Sketchy Pharm Notes PDF

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Sketchy Pharmacology Contents Sketchy Pharmacology..........................................................................................................................................................1 Autonomic Pharmacology.....................................................................................................................................................5 1. Parasympathetics.......................................................................................................................................................... 5 2. Sympathetics.................................................................................................................................................................5 1.1 – “I’d Like to Buy the World an Acetyl-Cola”: Cholinomimetics 5 1.2 – “Stigmata Gravis”: Cholinesterase inhibitors (neostigmine, pyridostigmine, edrophonium, physostigmine, organophosphates, galantamine, rivastigmine, donepezil) 6 2.1 – “Atropine in Wonderland”: Muscarinic Antagonists (atropine, ipratropium, tiotropium, oxybutynin, tolterodine, scopolamine, benztropine, trihexyphenidyl) 8 2.1 – “One Epic Summer Band Camp”: Direct Sympathomimetics (norepinephrine, phenylephrine, epinephrine, dobutamine, isoproterenol) 9 2.2 – “Catecholamine Catch & Release”: Indirect sympathomimetics (cocaine, ephedrine, amphetamine, methylphenidate, modafinil, atomoxetine) 12 2.3 – “The Phantom of the Alpha”: α-adrenergic drugs (α 2 agonists: clonidine, α-methyldopa tizanidine; α antagonists: phentolamine, phenoxybenzamine, prazosin, mirtazapine) 13 2.4 – “Brahms’s LOL Lullaby”: β blockers 13 Circulatory (CV & Renal)......................................................................................................................................................15 1.

Heart Failure............................................................................................................................................................15

2.

Diuretics..................................................................................................................................................................15

3.

Anti-hypertensives...................................................................................................................................................15

4.

Antiarrhythmics.......................................................................................................................................................15

1.1 – “Pretty in Yellow”: Digoxin, milrinone, nesiritide 15 1.2 – “The House Always Wins”: ACE-inhibitors, ARBs, aliskiren 17 2.1 – “Pro Cart Track”: Acetazolamide, mannitol 19 2.2 – “Loop-de-loop of Henle”: Loop Diuretics (furosemide, ethacrynic acid) 20 2.3 – “Distal Convoluted Tube Slide”: Thiazide diuretics 21 2.4 – “Salty Mineral Food Court”: Potassium Sparing Diuretics (amiloride, triamterene, eplerenone, spironolactone) 22 3.1 – “We All Scream for Calci-YUM!” Calcium Channel Blockers 24 3.2 – “High Tension on the High Seas”: Primary HTN & Hypertensive crisis 26 4.1 – “Soloist at the Heartbreak Hotel”: Class I (A, B, C) Antiarrhythmics – Na-channel blockers 27 4.2 – “β Brass Quartet”: Class II Antiarrhythmics - β 29 4.3 – “Tres Amigos”: Class III Antiarrhythmics – K+ channel blockers 30 4.4 – “Calci-YUM quartet”: Class IV antiarrhythmics 31 4.5 – “DJ Foxglove Discotheque”: Class V antiarrhythmics (basically everything else) 32 Blood & Inflammation.........................................................................................................................................................33 1

Anticoagulants and thrombolytics...........................................................................................................................33

2

Dyslipidemia............................................................................................................................................................33

3

Anti-inflammatory drugs.........................................................................................................................................33 1.1

– “Heparin Season”: Heparin & direct Factor X inhibitors

33

2 1.2 – “Warfarin, what is it good for?” 35 1.3 – “Bad News Platelets”: Antiplatelet Agents 36 1.4 – “Warning: Bleeding Hazard”. Thrombolytics 38 2.1 – “Statin Steampunks”: Statins 39 2.2 – “Twenty Thousand Lipids Under the Sea”: Cholestyramine, ezetimibe 41 2.3 – “Loch Niacin Monster”: Fibrates & Niacin 41 3.1 – “NSAIDs in the outfield” 43 3.2 – “Confessions of a knit-wit”: Gout drugs (allopurinol, febuxostat, probenecid, pegloticase) 46 Smooth Muscle...................................................................................................................................................................48 1. Vasoactive drugs..........................................................................................................................................................48 2. Allergy & Pulmonary drugs..........................................................................................................................................48 1.1 – “The Ballad of Johnny Nitro”: Nitrates 48 1.2 – “Pounding at the Sumo Festival”: Triptans & migraines 50 1.3 – “Pro-Slugger Sporting Goods”: Prostaglandins, prostacyclin, bosentan, PDE-5 inhibitors 51 2.1 – “A Midsummer Night’s Diphenhydramine”: Antihistamines 53 2.2 – “Fant-asthmic Parade”: Asthma treatment (β-2 selective agonists, leukotriene inhibitors, methylxanthines, cromolyn, sulfate omalizumab) 54 GI & Endocrine.................................................................................................................................................................... 56 1. Gastrointestinal...........................................................................................................................................................56 2. Diabetes...................................................................................................................................................................... 56 3. Thyroid, parathyroid, & adrenals.................................................................................................................................56 4. Hypothalamic & Pituitary............................................................................................................................................56 1.1 – “Stadium Vomitorium”: Anti-emetics – Ondansetron, metoclopramide, H1 receptor antagonists, scopolamine, aprepitant 56 1.2 – “Gastroesophageal Refund”: Acid control therapy with H2 receptor blockers & PPIs 58 1.3 – “Relaxatives”: Laxative agents (lactulose, magnesium, polyethylene glycol, docusate, Senna, psyllium, loperamide, diphenoxylate) & antidiarrheals 60 2.1 – “Langerhansel & Gretel”: Insulin, sulfonylureas, meglitinides, GLP-1 agonists, DPP-4 inhibitors 61 2.2 – “Rosiglitazones are Red, Pioglitazones are Blue…”: Metformin, Thiazolidinediones, Pramlintide, SGLT2 inhibitors 63 3.1 – “Iodine is Forever”: Propylthiouracil, methimazole, levothyroxine 65 3.2 – “The Natural h/o Osteoporosis”: Bisphosphonate, raloxifene, calcitonin, denosumab 67 3.3 - "PthD in Paleontology": Teriparatide, Vitamin D, Cinacalcet, Sevelamer 68 3.4 – “The Court of Sone Henge”: Glucocorticoids 70 4.1 - "JAK Stat and the Beanstalk": Growth Hormone, Mecasermin, Octreotide, Pegvisomant 71 4.2 - "Water Hazard": Posterior pituitary regulation (ADH, DDAVP, ADH Receptor Antagonists) 72 Neuro & psych Drugs...........................................................................................................................................................73 1.

Sedatives & hypnotics..............................................................................................................................................73

2.

Anesthetics & analgesics.........................................................................................................................................73

3.

Antidepressants & anxiolytics..................................................................................................................................73

4.

Mood stabilizers; antiepileptics...............................................................................................................................73

5.

Antipsychotics, Parkinson’s disease.........................................................................................................................73 1.1

– “L’eggo my Benzo!” Benzodiazepines, flumazenil

73

3 1.2 – “Catching some Zs”: Non-benzo hypnotics, melatonin, ramelteon 75 1.3 – “Barber Shop”: Barbiturates 76 2.1 – “You’re getting sleepy…” IV anesthetics (Propofol, etomidate, ketamine) 77 2.2 – “Laughing gas”: inhaled anesthetics, dantrolene 78 2.3 – “Utopia resort”: Opiates, naloxone, naltrexone 79 3.1 – “Serotonin sitcom”: SSRIs, SNRIs, cyproheptadine 81 3.2 – “I want to ride my tricycle”: Tricyclic antidepressants 83 3.3 – “Of Mice & MAOIs” 84 3.4 – “March Sadness”: Atypical antidepressants (Bupropion, mirtazapine, trazadone) 85 4.1 – “Ski Mania”: Lithium 86 4.2 – “Seize the land”: Broad spectrum anti-epileptics (valproate, topiramate, lamotrigine, levetiracetam) 87 4.3 – “Seize the night”: Narrow spectrum anti-epileptics (Carbamazepine, phenytoin, gabapentin, tiagabine, vigabatrin) 89 4.4 – “Seize the daydream”: Ethosuximide 91 5.1 – “The Typical Impressionist”: First generation antipsychotics (haloperidol, trifluoperazine, fluphenazine, chlorpromazine, thioridazine) 92 5.2 – “The Atypical surrealist”: Second generation antipsychotics (olanzapine, quetiapine, aripiprazole, ziprasidone, risperidone, clozapine) 94 5.3 – “Money for Old Rope”: Parkinson management (Levodopa, carbidopa, entacapone, tolcapone, selegiline, ropinirole, pramipexole, amantadine) 96 Antimicrobials.....................................................................................................................................................................98 1. Cell wall & membrane active antibiotics (β-lactams, vancomycin, daptomycin).........................................................98 2. Inhibitors of bacterial protein synthesis......................................................................................................................98 3. Antimycobacterial........................................................................................................................................................98 4. Other antibacterials.....................................................................................................................................................98 5. Antifungals..................................................................................................................................................................98 6. Antivirals: HIV..............................................................................................................................................................98 7. Antivirals: Hepatitis.....................................................................................................................................................98 8. Antivirals: others.........................................................................................................................................................98 1.1 – “Princess Ellen’s New Hope”: Penicillins 98 1.2 – “The Staphylococci Strike Back”: Nafcillin, oxacillin, dicloxacillin 100 1.3 – “Amped up at the Cantina”: Extended spectrum penicillins (Ampicillin, amoxicillin, piperacillin, ticarcillin) & βlactamase inhibitors (clavulanate, tazobactam, sulbactam) 101 1.4 – “Revenge of the Ceph”: Cephalosporins 103 1.5 – “The coverage is strong with this one”: monobactams & carbapenems 105 1.6 – “MRSA… why did it have to be MRSA?”: Vancomycin 106 1.7 – “Let my chickens go”: Daptomycin 107 2.1 – “Le Tour de Cyclines”: Tetracyclines 108 2.2 – “The Crow”: Macrolide antibiotics 109 2.3 – “Keeping it Clean at the Anaerobic Gym”: Clindamycin! 110 2.4 – “A Splash of Gray”: Chloramphenicol 111 2.5 – “Do Not Cross”: Linezolid 112 2.6 – “Feudal assassins”: aminoglycosides 113 3.1 – “The Magnificent Four” 114

4 3.2 – “For a Few Mycobacteria more”: Rifampin, rifabutin, ethambutol, clofazimine 115 4.2 – “Trick or Treat, Smell my Drugs”: Sulfa drugs (TMP/SMX, pyrimethamine/sulfadiazine) 116 4.2 – “A Nordic Spring”: Fluoroquinolones 117 4.3 – “Murder on the Metro Express” 118 5.1 – “Bio 101 meets Music 101”: amphotericin, flucytosine, nystatin 119 5.2 – “We’re not in Candida Anymore”: azole antifungals 120 5.3 – “There’s no place like Canada”: Griseofulvin, terbinafine, echinocandins 121 6.1 – “Le Morte d’HIV”: NRTIs (abacavir, diadnosine, emtricitabine, lamivudine, stavudine, tenofovir, zidovudine) 122 6.2 – “The Council of Elfavir”: NNRTIs (Nevirapine, efavirenz, delavirdine) 123 6.3 – “Lady Guinevere and the Sword in the Stone”: Protease inhibitors 124 6.4 – “How HIV was thwarted at the Gates of Camelot”: Entry inhibitors, fusion inhibitors, integrase inhibitors 125 7.1 – “Insert Cytocoin to Continue”: Interferon α, IFN-β, IFN-γ 126 7.2 – “Dr Liver-stone, I presume?”: Hep-C treatment (Ribavirin, sofosbuvir, simeprevir) 127 8.1 – “You are Now Free to move about the Ganglia”: Acyclovir, valacyclovir, famciclovir, cidofovir, foscarnet 128 8.2 – “Clean up on Aisle HHV-5”: CMV treatment (Ganciclovir, valganciclovir, cidofovir, foscarnet, probenecid) 129 Antineoplastic Drugs.........................................................................................................................................................130 1. Antimetabolites.........................................................................................................................................................130 2. DNA & Cellular division..............................................................................................................................................130 3. Kinase inhibitors, monoclonal antibodies..................................................................................................................130 1.1 – “Imitation folate”: methotrexate, leucovorin, 5-Fluorouracil, hydroxyurea 130 1.2 – “Hunchback of Notre DNA”: Azathioprine, 6-MP, mycophenolate mofetil 132 1.3 – “Neolithic antineoplastics”: cladribine, cytarabine, gemcitabine 133 2.1 – “Alkylating Odyssey”: Cyclophosphamide, Ifosfamide, Busulfan, Nitrosoureas 134 2.2 – “Breakfast at Cisplatin’s”: Cisplatin, carboplatin, amifostine 135 2.3 – “Doxorubicin’s Locker”: Bleomycin, anthracyclines, doxorubicin 136 2.4 – “Untangled”: Topoisomerase inhibitors 137 2.5 – “Me taxane, You Christine”: Microtubule inhibitors 138 3.1 – “Revolutionary Kinase inhibitors”: imatinib, erlotinib, sorafenib, sunitinib, vemurafenib139 3.2 – “The MAB who would be king”: Rituximab, cetuximab, bevacizumab, alemtuzumab, trastuzumab

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Autonomic Pharmacology 1. Parasympathetics 2. Sympathetics 1.1 – “I’d Like to Cholinomimetics

Buy

the

World

an

Acetyl-Cola”:

 acetylcholine (ACh) is the primary signal molecule of parasympathetic nervous system (PNS). Cholinomimetic agents mimic effects of ACh by acting as ACh-receptor agonists or directly modifying ACh (Acetyl-cola mime = ACh mimetic). None of the cholinomimetics are especially specific, so when using clinically, monitor for negative effects.  There are two types of ACh receptors: o Nicotinic receptors (nAChR) (smoker) are ion channels (smoker has his eye on tv channel in storefront). Found in ANS ganglia (electric transformers connected wire-to-wire, like ganglia), NMJ endplate (outlet plate), & adrenal glands (beanie hat)  ANS nerve typically synapse onto a ganglion before reaching target organs. The adrenal glands are an exception to this. o Muscarinic receptors (mAChR) (motorcycle parking spots) are found generally in autonomic effector tissues (heart, SM, some tissues, but not ANS ganglia). All are GPCRs (QIQ market for M1-M2-M3 inducers). In general, Muscarinic agents increase glandular secretion & smooth muscle activity.  M1: Gq → IP3-DAG cascade (3 dogs) →↑intracellular Ca (dog has bone). Found in CNS & enteric nervous system (brain helmet)  M2: Gi → ↓ intracellular cAMP (a rolled-up tent & packs with ↓↓arrows). Found in cardiac atria, SA & AV nodes (jacket with nodal jewels) →↓atrial contraction, ↓sinoatrial HR, ↓AV conduction velocity. Note that cardiac ventricles are controlled primarily by SNS, not PNS (cardiac jacket doesn’t show ventricles)  M3: Gq → IP3-DAG cascade (3 dogs). Found in glands, including bladder & eye, & smooth muscles (SM) (glandular sponge & muscle-like paint job of 3rd biker). In healthy vasculature, IV M3 agonists stimulate NO release → ↑cGMP release →→ vasodilation; with atherosclerosis NO interacts directly with mAChR → vasoconstriction. Cholinomimetic drugs  Bethanechol (Beth the construction worker). Primarily muscarinic. Indications: o Used in neurogenic ileus, non-obstructive GI dysmotility, & congenital megacolon (cement coming from colon spout), d/t stimulation of GI secretion & motor activity  contraindicated in obstructive processes (“DO Not Obstruct” sign). o Used to treat urinary retention from non-obstructive urinary retention, e.g. post-operatively or spinal injury (bladdershaped hose)  Pilocarpine (pile of carp). Primarily muscarinic. Indications: o Used to treat dry mouth, e.g. from Sjogren’s, nerve damage, prescription adverse effects d/t ↑salivary excretion (seawater around carp looks like drool) o Glaucoma. Stimulation of mAChR reduces IOP by contraction of ciliary body → relaxation of zonula fibers → outflow of aqueous humor (SM crane with zonula-like net fibers). Ciliary contraction also results in lens accommodation (round glass floats on top of net) o Activations sphincter pupillary muscle → pupillary constriction → miosis (dock worker with hoodie cinched all the way up – looks like miotic eyeball). Used in acute closed angle glaucoma  Carbachol (person on upper story with drawn hoodie). Nicotinic & muscarinic activity (dude is standing above smoker & looking at cyclists) o Pupillary constriction, used in acute angle closure glaucoma  Methacholine o Contracts bronchiolar SM. Used in pharmacological asthma challenge (marathon challenge = methacholine challenge). Will exacerbate existing obstructive pulmonary processes, such as asthma & COPD (wheezing runner in back)  Varenicline. Nicotinic partial agonists. (1-800-VERY-CLEAN smoking cessation) o Used for smoking cessation  Common adverse effects o COPD, asthma exacerbation o Peptic ulcer exacerbation

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1.2 – “Stigmata Gravis”: Cholinesterase inhibitors (neostigmine, pyridostigmine, edrophonium, physostigmine, organophosphates, galantamine, rivastigmine, donepezil)  Acetylcholinesterase (AChE) hydrolyzes ACh in post synaptic cleft, decreasing its availability for signaling (dumpster full of acetyl-cola bottles; anti-establishment graffiti).  Indirect cholinomimetics reversibly or irreversibly bind AChE, blocking ACh degradation →↑ availability for signaling in synaptic cleft (“Acetyl-Cola” billboard visible indistinctly, or indirectly, in the distance; acetyl-cola bottles spill out of knocked over dumpster, suggesting ↑ACh availability in synaptic cleft). Most end in -stigma drug suffix (stigma graffiti). Effect is similar to that of cholinomimetics in eye, GI tract, respiratory tract, & urinary tract. Specifically: o Enhances effects of ACh at NMJ endplate by acting on nicotinic ACh receptors (brick wall looks like skeletal muscle, with electrical outlet). Results in increased contraction strength, used in treatment of myasthenia gravis (Gravis graffiti with a grave marker).  Myasthenia gravis is an autoimmune disorder with production of antibodies against NMJ nicotinic receptors. Presents with progressive p...