MD Cardio Pharm 2

mdunk12's version from 2016-04-11 18:55

5a. Acute Coronary Syndrome Drugs MOA

Question Answer
ABC's of acute coronaryA = antiplatelet, anticoagulation, antithrombotics, ACEIs, B = beta-blocker, C = cholesterol management
AspirinIrreversibly binds COX-1/COX-2 and inhibits thromboxane-A synthesis
Ticlopidine/clopidogrel/prasugruelIrreversibly block the ADP receptor (increasing intra-cellular cAMP) -> Prevents GpIIb/IIIa expression on platelets
AbciximabGpIIb-IIIa inhibitors (block platelet surface integrin for fibrinogen -> prevents aggregation)
Reteplase/Tenecteplaserecombinant rPA and TNK-tPA -> do not require continuous infusion like Alteplase (can be given as a bolus injection) -> more predictable response
StreptokinaseForms a complex with plasminogen, facilitating its conversion to plasmin (not widely used because of allergic reactions and antibody production)
UrokinaseRenal enzyme that directly converts plasminogen to plasmin
tPAReleased by endothelial cells in response to vasoocclusive crisis (Alteplase is tPA -- somewhat outdated)
DabigitranOral Direct thrombin inhibitor (similar effect as "rudins")
Leprudin/BivalirudinIV direct thrombin inhibitor (blocks thrombin active site) -> indicated for use in pts with HIT (effectively has the same action as heparin, but without the antigenicity)
TicagrelorReversible ADP receptor inhibitor
AlteplasetPA -> converts plasminogen to plasmin -> degrades fibrin in thrombi (requires continuous infusion)
Heparincomplexes with Antithrombin III -> irreversible inactivates thrombin and factor Xa
Heparin subtypesUFH -> least control over dose/most off-target protein binding; LMWH (enoxaparin, daleteparin, tinzaparin) -> more predictable dose response/less antigneic/less responsive to protamine reversal; Fondiparinux -- similar to LMWH
Reversal of HeparinProtamine sulfate -- highly basic molecule that inhibits the highly acidic molecules of heparin --> less effective against LMWH/Fondiparinux
tinzaparin, enoxaparin, daleteparinLMWH

5b. Acute Coronary Drugs Pharmacokinetics/ADR

Question Answer
When is thrombolysis indicated in acute coronary syndromesWhen PCI is either contraindicated or can't be done within 90 minutes
Unfractionated Heparin ADRBleeding is the most common risk; Heparin induced thrombocytopenia (IgG against PF4 -> causes BOTH thrombosis and thrombocytopenia), Osteoporosis with chronic use
Treatment for heparin toxicityProtamine sulfate (basic drug inactivates acidic heparin) -> not as effective for LMWH and fondaparinux
Heparin monitoringaPTT -> LMWH do not require monitoring
Bivalirudin, Leprudin, Dabigatran useanticoagulation in HIT patients
Bivalirudin, Leprudin, Dabigatran ADRBleeding without a specific reversal agent; Anaphylaxis in "Rudins" -- antigenic
Prasugrel, Ticagrelor, Ticlopidine, Clopidogrel ADRTTP sometimes, but rarely seen; Ticlopidine can cause neutropenia (older drug, more problematic) manifesting as fevers and oral ulcers
Tirofiban, Eptifibatide, AbciximabBleeding, Thrombocytopenia with prolonged use
Use of GPIIa/IIIb inhibitorUA for prevention of progression to acute MI; Post PCI to prevent thrombosis/stenosis of lumen
Streptokinaseanaphylaxis and inactivating antibody production limit its use
Tenecteplase, Reteplase, AlteplaseBleeding, particularly cerebral hemorrhage
Reversal of thrombolytic toxicityAminocaproic acid prevents the conversion of Plasminogen to Plasmin -> can also administer FFP or cryoprecip.
Contraindications of fibrinolytic therapyAny active bleeding, history of intracranial bleeding or severe hypertension
Aspirin ADRPeptic ulcer/tinnitus; Chronic use can have serious ADR -- acute renal failure/interstital nephritis, Intestinal bleeding; Reye syndrome in children; Salicylate reaction (Resp. alkalosis/Met. acidosis

6a. Arrhythmia drug mechanisms

Question Answer
Mnemonic for remembering the type 1 drugsDouble Quarter Pounder, Lettuce Mayo Tomato, More Fries Please
(Disopyramide, Qunidine, Procainamide; Lidocaine, Mexiletine, Tocainide; Moricizine, Flecainide, Propafenone)
General mechanisms of the 4 types of anti-arrhythmicsType 1 (Na channel blockers), Type 2 (beta-blockers), Type 3 (Potassium channel blockers), Type 4 (Calcium channel blockers)
Type 1a drugs MOASlow phase 0 depolarization (greater affinity for open over inactivated channels)
Type 1b drugs MOAShortens phase 3 repolarization (greater affinity for inactivated channels over open ones)
Type 1c drugs MOAMarkedly slows phase 0 depolarization (greater affinity for open over inactivated channels)
Type 2 drugs MOABeta-blockers, which antagonize catecholamine effects at AV node (lengthen phase 4 depolarization)
Type 3 drugs MOAPotassium channel blockers --> slows the phase 3 potassium-induced repolarization (phase 0 unaffected)
Type 4 drugs (general MOA)Non-DHP Calcium channel blockers, which slow phase 4 repolarization (Diltiazem, Verapamil)
Digoxin MOAInhibits Na/K ATPase (competes with K for binding) and interferes with the Na/Cl exchanger (which uses Na to remove Ca, so intracellular Ca increases)
Digoxin effect in HFStrengthens contractility and lengthens the phase 4 --> phase 0 transition
Digoxin parasympathetic effectIncreases vagal activity (which further slows heart rate) --> used for rate control in Afib
Adenosine MOAActivates Gi receptors in conducting cells --> K-channel efflux --> hyperpolarization --> slow conduction

6b. Arrhythmia drug pharmacokinetics and ADRs

Question Answer
Can cause myocardial depression and have anticholinergic side effectsDisopyramide
Substrate of and inhibitor of P450 enzymesQuinidine
Cinchonism (tinnitus/ringing in ears, blurred vision, headache, nausea, delirium, psychosis) and anticholinerigc effectsQuinidine
Drug-induced lupus (it is acetylated) and hypotension if infused too rapidlyProcainamide
Turns unidirectional block into "no block"Lidocaine
Blocks fast-Na channels selective in diseased/ischemic tissueLidocaine
Penetrates the CNS (can be used as an anesthetic)Lidocaine
Agranulocytosis, thrombocytopenia, pulmonary fibrosisTocainide
Blocks Na channels and does NOT change the refractory periodType 1c anti-arrhythmics
Visual disturbancesFlecainide
Crosses blood-brain barrier, completely metabolized by P450s, and can cause dysgeusia (metallic taste/taste distortion)Propafenone
Situations in which using a beta-blocker might be appropriateSituations involving increased sympathetic tone (pheochromocytoma, anxiety, post-operative stress, exercise, anesthesia)
Has iodine in it and can interfere with thyroid functionAmiodarone
Long half-life, metabolized by P450s, and inhibits P450sAmiodarone
Pneumonitis, corneal deposits, optic neuritis, and numerous other neurologic problemsAmiodarone
Must constantly check vision, cardiac function, thyroid, pulmonary function tests, and liver function testsAmiodarone
Bradycardia and hypotensionCCBs (verpamail, diltiazem)
Highly protein boundDigoxin
Eubacteria can inactivate the drugDigoxin
Hypokalemia can make the use of this drug problematicDigoxin
Beware diuretics, quinidine, verapamil/diltiazem/amiodarone/propafenone when using this drugDigoxin
Prolongs QT, causes visual disturbances (green/yellow halos, fuzzy shadows), and can cause confusionDigoxin
Treat its toxicity by stopping, giving potassium, discontinuing drugs that interfere with its metabolismDigoxin
Antibody that can be used to reverse digoxin toxicityDigibind
Interacts with methylxanthines and interacts with dipyridamoleAdenosine
Bronchospasm, flushing, headache, sweating, chest pain, and hypotensionAdenosine

7a Heart Failure Drugs MOA/use

Question Answer
Digoxin MOAdirectly inhibits Na+/K+ ATPase on myocytes --> indirect inhibition of Na+/Ca2+ exchanger --> increased Ca2+ in myocytes --> positive ionotropy ALSO stimulates vagus nerve --> cholinergic effects
Digoxin use in HFacute use in systolic dysfunction states --> DOES NOT prolong life in HF patients
Digoxin use in AFIBparasympathetic effects (action on vagus nerve0 --> prolongation of PR interval --> increased nodal refractory period --> rate/rhythm control in AFIB

7b Heart Failure ADR/pharmacokinetics

Question Answer
Loop Diuretics ADROtotoxicity is celebrated ADR, Hypovolemia, Hypokalemia, Hyperuricemia (similar mechanism as other diuretics)
drugs that increase DigoxinQuinidine (most celebrated), Verapamil, Amiodarone (both block P-glycoprotein)
Antidote for massive Digoxin toxDigibind (MAB against digoxin)
Minor Digoxin antidotesNormalization of K+ (give K+ supplement), Magnesium, Anti-arrhythmic drugs (if increased automaticity present)