Cardiovascular Flashcards
Calcium Channel Blockers
Nifedipine, amlodipine, verapamil, diltiazem
(verapamil, diltiazem = non-dihydropyridines)
MECHANISM: Block voltage-dependent L-type Ca channels of cardiac and smooth muscle, reducing muscle contractility
Vascular smooth muscle (DHP): amlodpinie=nifedipine>diltiazem>verapamil
Heart (nonDHP): verapamil>diltiazem>amlodipine=nifedipine (“verapamil=ventricle”)
CLINICAL USE: HTN, angina, arrhythmias (not nifedipine), Prinzmetal’s angina, Raynaud’s.
TOXICITY: Cardiac depression (nonDHP’s), AV block, peripheral edema (common), flushing, dizziness, and constipation.
Hydralazine
Hydralazine and Minosidil
Direct arteriolar vasodilators
MECHANISM: Increase cGMP –> smooth muscle relaxation. Vasodilates arterioles>veins; afterload reduction.
CLINICAL USE: Severe hypertension, CHF. First-line therapy for hypertension in pregnancy, with methyldopa (alpha-agonist, dec catecholamine release)
Frequently coadministered with a Beta-Blocker to prevent reflex tachycardia.
TOXICITY: Compensatory tachycardia (contraindicated in angina/CAD), fluid retention, nausea, headache, angina. Lupus-like syndrome.
Malignant hypertension treatment (List 5 drugs)
Nitroprusside, nicardipine, clevidipine, labetalol, fenoldopam.
Nitroprusside
Malignant hypertension treatment
Short acting;increases cGMP via direct release of NO (and CN-). Can cause cyanide toxicity. (give amyl nitrate).
Balanced arterial/venous vasoodilator; decreases both preload and afterload –> Stroke volume unchanged, deliver same CO at a lower LVEDP.
Continuous in an IV.
Fenoldopam
Malignant hypertension treatment
Dopamine D1 receptor agonist (inc cAMP) - coronary, peripheral, renal, and splanchnic vasodilation. Decreased BP and increased natriuresis.
Diazoxide
Malignant hypertension treatment
K+ channel activator in smooth muscle –> relaxation and hyperpolarization. Blocks VG Ca2+ channels.
Nitroglycerine
MECHANISM: Vasodilate by releasing nitric oxide in smooth muscle, causing inc in cGMP and smooth muscle relaxation. (Do not use with sildenafil, causes a very large increase in cGMP).
Dilate veins >> arteries. Decreases preload (dec venous return due to venodilation)
CLINICAL USE: Angina, pulmonary edema
TOXICITY: Reflex tachycardia, hypotension, flushing, headache, “Monday disease” in industrial exposure: development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend results in tachycardia, dizziness, and headache upon reexposure.
NOTE: nitrate-free interval at night prevents tolerance.
Minoxidil
Contains nitric oxide moiety –> vasodilator and opens K+ channels. Used as an antihypertensive and for androgenic alopecia.
Ergonovine
Ergot alkaloid that constricts vascular smooth muscle (alpha-antagonist and 5-HT agonist), used to diagnose Prinzmetal’s angina.
In pts with hypercontractile coronary artery segments, low doses induces coronary spasm, chest pain, and ST-segment elevation.
Bepridil
Ca2+ channel blocker used for anti-angina only (second line)
NOT FOR HTN
HMG-CoA reductase inhibitors
Lovastatin, pravastatin, simvastatin (greatest risk of myopathy), atorvastin, rosuvastatin
First Line Lipid-lowering agents
Statins metabolized by CYP450 except pravastatin. *Beware P450 inhibitors (i.e. macrolides) may inc heptotoxicity and rhabdomyolysis.
Effect on LDL: Decrease by 20-50% due to inc LDL-R expression on hepatocytes secondary to decreased de novo cholesterol synthesis.
Effect on HDL: Inc 2-15%
Effect on triglycerides: Decrease
MECHANISM: Inhibit conversion of HMG-CoA to mevalonate (rate limiting step in cholesterol synthesis)
TOXICITIES: Hepatotoxicity (Inc LFT’s, discontinue if >3x nl. baseline). Rhabdomyolysis - especially when used with fibrates or niacin. Fibrates inc. the concentration of statins.
Niacin
Niacin - Vitamin B3
(aka nicotinic acid)
Effect on LDL: Decrease
Effect on HDL: Increase 25-35%, most effect agent for increasing HDL
Effect on triglycerides: Decrease (second line)
MECHANISM: Inhibits lipolysis in adipose tissue; reduces hepatic VLDL secretion into circulation, Inc HDL by reucing clearance.
TOXICITIES: Red, flushed face (Mediated by prostaglandins) that is decreased by ASA or long-term use.
Hyperglycemia (insulin resistance) –> acanthosis nigricans
Hyperuricemia (exacerbates gout)
Hepatotoxicity at high doses
Increased Vasodilation (decrease HTN meds if pt is taking any)
Bile Acid Resins
Cholestyramine, colestipol, colesevelam
Effect on LDL: Decrease Alot: Liver takes up Cholesterol to make new bile acids (GOOD)
Effect on HDL: Slightly increased
Effect on triglycerides: Slightly increased - due to inc VLDL and inc TG synthesis in liver (BAD) –> Hypertriglyceridemia
MECHANISM: Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more
Toxicities: Patients hate it; tastes bad, causes GI discomfort (constipation and bloating - avoid in pts with diverticulosis), decreased absorption of fat-soluble viatmins, decreased warfarin and digoxin absorption, Cholesterol gallstones due to dec BA’s
Cholesterol Absorption blockers
Cholesterol Absorption blockers - Ezetimibe
Effect on LDL: Decreases (second line)
Effect on HDL: No Change
Effect on triglycerides: No Change
MECHANISM: Prevents cholesterol absortion at small intestine border. Synergistic with Statins
TOXICITIES: Rare inc LFTs, diarrhea.
Use as monotherapy in pts who cannot tolerate statin toxicity/myopathy
Fibrates
Fibrates: Gemfibrozil, clofibrate, bezafibrate, fenofibrate
Effect on LDL: Decreased
Effect on HDL: Increased (10-20%)
Effect on triglycerides: Decreased ALOT; Best agent for dec TG’s (First line)
MECHANISM: Increase LPL by activating PPAR-alpha binding, which increases lipoprotein lipase activity and decreases hepatic VLDL secretion –> TG clearance
TOXICITIES: Myositis (especially fenofibrate), hepatotoxicity (inc statin concentration, inc LFTs), cholesterol gallstones via inc cholesterol syntehsis, dec 7alpha-hydroxylase (BA synthesis)
Lipid Lowering Agents - Summary of Toxicities
BA Resins and Fibrates = increased risk of cholesterol gallstones
Statins and Fibrates = increased risk of hepatotoxicity and myopathy
Statins and Niacin = Increased Risk of hepatotoxicity
Cardiac glycosides
Cardiac glycosides - Digoxin
75% bioavailability, 20-40% protein bound, T1/2 = 40 hours, urinary excretion
MECHANISM: Directi nhibition of Na+/K+/ATPase leads to indirect inhibition of Na+/Ca2+ exchanger.
Increased Ca concentration –> Positive inotropy. Stimulates vagous nerve –> Dec HR.
CLINICAL USE: CHF (increases contractility); atrial fibrilation (Decreased conduction at AV node by inc vagal output to AV node and conduction system, and depression of SA node)
TOXICITY: Cholinergic - nausea, vomiting, diarrhea, blurry yellow vision
ECG - increased PR, Decreased QT, ST scooping, T-wave inversion, arrythmia (ventricular tachyarrhythmia most serious and potentially fatal SE of digoxin; delayed after-depolarization due to inc Ca2+ in cell … Digoxin useful in Afib w rapid ventricular response (RVR), meaning HR>100).
Can lead to dose-dependent inc in K+; Hyperkalemia is a poor prognostic indicator.
Factors predisposing to toxicity: REnal failure (dec excretion), hypokalemia (permissive for digoxin binding at K+ site on Na+/K+ ATPase) quinidine (Dec digoxin clearance; displaces digoxin from tissue-binding sites)
Antidote: Slowly normalize K+. lidocaine, cardiac pacer, anti-digoxin Fab fragments, Mg2+ (may decrease influx via reactivation of Na+/K ATPase)
Milrinone
PEDE inhibitor –> Positive inotropic, vasodilates peripheral vessels (due to inc cAMP) –> Decreased preload/afterload–> IV administer only, may inc CHF mortality.
Antiarrhythmics - Class I
Class I - Na+ channel blockers - acts on ventricular myocytes
Local anesthetics. Slow or block conduction (especially in depolarized cells. Dec slope of phase 0 depolarization and increased threshold for firing in abdnormal pacemaker cells. Are state dependent.
Hyperkalemia causes inc toxicity for ALL class I drugs.
Class IA Antiarrythmics
Na+ Channel blockers - Class IA Antiarrythmics
Quinidine, Procainamide, Disopyramide
(“The Queen Proclaims Diso’s PYRAMID”)
- Intermediate inhibition of phase 0
MECHANISM: Inc AP duration, inc effective refractory period (ERP), inc QT interval. Affect both atrial and ventricular arrhythmias, especially reentrant and ectopic supraventricular and ventricular tachycardia.
TOXICITY: quinidine (cinchonism - headache, tinnitus); procainamide (reversible SLE-like syndrome esp in slow acetylators), disopyramide (HF); thrombocytopenia; torsades de points due to inc QT interval.
Class IB Antiarrhythmics
Class IB Antiarrhytmics - Na Channel Blockers
Lidocaine, Mexiletine, Tocainamide
(“I’d Buy LIDy’s MEXIcan Tacos,” Phenytoin can also fall into 1B category)
- Weak inhibition of Phase 0 (due to rapid binding and release)
- bind less avidly to non-resting Na+ channels and is thus the most selective for frequently depolarizing cells (ie ectopic pacemakers)
MECHANISM: Decrease AP duration. Preferentially affect ischemic or depolarized Purkinje and ventricular tissue. USeful in acute ventricular arrhythmias (especially post-MI) and in digitalis-induced arrhytmias.
TOXICITY: local anesthetic. CNS stimulation/depression, cardiovascular depression
***IB IS BEST POST MI***
Class IC Antiarrythmics
Class IC Antiarrythmics - Na+ channel blockers
Flecainide, propafenone, and Moricizine
(“MORe Fries Please”)
- Does not prolong QT
- Strong inhibition of phase 0
Slow rate of dissociation during diastole (more effective at higher rates of depolarization - “use dependence”)
MECHANISM: No effect on AP duration. Useful in ventricular tachycardias that progress ot Vfib and in intractable SVT. Usually used only as last resort in refractory tachyarrhythmias. For patients without structural abnormalities.
TOXICITY: proarrhythmic, especially post-MI (Contraindicated). Significantly prolongs refractoy period in AV node.
Class II Antiarrhythmics
Class II Antiarrhythmics - B-blockers (Act on SA/AV nodes)
Metopropolol, propanolol, esmolol, atenolol, timolol
MECHANISM: Decreases SA and AV nodal activty by decreasing cAMP, decreasing Ca2+ currents. Suppress abnl pacemakers by dec slope of phase 4.
CLINICAL USE: Ventricular tachycardia, SVT, slowing ventricular rate during Afib and A-flutter.
TOXICITY: Impotence, exacerbation of asthma, cardiovascular effects (bradycardia, AV block, CHF), CNS effects (Sedation, sleep alterations) May mask the signs of hypoglycemia.
Metopropolol can cause dyslipidemia. Treat overdose with glucogon (Inc cAMP via non-adrenergic pathway.)
Propanolol can exacerbate vasospasm in Prinzmetal’s angina.
Class III Antiarrhythmics
Class III Antiarrhythmics - K+ channel blockers (Act on ventricular myocytes)
Amiodarone, Ibutilide, Dofetilide, Sotalol (“AIDS”)
MECHANISM: Inc AP Duration, Inc effective refractory period. Used when other antiarrhythmics fail (last resort, many toxicities). Inc QT interval.
Toxicity: _Sotalol_ - inc QT interval --\> torsades de points, excessive B-block _Ibutilide_ - inc QT interval --\> torsades de points _Amiodarone_ - pulmonary fibrosis, hepatotoxicity, hypothyroidism/hyperthyroidism (amiodarone is 40% iodine by wt; monitor T3/T4 levels), corneal deposit, skin deposits (blue/gray) resulting in photodermatitis, neurologic effects, constipation, cardiovascular effects (bradycardia, heart block, CHF) Amiodarone has class I, II, III, and IV effects bc it alters lipid membrane. Remember to check PFTs, LFTs, and TFTs when using amiodarone
Class IV Antiarrhythmics
Class IV Antiarrhythmics - Ca2+ channel blockers
- *Verapamil, diltiazem**
- non-dihydropyridine Ca2+ - CB’s act mostly on heart to decrease conduction velocity through AV node. Class IV is most selective for rapidly depolarizing cells (use-dependent) - act on SA/AV nodes
MECHANISM - Dec conduction velocity, inc ERP, inc PR interval. Used in prevention of nodal arrhythmias (i.e. SVT)
TOXICITY: Constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression), gingival hyperplasia.
Adenosine
Adenosine
Antiarrhythmic that increases K+ out of cells in AV node, hyperpolarizing the cell and slowing phase 4. Also decreases Ca2+ influx into cell, slowing phase 0. Drug of choice in diagnosing/abolishing paroxysmal supraventricular tachycardia. Very short acting (15s).
- ACh uses same mechanism. Transient AV block, also coronary a. vasodilation
TOXICITY: Flushing, hypotension, chest pain (bronchospasm). Effects blocked by theophylline and caffeine (mimic adenosine structure; adenosine R antagonists)
Mg2+
Effective in torsades de points and digoxin toxicity
Nimodepine
Ca Channel blocker used to treat vasospasm following subarachnoid hemorrhage
Thiazide diuretics: drugs in this class and where they hit
- Hydrochlorothiazide
- chlorthalidone
- indapamide
- metolazone
inhibits the Na-Cl cotransporter in the early distal convoluted tubule
