Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
127 Cards in this Set
- Front
- Back
|
Relative refractory period
|
Only a string stimulus can elicit a response. Associated with arrhythmias.
|
|
|
Innervation of the SA and AV nodes
|
Parasympathetic via M2 receptors. Sympathetic via β1 receptors.
|
|
|
What effect does sympathetic stimulation have on SA and AV nodes
|
β1 activation increases cAMP, increasing upstroke velocity by increase of Ca conductance. Shortens action potential duration by increase of K conductance. Increases HR by increase of Na funny currents and increased phase 4 slope.
|
|
|
What effect does parasympathetic stimulation have on SA and AV nodes
|
M2 activation decreases cAMP. Decrease upstroke velocity by decreasing Ca conductance. Prolongs action potential duration by decrease of K conductance. Decreases HR by decrease of Na funny current and by increase K conductance.
|
|
|
Class 1A antiarrhythmics
|
Quinidine, procainamide
|
|
|
1A antiarrhythmics MOA
|
Block fast Na channels in the open state (decreases excitability and phase 0 slope) increasing APD and ERP. Block K channels which prolongs repolarization (decrease phase 3 slope).
|
|
|
Quinidine pharmacokinetics
|
Orally effective weak base enhanced absorption and toxicity by antacids. In atrial fibrilation needs intitial digitalization.
|
|
|
Quinidine pharmacodynamics
|
Class 1A effects plus muscarinic receptor blockade (increase HR and AV conduction); vasodilation via alpha block with reflex tachychardia.
|
|
|
Quinidine adverse effects
|
Cinchonism (GI, tinnitus, ocular dysfunction, CNS excitation), hypotension, QRS and QT prolongation associated with syncope torsades
|
|
|
Quinidine drug interactions
|
Hyperkalemia enhances effects and vice versa. Displaces digoxin from tissue binding sites, enhancing toxicity.
|
|
|
Procainamide pharmacokinetics
|
Phase 2 acetylation by N-acetyltransferase to N-acetylprocainamide (NAPA) active metabolite. Subject to genotypic variation/slow acetylators/drug-induced lupus.
|
|
|
Procainamide adverse effects
|
SLE-like syndrome (30%) in slow acetylators. Thrombocytopenia, agranulocytosis, torsades.
|
|
|
Class 1B antiarrhythmics
|
Lidocaine, mexiletine, tocainide
|
|
|
Class 1B antiarrhythmics MOA
|
Block fast Na channels in the inactive state, preferentially in hypoxic tissues results in increased treshold for excitation and less excitability of hypoxic heart muscle. Block of slow Na window currents with decreased APD (decreased phase 2 of AP). Increases dyastole and time for recovery (leads to asystolia)
|
|
|
Uses and side effects of lidocaine
|
Post MI, open heart surgery, digoxin toxicity. Seizures, least cardiotoxic antiarrhythmic. IV because of first-pass metabolism.
|
|
|
Class 1C antiarrhythmics MOA
|
Block fast Na channels specially in His-Purkinje fibers without altering the APD (decreases phase 0 slope at the expense of shortening phase 2 duration)
|
|
|
Flecainide
|
Class 1C antiarrhythmic. Limited use because of proarrhythmogenic effects. Increased risk of sudden death post-MI.
|
|
|
Effects of class 1A antiarrhythmics on action potential
|
Decrease slope of phase 0; increase APD and ERP.
|
|
|
Effects of class 1B antiarrhythmics on action potential
|
Decrease length of phase 2 (plateau) with no change in phase 0 or 3 which decreases APD.
|
|
|
Effects of class 1C antiarrhythmics on action potential
|
Decrease slope of phase 0 and decrease length of phase 2 which cancels out effect on APD.
|
|
|
Class II antiarrhythmics MOA
|
Block β1 receptors in the heart decreasing cAMP; Decrease upstroke velocity by decreasing Ca conductance (decreased phase 4). Prolongs action potential duration by decrease of K conductance (decreased phase 3 slope). Decreases HR by decrease of Na funny current and by increase K/ACh conductance (decreased phase 4)
|
|
|
Class II antiarrhythmics
|
Propranolol (nonselective), acebutolol, esmolol (β1 selective)
|
|
|
Uses of class II antiarrhythmics
|
Prophylaxis post MI, supraventricular tachyarrhythmias
|
|
|
Properties of propranolol
|
Nonselective β blocker, no sympathicomimetic activity, produces sedation and increases blood lipids.
|
|
|
Properties of acebutolol
|
Selective β1 blocker with intrinsic sympathicomimetic activity, no sedation, no increase in blood lipids.
|
|
|
Class III antiarrhythmics MOA
|
Decreased delayed rectifier K currents which slows phase 3 and increases APD and ERP.
|
|
|
Class III antiarrhythmics
|
Amiodarone, sotalol (combined K channel and β1 blocker)
|
|
|
Amiodarone pharmacokinetics
|
t1/2 > 80 days, large Vd.
|
|
|
Amiodarone pharmacodynamics
|
Blocks K channels in many tissues. Mimics class I, II and IV antiarrhythmics. Increases APD and ERP.
|
|
|
Amiodarone side effects
|
Large Vd affects many tissues: pulmonary fibrosis, blue pigmentation of skin, phototoxicity, corneal deposits, hepatic necrosis, thyroid dysfunction.
|
|
|
Sotalol MOA
|
Blocks K channels decreasing phase 3 of AP (increases APD); blocks β1 which decreases phase 4 and phase 3 slopes in pacemaker cells (which decreases HR and conduction)
|
|
|
Class IV antiarrhythmics MOA
|
Block slow Ca channels in pacemaker cells which decreases phase 4 and 0 slopes, which decreases HR.
|
|
|
Class IV antiarrhythmics
|
Verapamil, diltiazem
|
|
|
Uses of verapamil
|
Supraventricular tachyarhythmias
|
|
|
Verapamil side effects
|
Constipation, dizziness, flushing, hypotension, AV block
|
|
|
Verapamil drug interactions
|
Additive AV block with β-blockers and digoxin; displaces digoxin from tissue-binding sites.
|
|
|
Properties of adenosine
|
Activates adenosine receptors coupled to Gi, decreasing cAMP, decreasing SA and AV node activity. Used for paroxysmal supraventricular tachyarrhythmias. t1/2 < 10 seconds. Side effects: flushing, sedation, dyspnea. Antagonized by theophylline.
|
|
|
Drugs that cause torsades
|
Class IA and III antiarrhythmics, antipsychotics, tricylic antidepressants.
|
|
|
Drugs that displace digoxin
|
Verapamil, quinidine
|
|
|
Drugs that cause drug-induced lupus
|
Hydralazine > procainamide > isoniazid (slow acetylators)
|
|
|
Effects of hyperkalemia on heart
|
Decreases K efflux reducing repolarization. Membrane is depolarized. Can cause heart stop on systole. Peaked T waves.
|
|
|
Effects of hypokalemia on heart
|
Increases K conductance and hyperpolarization. Heart stops of dyastole.
|
|
|
What is the strategy to treat hypertension
|
Decrease TPR (α2 agonists, α1 blockers), decrease CO (β-blockers), decrease body fluids (diuretics), vasodilation (hydralazine, nitirites, ACEIs, ARBs).
|
|
|
α2 agonists
|
Clonidine, methyldopa
|
|
|
Uses and side effects of clonidine
|
Uses: Mild to moderate hypertension, opiate withdrawal; Side effects: CNS depression, edema.
|
|
|
Uses and side effects of methyldopa
|
Uses: mild to moderate hypertension, hypertension management in pregnancy; Side effects: positive Coombs test, CNS depression, edema.
|
|
|
Reserpine MOA and side effects
|
Destroys catecolamine vesicles leading to decrease in CNS and peripheral levels. Side effects: depression, edema.
|
|
|
Guanethidine MOA and side effects
|
Accumulates into nerve endings by reuptake, binds catecolamine vesicles and inhibits release of NE; Side effects: diarrhea, edema. Tricyclics block reuptake and actions of guanethidine
|
|
|
α1 blockers
|
Prazosin, doxazosin, terazosin
|
|
|
α1 blockers MOA
|
Decrease arteriolar and venous resistance. Decrease prostate and urinary sphincter tone.
|
|
|
α1 blockers side effects
|
First dose syncope, orthostatic hypotension, urinary incontincence
|
|
|
β-blockers cautions in use
|
Asthma, vasospastic disorders (atherosclerosis, Raynauds), diabetics (hypoglycemia normally induces tachychardia which is perceived by patient, but β-blockers prevent tachychardia warning signs).
|
|
|
Properties of hydralazine
|
Direct vasodilator as nitric oxide donor. Decreases TPR. Use in moderate to severe hypertension. Side effects: Drug-induced lupus in slow acetylators, edema, reflex tachychardia.
|
|
|
Drugs metabolized by acetylation
|
Hydralazine > procainamide > isoniazid (slow acetylators)
|
|
|
Nitroprusside
|
Nitric oxide donor vasodilates arterioles and venules. Used for hypertensive emergencies. Releases cyanide thus coadminister thiosulfate to form nontoxic thiocyanate. In case of cyanide poisoning give nitrites.
|
|
|
Direct vasodilators
|
Hydralazine (NO), nitroprusside (NO), minoxidil (opens K channels --> hyperpolarization --> vasodilation)
|
|
|
Minoxidil
|
Opens K channels in smooth muscle --> hyperpolarization --> vasodilation. Use in severe hypertension and alopecia. Side effects: hypertrichosis, edema, reflex tachychardia.
|
|
|
Diazoxide
|
Opens K channels in smooth muscle --> hyperpolarization --> vasodilation. Use in hypertensive emergencies. Side effects: hyperglycemia (decreases insulin release)
|
|
|
Arteriolar vasodilators
|
Ca channel blockers (verapamil, diltiazem, nifedipine), hydralazine, K channel openers (minoxidil)
|
|
|
Venular vasodilation
|
Nitrates (nitroprusside)
|
|
|
Orthostatic hypotension
|
Due to venular dilation not arteriolar. Usually from α1 blockers.
|
|
|
Calcium channel blockers MOA
|
Block L-type Ca channels in heart and blood vessels smooth muscle --> decrease intracellular Ca --> decreased CO and TPR.
|
|
|
Calcium channel blockers
|
Verapamil, diltiazem, nifedipines and derivatives.
|
|
|
Uses of calcium channel blockers
|
Hypertension, angina, antiarrhythmics (verapamil, diltiazem)
|
|
|
Side effects of calcium channel blockers
|
Reflex tachychardia (nifedipine and derivatives), gingival hyperplasia (nifedipine and derivatives), constipation (verapamil)
|
|
|
ACE inhibitors MOA
|
Block formation of angiotensin II --> no AT-1 receptor stimulation --> decreased aldosterone secretion and vasodilation; also prevent bradykinin degradation by ACE (dry cough). Captopril and other -prils
|
|
|
Angiotensin receptor blockers MOA
|
Block angiotensin receptors --> decreased aldosterone secretion and vasodilation. Losartan and other -sartans
|
|
|
Uses of ACEIs and ARBs
|
Mild to moderate hypertension, protective of diabetic neprhopathy, CHF
|
|
|
ACEIs side effects
|
Dry cough (no degradation of bradykinin), hyperkalemia (no aldosterone), acute renal failure in renal artery stenosis (angiotensin maintains RBF), angioedema
|
|
|
ARBs side effects
|
Hyperkalemia (no aldosterone), acute renal failure in renal artery stenosis (angiotensin maintains RBF), angioedema
|
|
|
Treatment strategy for heart failure
|
Decrease preload (diuretics, ACEIs, ARBs, venodilators), decrease afterload (ACEIs, ARBs, arteriodilators), increase contractility (digoxin, beta agonists), decrease cardiac remodeling (ACEIs, ARBs, spironolactone)
|
|
|
What drugs are beneficial in CHF and why?
|
ACEIs, ARBs and spironolactone prevent cardiac remodeling
|
|
|
Digoxin MOA
|
Inhibits cardiac Na/K ATPase --> increase intracellular Na --> decrease Na/Ca exchange --> increase intracellular Ca --> increase Ca release con sarcoplasmic reticulum --> increase contractile force. It also inhibits neuronal Na/K ATPase which increases vagal and sympathetic stimulation.
|
|
|
Digoxin pharmacokinetics
|
Long t1/2 needs loading dose; renal clearance; large Vd and displacement by verapamil and quinidine
|
|
|
Uses of digoxin
|
CHF and supraventricular tachychardias except Wolff-Parkinson-White syndrome
|
|
|
Wolff-Parkinson-White syndrome
|
Prexcitation of the ventricles due to accesory conduction bundle of Kent. Block accessory path with class IA or III antiarrhythmics, avoid β-blockers, CCBs and adenosine
|
|
|
Digoxin side effects
|
Anorexia, nausea, ECG changes, disorientation, visual halos, cardiac arrhythmias
|
|
|
Digoxin toxicity
|
Can cause cardiac arrhythmias. Use Fab antibodies against digoxin and class IB antiarrhythmics.
|
|
|
Digoxin drug interactions
|
Quinidine, verapamil displace digoxin; sympathicomimetics; diuretics
|
|
|
Phosphodiesterase inhibitors MOA
|
Inamrinone, milrinone. Phosphodiesterase normally converts cAMP into AMP, inhibitors increase cAMP and inotropy in heart and relax smooth muscle cells which leads to decreased TPR
|
|
|
Antianginal drugs
|
Nitroglycerin, isosorbide, CCBs (nifedipine), β-blockers and carvedilol
|
|
|
Nitrates MOA
|
Pro drugs of nitric oxide; NO activates smooth muscle guanylyl cyclase --> increase cGMP --> relaxation --> venodilation --> decrease preload --> decrease cardiac work and oxygen requirements
|
|
|
Nitroglycerin side effects
|
fluching, headache, orthostatic hypotension, reflex tachychardia, methhemoglobinemia.
|
|
|
Nitroglycerin interactions
|
Cardiovascular toxicity with sildenafil
|
|
|
Sildenafil MOA
|
Inhibits PDE5 in blood vessels of corpora cavernosa --> increase cGMP --> vasodilation --> erection
|
|
|
Uses and side effects of mannitol
|
Decreases IOP in glaucoma, decreases intracerebral pressure in cerebral edema. Side effects: hypovolemia
|
|
|
Carbonic anhydrase inhibitors drugs
|
Acetazolamide, dorzolamide
|
|
|
Azetazolamide MOA
|
Decreases H+ formation in PCT --> decrease Na/H+ antiport --> increases Na and HCO3 in lumen --> diuresis
|
|
|
Uses of azetazolamide and CA inhibitors
|
Glaucoma, acute moutain sickness (acidosis stimulates ventilation), metabolic alkalosis
|
|
|
Azetazolamide and CA inhibitors side effects
|
Bicarbonaturia/acidosis, hypokalemia (increases Na load dowstream), hyperchloremia, paresthesia, renal stones (alkalinizes urine), sulfa hypersensitivity
|
|
|
Loop diuretic drugs
|
Ethacrynic acid, furosemide
|
|
|
Loop diuretics MOA
|
Inhibit Na/K/2Cl cotransporter --> decrease intracell K+ --> decrease positive potential --> decrease reabsorption of Ca, Mg --> increased diuresis
|
|
|
Uses of loop diuretics
|
Acute pulmonary edema, CHF, hypertension, refractory edema, acute renal failure, anion overdose, hypercalcemia
|
|
|
Loop diuretic side effects
|
Sulfonamide hypersensitivity (except ethacrynic acid), hypokalemia, alkalosis, hypocalcemia, hypomagnasemia, hyperuricemia, ototoxicity (ethacrynic acid > furosemide)
|
|
|
Loop diuretics drug interactions
|
Enhanced ototoxicity with aminoglycosides; decrease clearance of lithium, increase digoxin toxicity
|
|
|
Thiazide drugs
|
Hydrochlorothiazide, indapamide
|
|
|
Thiazides MOA
|
Inhibit Na/Cl transporter in DCT --> increases Na and Cl in the lumen --> increase diuresis
|
|
|
Uses of thiazides
|
Hypertension, CHF, nephrolithiasis (calcium stones), nephrogenic diabetes insipidus
|
|
|
Thiazides side effects
|
Sulfonamide hypersensitivity, hypokalemia, alkalosis, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia
|
|
|
Thiazide drug interactions
|
Increase digoxin toxicity, avoid in diabetics
|
|
|
K+ sparing agents
|
Spironolactone, eplerenone, amiloride, triamterene
|
|
|
MOA spironolactone
|
Aldosterone receptor antagonist --> no sodium reabsorption --> no K+ secretion
|
|
|
Uses of spironolactone
|
Hyperaldosteronism, adjunct to K+ wasting diuretics, hirsutism, CHF
|
|
|
Spironolactone side effects
|
Hyperkalemia, acidosis, antiandrogenic (except eplerenone)
|
|
|
MOA amiloride/triamterene
|
Blocks Na+ channels in principal cells of collecting ducts --> decreased Na+ reabsorption and K+ secretion
|
|
|
Uses of K+ sparing agents
|
Adjunct to K+ wasting diuretics, lithium-induced nephrogenic diabetes insipidus (amiloride)
|
|
|
Side effects of K+ sparing agents
|
Hyperkalemia, acidosis
|
|
|
Electrolytes excreted by acetazolamide
|
Na, K, HCO3
|
|
|
Electrolytes excreted by loop diuretics
|
Na, K, Ca, Mg, Cl
|
|
|
Electrolytes excreted by thiazides
|
Na, K, Cl; Ca is reabsorbed
|
|
|
Electrolytes excreted by K+ sparing agents
|
Na; K is not secreted
|
|
|
Statins MOA
|
Inhibition of HMG-CoA-Reductase --> decreased cholesterol --> increased LDL receptor expression --> decresed LDLs
|
|
|
Statins side effects
|
Myalgia, myopathy, rhabdomyolysis due to decrease in farnesyl ppi
|
|
|
Statins drug interactions
|
Gemfribozil increases rhabdomyolysis; P450 inhibitors enhance toxicity
|
|
|
Bile acid sequestrant drugs
|
Cholestyramine, colestipol
|
|
|
MOA of bile acid sequestrants
|
Decreased enterohepatic circulation --> increased new bile salts in liver --> decreased liver cholesterol --> increased LDL receptor expression --> decreased blood LDL
|
|
|
Side effects of bile acid sequestrants
|
Increased VLDL and triglycerides; gastrointestinal disturbances; malabsorption of lipi-soluble vitamins
|
|
|
Drug interactions of bile acid sequestrants
|
Interact with orally administered drugs
|
|
|
Contraindications of bile acid sequestrants
|
Hypertriglyceridemia
|
|
|
Niacin MOA
|
Inhibits VLDL synthesis --> decreased plasma VLDL --> decreases LDL --> increases HDL
|
|
|
Niacin side effects
|
Flushing, pruritus, rashes, hepatotoxicity
|
|
|
Gemfibozil MOA
|
Activates lipoprotein lipase --> decreases VLDL and IDL --> decreases LDL --> increases HDL
|
|
|
Uses of gemfibrozil
|
Hypertriglyceridemia
|
|
|
Ezetimibe MOA
|
Prevents intestinal reabsorption of cholesterol --> decreased LDL
|
|
|
Which antihyperlipidemic: increased cholesterol
|
Cholestyramine, colestipol, ezetimibe
|
|
|
Which antihyperlipidemic: increased triglycerides
|
Gemfibrozil
|
|
|
Which antihyperlipidemic: increased cholesterol and triglycerides
|
Statins, niacin, ezetimibe
|
