir. Phosphorlation by viral kinase; perferentially inhibits CMV DNA polymerase. Clinical use of Ganciclovir. CMV, especially in immunocompromised patients. Symptoms of Ganciclovir toxicity. Leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclovir. Foscarnet p300 Mechanism of action of Foscarnet. Viral DNA polymerase inhibitor that binds to the pyrophophate binding site of the enzyme. Does not require activation by viral kinase. "FOScarnet = pyroFOSphate analog." Clinical use of Foscarnet. CMV retinitis in immunocompromised patients when ganciclovir fails. Symptoms of Foscarnet toxicity. Nephrotoxicity. HIV therapy p300 Saquinavir, ritonavir, indinavir, nelfinavir, amprenavir are example of this type of anti-HIV drug. Protease inhibitor. Mechanism of action of protease inhibitors. Inhibit assembly of new virus by blocking protease enzyme. Symptoms of protease inhibitor toxicity. GI intolerance (nausea, diarrhea), hyperglycemia, lipid abnormalities, thrombocytopenia (indinavir). Reverse transcriptase inhibitors: Zidovudine (AZT), didanosine (ddI), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), and abacavir are examples of --------- reverse transcriptase inhibitors. Nucleoside. Nevirapine, delavirdine, and efavirenz are examples of --------- reverse transcriptase inhibitors. Non-nucleoside. Mechanism of action of reverse transcriptase inhibitors. Preferentially inhibit reverse transcriptase of HIV; prevent incorporation of viral genome into host DNA. Symptoms of reverse transcriptase inhibitor toxicity. Bone marrow supression (neutropenia, anemia), periphral neuropathy, lactic acidosis (nucleosides), rash (non-nucleosides), megaloblastic anemia (AZT). Highly active antiretroviral therapy (HAART) generally entails combination therapy with ---------- and -----------. Protease inhibitors, reverse transcriptase inhibitors. When should HIV therapy be initiated? When patients have low CD4 counts (<500 cells/mm3) or high viral load. -------- is used during pregnancy to reduce risk of fetal transmission. AZT. Interferons p300 Mechanism of action of Interferons. Glycoproteins from human leukocytes that block various stages of viral RNA and DNA synthesis. Clinical use of Interferons. Chronic hepatitis B and C, Kaposi's sarcoma. Symptoms of Interferon toxicity. Neutropenia. Antiparasitic drugs p301 Clinical uses of Ivermectin. Onchocerciasis "rIVER blindness treated with IVERmectin". Clinical uses of Mebendazole / thiabendazole. Nematode/roundworm (e.g., pinworm, whipworm) infections. Clinical uses of Pyrantel pamoate. Giant roundworm (Ascaris), hookworm (Necator/Ancylostoma), pinworm (Enterobius). Clinical uses of Praziquantel. Trematode/fluke (e.g., schistosomes, Paragonimus, Clonorchis) and cysticercosis. Clinical uss of Niclosamide Cestode/tapeworm (e.g., Diphyllobothrium latum, Taenia species) infections except cysticercosis. Clinical uses of Pentavalent antimony. Leishmaniasis. Clinical uses of Chloroquine, quinine, mefloquine, atovaquone, proguanil. Malaria. Clinical uses of Primaquine. Latent hypnozoite (liver) forms of malaria (Plasmodium vivax, P.ovale). Clinical uses of Metronidazole. Giardiasis, amebic dysentery (Entamoeba histolytica), bacterial vaginitis (Gardnerella vaginalis), Trichomonas. Clinical uses of Pentamidine. Pneumocystis carinii pneumonia prophylaxis. Clinical uses of Nifurtimox. Chagas' disease, American trypanosomiasis (Trypanosoma cruzi). Clinical uses of Suramin. African trypanosomiasis (sleeping sickness). Pharmacology - CNS / Neurologic drugs p301 Parasympathetic preganglionic neurons release the neurotransmitter -------- which act on -------- receptors. Ach, nicotinic. Sympathetic preganglionic neurons to sweat glands release the neurotransmitter ------- which act on ------- receptors. Ach, nicotinic. Autonomic drugs p302 Cholinergic: Ach is synthesized from acetyl-CoA and choline by the enzyme ---------. Choline acetyltransferase. Noradrenergic: In the noradrenergic nerve terminal, tyrosine is hydroxylated to -------, which is decarboxylated to --------, which is finally hydroxylated to NE. DOPA, dopamine. The action of NE and DA is terminated by --------- and ----------. Reuptake, diffusion (different than for Ach). The drugs --------- and ---------- inhibit the reuptake of NE. Cocaine, TCA. Ach inhibits the release of NE from the noradrenergic nerve terminal by binding to --------- receptors. M1. Cholinomimetics p303 Direct agonists: Clinical application and action of Carbachol and Pilocarpine. Glaucoma. / Activates ciliary muscle of eye (open angle), pupillary sphincter (narrow angle). Indirect agonists (anticholinesterases): Clinical application / action of Neostigmine. Postoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of neuromuscular junction blockade (postoperative). / Increase endogenous Ach. Clinical application / action of Pyridostigmine. Myasthenia gravis. / Increase Ach; increase strength. Clinical application / action of Physostigmine. Glaucoma (crosses blood-brain barrier) and atropine overdose. / Increase endogenous Ach. Clinical application / action of Echothiophate. Glaucoma. / Increase endogenous Ach. Symptoms of cholinesterase inhibitor poisoning. Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle and CNS, Lacrimation, Sweating, Salivation (also abdominal cramping). "DUMBBELSS". Cholinesterase inhibitor poisoning may be caused by ---------. Parathion and other organophosphates. The cholinesterase regenerator ------- can be used as an antidote for cholinesterase inhibitor poisoning. Pralidoxime. Mechanism of action of Pralidoxime. Regenerates active cholinesterase, chemical antagonist, used to treat organophosphate exposure. Cholinoreceptor blockers: p303 Clinical uses of the muscarinic antagonist Atropine. Dilate pupils, decrease acid secretion in peptic ulcer disease, decrease urgency in mild cystitis, decrease GI motility, reduce airway secretions, and treat organophosphate poisoning. "Blocks SLUD: Salivation, Lacrimation, Urination, Defecation." Side effects of Atropine. Increase body temp, rapid pulse, dry mouth, dry/flushed skin, disorientation, mydriasis with cycloplegia, and constipation. "Atropine parasympathetic block side effects: Blind as bat, Red as a beet, Mad as a hatter, Hot as a hare, Dry as a bone." Hexamethonium (ganglionic blocker) blocks -------- receptors. Nicotinic. antimuscarinic drugs p. 304 "tropi" are anti-muscarinic while vacationing in the tropics you lie on a beach and your muscles waste away! benztropine is used to treat Parkinson's disease scopolamine is used to treat motion sickness scopolamine is an antimuscarinic that does not convert to the mnemonic! name 2 antimuscarinic drugs that act on the CNS benztropine, scopolamine name a muscarinic used to treat motion sickness scopolamine name a muscarinic used to treat Parkinson's disease benztropine mechanism of action of benztropine antimuscarinic mechanism of action of scopolamine antimuscarinic name three antimuscarinics that act on eye atropine, homatropine, tropicamide the action of atropine is ______ produce mydriasis, cycloplegia mechanism of atropine is antimuscarinic the action of homatropine is ______ produce mydriasis, cycloplegia mechanism of homatropine is antimuscarinic the action of tropicamide is produce mydriasis, cycloplegia mechanism of tropicamide is antimuscarinic ipatropium is used to treat asthma, COPD mechanism of ipatropium is antimuscarinic name an antimuscarinic used to treat asthma and COPD ipatropium neuromuscular blocking drugs p. 304 neuromuscular blocking drugs are used for muscle paralysis in surgery or mechanical ventilation name a depolarising neurmuscular blocking drug succinylcholine name 6 nondepolarizing neuromuscular blocking drugs tubocurarine *mnemonic -- the "cur" drugs are nondepolarizing neuromuscular blocking agents atracurium mivacurium pancuronium vecuronium rapacuronium is succinylcholine depolarizing or nondepolarizing? depolarizing is tubocurarine depolarizing or nondepolarizing? nondepolarizing is atracurium depolarizing or nondepolarizing? nondepolarizing is mivacurium depolarizing or nondepolarizing? nondepolarizing is pancuronium depolarizing or nondepolarizing? nondepolarizing is vacuronium depolarizing or nondepolarizing? nondepolarizing is rapacuronium depolarizing or nondepolarizing? nondepolarizing what is tubocurarine used for nondepolarizing neuromuscular blockade what agents are used to reverse neuromuscular blockade by succinylcholine? cholinesterase inhibitors in phase II (ex -- neostigmine) what phase of succinylcholine neuomuscular bloackade is reversible? phase II (repolarized but blocked) what agents are used to reverse pahse I neuromuscular blockade by succinylcholine? phase I Succinylcholine neuromuscular blockade cannot be reversed what phase of succinylcholine neuomuscular bloackade is irreversible? phase I Succinylcholine neuromuscular blockade cannot be reversed what is atracurium used for nondepolarizing neuromuscular blockade what is the effect of cholinesterase inhibitors on succinylcholine neuromuscular blockade? phase I: cholinesterase inhibitors potentiates the blockade phase II: cholinesterase inhibitors reverse the blockade what cholinesterase inhibitor is used to reverse phase II of succinylcholine neuromuscular blockade? neostigmine what is mivacurium used for nondepolarizing neuromuscular blockade Dantrolene p. 304 what is dantrolene used for treat malignant hyperthermia what causes malignant hyperthermia use inhalation anesthetics and succinylcholine together what inhalation anesthetic DOES NOT cause malignanat hyperthermia? N2O what is dantrolene used for neuroleptic malignant syndrome what is neuroleptic malignant syndrome a toxicity of antipsychotic drugs what drug is used to treat malignant hyperthermia dantrolene what is the mechanism of dantrolene prevents release of Ca++ from saarcoplasmic reticulum of skeletal muscle Sympathomimetics p. 305 epinephrine, NE, isoproterenol, dopamine, and dobutamine are all________________ catecholamines catecholamines are_____________________ sympathomimetics name 5 catecholamines EPI, NE, Isoproterenol, dopamine, dobutamine what receptors does epinephrine act on? alpha-1, alpha-2, beta-1, beta-2 adrenergics what receptors does NE work on? alpha-1, alpha-2, beta-1 adrenergics what receptors does isoproterenol work on? beta-1 = beta-2 adrenergics what receptors does dopamine work on? D1 = D2, D1 and D2 more than beta, beta more than alpha what receptors does dobutamine work on? beta-1 > beta-2 which catecholamines are agonists to alpha-adrenergic receptors EPI, NE > dopamine which catecholamines are agonists to beta-1 adrenergic receptors EPI, NE, Isoproterenol, dopamine, dobutamine which catecholamines are agonists to beta-2 adrenergic receptors EPI, isoproterenol, dopamine and dobutamine (less) what is epinephrine used to treat? anaphylaxis, open-angle glaucoma, asthma, hypotension what is norepinephrine used to treat? hypotension (but decreases renal perfusion) what is isoproterenol used to treat? AV block what is dopamine used to treat shock with renal failure, heart failure what is dobutamine used to treat shock, heart failure what catecholamine is used to treat anaphylaxis epinephrine ("EPI-pen") what catecholamines are used to treat hypotension EPI, NE what catecholamine is used to treat asthma epinephrine what catecholamine is used to treat AV block isoproterenol what catecholamines are used to treat shock doapmine, dobutamine what is the action of amphetamine indirect general adrenergic agonist, releases stored catecholamines what is the action of ephedrine indirect general adrenergic agonist, releases stored catecholamines what is amphetamine used to treat narcolepsy, obesity, attention deficit disorder what is ephedrine used to treat nasal decongestion, urinary incontinence, hypotension name three sympathomimetic drugs used to treat hypotension epinephrine, norepinephrin, ephedrine what is the action of phenylephrine adrenergic agonist, alpha-1 > alpha-2 what is the action of albuterol adrenergic agonist, beta-2 >beta-1 what is the action of terbutaline adrenergic agonist, beta-2 >beta-2 what is phenylephrine used for? pupil dilator, vasoconstriction, nasal decongestion what sympathomimetics are used to treat nasal congestion ephedrine, phenylephrine what is the mechanism of cocaine indirect general adrenergic agonist, catecholamine uptake inhibitor what is the action of cocaine vasoconstriction, local anesthesia what is the mechanism of clonidine centrally acting alpha-adrenergic agonist, decreases central adrenergic outflow what drug has the same mechanism as amphetamine ephedrine what is the mechanism of alpha-methyldopa centrally acting alpha-adrenergic agonist, decreases central adrenergic outflow what drug has the same mechanism as clonidine alpha-methyldopa what are clonidine and alpha-methyldopa used to treat hypertension, especially in renal disease because they do not decreased blood flow to the kidney what sympathomimetic is used to treat urinary incontinence ephedrine what sympathomimetic is used to treat attention deficit disorder amphetamine what sympathomimetic is used to treat narcolepsy amphetamine alpha-blockers p. 306 name a nonselective irreversible alpha blocker phenoxybenzamine name a nonselective reversible alpha blocker phentolamine what is the mechanism of phenoxybenzamine nonselective irreversible alpha blocker what is the mechanism of phentolamine nonselective reversible alpha blocker what are phenoxybenzamine and phentolamine used for pheochromocytoma what are the side effects of nonselective alpha blockers orthostatic hypotension, reflex tachycardia name 3 alpha-1 selective adrenergic blockers prazosin, terazosin, doxazosin what is the mechanism of prazosin alpha-1 selective adrenergic blocker what is the mechanism of terazosin alpha-1 selective adrenergic blocker what is the mechanism of doxazosin alpha-1 selective adrenergic blocker what are alpha-1 selective adrenergic alpha blockers used for hypertension, urinary retention in BPH what are the side effects of alpha-1 blockers orthostatic hypotension, dizziness, headache what is prazosin used for? hypertension, urinary retention in BPH what drugs have the same action as prazosin terazosin, doxazosin what are the side effects of terazosin? orthostatic hypotension, dizziness, headache what selective alpha blockers cause orthostatic hypotension phenoxybenzamine, phentolamine, terazosin, prazosin, doxazosin name an alpha-2 selective adrenergic blocker yohimbine what is yohimbine used for impotence (effectiveness controversial) what alpha blockers are used to treat pheochromocytoma phenoxybenzamine, phentolamine beta-blockers ("lol"s) p. 307 name some beta-blockers propranolol, metoprolol, atenolol, nadolol, timolol, pindolol, esmolol, labetalol what is the mechanism of propanolol selective beta-adrenergic blocker what is the mechanism of metoprolol selective beta-adrenergic blocker what is the mechanism of esmolol selective beta-adrenergic blocker what is the mechanism of pindolol selective beta-adrenergic blocker what are beta-blockers used to treat hypertension, angina, MI, SVT, CHF, glaucoma how do beta blockers treat hypertension decrease cardiac output, decrease renin secretion how do beta blockers treat angina decrease heart rate, decrease cardiac contractility, decreased O2 consumption why are beta blockers used to treat MI decrease MI mortality which beta blockers are used to treat SVT propanolol, esmolol how do propanolol and esmolol treat SVT decrease AV conduction velocity how do beta blockers treat CHF slow progression of chronic failure which beta blocker is used to treat glaucoma timolol what is timolol used to treat glaucoma decrease secretion of aqueous humor what are the toxic effects of beta blockers impotence, exacerbation of asthma, caution in diabetes what are the cardiovascular toxic effects of beta blockers bradychardia, AV block, CHF what are the CNS adverse effects of beta blockers sedation, sleep alterations which beta blockers are beta-1 selective acebutolol, betaxolol, esmolol, atenolol, metaprolol (A BEAM of beta-1 blockers) which beta-1 blocker is short-acting esmolol which beta blockers are non-selective propanolol, timolol, pindolol, nadolol, labetalol which beta blocker also blocks alpha receptors labetalol (all others are spelled "olol") glaucoma drugs p. 307 which alpha agonists are used to treat glaucoma epinephrine, brimonidine which beta blockers are used to treat glaucoma timolol, betxolol, carteolol which cholinomimetics are used to treat glaucoma pilocarpine, carbachol, physostigmine, echothiophate which diuretics are used to treat glaucoma acetazolamide, dorzolamide, brinzolamide which prostaglandin is used to treat glaucoma latanoprost what classes of drugs are used to treat glaucoma alpha agonists, beta blockers, cholinomimetics, diuretics, prostaglandins (*mnemonic -- treating glaucoma is easy as ABCD) what is the effect of epinephrine in glaucoma increase outflow of aqueous humor what are the side effects of epinephrine treatment in glaucoma mydriasis, stinging what glaucoma should epinephrine NOT be used for closed-angle glaucoma what is the effect of brimonidine in glaucoma decreased aqueous humor synthesis what are the side effects of brimonidine treatment in glaucoma no pupillary or vision changes what is the effect of beta-blocker treatment in glaucoma decrease aqueous humor secretion what are the side effects of beta blocker treatment in glauzoma no pupillary or vision changes what is the effect of cholinomimetics in glaucoma ciliary muscle contraction, opening of trabecular meshwork, increase outflow of aqueous humor what are the side effects of cholinomimetics in glaucoma miosis, cyclospasm what is the effect of diuretic treatment in glaucoma inhibition of carbonic anhydrase --> decrease HCO3 secretion --> decrease aqueous humor secretion what are the side effects of diuretics in glaucoma no pupillary or vision changes what is the effect of prostaglandin (latanoprost) treatment in glaucoma increase outflow of aqueous humor what is the side effect of prostaglandin treatment in glaucoma darkens color of iris (browning) which drugs used to treat glaucoma increase outflow of aqueous humor cholinomimetics, prostaglandin, epinephrine can you use epinephrine in closed-angle glaucoma NO brimonidine is used to treat what eye disease glaucoma what kind of drug is latanoprost prostaglandin latanoprost is used to treat what eye disease glaucoma which glaucoma drugs decrease aqueous secretion beta blockers, diuretics L-dopa/carbidopa p. 307 what does L-dopa stand for levodopa what is the mechanism of action of L-dopa/carbidopa increase dopamine level in brain what is L-dopa/carbidopa used to treat Parkinson's disease how is L-dopa different from dopamine L-dopa can cross the blood-brain barrier, dopamine cannot what happens to L-dopa after it crosses the BBB converted to dopamine by dopa decarboxylase what enzyme convertes L-dopa to dopamine dopa decarboxylase what is the function of carbidopa peripheral decarboxylase inhibitor why is carbidopa given with L-dopa increase L-dopa availability in CNS by inhibiting decarboxylase in periphery, also limits peripheral side effects what are the side effects of L-dopa.carbidopa treatment arrhythmias, dyskinesias why do patients taking L-dopa get arrhythmias peripheral effects of dopamine why do patients taking L-dopa get dyskinesias excess dopamine stimulation in CNS Parkinson's disease drugs p.308 what drugs are used to treat Parkinson's disease dopamine agonists, MAO inhibitors, antimuscarinics specifically, which drugs are used to treat Parkinson's Bromocriptine, Amantadine, Levodopa, Selegiline, Antimuscarinics (BALSA) which dopamine agosts are used to treat Parkinson's L-dopa/carbidopa, bromocriptine, pramipexole, ropinirole, amantadine what is the action of bromocriptine in Parkinson's ergot alkaloid, partial dopamine agonist what is the action of amantadine in Parkinson's enhances dopamine release what MAOI is used to treat Parkinson's selegiline what is the mechanism of selegiline selective MAO type B inhibitor what antimuscarinic is used to treat Parkinson's benztropine what is the effect of benztropine in Parkinson's improves tremor, rigidity, little effect on bradykinesia Sumatriptan p. 308 what is sumatriptan used for acute migraine, cluster headache attacks what is the mechanism of sumatriptan 5-HT1D agonist what is the half life of sumatriptan less than 2 hours what are the side effects of sumatriptan chest discomfort, mild tingling what are the contraindications for sumatriptan patients with CAD or Prinzmetal's angina Epilepsy drugs p. 308 which drugs are used for simple and complex partial seizures phenytoin, carbamazapine, lamotrigine, gabapentin, topiramate, phenobarbital what types of seizures is phenytoin indicated for simple and complex partial, tonic-clonic, status epilepticus what types of seizures is carbamazepine indicated for simple and complex partial, tonic-clonic what types of seizures is lamotrigine indicated for simple and complex partial, tonic-clonic what types of seizures is gabapentin indicated for simple and complex partial, tonic-clonic what types of seizures is topiramate indicated for simple and complex partial what types of seizures is phenobarbital indicated for simple and complex partial, tonic-clonic what drugs can be used for tonic-clonic seizures phenytoin, carbamazapine, lamotrigine, gabapentin, phenobarbital, valproate what drugs can be used for absence seizures valproate, ethosuximide what drugs can be used for status epilepticus phenytoin, benzodiazapines (diazepam, lorazepam) what types of seizure is valproate indicated for tonic-clonic, absence what types of seizure is ethosuximide inidcated for absence what type of seizure are benzodiazepines indicated for status epilepticus other than anti-seizure, what else is phenytoin used for class 1B anti-arrhythmic how should a patient taking carbamazepine be followed monitor LFT's weekly which seizure drugs have adjunct use gabapentin, topiramate which seizure drug is safest in pregnant women phenobarbital which seizure drug is used in Crigler-Najjar II phenobarbital what are the advantages of phenobarbital can be used in pregnant women, Crigler Najjar II Epilepsy drug toxicities p. 309 what are the side effects of benzodiazepines sedation, tolerance, dependence what are the side effects of carbamazepine diplopia, ataxia, CYP induction, blood dyscrasias, liver toxicity what are the side effects of ethosuximide GI distress, lethargy, headache, urticaria, Stevens-Johnson syndrome what are the side effects of phenobarbital sedation, CYP induction, tolerance, dependence what are the side effects of phenytoin nystagmus, diplopia, ataxia, sedation, ginigival hyperplasia, hirsutism, anemias, teratogenic what are the side effects of valproate GI distress, rare by fatal hepatotoxicity, neural tube defects (spina bifida) what are the side effects of lamotrigine life-threatening rash, Stevens-Johnson syndrome what are the side effects of gabapentin sedation, movement disorders what are the side effects of topiramate sedation, mental dulling, kidney stones, weight loss which anti-epileptic drug is teratogenic phenytoin which anti-epileptic drug can cause dependence benzodiazepines, phenobarbital which anti-epileptic drug can cause neural tube defects valproate which anti-epileptic drugs can cause GI distress valproate, ethosuximide it is necessary to check LFT's with which anti-epileptic drugs carbamazepine, valproate which anti-epileptic drugs cause CYP induction phenobarbital, carbamazepine which anti-epileptic drugs can cause blood problems carbamazepine, phenytoin which anti-epileptic drugs can cause Stevens-Johnson syndrome lamotrigine, ethosuximide which anti-epileptic drugs can cause diplopia carbamazepine, phenytoin Phenytoin p. 309 what is the mechanism of phenytoin action use-dependent blockade of Na+ channels what is the clinical application of phenytoin grand mal seizures what are the toxicities of phenytoin nystagmus, ataxia, diplopia, lethargy what are the chronic toxicities of phenytoin gingival hyperplasia in children, peripheral neuropathy, hirsutism, megaloblastic anemia, malignant hyperthermia (rare) should pregnant women take phenytoin NO -- teratogenic why does phenytoin cause megaloblastic anemia causes decreased vitamin B-12 Barbiturates p. 309 name 4 barbiturates phenobarbital, pentobarbital, thiopental, secobarbital what is the mechanism of barbiturate action increase duration of Cl channel opening --> decreased neuron firing --> facilitate GABA-A action how do barbiturates facilitate GABA-A action increase duration of Cl channel opening which decreases neuron firing (Barbidurate increases duration is barbiturate action on the CNS stimulatory or inhibitory inhibitory what is the clinical application of barbiturates sedative for anxiety, seizures, insomnia, anesthesia induction (thiopental) which barbiturate is used for anesthesia induction thiopental what are the side effects of barbiturates dependence, additive CNS depression effects with alcohol, respiratory or CV depression (death), drug interactions due to CYP induction what should you find out before giving a patient barbiturates what other medications they take, because of CYP induction and many drug interactions what happens if you give barbiturates to a patient in alcohol-induced coma or DT's they might DIE!! Because of additive effect of barbiturates and alcohol --> respiratory depression when are barbiturates contra-indicated porphyria can barbiturates cause dependence YES My friend Barb was very anxious so her doctor gave her barbiturates to increase the duration of the time she could speak in public without freaking out and having a seizure. She became so dependent on it that she recommended it to her friend Portia who couldn't take it because of porphyria. One day Barb drank too much alcohol and took her barbiturates and never woke up! THE END clinical pharmacology made ridiculous. Period Benzodiazepines p. 309 name a bunch of benzodiazepines diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide (all have ZZZ in them) what is the mechanism of benzodiazepines increase frequency of Cl channel opening --> facilitate GABA-A action (Frenzodiazepines increase frequency) which GABA receptors are facilitated by barbiturates and bezodiazepines GABA-A what are the clinical applications of benzodiazepines anxiety, spasticity, status epilepticus (diazepam), detoxification (alcohol withdrawal, DT's) which benzodiazepine can be used for status epilepticus diazepam what drugs can be used to treat alcohol withdrawal benzodiazepines which benzodiazepines are short-acting TOM thumb: Triazolam, Oxazepam, Midazolam what are the toxic effects of benzos dependence, additive CNS depression effects with alcohol how are benzos better than barbiturates less respiratory depression and coma risk how do you treat benzo overdose flumazenil what is flumzenil used for benzo overdose how does flumazenil work competitive antagonist at GABA receptor can a patient become benzodiazepine dependent YES are barbiturates or benzodiazepines used for alcohol withdrawal benzodiazepines Antipsychotics (neuroleptics) p. 310 what is another name for antipsychotics neuroleptics name 4 antipsychotic drugs thioridazine, haloperidol, fluphenazine, chlorpromazine how do you keep benzos straight from antipsychotics Benzos help 3rd year Jon Kazam be less anxious around patients: Shazam Kazam! Without antipsychotics patients talk like a crazy 'zine (well, not perfect, but I'm working on it) what is the mechanism of most antipsychotics block dopamine D2 receptors what is the clinical application of antipsychotics schizophrenia, psychosis what are the side effects of antipsychotics extrapyramidal side effects (EPS), sedation, endocrine, muscarinic blockade, alpha blockade, histamine blockade what is a long-term effect of antipsychotic use tardive dyskinesia what is neuroleptic malignant syndrome a side effect of antipsychotics; rigidity, autonomic instability, hyperpyrexia how do you treat neuroleptic malignant syndrome dantrolene, dopamine agonists what is tardive dyskinesia side effect of neuroleptics; stereotypic oral-facial movements, may be due to dopamine receptor sensitization what is the "rule of 4" with EPS side effects from antipsychotic drugs evolution of EPS side effects: 4 hours -- acite dystonia, 4 days -- akinesia, 4 weeks -- akasthesia, 4 months -- tardvie dyskinesia is tardvie dyskinesia reversible often irreversible what is fluphenazine used for schizophrenia, psychosis Atypical antipsychotics p. 310 name 3 atypical antipsychotics clozapine, olanzapine, risperidone what type of antipsychotic is clozapine atypical what type of antipsychotic is olanzapine atypical what type of antipsychotic is risperidone atypical what is the mechanism of atypical antipsychotics block 5-HT2 and dopamine receptors what is the mechanism of clozapine block 5-HT2 and dopamine receptors what is the mechanism of olanzapine block 5-HT2 and dopamine receptors what is the mechanism of risperidone block 5-HT2 and dopamine receptors what is the clinical application of clozapine schizophrenia positive and negative symptoms what is the clinical application of olanzapine schizophrenia positive and negative symptoms, OCD, anxiety disorder, depression what is the clinical application of risperidone schizophrenia positive and negative symptoms how are atypical antipsychotics different from classic ones atypicals treat positive and negative symptoms of schizophrenia, fewer extrapyramidal and anticholinergic side effects than classic antipsychotics which antipsychotics should be used to treat positive and negative symptoms of schizophrenia atypical ones -- clozapine, olanzapine, risperidone which antipsychotics should be used for fewer side effects atypical ones -- clozapine, olanzapine, risperidone what is a potential toxicity of clozapine agranulocytosis which antipsychotic drug can cause agranulocytosis clozapine what test must be done weekly on patients taking clozapine WBC count because of potential agranulocytosis Lithium p. 310 what is the mechanism of action of lithium unknown; may be related to inhibition of phosphoinositol cascade what is the clinical application of lithium mood stabilizer for bipolar disorder how does lithium help people with bipolar disorder prevents relapse and acute manic episodes what are the side effects of lithium tremor, hypothyroidism, polyuria, teratogenic is it OK for women taking lithium to get pregnant NO -- teratogenic what does lithium cause polyuria ADH antagonist --> nephrogenic diabetes insipidus Antidepressants pg 311 What do the following drugs inhibit: 1. MAO inhibitors, 2. Desipramine/maprotilline, 3. Mirtazapine and 4. Fluoxetine/trazodone? 1. MAO 2. NE reuptake 3. Alpha 2-R 4. 5HT reuptake All of the above actions are ------synaptic PRE List the Tricyclic Antidepressants pg 311 Imipramine, amitriptyline, desipramine, nortriptyline, clomipramine, doxepin What are the three C's of their toxicity? Convulsions, Coma, Cardiotoxicity (arrythmias). Also respiratory depression, hypyrexia. How about toxicity in the eldery? confusion and hallucinations due to anticholinergic SE What is the mechanism of TCA? block reuptake of NE and 5HT What is the clinical uses of TCAs? Endogenous depresion. Bed wetting - imipramine. OCD- clomipramine. How are tertiary TCA's different than secondary in terms of side effects? Amitriptyline (tertiary) has more anti-cholinergic effects than do secondary (nortriptyline). Desipramine is the least sedating. what are the SE of TCAs? sedation, alpha blocking effects, atropine-like anti cholinergic side effects (tachycardia, urinary retention) Fluoxetine, sertraline, paroxetine, citalopram are what class of drugs? pg 311 SSRI's for endogenous depression How long does it take an anti-depressant to have an effect? 2-3weeks How does the toxicity differ fromTCA's and what are they? Fewer than TCA's. CNS stimulation - anxiety, insomnia, tremor, anorexia, nausea, and vomiting. What toxicity happens with SSRI's and MAO inhibitors given together? Seratonin Syndrome! Hyperthermia, muscle rigidity, cardiovascular collapse What are heterocyclics? pg 312 2nd and 3rd generation antidepressants with varied and mixed mechanisms of action. Used major depression. Examples of heterocyclics? trazodone, buproprion, venlafaxine, mirtazapine, maprotiline Which one is used for smoking cessation? Buproprion. Mechanism not known. Toxicity - stimulant effects, dry mouth, aggrevation of pyschosis Which one used in GAD? Venlafaxine - inhibits 5HT and DA reuptake. Toxicity - stimulant effects which one blocks NE reuptake maprotiline Which one increases release of NE and 5HT via alpha 2 antagonism? mirtazapine. Also potent 5HT Rantagonist. Toxicity - sedation, increase serum cholesterol, increase appetite What is trazodone and it' SE? primarily inhibits seratonin reuptake. Toxicity - sedation, nausea, priapism, postural hypotension Give 2 examples of MAO pg 312 phenelzine. Tranylcypromine Mechanism and Clinical Uses? non selevtive MAO inhibition. Atypical antidepressant, anxiety, hypochondriasis What is the toxicity with tyramine ingestion (in foods) and meperidine? Hypertensive crisis Other toxicities? CNS stimulation, contraindicated with SSRI's or B-agonists What is the mechanims of selgiline (deprenyl)? pg 312 Selectively inhibits MAO-B, increasing DA what is the clinical use and toxicity? adjunctive agent to L-dopa for Parkinsons. May enhance adverse effects of L-dopa Analgesics/ Anesthetics pg 312 General principles pg 312 What is the significance of drugs with decreased solubility in blood? rapid induction and recovery times . Ie. N20 What is the significance of drugs with increased solubility in blood? increased potency = I/ MAC. Ie. Halothane Inhaled Anesthetics pg 312 list them halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide What is good about lower solubility? the quicker the anesthetic response, and the quicker the recovery What are these drug's effects? myocardial depression, respiratory depression, nausea/emesis, increase cerebral blood flow What toxicity mactches the following drugs 1. Halothane 2. Methoxyflurane 3. Enflurane 4. Rare 1. Hepatotoxcity 2. Nephrotoxicty 3. Proconvulsant 4. Malignant hyperthermia IV anesthetics pg313 What do barbituates, benzodiazepines, arylcyclohexylamines and narcotic analgesics have in common? they are IV anesthetics What the pharmacokinetics and uses of thiopental? high lipid solubility, rapid entry into brain. Used for induction of anesthesia for short surgical procedures. Terminated by redistribution from brain. Decreased cerebral blood flow Give an example of a benzo and what is this class's shortcoming? midazolam used for endoscopy. Used with gaseous anesthetics and narcotics. May cause severe post-op respiratory depressio and amnesia What does Ketamine (PCP analog and an arylcyclohexylamine) do? dissociative anesthetic. Cardiovascular stimulant. Causes disorientation, hallucination, bad dreams. Increases cerebral blood flow. How are narcotic analgesics used? Examples? Morphone and fentanyl are used with CNS depressant during general anesthesia. What is the advantage of propofol used for rapid anesthesia induction and short procedures. Less post-op nausea than thiopental Local anesthetics pg 313 Name some esters? procaine, cocaine, tetracaine, Name some amides? lidocaine, bupivacaine, (amides have two I's in name!) What is the mechanism and clinical use? bind receptor and block Na channels. Tertiary amine local anesthetics penetrate membrane in uncharge form, then bind charged form. Use for minor surgical procedures, spinal anesthesia. How do you decide to use ester or amides? if allergic to esters, give amides what is the toxicity CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension, arrhythmias (cocaine) In infected ________ tissue, anesthetics are charged and cannot penetrate membrane. Therefore, ______ anesthetics are needed. acidic; more What is the order of nerve blockade for size and myelination? Which factor predominates? small diameter> large diameter. Myelinated fibers> unmyelinated fibers. Size factor predominates what is the order of loss of sensation? pain first, then temp, then touch, then pressure Why would you give these drugs with vasoconstrictors? to enhance local action Opiod analgesics pg 313 List as many as you can. morphine, fentanyl, codeine, heroin, methadone, meperidine, dextromethorphan Mechanism: They act as _____ for opiod receptors to modulate synaptic transmission agonists which drugs act at the mu, delta, kappa receptors? morphine enkephalin, dynorphin Clinical use? pain, cough supression (dex), diarrhea (loperamide), acute pulmonary edema, methadone maintenance programs What are the major toxicities? addiction, respiratory depression, constipation, miosis, additive CNS depression wth other drugs Tolerance does not develop to __________and ______ miosis and constipation How would you treat toxicity? naloxone, naltrexone (opiod R antagonist) Other NSAIDS pg 313 List three NSAIDS? ibuprofen, naproxen, indomethacin What is their mechanism? reversibly inhibit COX 1 and 2. Blocks PG synthesis What is their clinical use (3As)? Antipyretic, analgesic, anti-inflammatory. Indomethacin is used to close a PDA. What are common toxicities? renal damage, aplastic anemia, GI distress, ulcers COX 2 Inhibitors pg 314 Where is cox2 found? in inflammatory cells and mediates inflammation and pain Why is cox2 inhibition better than cox1? cox1 helps to maintain gastric mucosa, thus, should not have the corrosive effects of other NSAIDs on the GI lining (less incidence of ulcers and bleeding) Clinical Use? RA and osteoarthritis Acetaminophen pg 314 What is its mechanism and where does it work? reversibly inhibits cox, mostly in CNS. Inactivated peripherally. What are its 2 As? antipyretic, analgesic but NOT anti-inflammatory. Overdose effects? hepatic necrosis, acetaminophen metabolites depletes glutathine and forms toxic tissue adducts in the liver cardiovascular therapy pg 314 Changes in CO affect two major pathways? 1. Carotid sinus firing, sympa discharge 2. Renal blood flow, renin-ang pathway What is the effect of the following drugs: 1. Positive inotropic drugs 2. Beta blockers 3. Ace inhibitors 4. AII antagonists 5. Vasodilators and 6. Diuretics 1. Increases cardiac output. 2. Inhibit renin release. 3. Inhibit ACE 4. Inhibits effects of AngII including increasing the preload, increasing the afterload and remodelling. 5. Decrease the preload and afterload. 6. Decrease the preload and afterload antihypertensive drugs pg 315 What are the adverse effects of these two diueretics: hydrochlorothiazide, loop diuretics 1. Hypokalemia, hyperlipidemia, hyperuricemia, lassitude, hypercalcemia, hyperglycemia 2. Hypokalemia, met alk, hypotension, ototoxicity These are wahat class of drugs: clonidine, methyldopa, ganglionic blockers, reserpine, guanethidine, prazosin, beta blockers? sympathoplegics Adverse effects of clonidine? dry mouth, sedation, severe rebound HTN Adverse effects of methyldopa? sedation, positive coombs test Adverse effects of ganglionic blockers? orthostatic HTN, blurred vision, constitpation, sexual dysfuncction Adverse effects of reserpine? sedation, depression, nasal stuffiness, diarrhea adverse effects of beta blockers? impotence, asthma, cardiovascular, cns Adverse effects of guanethidine? orthostatic and exercise Hypotension, sex dysfxn, diarrhea Adverse effects of prazosin? 1st dose orthostatic hypotension, dizzy, headache The following are what class: hydralazine, minoxidil, nifedipine, verapamil, nitroprusside vasodilators which one causes lupus like syndrome? Other toxicities? hydralazine, nausea, headache, reflex tachycardia, angina, salt retention adverse effets of minoxidil? hypertrichosis (hair growth - think Rogaine with minoxidil!), pericardial effusion, reflex tachycardia, angina, salt retention Side effects of nifedipine, verapamil? dizziness, flushing, constipation, nausea which one causes cynide toxicity? nitroprusside Adverse effects of ACE-I Captorpil? Think CAPTOPRIL C: cough, A: angioedema, P: proteinuria, T: taste changes, O: hypOtension, P: pregnancy problems like fetal renal damage, R: rash, I: increased renin, L: lower angiotensin. Also hyperkalemia. Losartan is a ----------- R-Inhibitor? With ____-toxicity and ____kalemia angiotensin II, fetal renal, hyper Hydralizine pg 315 Which two anti-htn drugs do you use with B blockers to prevent reflex tachycardia, diuretic to block salt retention? hydralizine, minoxidil What is hydralizine's mechanims and clinical use? increase cGMP --> smooth muscle relaxation. Vasodilates arteries > veins. Reduces afterload. Used for severe HTN or CHF Calcium channel blockers, name three pg. 315 - nifedipine, verapamil, diltiazem Mechanism: block _____ chanels of cardiac and smooth muscles to reduce contractility voltage dependednt L type Ca Rank their effects on vascular smooth muscle ad on the heart. smooth muscle nifed> diltia > verapamil heart: vera> diltia> nifedepine What is the calcium channel blockers use? HTN, angina, arrythmias (not nifedipine) ACE -I, name three pg 316 - captopril, enalapril, lisinopril Mechanim considering bradykinin and renin release? reduce lvels of ang II, prevent inactivation of bradykinin, renin release is increased to to loss of feedback inhibition what is the clinical use of these? HTN, CHF, diabetic renal disease Diuretics- site of action pg 316 What is the site of action of 1. Acetazolamide, 2. Osmotic agents, 3. Loop agents, 4. Thiazides, 5. Potassium sparing, 6. ADH antagonists 1. PCT 2. PCT, thin desc limb, CD 3. Thick ascending limb 4. Distal conv tubule 5. DCT a bit later 6. CD in inner medulla How does mannitol an osmotic diuretic work? increase tubular fluid osmolarity, producing increased urine flow what is the use and toxicity? Use: shock, drug overdose, decrease intracranial pressure. Toxicity - pulmonary edema, dehydration. Contraindicated in anuria, CHF Acetazolamide pg 317 Is a ______inhibitor. Causes ______diuresis and _____ in total body HC03 stores. Carbonic anhydrase, self-limited NaHCO3, reduction. What electrolye disturbace does it treat? Does it cause? treats met alk, causes in toxicity hyperchloremic met acidosis. ACIDazolamide caues ACIDosis. Other toxicity? neuropathy, NH3 toxicity, sulfa allergy uses? glaucoma, urinary alk, met alk, altitude sickeness Furosemide pg 317 This sulfonamide loop diuretic inhibits _______cotransport NA, K, 2CL Furosemide also works by? abolishes hypertonicit y of medulla, prevent concentration of urine. Increase Caexcertion. Loops Lose calcium The three uses for this loop diuretic? edematous states, htn, hypercalcemia Toxicity using the OH DANG? ototoxicity, hypokalemia, dehydration, allergy, nephritis interstitial, gout Ethacrynic Acid pg 317 How is this drug different from furosemide? And how does that affect its use? Although both have the same action, ethacrynic is a phenoxyacetic acid derivative not a sulfonamide. Therefore use this drug when you are allergic to sulfa. What drug can be used to treat acute gout? ethacrynic acid Hydrochlorothiazide p.318 Hydrochlorothiazide is a thiazide diuretic that inhibits the reabsorption of ----- in the ---- tubule NaCl; early distal tubule Does hydrochlorothiazide increase or decrease the excretion of calcium ion? decrease A toxic dose of hydrochlorathiazide will do what to the blood levels of these electrolites: potassium, sodium, glucose, lipid, uric acid, calcium hypokalemic metabolic alkalosis, hyponatremia, hyperGlycemia, hyperLipidemia, hyperUricemia, hyperCalcemia (hyperGLUC) K+-sparing diuretics p.318 Spironolactone is a competitive antagonist to the --- receptor in the ---- tubule aldosterone; cortical collecting tubule Name two K+-sparing diuretics that block Na+ channels in the cortical collecting duct Triamterine and amiloride Besides causing hyperkalemia, a toxic dose of spironolactone will cause this endocrine effect Gynecomastia (antiandrogen effect) Name three K+-sparing diuretics Spironolactone, Triamterene, Amiloride (The K+ STAys.) Diuretics: electrolye exchange p.318 Diuretics are classified as carbonic anhydrase inhibitors, loop diuretics, thiazides, and K+-sparing diuretics. Which of these causes in increase in urine NaCl? All of them! Which types of diuretucs increase urine K+? All except K+-sparing diuretics. Carbonic anhydrase inhibitors, loop diuretics, thiazides. Do carbonic anhydrase inhibitors increase or decrease blood pH? Decrease, cause acidosis Do K+-sparing diuretics cause acidosis or alkalosis? Acidosis, decreases pH Do loop diuretics cause acidosis or alkalosis? Alkalosis, increases pH Do thiazide diuretics cause an increase or decrease in blood pH? Increase, cause alkalosis Do loop diuretics increase or decrease levels of urine calcium ion? Increase Do thiazide diuretics increase or decrease levels of urine calcium ion? Decrease Antianginal therapy p.319 Name four determinants of the level of myocardial oxygen consumption There are five: end diastolic volume, blood pressure, heart rate, contractility, ejection time Do nitrates affect preload or afterload? preload Do Beta-blockers affect preload or afterload? afterload What is the effect of nitrates on: diastolic volume, blood pressure, contractility, heart rate, ejection time? decrease EDV, decrease BP, increase contractility (reflex response), increase HR (reflex response), decrease ejection time What is the effect of Beta-blockers on: diastolic volume, blood pressure, contractility, heart rate, ejection time? increase EDV, decrease BP, decrease contractility, decreased HR, increase ejection time The effects of using nitrates and Beta-blockers together will: a) decrease myocardial oxygen demands by the same amount as using either alone, b) decrease myocardial oxygen demands by an amount greater than if each were used alone, or c) have no effect on myocardial oxygen demand b) Decrease myocardial oxygen demands by an amount greater that if each were used alone Nifedipine blocks -- channels calcium In its effects on myocardial oxygen consumption, is Nifedipine similar to Nitrates or B-blockers? Nitrates (Nifedipine is similar to Nitrates) In its effects on myocardial oxygen consumption, is Verapamil similar to Nitrates or B-blockers? B-blockers Nitroglycerine, isosorbide dinitrate p.319 Dose nitroglycerin dilate arteries or veins more? Veins>>arteries Does nitroglycerin increase or decrease cGMP in smooth muscle? Increase In industrial exposure to nitroglycerine, weekend withdrawal is characterized by which three symptoms? Tachycardia, dizziness , and headache ("Monday disease") Toxic dosage of nitroglycerine causes which three symptoms? Tachycardia, hypotension, headache Cardiac drugs: sites of action p.320 Digitalis has its action on which cell membrane transporter? Na/K ATPase Ryanodine has its action on which channel? Calcium release channel in the sarcoplasmic receptor Calcium enters cardiac cells through which channel? Voltage-gated calcium channel Cytoplasmic calcium concentrations in cardiac cells can be decreased by sequestering calcium in the sarcoplasmic reticulum. Calcium enters the SR through which transporter? Calcium pump in the wall of the SR Calcium channel blockers have their effect on which calcium transporters? Voltage-gated calcium channel Cardiac Glycosides p.320 What is digoxin's effect on the intracellular Na+ level? Increase What is digoxin's effect on the intracellular calcium level? Increase Name two ECG changes ellicited by digoxin administration There are 4: increase PR, decrease QT, scooping of ST segment, T-wave inversion Name three symptoms of digoxin toxicity Nausea, vomiting, diarrhea, blurry vision, arrhythmia Which potentiates the effects of digoxin- hypo- or hyperkalemia? hypokalemia Antiarrhythmics- Na+ channel blockers (classI) p.321 Which phase of the cardiac action potential do antiarrhythmics decrease the slope of? Phase 4 depolarization What type of antiarrhythmic is Amiodarone? Class 1A (Class 1A includes Quinidine, Amiodarone, Procainamide, Disopyramide, "Queen Amy Proclaims Diso's pyramid." Do class 1A antiarrhythmics increase or decrease the effective refractory period, AP duration, and QT interval? Increase ERP, increase AP duration, increase QT interval What do class 1B antiarrhythmics do to the AP duration? Decrease AP duration What type of antiarrhythmic is mexiletine? Class 1B (includes Lidocaine, mexiletine, tocainide) What type of antiarrhythmic is encainide? Class IC (includes flecainide, encainide, propafenone) What effect do class 1C antiarrhythmics have on the AP duration? No effect! Antiarrhythmics- Beta-blockers (classII) p. 322 What does esmolol do to the cAMP in cardiac cells? decreases cAMP (a beta-blocker) What does atenolol do the calcium currents in cardiac cells? decreases calcium current (beta-blocker) Timolol decreases the slope of which phase of the cardiac AP cycle? Phase 4 (a beta-blocker) What does propanolol do the the PR interval? Increases interval (beta-blocker) Is esmolol a short- or long-acting beta blocker? short-acting Antiarrhythmics- K+ channel blockers (class III) p. 322 Does amiodarone increase or decrease AP duration? Increase (K+ channel blocker) Does sotalol increase or decrease the effective refractory period? Increase (K+ channel blocker) Does bretylium increase or decrease the QT interval? Increase (K+ channel blocker) Name a symptom of sotalol toxicity. Torsades de pointes (K+ channel blocker) Name three of the symptoms of amiodarone toxicity. Pulmonary fibrosis, corneal deposits, hepatoxicity, skin deposits resulting in photodermatitis, neurologic effects, constipation, bradychardia, heart block, CHF, hypothyroidism/hyperthyroidism. (Therefore, should check PFTs, LFTs, and TFTs) Antiarrhythmics- Ca2+ channel blockers (class IV) p. 323 Does verapamil increase or decrease the conduction velocity of the AV nodal cells? Decrease (calcium channel blocker) How does diltiazem affect the effective refractory period and the PR interval? Increases ERP, increases PR (calcium channel blocker) Other antiarrhythmics p. 323 Name a potential use of Mg+ to treat arrhythmias. To treat torsades de pointes and digoxin toxicity Name a potential use of K+ to treat arrhythmias. Depress ectopic pacemakers, especially in digoxin toxicity Name a use of adenosine in treating arrhythmias. To diagnose and abolish AV nodal arrhythmias. Lipid-lowering agents p. 324 What is the effect of cholestyramine on the serum triglyceride level? Slight increase (cholestyramine is a bile acid resin) What is the effect of colestipol on HDL? No effect! (colestipol is a bile acid resin) What is the effect of lovastatin on HDL? Increase (lovastatin is an HMG-CoA reductase inhibitor) Name 2 side effects of pravastatin. Increase LFTs and cause myositis (prevastatin is an HMG-CoA reductase inhibitor) What is the effect of Niacin on HDL? Increase What are the side effects of clofibrate? Incease LFTs and cause myositis (Clofibrate is a "Fibrate") Which increases HDL most: simvastatin, niacin, or gemfibrozil? Niacin Which decreases triglyceride level most: colestipol, Atorvastatin, niacin, or bezafibrate? Bezafibrate What is the main effect of ezetimibe? decrease serum LDL (a cholesterol absorption inhibitor) Gemfibrozil increases the activity of which enzyme? Lipoprotein lipase (which converts VLDL to IDL) Arachidonic acid products p.325 What enzyme breaks down membrane lipid into arachidonic acid? Phospholipase A2 What two enzymes are responsible for the production of Hydroperoxides (HPETEs) and Endoperoxidases, respectively from arachidonate? Lipoxygenase= HPETE, Cyclooxygenases=endoperoxidases What major class of products do HPETEs give rise to? Leukotrienes What are the 3 major products of Endoperoxidases? Prostacyclin (PGI), Prostaglandins (PGE, PGF), Thromboxane (TXA) In general what effect do leukotrienes have on bronchial tone? Leukotrienes in general increase bronchial tone In the arachodonic acid pathway, what two enzymes do corticosteroids block? Phospholipase A2, COX-2 NSAIDs, Acetaminophen and COX-2 inhibitors block which arachadonic acid pathway enzymes NSAIDs-non-selectively block COX-1 and COX-2, acetaminophen doesn't block COX-1 or COX-2, but instead it may block COX-3 in found in the brain, COX-2 inhibitors block COX-2 What are the 4 major effects of Prostacyclin decrease platelet aggregation, decrease vascular tone, decrease bronchial tone, decrease uterine tone What are the 3 major effects of Prostaglandins increased uterine tone, decrease vascular tone, decrease bronchial tone What are the 3 major effects of Thromboxane increase platelet aggregation, increase vascular tone, increase bronchial tone Zileuton is a ________ pathway inhibitor? Lipoxygenase Zariflukast is associated with what enzymes? Lekukotrienes Asthma drugs p 326 Bronchodilation is mediated by what molecule cAMP Bronchoconstriction is mediated by _________ and ___________ Ach and adenosine How many asthma drug categories are there? 7- (1) nonspecific B-agonists, (2) B2 agonists, (3) Methylxanthines, (4) muscarinic antagonist, (5) cromolyn, (6) corticosteroids, (7) Antileukotrienes What is the only nonspecific B-agonist drug and what are its effects? Isoprotenerol-relaxes bronchial smooth muscle (B2) and tachycardia (B1) (adverse effect). What are the two B2 selective agonist asthma drugs? Albuterol- relaxes bronchial smooth muscle (B2), Salmetrol What are the indications for Albuterol and Salmetrol, respectively? Albuterol- use during acute exarcebation, Salmetrol- long-acting agent for prophylaxis what are the notable adverse effects of B2 agonist? arythmias and tremor B2-agonists activate this enzyme in bronchial smooth muscle that leads to an increase in ________ = bronchodilation B2 agonists activate adenylate cyclase and increase conversion of ATP to cAMP What are the likely mechanism of action theophylline? bronchodialation by inhibition phosphodiesterase (PDE), decreasing cAMP hydrolysis and antagnonizing adenosine action Why is usage of theophylline limited? limited b/c narrow therapeutic index (cardiotoxicity, neurotxicity) What kind of drug is Ipratropium? muscarinic antagonist How does mechanism of action of Ipratropium? competitive block of muscarinic receptors= prevention of bronchoconstriction cromolyn works by inhibiting the release of _______ from ______ cell? prevents release of medicators from mast cells Cromolyn is mainly used for the ______ of athsma and it is not indicated for _______ treatment of athsma? Used only for prophylaxis, not effective during acute episode. Also, toxicity rare __________and ________ are two major corticosteroids used for treatment of what kind of asthma? Beclomethasone and prednisone are 1st line therapy for chronic asthma What is the mechanism of action of corticosteroids? inhibits the synthesis of virtually of cytokines-->inactivates NF-KB, the transcription factor that induces the production of TNF-a, amonth other inflammatory agents. Zileuton blocks the conversion of _______ to ________. zileuton is a 5-lipoxygenase pathway inhibitior. Blocks the conversion of arachidonic acti to leukotrienes Zafirlukast works by_______ ________ ________ bloking leukotriene receptors What the most basic asthma treatment strategy? avoidance of exposure to antingen (dust, pollen, etc) After exposure to antigen crosslinks IgE on mast cells. This is prevented by the following drugs: _________ and ________ cromolyn and steroids Following allergen exposure mediators are released (ex. _______ and _________). This triggers an ______ asthmatic response characterized by ________ and may be treated with the following 3 asthmatic drug categories to treat the symptoms. examples of mediators are leukotrienes and histamine. Following allergen exposure an early asthmatic response characterized by bronchoconstriction that can be treated with B-agonsists, methylxanthines, and muscarinic antagonists. Also, mediators elicit a ________ response is which leads to bronchial __________ and is treated with __________. mediators elicit a late response and this leads to bronchial hyperactivity. This is best treated with steroids. GI therapy p. 327 the following questions are from the diagram at the top of the page _____ cells are predominatly found in the antrum and _________ cells are predominatly found in the fundus. Gastrin cells are predominant in the antrum and parietal cells are predominant in the fundus. What are the 3 main stimuli of acid secretion? Ach, histamine, gastrin Gastrin stimulates the ECL cells to secrete histamine that stimulates ______ cells. Gastrin also activate the ______ cells to increase expression of _______ that increases ______secretion. Gastrin stimulates the ECL cells to secrese histamine that stimulates parietal cells. Parietal cells are also activated by gastrin to increase the expression of the H,K ATPase that increases acid secretion. This type of drug acts by inhibiting M1 and M3 receptors on ECL cells and Parietal cells, respectively. muscarinic antagonists block M1 receptors in ECL cells and M3 receptors in parietal cells. This type of drug inhibits the ability of the ECL cell to stimulate acid secretion by interfering with the _____ receptor. H2 blocker inhibits the ability of the ECL cell to stimulate acid secretion by interfering with the parietal H2 receptor. The most direct way of inhibiting acid secretion is by using this type of drug which acts on this enzyme. the most direct way of inhibiting acid secretion is by using proton pump blockers which inhibit the H,K ATPase on parietal cells. ____________ acts by binding to the ulcer and increasing its healing. It may interfere with drug absorption in the stomach. sucralfate binds to the ulcer base and provides physical protection. It allows HCO3- secretion to reestablish pH gradient in the mucus layer. What hormone binds ECL cells and decreases acid secretion? somatostatin These type of drugs used to decrease pH in the stomach. antacids….duh….jk. (I was instructed to make a question of every word) questions not from the diagram ____________, ___________, ___________, and ___________ are examples of H2 blockers and they act by (reversibly/irreversibly) cimetedine, ranitidine, famotidine, nizatidine reversilbly block H2 receptors. This H2 blocker is the only one that has many side effects which include potent inhibition of ______, _____ effects, and _____ renal excretion of creatinine. cimetedine is a potent inhibitor of P450, it has antiandrogenic effect and decrease renal excretion of creatinine. Other H2 blockers are relatively free of these effects. _________ and _________ (reversibly/irreversibly) inhibit the H/K ATPase in the stomach _______cells. Omeprazole and Iansoprazole irreversibly inhibit the H/K ATPase in stomach parietal cells Proton pump inhibitors are indicated for peptic ulcer, ________, _______, and _________ syndrome peptic ulcer, gastritis, esophageal reflux, and Zollinger-Ellison syndrome T/F: Bismuth and sucralfate allow HCO3- secretion. True: bismuth and sucralfate bind to ulcer base and provide physical protection, and allow HCO3- secretion to reestablish pH gradient in the mucus layer=increased ulcer healing T/F: misoprostol is a PGE2 analog and increases the production and secretion of gastric mucous barrier. False: misoprostol is a PGE1 analog and it increases the production and secretion of gastric mucous barrier. What are the 3 indications for misoprosol? prevention of NSAID-induced peptic ulcers, maintains a PDA and used to induce labor In what population is misoprostol contraindicated? women of childbearing potential (abortifacient). It also casues diarrhea Infliximab is ___________ against ______. monoclonal antibody to TNFa The clinical indication for Infliximab is: Crohn's, along with fistula healing T/F: Infliximab can cause respiratory infection, fever, hypotension TRUE GI Drugs (cont.) p. 328 This drug offers both anitbacterial action and anti-inflamatory effects. It is used for 2 inflammatory GI diseases ______ and _______. sulfasalazine: combination of sulfapyridine (antibacterial) and mesalamine (anti-inflammatory effects). It is used for Ulcerative colitis and remission of Crohn's. T/F: Side effects of the above include: malaise, sulfonamide toxicity, neutropenia false: side effects: malaise, nausea, sulfonamide toxicity ___________ is a powerful central-acting antiemetic. It acts by antagonizing the______ receptor. Ondansetron: is a powerful antiemetic. Think: you will not vomit with ondansetron, so you can go on dancing. T/F used to treat vomiting preoperatively and for cancer chemo therapy pts. False: it is used to treat vomiting postoperatively. Headache and __________ are side effects constipation (can't vomit or poop) Antacid overuse can affect:_________, __________, or ______ excretion of other drugs by altering ______ and ______ pH or by delaying gastric _________. Antacid overuse can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying. Constipation and (hypo/hyper) phosphatemia is seen with overuse of ________________ aluminum hydroxide - Aluminimum amt. of feces Magnesium hydroxide overuse = ___________ diarhea; Mg = Must go to the bathroom Calicium carbonate= hypercalcemia and (increase/decreased) acid causes hypercalcemia and increased acid. T/F: hyperkalemia can be seen with AlOH, MgOH, CaCO2 False! hypokalemia Hematologic Drugs p328 heparin Catalyzes activation of ____________, decreases ________ and __________. It has a ____t1/2. check PTT catalyzes the activation of antithrombin III, decreases thrombin and Xa. It has a short t1/2 It is used for immediated anticoagulation for pulmonary embolism,_______, _______, MI, and ________. Follow PTT used for pulmonary embolism, stroke, angina, MI, and DVT. T/F: Is used during pregnancy true: it is used during pregnancy because it does not cross the placenta. It can cause bleeding,___________, and drug-drug interactions. thrombocytopenia ___________ is used for rapid reversal of heparization (it is a _______ charged molecule that binds the ________ charged heparin) protamine sulfate is used for rapid reversal of heparinization (it is a positively charged molecule that binds the negatively charged heparin). Newer________________ (enoxaparin) act more on _____, have better bioavailability and 2-4 times longer t1/2. Can be administered subcut and (with/without) lab monitoring. lower-molecular-weight heparins (enoxaparin) act more on Xa, have better bioavailabitlity and 2-4 times longer half-life. Can be adm. Subcut and without lab monitoring. warfirin (coumandin) p. 328 Interferes with normal synthesis and gamma-carboxylation of vitamin K-dependent factors ___, ___, ___, and ___, also, ___ and ___ via ______ antagonism. Interferes with normal synthesis and gamma-carboxylation of vitamin K-dependent clotting factors II, VII, IX, and X, protein C and S via vitamin K antagonism. t1/2 (short/long) long Used for _______ anticoagulation. Follow PT WEPT - Warfirin affects the Extrinsic pathway and prolongs PT T/F: is used during pregnacy False! (warfarin, unlike heparin, can cross the placenta). Toxicity: bleeding, _________, drug-drug interactions teratogenic heparin vs. warfarin p. 329 Heparin is a (large/small) _____charged acicid polymer while Warfarin is (large/small) (charged/neutral) molecule Heparin is a large negatively charged acidic polymer while Warfarin is a small neutral charged lipid-soluble molecule T/F: Heparin is given orally while warfarin is given SC/IV False! Heparin is given IV/SC and warfarin is give oral Site of action: heparin _________, warfarin ______ heparin's site of action is the blood; warfarin's site of action is the liver (synthesises clotting factors) Onset of action of _________ is slow; the onset of action of ______ is rapid onset of action of heparin is rapid (secs) and the onset of action of warfarin is slow, limitd by t1/2 of normal clotting factors. Warfarin works by imparing the synthesis of _______ dependent factors __, ___, ___, and ___ also _____, and ____; heparin activates _____, ____ and ___ Warfarin works by imparing the synthesis of vitamin K dependent factors II, VII, IX, and X also protein S and protein C; heparin activates ATIII, Iia (thrombin) and Xa. Heparin 's duration of action is (acute/chronic); warfarin's duration of action is (actue/chronic) Heparin's duration of action is actute and warfarin's duration of action is chronic. Tx of acute OD: Heparin = _________; warfarin=______ Tx of heparin OD is protamine sulfate; Tx of warfarin= IV vit. K and fresh frozen plasma. Warfarin is monitored by _________ while Heparin is monitored by ___________. Warfrin is monitored by PT (extrinsic pathway) (WEPT) and heparin is monitored by PTT (intrinsic pathway) Thrombolytics p. 329 questions from diagram at bottom of page plasmin is the major ___________ enzyme. It breaks down both _______ and _______ fibrinolytic enzyme. It accelerates breaks down of both fribin and fibrinogen yielding fibrin splip products and degradation products, respectively. Fibrinogen is converted to fibrin by _________ thrombin tPA and urokinase promote the converson of ______ to ________ thereby increasing fibrinolysis. plasminogen to plasmin Various stimuli activate a blood proactivator to a blood activator that promotes conversion of _________ to blank thereby increasing fibrinolysis plasminogen to plasmin Streptokinase and anistreplase both activate and Activator that increases convesion of plasminogen to plasmin. Aminocaproic acid:____________ fibrinolysis. inhibits fibrinolysis by inhibition of plasminogen conversion to plasmin. 4 examples of thrombolytics include: ________, _________, _____________, and ___________ Streptokinase, urokinase, tPA(altepalse), APSAC (anistreplase) work by directly or indirectly aiding the conversion of ___________ to __________, which cleaves ______ and ________ clots. tPA specifically coverts _______________ to plasmin Directly or indirectly aid conversion of plaminogen to plasmin, which cleaves thrombin and fribrin clots. It is claimed that tPA specifically coverts fribrin-bound plasminogen to plasmin. T/F: clinical use is for DVTs False: used for early MI pts. receiving this medication are at most risk for: ______ bleeding Hematologic Drugs p. 330 mechanism of antiplatelet interaction questions from diagram at top of page When a break in the endothelium occurs _________ and _________ are exposed. collagen and vWF Platelets are activated by binding to the above macromolecules. The two structures expressed by the platelets involved in this process are __________ and _________ and they bind to _________ and __________, repectively Platelets bind to collagen and vWF. The two structures expressed by platelets that are involved in this process are GP 1a and GP 1b. GP 1a and GP 1b bind to collagen and vWF, respectively. After platelet activation _________ is expressed on their surface. What is the role of this structure? after platelets are activated they express GP IIb/IIIa. This molecule is important in platlelet-platelet aggregation. _________ and _________ interaction is needed in order for platelet aggregation to occur. GP IIb/IIIa and fribinogen 5-HT, _______, and ________ are molecules that play a role in the glycoprotein expression of activated platelets. 5-HT, ADP, and TxA2 are molecules that play a role in the glycoprotein expression of activated platelets. Aspirin acts by inhibiting production of ________ that in turn inhibits glycoprotein expression in activated platelets. TxA2 ADP production is inhibited by the drug _________. ticlopidine This antibody drug targets the _______ on platelets. Abciximab Copidogrel, ticlopidine p. 330 T/F: inhibits platele aggregation by irreversibly inhibiting the ADP pathway involved in the binding of fibrinogen TRUE It is used for ______ ________ syndrome, coronary _______, and it has been shown to decrease the incidence or recurrence of___ ____. it is used for acute coronary syndrome, coronary stenting. Decreases incidence or recurrence of thrombotic stroke Ticlopidine is associated with_________ as a side effect. Ticlopidine causes neutropenia and it is reserved for those who cannot tolerate aspirin. Abciximab p. 330 This drug binds to __________ on activated platelets. gp IIb/Iia It is used for ___________ and ________ _________ ___________ ___________ acute coronary syndromes and percutanous transluminal coronary angioplasty toxiciites are _______ and ________ bleeding and thrombocytopenia Aspirin p 330 It ________ and (reversibly/irreversibly) inhibits COX1 and COX2 to prevent the conversion of _______ to prostaglandins. acetilates and irreversably inhibits COX-1 and COX-2 T/F: aspirin has an effect of PT, PTT false it has no effect What are the 4 A's of aspirin and NSAIDS in general Antipyretic, Analgesic, Anti-inflam, antiplatelet Important toxicities include _________, bleeding, hyperventilation, __________- in children, and CN ____ toxicity gastric ulceration, bleeding, hyperventilation, Reyes syndrome and tinnitus (CNVIII). Endocrine Drugs pg 332 Hydrocortisone, prednisone, triamcinolone, dexamtasone, bleclomethasone are examples of what kind of drugs? Glucocorticoid Glucocorticoids decrease the production of ___ and ____ Leukotrienes and prostanglandins To treat Addison's disease, inflammation, immune suppression, asthma, use ____ Glucocorticoids An important side-effect of Glucocortioid usage is ____ Iatrogenic Cushing's Syndrome Buffalo hump, moon facies, truncal obesity, muscles wasting, thin skin, easy bruisability, osteoporosis, adrenocortical atrophy, peptic ulcers characterize what syndrome? Cushing's Syndrome Reproductive Drugs pg 332 Which two drugs inhibit cGMP phosphodiesterase, leading to smooth muscle relaxation in the corpus cavernosum and penile erection? Sildenafil and Verdenafil --they fill the penis What class of drugs are used tto treat erectile dysfunction cGMP Inhibitors CGMP inibitors taken with ____have a high risk of liofe-threeatening hypotension nitrates Which drugs is a partial agonist of estrogen recpetors in the pituitary gland, stimulating increase in LH and FSH, which stimulates ovulation to treat infertility clomiphene Clomiphene's side effects include: Hotflashes, ovarian enlargment, multiple simultaneous pregnancies, visual disturbances What abortifacient is a competitite inhibitor of preogestins at progesterone recpetor and may lead to heavy menstrual-like bleeding? Mifepristone (RU486) The advantage of this drug is that it is reliable, decreases incidence of ectopic pregnancy, decreases risk of pelvic infections, and regulates menses; however it also puts you in a hypercoagulable stat and may increase your trigylcerides, weight, and blood pressure Oral Contracpetices - syntheitc progestins/estrogen Rheumatologic Drugs pg 333 ____is converted to uric acid which leads to gout Xanthine (converted from excess purines) This drug depolymerizes microtubules, impairing leukocyte chemotaxis and degranulation, and used to treat acute gout Colchicine This drugs inhibits reabsorption of uric acid and used to treat chronic gout Probenecid This drug is used to treat chronic gout, but also inhbits secretion of penicillin Probenecid This drugs inhibits xanthine oxidase decreasing the conversion fo xanthine to uric acid Allopurinol Oncologic Drugs pg 333-336 What are the cell cycle specific oncologic drugs antimetabolites, plant alkaloids, stroid hormones, bleomycin, paclitaxel, etoposide What are the cell cycle Nonspecific oncologic drugs? alkylating agents and antibiotics ____is an S-phase-specific anti-metabolite that is an folic acid analog that inhibits dihydrofolate reducate decreasing dTMP(thymidine and purines) and decreaing DNA/prtein synthesis. Methotrexate ____is an S-phase-specific anti-metabolite that is a pyrmidine analog which complexed to folic acid, inhibiting thymidylate synthase, decreasing dTMP and decreasing DNA/protein synthesis 5-Fluorouracil (5-FU) Myelosuppression by methotrxate is reversible with ____ leucovorin (folinic acid) rescue Which drug blocks purine synthesis and is used to treat leukemias, lymphomas (not CLL or Hodgkins) 6-mercaptopurine (6-MP) Which drug alkylates DNA and is used to treat CML? Busulfan Which drug inhibits DNA polymerase and is used to treat AML? cytarabine This drug used to treat Leukemias and Lymphomas is metaboilized by xanthine oxidase 6-mercaptopurine (6-MP) Used to treat leukemias, lymphomas, choricarcinoma, sacromas, rheumatoid arthritis, psoriasis, and can be an abortifacient; it may lead to myelosuppression Methotrexate Used to treat colon cancer and other solid tumors, basal cell carcinoma (topically) 5-Fluorouracil (5-FU) Myelosuppression by 5-FU is ______ Not reversible This drug used to treat AML may lead to leukopenia, thrombocytopenia, megaloblastic anemia? cytarabine This drugs used to treat CML may lead to pulmonary fibrosis and hyperpigmentation? Busulfan ____is an alkylating agent acivated by liver that covalently x-links DNA at guanine N-7, and is used to treat non-hodgkin's lymphoma, breast/ovarian carcinomas cyclophosphamides ____ alkylates DNA after bioactivation and can cross the BBB and treats brain tumors (glioblastoma multiforme) Nitrosoureas (Carmustine, lomustine, semustine, streptozocin) ____acts like an alkylating agent, x-linking via hyrdolysis of Cl and platinum; used to treat testicular, bladder, lung carcinomas Cisplatin This alkylating agent can cause myelosuppression and hemorhagic cystitis cyclophosphamides This combination of drugs is used to treat Hodgkin's and myelomas, sarcomas, and solid tumors (breast, ovary, lung) ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine ____noncovalently intercalates in DNA, creating breaks to decrease replication and transcription Doxorubicin (adriamycin) ____intercalates DNA strands and induces free radical fromation which causes strand breaks Bleomycin, Dactinomycin Which drugs causes cardiotoxicity, alopecia, and myelosuppression? Doxorubicin (adriamycin) Which drug is used to trat oat cell carcinoma of the lung and prostate/testicular carcinoma? Etoposide This combination of drugs is used to treat lymphoma, CLL, Hodgkin's, Wilm's tumor, choriocarcinoma MOPP (Mustargen, Oncovin (Vincristine), Procarbazine (Matulane), Prednisone) Which glucocorticoid may trigger apoptosis and may even work on nondividing cells Prednisone This drug is a G2-phase specific inhibitor of Topisiomerase II, leaving double strand breaks in DNA following DNA replication Etoposide This drug used to treat testicular cancer and lymphomas may cayse pulmonary fibrosis, skin chnages, and myelosuppression Bleomycin, Dactinomycin This drugs used as an immunosuppressant and in lymphomas may cause acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis? Prednisone ____is an estrogen receptor mixed agonist/antagonist that blocks the binding of estrogen to ER+ cells. Tomoxifen/Raloxifene ____is n M-phase-specific alkaloid that binds to tubulin and blocks polymerization of microtubules, preventing spindle formation Vincristine and Vinblastine ____is an M-phase-specific agen that binds to tubulin and hyperstabilizes the polymerized microtubules, so that the mitotic spindle cannot break down Paclitaxel What drugs is used to treat breast cancer, but may increas the risk of endometrial carcinomas and hot flashes Tomoxifen Side-effects of Vinblastine include…. VinBASTine BLASTs Bone Morraow, causing myelosuppression, as well as neurotoxicity and paralutic ileus. Side effects of Paclitaxel include…. Myelosuppression and hypersensitivity Immunosuppressants and Cytokine Therapy pg 336-337 This drug binds to cyclophilins, blocking differentiation and activation of T cells mainly by inhibiting IL2 production cyclosporine This antimetabolite derivative of 6-mercaptopurine interferes with the metabolism and synthesis of nucleic acid, therefore toxic to proliferating lymphocytes azathioprine This potent immunosuppressive drug binds to the FK-binding protein and inhibits secretion of IL2 and other cytokines tacrolimus (FK506) This drug is used to suppress organ rejection after transplantation, but may predispose patient to viral infections and lymphoma cyclosporine Azaothioprine is used to in what setting? Kidney transplants, autoimmune disorders (glomerulonephritis, hemolytic anemia) Recombinant Cytokine- Aldesleukin (interleukin-2) is used for? Renal cell carcinoma, metastatic melanoma Recombinant Cytokine- Erythropoietin (epoetin) is used for? anemia Recombinant Cytokine- Filgrastim is used for? Recovery of Bone Marrow; it is a granulocyte colony stimulating factor Recombinant Cytokine- alpha interferon is used for? Hep B/C, Kaposi's sarcoma, leukemia, malgnant melanoma Recombinant Cytokine- beta interferon is used for? Multiple Sclerosis Recombinant Cytokine- gamma interferon is used for? Chronic Granulomatous disease Recombinant Cytokine- oprelvekin (interleukin2) is used for? Thrombocytopenia Recombinant Cytokine- sargamostim is used for? Recovery of Bone Marrow (it is a granulocyte-macrophage colony stimulating factor) Recombinant Cytokine- thrombopoietin is used for? Thrombocytopenia Toxicology pg 338 What is the antidote for acetaminophen toxicity/overdose N-acetylcysteine What is the antidote for salicylates toxicity/overdose Alkanize urine/dialysis What is the antidote for antichoinesterase toxicity/overdose Atropine, pralidoxime What is the antidote for antimuscarinic/anticholinergic agents toxicity/overdose physostigimine salicylate What is the antidote for Beta-blockers toxicity/overdose glucagon What is the antidote fordigitalis toxicity/overdose Stop digitalis, Normalize K+, lodpcaine, anti-digitialis Fab Fragments, Magnesium What is the antidote for lead toxicity/overdose CaEDTA, dimercaprol, succimer, penicillamine What is the antidote for iron toxicity/overdose Deferoxamine What is the antidote for aresnic/mercury/gold toxicity/overdose Dimercaprol (BAL), succimer What is the antidote for copper, arsenic, gold toxicity/overdose Penicillamine What is the antidote N-acetylcysteine used to treat? Acetaminophen toxicity/overdose What is the antidote for cyanide toxicity/overdose nitrite, hydroxocobalamin, thiosoulfate What is the antidote for methemoglobin toxicity/overdose methylene blue What is the antidote glucagon used to treat? Beta-blocker toxicity/overdose What is the antidote for carbon monoxide toxicity/overdose 100% oxygen, hyperbaric oxygen What is the antidote atropine used to treat? anticholinesterase toxicity/overdose What is the antidote for methanol toxicity/overdose Ethanol, dialusis, fomepizole What is the antidote for opiods toxicity/overdose Nalozone/naltrexone What is the antidote for ethylene glycol toxicity/overdose Ethanol, dialusis, fomepizole What is the antidote for benzodiazepines toxicity/overdose Flumazenil What is the antidote for (TCA) Tricyclic Antidepressants toxicity/overdose NaHCO3 What is the antidote for Heparin toxicity/overdose Protamine What is the antidote Deferoxamine used to treat? Iron toxicity/overdose What is the antidote for warfarin toxicity/overdose vitamin K, fresh frozen plasma What is the antidote Naloxone/naltrexone used to treat? opioid toxicity/overdose What is the antidote for tPA/streptokinase toxicity/overdose aminocaproic acid What is the antidote Physostigmine salicylate used to treat? Antimuscarinic/anticholinergic agents toxicity/overdose What is the antidote Flumazenil used to treat? Benzodiazepine toxicity/overdose What is the antidote Protamine used to treat Heparin toxicity/overdose Children living in old houses might eat the paint chips which could cause ____ Lead Poisoning Signs of Lead poisoning include: Lead Lines on gingivae and epiphyses of Long bones, Encephalopathy and Erythrocyte Basophilic stippling, Abdominal colic and sideroblastic Anemia, Wrist and Foot Drop 1st line of Treatment for Lead Poisoning include Dimercaprol and EDTA Weak acids, such as phenobarbitol, methotreaxate, aspirin, alkanize urine with ____ to increase clearance bicarbonate Weak bases, such as amphetamines, acidify urine with NH4Cl to ____ clearance increase AUTHOR Lakshmi Swamy Drug reactions p. 339 For each drug reaction, give the pharmacological agents responsible. The number of drugs you should list are given in parentheses. You could also quiz yourself in reverse by going down the list of drugs on the right. Pulmonary fibrosis (3) bleomycin, amiodarone, busulfan Hepatitis (2) isoniazid, halothane Focal to massive hepatic necrosis (4) halothane, valproic acid, acetaminophen, amanita phalloides Anaphylaxis (1) penicillin SLE-like syndrome (4). [mnemonic: it's not HIPP to have lupus] hydralazine, INH, procainamide, phenytoin Hemolysis in G6PD-deficient patients (8) sulfonamides, INH, aspirin, ibuprofen, primaquine, nitrofurantoin, pyrimethamine, chloramphenicol Thrombotic complications (1 class) OCPs (e.g. estrogens and progestins) Adrenocortical insufficiency (withdrawal of what class of drugs causes adrenocortical insufficiency?) withdrawal of glucocorticoids causes hypothalamic-pituitary-axis suppression Photosensitivity reactions (3) [mnemonic: SAT for a photo] Sulfonamides, amiodarone, tetracycline Induce P-450 system (6) barbiturates, phenytoin, carbamazepine, rifampin, griseofulvin, quinidine Inhibit P-450 system (6, including one fruit) cimetidine, ketoconazole, grapefruit, erythromycin, INH, sulfonamides Tubulointerstitial nephritis (5) sulfonamides, furosemide, methicillin, rifampin, NSAIDs (except aspirin) Hot flashes (1) Tamoxifen Cutaneous flushing (4) niacin, Ca++ channel blockers, adenosine, vancomycin Cardiac toxicity (2) doxorubicin (adriamycin), daunorubicin Agranulocytosis (3, all start with letter C) clozapine, carbamazepine, colchicine Stevens-Johnson syndrome (3) ethosuximide, sulfonamides, lamotrigine Cinchonism (2) quinidine, quinine Tendonitis, tendon rupture and cartilage damage (kids) (1) fluoroquinolones Disulfiram-like reaction (4) metronidazole, certain cephalosporins, procarbazine, sulfonylureas Otoxicity and nephrotoxicity (3) aminoglycosides, loop diuretics, cisplatin Drug-induced Parkinson's (4) haloperidol, chlorpromazine, resperine, MPTP Torsades de pointes (two subclasses of antiarrhythmics) Class III (sotalol), class IA (quinidine) antiarrhythmics Aplastic anemia (3) chloramphenicol, benzene, NSAIDs Neuro/nephrotoxicity (1) polymyxins Pseudomembranous colitis (2) clindamycin, ampicillin Gynecomastia (5) [mnemonic: Some Drugs Create Awesome Knockers] spironolactone, digitalis, cimetidine, chronic Alcohol use, estrogens, ketoconazole Atropine-like side effects (1) tricyclics Cough (1) ACE inhibitors (losartan --> no cough) Gingival hyperplasia (1) phenytoin Diabetes insipidus (1) lithium Tardive dyskinesia (1) antipsychotics Fanconi's syndrome (1) tetracycline Gray baby syndrome (1) chloramphenicol Extrapyramidal side effects (3) chlorpromazine, thioridazine, haloperidol Osteoporosis (2) corticosteroids, heparin Alcohol toxicity p. 340 Ethylene glycol is converted to ------- ------ by alcohol dehydrogenase. This product can lead to acidosis and nephrotoxicity. oxalic acid. Alcohol dehyrogenase also converts methanol to formaldehyde and formic acid, which can cause severe ----- and damage to the -------. acidosis. retina Ethanol competes with ethylene glycol and methanol (if present) for alcohol dehydrogenase. ADH action on EtOH produces -------. acetaldehyde What symptoms does acetaldehyde cause? nausea, vomiting, headache, hypotension Acetaldehyde itself can be metabolized by acetaldehyde dehydrogenase to ----- -----. acetic acid. Acetaldehyde dehydrogenase is inhibited by what drug? disulfiram. Herbal agents p. 341 Give the clinical uses for the following herbal agents. echinacea common cold ephedra as for ephedrine feverfew migraine ginko intermittent claudication kava chronic anxiety milk thistle viral hepatitis saw palmetto benign prostatic hyperplasia St. John's wort mild to moderate depression dehyroepiandrosterone symptomatic improvement in females with SLE or AIDS Melatonin jet lag, insomnia Give the toxicities for the following herbal agents. echinacea GI distress, dizziness, and headache ephedra CNS and cardiovascular stimulation; arrhythmias, stroke and seizures at high doses. feverfew GI distress, mouth ulcers, antiplatelet actions ginko GI distress, anxiety, insomnia, headache, and antiplatelet actions kava GI distress, sedation, ataxia, hepatotoxicity, phototoxicity, dermatotoxicity milk thistle loose stools saw palmetto GI distress, decreased libido, hypertension St. John's wort GI distress and phototoxicity; serotonin syndrome with SSRIs dehyroepiandrosterone Androgenization (premenopausal women), estrogenic effects (postmenopausal), feminization (young men) Melatonin Sedation, suppresses midcycle LH, hypoprolactinemia Drug name p. 341 For each drug name ending, give the general category of drug it indicates and an example of a drug in that category. -ane inhalational general anesthetic. Halothane -azepam benzodiazepine. Diazepam -azine phenothiazine (neuroleptic, antiemetic). Chlorpromazine -azole antifungal. Ketoconazole -barbital barbiturate. Phenobarbital -caine local anesthetic. Lidocaine -cillin penicillin. Methicillin -cycline antibiotic, protein synthesis inhibitor. Tetracycline -ipramine tricyclic antidepressant. Imipramine -navir protease inhibitor. Saquinavir -olol beta antagonist. Propranolol -operidol butyrophenone (neuroleptic). Haloperidol -oxin cardiac glycoside (inotropic agent). Digoxin -phylline methylxanthine. Theophylline -pril ACE inhibitor. Captopril -terol beta-2 agonist. Albuterol -tidine H2 antagonist. Cimetidine -triptyline tricyclic antidepressant. Amitriptyline -tropin pituitary hormone. Somatotropin -zosin alpha-1 antagonist. Prazosin