USMLE PHARMACOLGY WORKSHEETS Drug mechanism of action side effects ANS Cholinergic agonists DUMBELS Direct acting acetylcholine D iarrhea and Decr BP bethanechol stims bladder and bowel U rination carbachol M iosis pilocarpine miosis and contraction of ciliary mm B ronchoconstriction methacholine E xcitation of skeletal mm nicotine L acrimation S alivation and Sweating Indirect acting edrophonium dx of myasthenia gravis physostigmine tertiary amine - can enter CNS neostigmine quaternary amine – no CNS Cholinergic antagonists opposite of DUMBELS Muscarinic antags atropine scopolamine ipratropium NMJ blockers Non-depolarizing eye and face first, respiratory last bronchoconstrict and hypotension tubocurarine vecuronium atracurium Depolarizing - succinylcholine metab’d by plasma cholinesterase Ganglionic blockers nicotine depolarizing – no clinical uses tachy, vasodilate, mydriasis, ↓ GI Parasympathetic Agonists Synthetic choline esters carbachol no hydrolysis by AChE bethanechol no hydrolysis by AChE methacholine small hydrolysis by AChE

2

Drug mechanism of action side effects Muscarinic agonists muscarine pilocarpine Nicotinic agonists – nicotine Indirect agonists inhib AChE edrophonium short acting, reversible neostigmine medium acting, reversible physostigmine medium acting, reversible pyridostigmine long acting, reversible organophosphates irreversible Antagonists Muscarinic antags atropine scopolamine homotropine ipratropium bromide Nicotinic antags hexamethonium non-depolarizing, ganglia and NMJ D-tubocurarine non-depolarizing, NMJ only succinylcholine depolarizing, NMJ only, short acting decamethonium depolarizing, NMJ only Indirect antagonists hemicholimium blocks vesicular uptake of choline Sympathetic α – Adrenergic receptors Agonists effects of stimulation: NE not used clinically vasoconstriction phenylephrine mydiasis radial mm in eye methoxamine ejaculation metaraminol has both direct and indirect effects stim of pilomotor mm clonidine α2-selective partial agonist guanabenz, guanfacine α2-selective

3

Drug mechanism of action side effects Antagonists ergot alkaloids phentolamine reversible phenoxybenzamine irreversible prazosin α1-selective terazosin α1-selective β receptor agonists β1 selective agonists effects of stim: ↑ HR, ↑CTY, dobutamine ↑ CTY without ↑ heart rate or SVR ↑ AV node condctn, ↑ CO β2 selective agonists asthma effects of stim: albuterol ↑ bronchodilation salmeterol ↑ relaxation of viscera terbutaline metaproterenol β1, β2 nonselective agonists pressor agent isoproterenol Mixed agonists (α and β) α1 Epi > NE >> Iso epi α2 Epi > NE >> Iso ephedrine β1 Iso > Epi = NE mephantermine β2 Iso > Epi >> NE β receptor antagonists β1 selective antagonists anti-HTN metoprolol atenolol esmolol acebutolol β1, β2 nonselective antagonists propranolol nadolol timolol pindolol Adrergic neuron blockers reserpine blocks vesicular uptake of NE guanethidine blocks NE release

4

Drug mechanism of action side effects CNS/Neurologic Antiparkinson drugs that replete dopamine Levdopa prodrug Carbidopa inhib Lev→DA conversion in periphery Entacapone COMT inhib (prolongs DA ½ life) dopamine agonists Bromocriptine D2 agonist – not very effective Apomorphine D2 agonist – very effective Pramipexole D2/D3 Ropinarole D2/D3 ACh neuron inhibitors Trihexyphenidyl helps sialorrhea, not bradykinesia Benzotropine Diphenhydramine Adjuvants Amantadine treats Levdopa side effects Diprenyl allows lower dose of Levdopa Stimulants drugs affecting catechol amphetamine neurons methamphetamine ephedrine methylphenidate (Ritalin) cocaine Alzheimers AChE inhibitors low therapeutic index Donezapil Rivastigmine memantine non-competitive antag of NMDA low therapeutic index other stimulants caffeine theobromine modafinil

5

Drug mechanism of action side effects ETOH naltrexone opioid antag acamprosate glutamate antag disulfiram aldehyde dehydrogenase inhib Anti-epileptics Na channel inactivators phenytoin inactivates rapid firing Na channel arrhythmias fosphenytoin prodrug of phenytoin, less toxic carbamazepine prolongs inactivation of Na diplopia lamotrigine tobrimate valproate liver, GI, no use w/phenobarb Ca channel blockers valproate ethosuxamide GABA potentiators tigapine prevents GABA reuptake phenobarbitol post-synaptic GABA agonist felbamate post-synaptic GABA agonist aplastic anemia Unknown GABApentin Status epilepticus diazepam lorazapam phenytoin Psychiatric Anti-psychotics typical reserpine parkinsonism, tardive dyskinesia chlorpromazine (after prolonged use), sedation, thioridazine anti-cholinergic haloperidol domperidone thiothixine benzotropine trihexyphenidyl

6

Drug mechanism of action side effects atypical clozapine not as many extra-pyramidal olanzapine effects, weight gain risperidone aripiprazole Anxiolytics Anxiety Benzodiazepines GABA inhibs, can not OD dependence alprazolam short acting diazepam intermediate acting lorazapam long acting triazolam 5HT/NE uptake inhibs SSRI SNRI imimpramine venalfixine Buspirone Herbal kava kava + diazepam = coma valerian Insomnia Benzodiazepines Flurazepam Temazepam Non-benzos zolpidem (ambien) Barbituates sedative pentobarbital ½ life – 18-48h phenobarbitol ½ life – 4 days

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Drug mechanism of action side effects Anti-depressants Depression TCA’s low therapeutic index, dry mouth, Tertiary amines inhibit 5HT uptake, muscarinic & dizziness, constipation, tachy, Imipramine α-1 antags orthostatic HTN Amitryptiline Secondary amines inhibit NE uptake, muscarinic & Desipramine α-1 antags Nortryptiline MAOIs MAO-A – NE and DA neurons, Phenalzine non-selective MAOI involved in tyramine metab in gut Tranylcypromide MAO-B – 5HT neurons deprenyl MAO-B but non-selective at dose SSRIs 5 HT uptake inhib Fluoxetine Sertraline Paroxetine Other Trazadone Nefazadone Venalfixine Buproprion NE and DA uptake inhib Mirtazapine Bi-polar Lithium low therapeutic index Valproate Lamotrigine Olanzapine

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Drug mechanism of action side effects Cardiovascular Atherosclerosis Statins Lovastatin HMG Co-A reductase inhib which upregs GI upset, muscle ache, hepatitis Fluvastatin LDL receptors Atorvastatin Pravastatin Simvastatin Bile acid binding resins Cholestyramine prevent reabsorp of bile bloating Colestipol Niacin Nicotinic acid inhibit mobilization or peripheral FFAs flushing Vitamin B3 Fibrates Gemfibrozil enhanced oxidation of FFAs potentiates warfarin Clofibrate Fenofibrate Antithrombosis Anticoagulants heparin stims antithrombin III which binds

thrombin

fondaparinaux sulfate binds to ATIII selective inhib of FX/Xa warfarin (coumadin) vitK analog – competive inhibitor Anti-platelets inhibs of platelet signaling aspirin irreversibly inhib cyclooxygenase clopidigrel irreversibly blocks platelet P2Y12 ADP ticlopidine interferes w/platelet aggegation neutropenia and TTP dipyridamole ↑ platelet cAMP → ↓platelet activation cardiac death glycoprotein IIb/IIIa antags abmixicab eptifibitide tirofiban

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Drug mechanism of action side effects Thrombolytics streptokinase convert plasminogen → plasmin contraindicated in pxs w/strep inf TPA (alteplase & retaplase) urokinase anistrplase Prothrombotics aprotinin inhibs lakikrein-kinin → inhibs

fibrinolysis

Anti-arrhythmics Class I – Na channel Class Ia incr ARP and AP sudden death arrhythmias quinidine procainamide Class Ib – lidocaine raise threshold and prolong RRP pro-arrhythmic (not as bad) Class Ic – flecainide raise threshold and slow conduction sudden death arrythmias Class II – β blockers propanolol contraindicated w/asthma Class III – K channel amiodarone block DRK channels + Class I, II, and IV soltalol block DRK channels + Class II torsades de pointed (ventr tachy) Class IV – Ca channel verapamil diltiazem other adenosine temporary asystole digitalis Cardiac glycosides Digitalis glycosides digoxin digitoxin digoxin immune Fab Bipyridines milnirone select α non-selec β blocker carvidilol

10

Drug mechanism of action side effects β1 agonist dobutamine Anti-hypertensives Central acting clonidine stimulates central α2 guanbenz methyldopa Noradrenergic blockers guanethidine Adrenreceptor antags Beta blockers propranolol pindalol labetolol metoprolol atenolol Alpha blockers prazosin phentolamine Diuretics see below Ca channel blocker see below ACE inhibitors see below ARBs see below Diuretics Osmotic mannitol urea Carbonic anhydrase inhibs acetazolamide block HCO3 reabsorption Loop furosemide block Na/K/2 Cl bumetanide

11

Drug mechanism of action side effects Thiazides HCTZ block Na/Cl metolazone K sparing spironolactone blocks upreg of Na channel amiloride blocks Na channel triamterene block Na channel Vasodilators & antianginal K channel openers minoxidil Ca channel blockers verapamil diltiazem nifedipine nimodapine Nitrodilators nitroglycerin isosorbide dinitrate nitric oxide nitroprusside ACE inhibs captopril enalapril ramipril ARBs losartan cGMP PDE Type 5 inhibs sildenafil Natiuretic factors nesiritide

12

Drug mechanism of action side effects GI Drugs Control of gastric acidity PPIs omeprazole irreversible proton pump inhibs nausea and diarrhea lansoprazole labeprazole pantoprazole esomeprazole H2R antagonists cimetidine inhibs GS protein needed to activate pump p450 inhib, nausea, ↑ prolactin ranitidine famotidine nizatidine Prostaglandin analog misoprostol stims Gi which inhibs proton pump diarrhea, uterine contractions Anti-emetics 5HT3R antagonists odansetron granisetron dolasetron Dopamine R antagonists thenothiazine antag the DA R on the Chemoreceptor TZ metaclopramide CNS effects domperidone No CNS effects Antihistamines cyclizine hydroxyzine promethazine diphenhydramine Anticholinergics scopolamine dronabinol Glucocorticoids & NSAIDs

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Drug mechanism of action side effects Prokinetics Cholinergic agonists carbechol ACh is main NT for GI motility lots of global side effects bethanechol AChE inhibitor neostigmine Dopamine D2R antags metaclopramide dopamine inhibs gastric motility domperidone Serotonin R modulators metaclopramide 5HT4R agonist (stimulatory receptor) cisparide blocks DRKs in heart-arrhythmia tegaserod Somatostatin analog octreotide enhances gastric emptying Motilin R agonist erythromycin Motilin is a potent contractile hormone IBS 5HT4R agonist tegaserod Diarrhea Intraluminal fiber Opiates loperamide anti-secretory and anti-motility dipenoxylate difenoxen Somatostatin analog octreotide cholestyramine binds bile acids can bind and inactivate drugs bismuth antisecretory, -inflammatory, -microbial

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Drug mechanism of action side effects IBD 5 aminosalicylates sulfasalazine COX/lipoox pthwy inhibs mesalamine Immunosuppression 6-mercaptopurine methotrexate inhibs DHFR cyclosporine Monoclonal antibody Inflliximab Monoclonal Ab to TNFα Respiratory Asthma β2 agonists albuterol short acting tachy and tremor salmeterol long acting Corticosteroids beclomethasone all the probs with steroids fluticasone Anticholinergics ipratropium few due to poor systemic absorp Leukotriene inhibs zileuton inhib Arach Acid → Leuko – 5-lipox inhib not for acute zafirlukast LTD4 R antag Methylxanthines theophylline ↑cAMP → bronchodilation seizures and arrythmias cromolyn sodium prophylactic - stabilize mast cells laryngeal edema nedocromil prophylactic - stabilize mast cells bad taste

15

Drug mechanism of action side effects Endocrine Osteoporosis Ca and Vit D supplements ERT SERM raloxifene agonist on bones, antag on breasts tamoxifen Bisphosphonates etidronate long term inhibs of bone resorption pamidronate alendronate risendronate calcitonin decr osteoclast activity anabolic agents teriparatide stims bone formation Insulin and anti-diabetics Biguanides metformin ↓ gluconeogenesis in liver, insulin dep lactic acidosis Thiazolidinediones pioglitazone ↑↑ glucose uptake peripherally via PPARγ edema and weight gain rioglitazone activation, ↓ gluconeo in liver Sulfonylureas and glinides nateglinide insulin secretagogues, stimulate beta cell hypoglycemia repaglinide production of insulin meglitinide glipizide Alpha-glucosidase inhibs acarbose delay absorption of carbs and so moderate flatulence and incr LFTs miglitol post prandial spike Insulin glargine slow absorp and sustained release lispro and aspart fast acting – moderate post prandial spike regular fast acting but give 30 mins before meal NPH long acting but not as long as glargine

16

Drug mechanism of action side effects Hyperlipidemia Statins see above lower LDL Bile acid sequestrants cholestyramine lower LDL colestipol colesevalam Cholesterol absorp inhibs ezetimibe lower LDL plant stanol and sterol esters Niacin see above lower TGs Fibrates see above lower TGs and incr HDL + statin = rhabdomyalisis Omega 3 fatty acids lower TGs Anti-obesity Adrenergic dexamphetamine phentermine Serotonergic sibutramine reuptake inhibitor fenfluramine dexfenfluramine serotonin releasers nutrient absorption blockers orlistat Antibiotics Nucleic acid inhibs sulfamethoxazole bacteriostatic PABA analog kernicterus,p450 inhib,crystalluria trimethoprim bacteriostatic DHFR inhib, can cross BBB nitrofurantoin uncomplicated UTI Fluoroquinolones ciprofloxacin DNA gyrase inhib cartilage dmg ofloxacin

17

Drug mechanism of action side effects β-lactams Penicillins penG inhib bacterial cell wall transpeptidation penV penicillinase resistant β-lactamase producing S. aureus oxacillin nafcillin ampicillin ampicillin + sulbactam amoxicillin amoxicillin + clavulante ticaracillin ticaracillin + clavulante piparcillin piparacillin + tazobactam aztreonam imipenem broad spectrum but not MRSA β-lactamase inhibs sulbactam clavulante tazobactam Cephalosporins 1st generation – cephalexin gram pos 2nd generation – cefuroxime gram neg like HIB, Neisseria, S. pneumo 3rd generation gram neg ceftriaxone cefotaxime ceftazadime vancomycin inhib bacterial cell wall transglycosylation Protein synthesis inhibitors Aminoglycosides gentamicin bactericidal; aerobic; 30s subunit ototoxicity and nephrotoxicity amikacin trobramicin streptamicin

18

Drug mechanism of action side effects Tetracyclines doxycycline 30s, chlamydia, cholera, lyme hepatotox, dep in bones and teeth minocycline Macrolides erythromycin 50s,legionella,mycoplas,chlamdia,anthrax GI irrit, hepatotox, p450 inhib azithromycin does NOT inhib p450 clarithromycin chloamphenicol 50s, serious infections, incl CNS aplastic anemia and p450 inhib clindamycin 50s; anaerobic, S.aureus, PCP psuedomemb colitis, hepatotox Oxazolidinones linezoilid 50s, VRSE, MRSA, PRSP MAO inhib, superinfections Streptogramins dalfopristin 50s, bactericidal when given together, quinupristin VRSE, MRSA, PRSP metronudazole anaerobes TB drugs bactericidal except Ethambutol isoniazid mycolic acid synth inhib; periph neuritis,slow/fast acetyl rifampin Tb DNA dep RNA pol inhib GI, hepatotox, p450 induce ethambutol only dividing mycobacs;for MAC + clarith retrobulbar neuritis,periph neuritis pyrazinamide hepatotox, gout-like sx Anti-fungals Amphoteracin B complex w/sterols results in apoptosis nephro, cardio, and neurotoxic Flucytosine fungal uracil analog; chain termin bone marrw suppr, alopecia, GItox Azole family Imidizole – ketoconazole Triazoles fluconazole CSF itraconazole

19

Drug mechanism of action side effects Anti-parasitics Entamoeba, giardia, trich metronidazole Malaria chloroquine erythrocytic cidal primaquine exoerythrocytic cidal; leukopenia, hemlytic crisis (G6PD mefloquine Trypanosomiasis saramin tx pre-CNS neurotox Worms Round – mebendazole poor GI absorb so intraluminal effect Flat Flukes - praziquantal ↑ Ca++ perm of worm cell membrane Tapeworms niclosamide praziquantal T. solium Anti-virals Influenza amantadine flu A by blocking M2 so no uncoating paranoia, depression neuramidase inhibs prevent cleave of sialic acid-virus no exit zanamivir inhaled can be prob for asthmatics oseltamavir oral Herpes trifluorothymadine thymidine analog, topical acyclovir guanine analog; 100x affinity of viral TK AIDS RT inhib – azidothymadine Protease inhibitor combo lopinavir-ritonavir inhib viral replic Fusion inhib - enfuvirtide blocks HIV attachment to cells

20

Drug mechanism of action side effects Analgesics and Anesthetics Opioids opioid work on three receptors in CNS: Endogenous endorphins µ – analges,euphor,resp depr,miosis,constp enkephalins κ – analges, sedation, dysphoria, miosis dynorphins δ - analgesia Alkaloids morphine µ κ δ codeine heroin Synthetic fentanyl µ methadone µ long ½ life(resp dep after 2-3days) pentazacine agonist κ δ antag µ δ hydrocodone meperidine µ + MAOIs = severe resp depression Antagonists naloxone comp antag for µ κ δ naltrexone comp antag for µ κ δ Chronic pain Non-opioid NSAIDs Opioid Full agonist fentanyl µ hydromorphone µ heroin µ κ δ morphine µ κ δ methadone µ meperidine µ Partial agonist buprenorphine µ oxycodone µ hydrocodone µ codeine µ propoxyphene µ

21

Drug mechanism of action side effects Adjuvant Muscle relaxants cyclobenaprine methocarbamol diazepam baclofen anti-convulsants – see above local anesthetics – see below anti-depressants – see above Local anesthetics Ester linked cocaine metabolized by blood = short ½ life; if arrythmias, euphoria procaine administer w/epi, vasoconstr prevents benzocaine blood from reaching site and incr ½ life tetracaine Amide linked lidocaine metabolized by liver = longer ½ life etidocaine mepvicaine bupivacaine (S)-ropivacaine General anesthetics Inhalational halothane hepatitis, malign hyperthermia enflurane isoflurane desflurane sevoflurane nitrous oxide Injectable/IV propofol ketamine NMDA-R antag, dissociative anesthesia bad dreams barbiturates – thiopental benzodiazapenes midazolam diazepam

22

Drug mechanism of action side effects lorazepam Immunosuppression Prototype mediators thromboxanes prostacyclin (PGI2) prostaglandin E2 leukotrienes histamine IL-1 IL-2 TNF NSAIDs Non-specific aspirin acetaminophen ibuprofen naproxen piroxicam etodolac nabumetone endomethacin COX-2 celecoxib Leukotriene inhibitors zileuton zafirlukast Anti-rheumatics Disease modifying entanercept “decoy” TNF-receptor infliximab anti-TNF monoclonal antibody Slow acting methotrexate gold salts penicillamine hydroxychloroquine

23

Drug mechanism of action side effects Anti-gout indomethacin NSAID colchicine acute attack – inhib MTs allopurinol Inhib xanthine oxidase - uric acid synth uricosuric agents reduce resorbtion of urate from the urine Anti-histamine dimenhydrinate penetrate CNS - sedation diphenhydramine penetrate CNS - sedation loratidine cetirizine fexfenadine Immunosuppressive Cytotoxic methotrexate Inhibit prod of immune system cells azathioprine cyclophosphamide Corticosteroids hydrocortisone interrupt of adren-pituit axis, Na & dexamethasone H2O retention, cushingoid effects, methylprednisone general immunosup, osteoporosis Selective cyclosporine inhibition of clonal expansion of T cells tacrolimus iInhibition of clonal expansion of T cells sirolimus inhibition of clonal expansion of T cells mycophenolate mofetil inhibits nucleoside synthesis in T cells anti-CD3 monoclonal Ab against T cell receptor anti-IL-2 monoclonal Ab against IL-2 daclizumab basiliximab Immunostimulant GM-CSF increase the production of hematopoietic G-CSF cells

24

Drug mechanism of action side effects Chemotherapy Cell cycle nonspecific Alkylating agents cyclophosphamide alkylate DNA, cause DNA cross-linking carcinogenic nitrourea cisplatin renal Antibiotics (except bleo) anthracyclines intercalate DNA, breaks via Topo II cardiac, carcinogenic doxorubicin daunorubicin dactinomycin intercalate DNA, inhib RNA synth Cell cycle specific Antimetabolites Folate analogs - methotrexate inhibs DHFR leucovorin reduces myelosuppres Purine analogs antag HGPRT 6-mercaptopurine 6-thioguanine Pyrimidine analogs 5-fluorouracil inhib thymidilate synthase cytosine arabinoside- ara-C inhib DNA pol Plant deriviatives Vinca alkaloids bind tubulin → depol so no MTs form vinblastine vincristine peripheral neuropathy Podophyllotoxins etoposide inhib Topo II religation tenoposide Taxanes - paclitaxel bind to tubulin →pol & overstabilization Antibiotics bleomycin DNA breaks via free radicals pulmonary Hormones Anti-estrogen - tamoxifen estrogen antag GnRH agonists initially agonists but cause recep downreg leuprolide goserelin Steroids - prednisone

25

Drug mechanism of action side effects Miscellaneous hydroxyurea inhib RNA reductase → inhib DNA synth L-asparaginase uses up asparagine (essntl aa for tumors) hypersensitivity