Anti-anginals
Organic Nitrates
 Nitroglycerin, Isosorbide dinitrate, Pentaerythritol tetranitrate, amyl & butyl nitrite
 all act through formation of NO increase the formation of cGMP which activates a cGMP dependent
cyclase
 causes relaxation of smooth muscle, mostly in viens
 decreases preload (venodilation) and afterload (arteriole dilation)
 coronary vasodilation reduces spasms in variant angina
 useful for angina and CHF symptoms
 side effects: orthostatic hypotension, reflex tachycardia
 interacts with Viagra to produce coronary steal, life-threatening hypotension, ischemic optic
neuropathy
 tx toxicity alpha-1 agonists
Calcium channel blockers
 Nifedipine, Amlodipine, Diltiazam, Verapamil
 block L-type Ca channel, decreasing intracellular Ca levels
 cardiac muscle: reduce contractility, CO, trigger events for Ca release, SA/AV node depolarizations
 smooth muscle: reduce contractile tone, cause relaxation in arterioles more than veins, reduce
coronary artery tone
 useful for angina, arrhythmias, hypertension, variant angina
 side effects: nifedipine increases risk of MI, cardiac depression when used with Beta blockers,
verapamil increases dig levels
Beta blockers
 decrease HR, BP and contractility
 results in decreased oxygen requirement
 increases myocardial perfusion
 lowers likelihood of vascular events and infarctions
 lowers mortality rates with Mis
 abrupt discontinuation can result in exacerbation of angina or MI
All drugs decrease oxygen demand by heart
Nitrates decrease preload, afterload, coronary artery spasm
CCBs decrease contractlility, HR, afterload, coronary artery spasm
Betas decrease contractility, HR, afterload
coronary steal phenomenon – potent arteriolar dilators reduce perfusion pressure in main coronary
arteries, further reducing flow to obstructed areas of coronaries
Anti-Hyperlipidemics
Bile Acid Binding Resins
 Cholestyramine, Colestipol, Colesevelam
 Bind and increase fecal excretion of bile acids







Remove feedback inhibition of bile acid synthesis from cholesterol in liver
Decrease intestinal absorption
Increase activity of LDL receptors and HMG-CoA reductase by removing gene repression
Decrease LDL
Need functional LDL receptors to work. Not useful for homozygous hypercholesteremia
Most effective in familial or polygenic hypercholesteremia
Side effects: GI discomfort, aggravation of hemorrhoids, decreased abs. of fat soluble drugs/vitamins
HMG-CoA reductase Inhibitors (Statins)
 Atorvastatin, Lovastatin, Simvastatin, Pravastatin, Fluvastatin, Rosuvastatin
 Decrease intracellular cholesterol levels
 Increased transcription of HMG-CoA synthase, reductase, and LDL receptor
 Increased uptake of IDL and LDL
 Use for heterozygous familial hypercholesteremia
 Decrease LDL, TG, cholesterol content of secreted VLDL
 Increase HDL
 Side effects: myopathy, CPK elevations, rhabdomyolysis, memory loss, mental confusion
 Associated with lower incidence of bone fracture and Alzheimer's disease
 Use of antioxidants decreases effectiveness
Ezetimibe
 Selectively inhibits uptake of cholesterol from intestinal lumen
 No effect on other sterols or lipid soluble vitamins
 Decrease LDL
 Increase HDL
 Side effects: diarrhea
 Used in combo with statins when not sufficient response to statins alone
Niacin
 Decreases adipocyte lipoprotein lipase activity and production of VLDL
 Lowers IDL and LDL
 Decreases TG and VLDL levels first, then LDL levels
 Used in combo with bile acid binders or statins in mixed hyperlipoproteinemias
 Side effects: skin flushing, pruritis, GI distress. May be relieved by lower starting dose or asprin
Fibric Acids
 Gemfibrozil, Clofibrate, Fenfibrate
 Inhibit hepatic synthesis of ApoCIII and adipocyte lipoprotein lipase
 Lowers VLDL, TG, LDL
 Special efficacy of clofibrate for familial type-3 hyperlipoproteinemia
 Side effects: Mild GI distress, myopathies, increased gallstones
Increase the effects of certain drugs like coumarins by displacing them from serum albuminsAnti-
Arrhythmics
Class 1 – Sodium Channel Blockers
A. all block Na and K channels
Quinidine
 prolongs AP, QRS complexes, and QT interval


used for atrial and ventricular rhythms
induces alpha receptor block and vagal inhibition
 causes hypotension, sinus tachycardia, increased AV nodal transmission of atrial arrhythmias
 use Ca channel blockers, Beta blockers, digitalis to reduce AV conduction
 Side effects: diarrhea, thrombocytopenia, hepatitis, bone marrow depression, lupus syndrome,
torsades de pointes
Procainamide
 actions similar to quinidine
 lacks vagolytic and alpha blocking activity
 side effects: hypotension, lupus syndrome
Disopyramide
 actions similar to quinidine
 doesn't block alpha receptors
 prominent anticholinergic actions
 precipitates glaucoma, causes dry mouth, constipation, urine retention
 side effects: precipitates HF by depressing contractility, torsades de pointes
B. Lidocaine, Mexiletine, Tocainide
 used for ventricular arrhythmias ass. with acute MI
 extensive 1st pass metabolism and short half life with lidocaine
 no effects on PR, QRS, or QT duration
 side effects: nystagmus, tremor, mental status changes with lido; bone marrow aplasia and pulmonary
fibrosis with tocainide
C. block Na and K channels
Flecainide
 also block Ca currents
 used for supraventricular arrhythmias
 prolongs PR, QRS, QT
 side effects: potentially lethal arrhythmias
Propafenone
 used for supraventricular arrhythmias and ventricular arrhythmias
 side effects: acceleration of ventricular rate, and sinus bradycardia, bronchospasm due to beta effects
Class 2 – Beta blockers
 Propanolol, Metaprolol, Atenolol, Esmolol, Sotalol
 reduce Ca current and K current
 reduce HR, increase AV conduction time, elongate PR interval
 used for reentrant arrhythmias in AV node, atrial arrhythmias, arrhythmias due to Na blockers
 Esmolol used for rate control of very rapidly conducted atrial fibrillation
 Sotalol used for both ventricular and atrial arrhythmias
 causes torsades de pointes
 side effects: fatigues, asthma, impotence, depression, aggravation of HF
Class 3 – Action potential prolongers
 Amiodarone
 blocks Na channels, decreases Ca and K currents
 prolongs AP, increases QT , PR, QRS, increases refractory period
 effective in treating reentry
 thyroid analog
 side effects: bradycardia, pulmonary fibrosis, corneal deposits, hepatotoxicity, hypo/hyperthyroid,
neuromuscular symptoms, photosensitivity, torsades de pointes
Class 4 – Ca channel blockers
 Verapamil, diltiazem
 decrease HR, AV conduction velocity
 increase AV nodal refractory time, prolong PR interval
 used for reentrant and atrial arrhythmias
 side effects: hypotension, heart block when used with beta blockers, reduce contractility
Unclassified
Adenosine
 increases K current
 hyperpolarizes
 HR and AV nodal refractory time are reduced
 used in acute termination of reentrant arrhythmia
 very short half life
Magnesium
 prevention of recurrent torsades de pointes
 treatment of digitalis intoxication
Torsades de pointes - ventricular tachycardia that is characterized by fluctuation of the QRS
complexes around the electrocardiographic baseline and is typically caused by a long QT interval
Agents causing TDP:
Quinidine
Disopyramide
Sotalol
Amiodarone
Anti-Hypertensives
Diuretics
Acetazolamide
 inhibits carbonic anhydrase
 causes alkaline diuresis and hyperchloremic metabolic acidosis
 retention of Cl at expense of bicarbonate in proximal tubule
 side effects: metabolic acidosis, hypokalemia, renal stones, NH4 retention, increased excretion of
acidic drugs, decreased excretion of basic drugs
Furosemide
 loop diuretic, inhibits Na/K/2Cl transporter in thick ascending loop
 reduces Na reabsorption
 results in K and proton loss, large amounts of NaCl excreted
 direct effects of pulmonary congestion
 NSAIDs decrease effects
 side effects: hypokalemia, metabolic alkalosis, hyperuricemia, hypomagnesemia, ototoxicity,
dehydration with hypercalcemia
Hyrdochlorothiazide, cholthalidone




thiazide diuretic, inhibits Na/Cl symporter in distal convoluted tubule
less powerful than loop diuretics
NSAIDs decrease effects
side effects: hypokalemia, metabolic alkalosis, hyperuricemia, hypomagnesemia, hyperlipidemia,
hypovolemia, hyponatremia, impaired carbohydrate tolerance
Amiloride
 K-sparing diuretic, inhibits epithelial Na channels in principal cells
 makes lumen potential more positive
 favors reabsorption of K, protons, Ca, Mg
 use in combo with thiazide or loop diuretics to reduce K loss
 side effects: nausea, vomiting, diarrhea
Spironolactone
 Aldosterone antagonist
 decreases Na retention in late distal tubule
 decreases Na channnels
 beneficial effects in severe CHF
 reduces morbitity and mortality or patients on ACE inhibitors
 used in combo with thiazide and loop diuretics to reduce K loss
 used in primary and seconday aldosteronism
 side effects: hyperkalemia, gynecomastia, impotence, peptic ulcers, increased risk of breast cancer
Treat CHF pulmonary edema with loop diuretics
Treat Kidney disease Na and water retention with loop diuretics
Treat hepatic cirrhosis edema with spironolactone
All diuretics lower peripheral resistance without affects on HR or CO. Decrease plasma volume and
renal blood flow. Increase plasma renin activity.
Angiotensin II agents
Lisinopril
 ACE inhibitor, reduces angiontensin II synthesis
 effective in low renin hypertensions
 increase bradykinin levels --> vasodilates
 NSAIDs antagonize effects
 pro-drug activated in liver
 side effects: hypotension, dry cough, hyperkalemia, acute renal failure, teratogenic
Losartan
 angiotensin I blocker that antagonizes effects of angiotensin II
 NSAIDs decrease effects
 side effects: hepatic dysfunction, teratogenic, hypotension, hyperkalemia, acute renal failure
Ca Channel antagonists
Dihydropyridines
 Nifedipine, amlodipine
 affect vascular Ca channels more than cardiac
 cause reflex tachycardia
 worsen HF due to negative ionotropic effects, except amlodipine
Non-DHPs
 Verapamil, diltiazem
 less vasoselective
 depress cardiac rate and force enough to blunt reflex effects
 verapamil decreases digoxin clearance
side effects: flushing, edema, dizziness.
Cardiac depressions, hypotension more common when used with beta blockers
Relax arteriolar smooth muscle and reduce peripheral resistance
Beta blockers
 Propanolol, Metoprolol, Atenolol, Pindolol, Labetalol
 reduce HR, CO, and renin release
 best when combined with diuretics
 side effects: bradycardia, HF, hypotension, bronchospasm, depression, fatigue, hypoglycemia,
increase TG, lower HDL,
 NSAIDs reduce effects
 sudden withdrawal of propanolol = MI
Sympatholytic agents
Methyldopa, Clonidine
 inhibit brainstem centers: Methyldopa inhib NTS, clonidine inhib NTS and imidazoline receptors
 lower peripheral resistance without affecting HR, CO, renal flow, plasma volume, renin secretion
 inhibit NE release
 side effects of MD: reduced libido, Parkinson signs, hypoprolactinemia, hepatotox, hemolytic anemia
 side effects of Cl: sedation, dry mouth, depresseion, withdrawal HTN, tachycardia with missed dose
 best when used with diuretics
Prazosin
 alpha 1 receptor antagonist
 causes decreased arteriolar resistance and venous capacitance
 initially increases HR, CO, renin
 No effect on serum lipids
 side effects: orthostatic hypotension with first dose
 best when combined with diuretic or beta blockers
Arteriolar vasodilators
Hydralazine
 relaxes arterial smooth muscle
 baroreceptor reflex increases HR and CO
 fast and slow acetylators
 side effects: nausea, palpitation, angina pectoris, lupus-like syndrome
 best when used with sympatholytic agent or diuretic
Minoxidil
 activates K channel, hyperpolarizing arterial smooth muscle
 increases CO and HR, stimulates renin secretion
 leads to accumulation of salt and fluid
 causes hair growth

best when used with loop diuretics
Nitroprusside
 used IV in HTN emergencies
 broken down to NO, SCN, CN
 dilates arterial and venous smooth muscle
 CN causes severe lactic acidosis