Cardio Pharmacology

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Clonidine

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Class - Central Sympatholytic
Properties - stimulates central and peripheral α2 receptors --> decreased sympathetic outflow.
Met/Excr - 50% liver met, 50% excr unchanged in kidney
Indications - mod-severe HTN (esp. renal HTN because it doesn't decrease RBF)
SE, Tox - sedation, dry mouth frequent. insomnia, nightmares, depression. orthostatic hypotension and fluid retention fixed by adding a diuretic. rebound HTN after abrupt withdrawal.
Drug Interactions - TCA cancel out its effects. Ca channel blockers add to cardiosuppression.

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Methyldopa

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Class - Central Sympatholytic
Properties --> converted to something that stimulates central α2 receptors --> decreased sympathetic outflow
Indications - methyldopa + diuretic are the drugs of choice for HTN in pregnancy
SE, Tox - gives a + direct coombs test but doesn't cause hemolysis. sedation, dry motuh, headaches, nightmares, depression, postural hypotension, salt and water retention if given without a diuretic, impotence, drug fever, lactation, hepatitis. rebound HTN following sudden withdrawal is less than with clonidine.

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β blockers

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β1 selective - Acebutolol*, Betaxolol, Esmolol, Atenolol, Metoprolol
β unselective - Propranolol, Nadolol, Timolol, Pindolol*, Labetalol
*Pindolol, acebutolol have intrinsic sympathomimetic activity --> less inotropic, chronotropic effects, do not increase TAG or decrease HDL therefore can be used in people with decreased cardiac fxn.
Indications - mild-severe HTN, supravent + vent tachyarrhythmias, angina, acute MI, hypertrophic cardiomyopathies, hyperthroidism, anxiety, migraine prophylaxis, glaucoma, HTN crisis, pheochromocytoma.
SE, Tox - CI in pts with asthma (β2), DM (masks sympathetic responses to hypoglycemia). can increase/precipitate CHF, heart block, bradycardia, vasospasm. hallucinations, nightmares, depression, impotence. nausea, diarrhea, constipation. withdrawal --> rebound HTN, angina, MI.
Drug Interactions - cimetidine (H2 blocker) and chlorpromazine (antipsychotic) decrease metabolism.

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α1 Selective Adrenergic Blockers

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Examples - Prazosin, Terazosin, Doxazosin
Properties - relax both arteriolar and venous smooth muscle, do not increase HR.
Indications - mild-mod HTN with diuretic or βblocker, CHF preload and afterload reduction, pheochromocytoma, urinary retention in BPH
SE, Tox - postural hypotensions, relex tachycardia at first, dizziness, sedation, headache.

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Nonselective α Andrenergic Blockers

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Examples - Phenoxybenzamine (irreversible - PO, IV)and Phentolamine (reversible - IV)
Indications - Dx of pheochromocytoma, HTN emergencies in pheochromocytoma, peripheral vascular disease, Raynaud's, autonomic hyperreflexia caused by spinal cord lesions.
SE, Tox - sedation, miosis, postural hypotensions, reflex tachycardia.

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Hydralazine

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Properties - causes direct relaxation of vasc smooth muscle, greatest effect on ARTERIOLES.
Met/Excr - N-acetylated in liver in first pass --> rapid acetylators have lower bioavailability.
Indications - with β blockers (prevent reflex tachy) and diuretics for mod-severe HTN. with nitrates for CHF as an alternative to ACE-I.
SE, Tox - reflex tachy, increased myocardial oxygen consumption (prevented by adding β blocker), headache and flushing, nausea, dizziness, diaphoresis. LUPUS-LIKE SYNDROME with + ANA seen in slow acetylators (usually caucasion).

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Resperine

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Class - Adrenergic neuron blockers
Properties - Resperine blocks uptake of neurotransmiiters into storage vesicles in brain, adrenal medulla and periphery leading to decreased CO and PVR. Indications - HTN, tho never used clinically.
SE, Tox = sedation, depression (watch it with the suicidal pts!), nasal stuffiness, diarrhea.

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Guanethidine

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Class - Adrenergic neuron blocker
Properties - Guanethidine inhibits relase of stored NE in the periphery.
Indications - HTN, tho never used clinically.
SE, Tox - orthostatic and exercise hypotensions, sexual dysfunction, diarrhea

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Minoxidil

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Properties - casuses vasodilation by opening potassium channels --> hyperpol --> relaxation of vascular smooth muscle.
Indications - severe HTN refractory to conventional regimens. Use with β blocker (prevent reflex tachy) and diuretic.
SE, Tox - salt and water retention, reflex tachy, HYPERTRICHOSIS (the rogaine with minoxidil commercials!), pericardial effusion, angina

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Sodium Nitroprusside

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Properties - directly relaxes both arteriolar and venous smooth muscle. Short half life --> IV infusion.
Met/Excr - nitroprusside + sulfhydryl groups in RBC --> cyanide anion + NO (NO stimulate GC --> increased cGMP --> vasodilation). at liver cyanide --> thiocyanate which is cleared by kidney.
Indications - hypertensive emergencies, acute CHF (reduces both preload and afterload), severe mitral regurg. needs to be given in a well monitored setting.
SE, Tox - hypotension, nausea, headache, palpitations, diaphoresis, anxiety. thiocyanate poisoning --> nausea, psychosis, muscle spasm, tissue hypoxia.

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How do you treat cyanide toxicity caused by nitroprusside?

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Well, it's quite simple. nitrites will reduce hemoglobin to methemoglobin which will bind cyanide to make cyanomethemoglobin. This will prevent cytochrome oxidase inhibition in the electron transport chain. Giving thiosulfate will allow cyanide to be secreted as thiocyanate (also toxic) and therefore reconvert CNHb to Hb. Yay!

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Ca Channel Blockers

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Examples - verapamil, diltiazem, nifedipine, nicardipine, nimodipine
Properties - block Ca entry into --> inhibiting excitation-contraction coupling --> decreased PVR. DILTIAZEM and VERAPAMIIL also slow conduction through the AV node.
Indications - mild-mod HTN, esp. with angina or supreventricular tachyarrhythmia, coronary vasospasm, verapamil, diltiazem for supravent tachyarrhthmias, migraine prophylaxis, esophageal spasm, Raynaud's.
SE, Tox - dizziness, headache, nausea, heart block (especially verapamil), exacerbation of CHF, hypotension (beacuse of negative inotropy, esp. with verapamil)

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Captopril

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Class - ACE Inhibitor
Properties - blocks conversion of AI to AII and decreases bradykinin inactivation so bradykinin has more vasodilatory effects. Decrease in AII also leads to reduction of aldo. Vasodilation greatest at efferent arterioles --> decreased GFR.
Met/Excr - 50% metabolized to inactive products, everything renally excreted.
Indications - CHF (reduces preload and afterload) and mild-moderate HTN. often used with a thiazide diuretic. decreases preteinuria and rate of renal failure in diabetics.
SE, Tox - loss of taste, dry cough, angioedema, dizziness, orthostatic hypotension, renal damage in pts with preexisting renal disease!, proteinuria, rash, pruritus, eosinophilia, rare bone marrow tox (agranulocytosis), RENAL DAMAGE IN FETUS.

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Enalapril

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Class - ACE Inhibitor
Properties - prodrug that is hydrolyzed to enalaprilat which is active and has a longer half-life than captopril
Indications - same as captopril but can also be given IV in ICU.
SE, Tox - same as captopril but with less eosinophilia and less taste disturbance.

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Losartan

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Class - AII receptor antagonist
SE, Tox - doesn't cause cough

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Class I Antiarrhythmics (Properties)

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Na channel blockers - Local anesthetics that slow or block conduction (esp. in depolarized cells = state dependent) --> decrease slope of phase 4 depol and increase threshold for firing in abnormal pacemaker cells.

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Class IA Antiarrhythmics

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Examples - Quinidine, Amiodarone, Procainamide, Disopyramid
Properties - increase AP duration, increase effective refractory period, increase QT interval. affect both atrial and ventricular arrhythmias.
SE, Tox - Quinidine --> cinchonism = headache, tinnitus, thrombocytopenia. torsade de pointe due to increase QT interval. procainamide - reversible SLE-LIKE SYNDROME.
*See class III for amiodarone.

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Class IB Antiarrhythmics

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Examples - Lidocaine, mexiletine, tocainide.
Properties - decrease AP duration. Affect ischemic or depolarized Purkinje and ventricular tissue.
Indications - Acute ventricular arrhthmias esp. post MI and in digitalis-induced arrhythmias.
SE, Tox - local anesthetic. cns stimulation/depression, cardiovascular depression.

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Class IC Antiarrhythmics

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Examples - Flecainide, encainide, propafenone.
Properties - no effect on AP duration.
Indication - useful in Vtachs that progress to Vfib and in intractable SVT. last resort in refractory tachyarrhythmias.
Toxicity - proarrhythmic. CI POSTMI.

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Class II Antiarrhythmics

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Examples - Propranolol, esmolol, metoprolol, atenolol, timolol
Properties - β blockers. decrease cAMP, decrease Ca currents. Suppress abnormal pacemakers by decreasing slope of phase 4. AV node is particularly sensitive --> increase PR interval. esmolol is very short acting.
SE, Tox - Impotence, exacerbation of asthma, bradycardia, AV block, CHF, sedation, sleep alterations. masks the signs of hypoglycemia.

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Class II Antiarrhythmics

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Examples - Sotalol, ibutilide, breylium, amiodarone*, dofetilide
Properties - K channel blockers. Increase AP duration, incrase effective refractory period. increase QT interval.
Indications - used when other antiarrhythmics fail.
SE, Tox - Sotalol - torsades, excessive β block. ibutilide - torsades. bretylium - new arrhythmias, hypotension. amiodarone - PULMONARY FIBROSIS, corneal deposits, HEPATOTOXICITY, skin deposits --> photodermatitis, neurologic effects, constipation, bradycardia, heart block, CHF, hypo/hyperthyroid. ALWAYS CHECK PFT, LFT, TFT when using amiodarone.

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Class IV Antiarrhythmics

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Examples - verapamil, diltiazem
Properties - Ca channel blockers. Primarily affect AV nodal cells. decrease conduction velocity, increase effective refractory period, increase PR interval.
Indications - Prevention of nodal arrhythmias (eg SVT)
SE, Tox - constipation, flushing, edema, CHF, AV block, sinus node depression.

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Glycosides (properties)

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Examples - digoxin, digitoxin
Properties - inhibit Na/K ATPase --> diminished NA gradient --> less Na-Ca exchange --> intracellular Ca accumulation --> positive inotropic effect. prolong ERP at AV nodem diminish rate at which impulses are transmitted to the ventricles because of enhanced vagal activity. decreased QT, Twave inversion. serum levels need to be monitored as bioavailability (approx 75%) is affected by food in GI tract, delayed gastric emptying, malabsorption and ANTIBIOTICS.
Met/Excr - 20-40% pro bound, t1/2 = 40 hrs, urinary excretion.
Indications - CHF (+ inotropic effect), AV nodal depression in paroxysmal supravent tachy, afib, aflutter.
SE, Tox - life-threatening arrhythmias (vent ectopy, vent dysrrhythmias, paroxysmal atrial tachy with block, 2nd and 3rd degree block). GI, CNS, visual disturbances. toxicity precipitated by HYPOKALEMIA, alkalosis, hypoxia, hypercalcemia, hypomagnesemia, hypothyroid, hyponatremia. drugs that increase tox - VERAPAMIL, QUINIDINE, corticosteroids, THIAZIDES and other k-wasting DIURETICS. to fix tox - discontinue drug, fix hypoK, control arrhythmia with phennyoin, lidocaine, procainamide if tachy; atropine and pacing if brady. if severe, give antidigoxin Ig. CI in toxicity - electrical cardioversion because -->vfib because of reduced fib threshold.

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Niacin

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Properties - decreases VLDL production in liver. increases HDL, decreases TAG.
Indications - all buy type I hyperlipidemias. Esp good in Type IIb (increased synth of VLDL). prevents pellagra. used in peripheral vascular insufficiency (causes peripheral vasodilation).
SE, Tox - pruritus, flushing which is decreased with aspirin or long-term use), vomiting, diarrhea, dyspepsia, hyperpigmentation, increased liver enzymes, hyperuricemia, hyperglycemia.

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Clofibrate

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Class - fibric acid derivative
Properties - increases activity of lipoprotein lipase breaking down TAG to FA. decreases VLDL, no change HDL (according to kaplan) or slightly increased HDL (according to First Aid), inhibits cholesterol sythnesis in liver (because more LDL comes back?)and increases its excretion in bile. decreases TAG.
Indications - pts with increased VLDL and LDL leves who have rfailed to respond to diet therapy. esp. good in type III (defective ApoE --> increased VLDL, TAG, chol.)
SE, Tox - nausea, diarrhea, alopecia, rash, impotence, myalgias, ELEVATED SGOT, CPK, cholethiasis, cholcystitis, arrhythmias, myositis.
Drug Interactions - displaces phenytoin, warfarin from albumin, watch PT!

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Gemfibrozil

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Class - Fibric acid derivative (analog of clofibrate).
Properties - Lowers VLDL and TAG, raises HDL levels.
Indications - pts with increased VLDL, LDL, who failed diet therapy, esp. type III.
SE, Tox - mild GI upset, abdominal pain, nausea, eosinophilia, rash. gallstone formation, mild hyperglycemic effect. potentiates warfarin.

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Lovastatin, et. al.

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Properties - inhibit HMG CoA reductase --> decreased cholesterol snthesis --> increased breakdown of LDL, increased HDL. excreted through bile and feces.
Indications - type IIa and IIb, secondary hyperlipoproeinemia (nephrotic syndrome, diabetes).
SE, Tox - GI symptoms, headache, rash. asymptomatic reversidble increase in liver enzymes. monitor liver function, disconstinue if you see abnormalities. increase muscle CPK, rhabdomyolysis possible.