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87 Cards in this Set
- Front
- Back
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ANTI-HYPERLIPIDEMIC DRUGS
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STATINS:
1. Lovastatin ( mevacor) 2. Atorvastatin (lipitor) 3. Fluvastatin (lescol) 4. Simvastatin (zocor) 5. Pravastatin (pravachol) 6. Rosuvastatin (crestor) *Vytorin = SIMVASTATIN/EZETIMIBE Fibric-Acid Derivatives: 1. Gemfibrozil (lopid) 2.Clofibrate (tricor) 3. Fenofibrate (lofibra) BILE-ACID SEQUESTRANTS 1. Cholestyramine (Questran) 2. Colestipol (colestid) 3. Colesevelam (Welchol) - Niacin (nicotinic acid) - Niaspan - Ezetimibe (zetia) |
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Plasma lipoprotein Metabolism
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Lipid: Free & esterified cholesterol, triglycerides, & phospholipids
Protein: apolipoporteins or apoproteins Chylomicrons (mostly triglycerides; majority) --> VLDL (5:1 Triglyc:Cholesterol): MADE IN LIVER -->ILD (equa) --> LDL (all cholesteryl esters - HDL (Phosphilipids & cholesteryl esters): made in liver/intestines/plasma - Lp(a) Particles: ONLY cholesteryl esters (BAD) - made in liver |
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LDL & ATHEROSCLEROSIS
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1. oxidized
2. taken up by macros in the vessel wall = FOAM CELLS *foam cells are precursors to the atherosclerotic plaque |
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Functions of HDL & LP(A)
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HDL: Protective against atherosclerosis
- Reverse cholesterol transport (--> liver for excretion) - Direct anti-inflamm, antioxidant, anticoag, antiplatelet Lp(a): atherogenic - inhibit intrinsic lysis of thrombi |
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STATINS
DOC, indications, clinical use low dose & short half-life (4 hr): lova- simva- prava- fluva- higher dose & longer half life (20 hr) atorva- rosuva- |
DOC: Lowering LDL cholesteral levels
- also raise HDL a little - Reduce VERY high triglyceride levels Recommended: Pts with overt CAD or very high risk; until LDL <70 mg/dL CLINICAL: Rpt lipid levels & hepatic transaminases ~6 wks after starting - take in evening if short half life *Hepatic cholesterol synthesis is maximal bw 12am-2am. |
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STATINS
Mechanism, side effects *excreted in the liver-->feces* |
Mech:
Competitive Inhib of HMG-CoA Reductase (rate limiting step in cholesterol synth) = ^ # LDL receptors on surface of hepatocytes = ^ removal of LDL from blood *also improves vascular endothelial fxn *anti-inflamm (less CRP) *reduce platelet aggreg SIDE EFFECTS: - MYOPATHY: myalgias are common, but actual rhabdomyolysis is rare - Hepatotoxicity: ^ transaminases CONTRAINDICATIONS: ^ risk of myopathy - Use of 1 drug that diminishes statin catabolism (many drugs) *ESP GEMFIBROZIL: - inhibits OATP2: no uptake of the active hydroxyl acid form of statins *other drugs that interfere w/ statin oxidation are metabolized mainly by CYP3A4. |
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FIBRIC ACID DERIVATIVES
doc, mech, Gemfibrozil (Lopid) - 1.1hrs clofibrate (tricor) fenofibrate - 20 hrs |
DOC: SEVERE hypertriglyceridemia & chylomicronemia syndrome
- decrease by 1/2 - increase HDL a little - LDL may fluctuate a little up or down - no effect on total mortality due to cardio events (although CV events decreased) MECH: ??? - Reduce triglyc by binding PPARs (gene tsc regs) --> stimulate FA ox, ^ lipoprotein lipase synthesis, decrease expression of apoC-III **don't know how they reduce lipoprotein levels** |
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FIBRIC ACID DERIVATIVES
- SIDE EFFECTS - METABOLISM - contraindicated |
SIDE EFFECTS:
- MAINLY GI - rash, urticaria, myalgia, fatigue, headache, impotence, anemia *can POTENTIATE oral anticoags (displace them from binding sites/albumin) *Gemfibrozil + statin = statin myopathy MONITOR ANTICOAG STATUS & CHECK FOR MYOPATHY *excreted in urine ONLY - NOT for pts w/ renal failure |
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BILE ACID SEQUESTRANTS
Indications, mech, side effects, contraindicated - Cholestyramine (questran) - colestipol - colesevalam |
Indication:
- Lower LDL - Increase HDL - Reduce # of CV events Mechanism: - Too big to be absorbed - + charged, bind negative bile acids = excretion of bile acids in stool *BUT, when bile acid pool decreases, Hepatic bile SYNTHESIS increases! - Increase LDL receptors (dec LDL) BAD THINGS: - Upreg HMG-CoA Reductase - Increase in triglyc synthesis *contraindicated in pre-existing SEVERE hypertriglyceridemia SIDE EFFECTS: - bloating, dyspepsia, constipation - can ^ triglycerides - bind & decrease absorption of other drugs (many) *ONLY USE in pts who can't tolerate statins or the max dose of statins doesn't work - compliance sucks of the crappy GI symptoms |
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NIACIN (NICOTINIC ACID)
NIACIN = NIASPAN (extended release) |
Good on all fronts
DOC: Increasing HDL (30-40%) - Lowers triglycerides, LDL, Lp(a) *ONLY drug to lower lp(a)* - reduces CV events MECH: - Adipocytes: inhibits hormone-sensitive lipase and dec hepatic glyceride synthesis - Also inhibits a rate-limiting enzyme of triglyceride synth - less FAs returning to liver - Less FAs made in liver (synthesis and esterification of FAs blocked) - Decreases fractional clearance of apoAI in HDL (not increasing synthesis) |
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NIACIN
- SIDE EFFECTS - METAB - CLINICAL USE |
SIDE EFFECTS: BIG, reduce compliance
*CUTANEOUS: flushing & pruritis on face, trunk, skin rashes, acanthosis nigricans (dark folds) - PG mediated (worse when you start/UP tx) - aspirin can help with flushing - also dyspepsia, & other GI - hepatotoxicity - DM: Induced insulin resistant --> hyperglycemia CLINICAL: - Use for pts who can't tolerate statins - start at VERY low doses, increase slowly *check for hepatotox & hyperglycemia |
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EZETIMIBE (ZETIA)
- INDICATION - MECH |
Monotx: reduced LDL 15%
COMBO with high dose simvastatin = 60% reduction in LDL MECH: Inhibits Jejunal enterocytes - can't take up cholesterol from lumen *doesn't affect intestine TRIGLYCERIDE absorption **may cause compensatory INCREASE in cholesterol synthesis** - also inhbiits intestinal absrption of plant sterols |
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EZETIMIBE
- metab - side effects - clinical use |
Water INsoluble --> enterohepatic recirculation --> FECES
*bILE-ACID SEQUESTRANTS INHIBIT ABSORPTION* only RARE allergic rxns; no real side effects USE: - IN COMBO W/ STATIN - NOT really as monotx - NOT w/ bile acid sequestrant |
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Cholesteryl Ester Transfer Protein Inhibitors
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CETP: plasma glycoprotein
- mediates transfer of cholesteryl esters from HDL to lipoproteins & LDL for 1 triglyceride *Inhibition of CETP = higher hDL & less LDL BUT, Torcetrapib SUCKED bc ^ incidence of CV events & cardiac mortality - still raised HDL |
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DRUGS FOR HEART FAILURE
- Diuretics - Vasodilator - ACE-Inh - AT-R Antag - Beta-blocker - Beta-agonist - Bypiridines - Cardiac Glycosides |
Diuretic:
- Spironolactone (Aldactone) - Eplerenone (Inspra) Vasodilator: - Nitroprusside (Nipride) - Hydralazine (Apresoline) - Nesiritide (Natrecor) ACE-INHIB: Enalapril (Vasotec) AT-R Antag: Valsartan (Diovan) Beta-Blocker Metoprolol (Lopressor, Toprol XL) Beta-Agonist: Dobutamine (dobutrex) Bypiridines: Milrinone (primacor) Cardiac Glycoside: Digoxin (lanoxin) |
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DRUGS SHOWN TO IMPROVE SURVIVAL IN PATIENTS WITH HEART FAILURE
(REDUCE MORTALITY) |
1. Hydralazine/Isosorbide dinitrate combo
- esp in blacks also taking ACE-I & Beta-Blockers 2. ACE-Inhibitors 3. Beta-R antagonists 4. Spironolactone & Eplerenone |
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HEART FAILURE
- Classic vs. RECENT definition |
CLASSIC
Inability of the heart to supply the metabolic needs of the body RECENT: Clinical state manifested by myocardial dysfunction w/ neurohormonal activation & congestion |
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DIURETICS
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Spironolactone (aldactone) & Eplerenone (inspra)
Many classes - Cause net urinary loss of Sodium & Water = Decreased PRELOAD *Lowered Venous pressure = improved congestive symptoms - peripheral edema, dyspnea - also reduces myocardial oxygen demand NO effect on mortality (except spironolactone) - just used to tx symptoms *used to tx HEART FAILURE |
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SPIRONOLACTONE
(ALDACTONE) - indications for use - mechanism - Clinical use |
Indication
- Reduces Mortality in pts w/ ADVANCED heart fail when added 2 other std therapy MECH: Competitive Inhibitor of Aldosterone; blocks mineralocorticoid-R - net urinary excretion of Na+ & H2O (weak diuretic) - K+ sparing (prevents hypokalemia) *May prevent <3 arrhythmias* ** blocks deleterious effects of aldosterone ( cardiac remodeling & elevated <3 filling pressures)** CLINICAL: - low doses in pts w/ <3 fail (high doses for cirrhosis) - Monitor K+ levels (fatal hyperkalemia) *contraindicated in pts w/ pre-existing hyperkalemia or high risk of dev it. |
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SPIRONOLACTONE
- Side effects (unique) - Significant drugs interactions - metabolism |
METAB:
- highly protein bound - active metabolite (canrenone): long 1/2 life COMMON SIDE EFFECTS: - Hyperkalemia (can be fatal) UNIQUE: - BLOCKS other steroid receptors --> Gynecomastia & menstrual irregularities DRUG INTERAXNS: - Salicylates decrease efficacy - Spironolactone decreases clearance of digitalis glycosides (increased levels) |
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NITROPRUSSIDE
- indication - mech - Route of admin - other drugs in this class: Organic nitrates, Isosorbide Dinitrate (more venodilation) |
INDICATION:
ACUTE, in-pt tx of SEVERE, acutely decompensated heart fail (esp assc'd w/ HTN - hypertensive crisis) MECH: VASODILATOR - Releases NO --> +cGMP --> relax smooth muscle - Affects arterioles & venules *Arteriolar vasodilation predominates in heart failure* = Decreased AF & Increased CO ROUTE: IV - fast onset (30 sec) - short duration (peaks at 2 min) **very unstable; decomposes to light & ^ pH** |
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VASODILATORS OF HEART FAILURE
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- NITROPRUSSIDE (NIPRIDE)
- HYDRALAZINE (APRESOLINE) - Nesiritide (Natrecor) |
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NITROPRUSSIDE (NIPRIDE) - IV
- metab - Side effects - Contraindications |
METAB:
- Metabolized by Smooth muscle --> Release of Cyanide & the NO - Liver: Cyanide --> Thiocyanate --> urine SIDE EFFECTS: - Hypotension (excess vasodilation) UNIQUE: (prolonged infusion) - Cyanide toxicity - Lactic acidosis CONTRAINDICATION: - Pts w/ hypotension *limit infusions to <24 hrs, esp if renal fxn is impaired |
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HYDRALAZINE (APRESOLINE): oral
- Indications - Mech - Elim: LIVER - Side effects |
INDICATION:
- Reduces mortality due to <3 fail (when used w/ Isosorbide dinitrate) *esp in Af-Ams w/ std therapy MECH: Direct Vasodilator - exact mech is uncertain - not much effect on veins SIDE EFFECTS: - Headache - Reflex sympathetic activity: tachy, ^ plasma renin, fluid retention *taken with ACE-Is & B-blockers* UNIQUE: - Drug-induced lupus (at least 6 mo tx) --> 10% pts (white women) |
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NESIRITIDE (NATRECOR): IV
- indication - Mech - METAB: short half life (18 min) - SIDE EFFECTS |
INDICATION: ACUTE excerbation of congestive <3 fail --> Dyspnea
MECH: - Recombinant form of human brain natriuretic peptide (BNP) (Natural BNP made by <3 cells 2' stretch) = Vasodilation, Natriuresis, Diuresis = Decreased preload w/o direct chronotropic or inotropic effects SIDE EFFECTS: - Hypotension *contraindicated in pts w/ sys BP <90mmHg |
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ENALAPRIL (VASOTEC)
indication mechanism clinical use - contraindications |
INDICATION: bc it's awesome
- Decreases Mortality - Decreases Symptoms - Dec. Hospitalizations - Improves LV fxn - Reduces PROGRESSION TO <3 FAIL (in asymptomatic pts) MECHANISM: 1. Blocks ACE = Less ANGII - less aldosterone & <3 remodeling 2. Blocks inactivations of Bradykinin - Vasodilation = Dec. AF (^ CO) - Releases NO & PGI2 3. Improves Endothelial fxn: - anti-inflamm, anti-thrombotic CLINICAL: - start at low dose, titrate up slow - Monitor BP, RENAL FXN, K+ - MUST BE USED IN ALLLL <3 FAIL PTS w/o contraindications contraindications: hyperkalemic, renal failure, pregnant |
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ENALAPRIL (VASOTEC)
- METAB - SIDE EFFECTS - SIMILAR DRUGS |
METAB: CASI TODO KIDNEYS!
SIDE EFFECTS: - Dec ANGII = HypoTN, Hyperkalemia, impaired renal fxn *esp bad in pts w/ renal a. stenosis* - Dry cough (bradykinin) UNIQUE: - ANGIOEDEMA: swollen face/throat *not does related; occurs w/in 1st week of tx* *Fetopathic effects in 2nd/3rd trimesters* DON'T USE IN PREGGERS SIMILAR DRUGS: -pril - captopril, ramipril, lisinopril, quinapril, fosinopril |
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NESIRITIDE (NATRECOR): IV
- indication - Mech - METAB: short half life (18 min) - SIDE EFFECTS |
INDICATION: ACUTE excerbation of congestive <3 fail --> Dyspnea
MECH: - Recombinant form of human brain natriuretic peptide (BNP) (Natural BNP made by <3 cells 2' stretch) = Vasodilation, Natriuresis, Diuresis = Decreased preload w/o direct chronotropic or inotropic effects SIDE EFFECTS: - Hypotension *contraindicated in pts w/ sys BP <90mmHg |
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ENALAPRIL (VASOTEC)
indication mechanism clinical use - contraindications |
INDICATION: bc it's awesome
- Decreases Mortality - Decreases Symptoms - Dec. Hospitalizations - Improves LV fxn - Reduces PROGRESSION TO <3 FAIL (in asymptomatic pts) MECHANISM: 1. Blocks ACE = Less ANGII - less aldosterone & <3 remodeling 2. Blocks inactivations of Bradykinin - Vasodilation = Dec. AF (^ CO) - Releases NO & PGI2 3. Improves Endothelial fxn: - anti-inflamm, anti-thrombotic CLINICAL: - start at low dose, titrate up slow - Monitor BP, RENAL FXN, K+ - MUST BE USED IN ALLLL <3 FAIL PTS w/o contraindications contraindications: hyperkalemic, renal failure, pregnant |
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ENALAPRIL (VASOTEC)
- METAB - SIDE EFFECTS - SIMILAR DRUGS |
METAB: CASI TODO KIDNEYS!
SIDE EFFECTS: - Dec ANGII = HypoTN, Hyperkalemia, impaired renal fxn *esp bad in pts w/ renal a. stenosis* - Dry cough (bradykinin) UNIQUE: - ANGIOEDEMA: swollen face/throat *not does related; occurs w/in 1st week of tx* *Fetopathic effects in 2nd/3rd trimesters* DON'T USE IN PREGGERS SIMILAR DRUGS: -pril - captopril, ramipril, lisinopril, quinapril, fosinopril |
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VALSARTAN (DIOVAN)
- indication - mech - metab - side effects *similar clinical use as ACE-Inhib (monitor all, start low) Similar drugs: end in "-sartan" |
INDICATION:
- Pts who can't tolerate ACE-inhibs (usually bc cough or angioedema) - Not sure if it also decreases mortality - Renoprotective in DMII pts MECH: Competitive blocker of ANGII - Higher affinity for AT-1 than AT-2 - Peripheral vasodilation (dec AF) - Also lessens cardiac remodeling (*does NOT affect bradykinin breakdown) METAB: Mainly LIVER SIDE EFFECTS: - Similar to ACE-Inhibs: HypoTN, hyperkalemia, renal failure - DON'T CAUSE COUGH UNIQUE: - Angioedema (not as frequently as in ACE Inhibs tho) |
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METOPROLOL (LOPRESSOR, TOPROL XL)
& Carvedilol & bisoprolol indication - mech - clinical use |
INDICATION: MOST POWERFUL DRUGS for HEART FAILURE
- Improves symptoms - Improves LV fxn (^ Ejection fraction) - Improves Mortality in pts w/ heart failure MECH: Beta-1 Selective Antag EARLY: - Reduced contractility - Reduced HR *Initially Decreases LV sys fxn, Eventually INCREASES LV sys fxn above baseline LATER: - Reduces sym. activation of JG cells (renin) & circ catecholamines -Prevent down-reg of B-R in <3 - Reduce Myocardial ischemia/work CLINICAL USE: - Start @ VERY low doses & titrate up slowy (risk of worsening <3 fail) - Use in clinically stable pts - Monitor carefully (BP & HR) |
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METOPROLOL (LOPRESSOR, TORPOL XL)
- metab - side effects |
Metab: LIVER
SIDE EFFECTS: - bradycardia - hypotension - peripheral vasospasm - claudication - worsening of <3 fail (acute effect) Metabolic side effects: - Impaired resonse 2 hypoglycemia - Dec HDL levels - Increased Triglycerides *Sig. Neuro side effects (sleepy, fatigue, memory loss) - sexual dysfxn - rarely depression |
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BETA-BLOCKERS
(METOPROLOL) - OTHER USES THAN HEART FAILURE - SIMILAR DRUGS TO METOPROLOL |
*Used for lots of <3/vascular things*
- also for performance anxiety SIMILAR DRUGS: - Carvediolol (coreg): non-selective B-blocker & a1-R antag - Bisoprolol (zebeta): beta-1 selective antag (like metoprolol) *Bisoprolol, carvedilol, & Metoprolol = only beta blockers shown to improve outcomes of heart failure pts |
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DOBUTAMINE = IV ONLY
(DOBUTREX) - INDICATION - MECH - SIDE EFFECTS - METAB: SHORT HALF LIFE **NO CONTRAINDICATIONS - but use carefully in pts w/ ischemic heart dz DOPAMINE IS SIMILAR: also vasoconstricts (+ inotropic) |
INDICATION: Acute, short-term tx of SEVERE decompensated heart failure
- bridge to transplant MECH: - Beta 1 & Beta 2- R agonist - Beta1-R effects predominate --> ^ cAMP = ^ contractility --> small Dec in TPR = INCREASED CO SIDE EFFECTS: - Worsened angina (increased myocardial O2 demand) - Tachycardia - Worsen vent. arrhythmias (^ HR) |
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MILRINON (PRIMACOR) = IV ONLY
- INDICATION - MECH - METAB: longer 1/2 life than DA - SIDE EFFECTS *similar drug: Inamrinone (higher incidence of thrombocytopenia) |
INDICATION: Short term, ACUTE, tx of Severely decomp congestive <3 fail
- harmful longterm MECH: Inhibit phosphodiesterase3 - less breakdwon of cAMP - ^ cAMP = increased contractility & peripheral vasodilation = INCREASED CARDIAC OUTPUT SIDE EFFECTS: similar to DA - ^ myocardial O2 demand - tachycardia UNIQUE: thrombocytopenia can rarely occur - more common in inamrinone |
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DIGOXIN
(LANOXIN, DIGITEK) - INDICATION - MECH - PHARMACOKINETICS - CLINICAL USE **precursor to digoxin = Digitalis* |
INDICATION: In Chronic congestive heart failure
- Improves symptoms - decreases hospitalizations - may ^ survival at low doses (worse w/ high doses) MECH: Inhibits Na/K ATPase - Increased intracellular Na+ = Prevent extrusion of intracellular Ca2+ during repolarization = ^ Intracellular Ca2+ = ^ contractility (inotropic) (less than beta-blockers tho) PHARMACOKINETICS: - long 1/2 life - Excreted by kidneys (GFR clearance); renal fail is BAD!! - Primary reservoir = sk. mm CLINICAL USE: - LOW DOSES - monitor renal fxn |
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DIGOXIN
- SIDE EFFECTS - DRUG INTERACTIONS |
SIDE EFFECTS:
- Conduction problems: AV block - CLASSIC = Atrial tachy w/ variable block - Vent Arrythmias - Severe brady - GI problems: nausea, vomit, anorexia - CNS: fatigue, malaise, confusion, seizures DRUG INTERAXNS: TONS =/ - Quinidine * - AMIODARONE * - Broad-spec Abx (erythro & tetracyc) ^ serum digoxin ---> alter GI bacteria that would metabolize digoxin |
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DIGOXIN TOXICITY
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STOP DRUG
- K+ REPLACEMENT - TEMPORARY PACING - ATROPINE FOR BRADY - IV-DIGoxin specific Ab in severe toxicity |
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DOBUTAMINE = IV ONLY
(DOBUTREX) - INDICATION - MECH - SIDE EFFECTS - METAB: SHORT HALF LIFE **NO CONTRAINDICATIONS - but use carefully in pts w/ ischemic heart dz DOPAMINE IS SIMILAR: also vasoconstricts (+ inotropic) |
INDICATION: Acute, short-term tx of SEVERE decompensated heart failure
- bridge to transplant MECH: - Beta 1 & Beta 2- R agonist - Beta1-R effects predominate --> ^ cAMP = ^ contractility --> small Dec in TPR = INCREASED CO SIDE EFFECTS: - Worsened angina (increased myocardial O2 demand) - Tachycardia - Worsen vent. arrhythmias (^ HR) |
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MILRINON (PRIMACOR) = IV ONLY
- INDICATION - MECH - METAB: longer 1/2 life than DA - SIDE EFFECTS *similar drug: Inamrinone (higher incidence of thrombocytopenia) |
INDICATION: Short term, ACUTE, tx of Severely decomp congestive <3 fail
- harmful longterm MECH: Inhibit phosphodiesterase3 - less breakdwon of cAMP - ^ cAMP = increased contractility & peripheral vasodilation = INCREASED CARDIAC OUTPUT SIDE EFFECTS: similar to DA - ^ myocardial O2 demand - tachycardia UNIQUE: thrombocytopenia can rarely occur - more common in inamrinone |
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DIGOXIN
(LANOXIN, DIGITEK) - INDICATION - MECH - PHARMACOKINETICS - CLINICAL USE **precursor to digoxin = Digitalis* |
INDICATION: In Chronic congestive heart failure
- Improves symptoms - decreases hospitalizations - may ^ survival at low doses (worse w/ high doses) MECH: Inhibits Na/K ATPase - Increased intracellular Na+ = Prevent extrusion of intracellular Ca2+ during repolarization = ^ Intracellular Ca2+ = ^ contractility (inotropic) (less than beta-blockers tho) PHARMACOKINETICS: - long 1/2 life - Excreted by kidneys (GFR clearance); renal fail is BAD!! - Primary reservoir = sk. mm CLINICAL USE: - LOW DOSES - monitor renal fxn |
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DIGOXIN
- SIDE EFFECTS - DRUG INTERACTIONS |
SIDE EFFECTS:
- Conduction problems: AV block - CLASSIC = Atrial tachy w/ variable block - Vent Arrythmias - Severe brady - GI problems: nausea, vomit, anorexia - CNS: fatigue, malaise, confusion, seizures DRUG INTERAXNS: TONS =/ - Quinidine * - AMIODARONE * - Broad-spec Abx (erythro & tetracyc) ^ serum digoxin ---> alter GI bacteria that would metabolize digoxin |
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DIGOXIN TOXICITY
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STOP DRUG
- K+ REPLACEMENT - TEMPORARY PACING - ATROPINE FOR BRADY - IV-DIGoxin specific Ab in severe toxicity |
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MODALITIES FOR TX OF MYOCARDIAL ISCHEMIA
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1. Lifestyle changes
2. Meds 3. Percutaneous coronary interventions - angioplasty, stents, etc 4. CABG |
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ORGANIC NITRATES
- indication / role in M. ischemia - Mech 1. Decreases Preload 2. Increases CBF 3. Decreases AF |
Acute resolution of symptoms
- Chronic prevention of symptom - used in ALL manifestations of m. ischemia MECH: PRODRUG of NO - NO activates Guanylyl Cyclase - Increased cGMP - Relaxation of smooth m. --> Vasodilation (veins >> aa) (DECREASED PRELOAD) - also directly dilate epicardial coronary aa (INCREASED CBF) - Peripheral vasodilation (DECREASED AF) = Decreased work & O2 demand *Also inhibits platelet aggregation - relaxes smooth muscle (Bronchi & GI tract) |
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ORGANIC NITRATES
- DRUGS? |
1. NITROGLYCERIN (nitrostat)
2. Isorbide denitrate (isordil) 3. Isorbide-5 mononitrate (imdur) |
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ORGANIC NITRATES
- metab - Side effects - toxicity |
Fast acting, short duration
- glucuronide conjugation - great bioavailabilty SEs: mostly 2' vasodilation 1. Headache (bad) 2. Hypotn: Dizzy & lightheaded 3. Facial flushing 3. Postural hypoTN & syncope Toxicity: accentuated by PDE-5 inhibitors (-fils; ED drugs) - inhibit breakdown of cGMP --> major hypoTN & death |
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ORGANIC NITRATES
-TOLERANCE - REBOUND - cinical use |
Cont. exposure at high doses = marked attenuation
Mechanisms of tolerance: 1. Volume expansion 2. Neurohumoral activation 3. Cellular depletion of sulfhydryl groups 4. Generation of free radicals - Concomitant use of drugs that affect free radical formation can decrease tolerance (?) *Only way to prevent tolerance is to interrupt tx for at least 8 hrs / day** - REBOUND INCREASE IN ANGINA POSSIBLE CLINICAL USE: - sublingual NG = acute tx of angina pectoris - oral preps: prevention during the day - observe nitrate-free interval; watch out for viagra |
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DRUGS TO TX MYOCARDIAL ISCHEMIA
(and its manifestations) |
1. Organic nitrates
2. Beta blockers 3. Ca2+ channel blockers 4. Anti-platelet 5. Anti-thrombotics 6 Fibrinolytic drugs 7. Drug-eluting endovascular stents |
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BETA BLOCKERS & MYOCARDIAL ISCHEMIA
(Metoprolol, propranolol, atenolol, carvedilol) - indications - mech |
INDICATIONS:
- Stable & unstable angina pectoris - acute & long-term in acute MI **improvement in survival post-MI** NO ROLE IN VARIANT ANGINA MECH: - Bind Beta-R - Prevent effects of catecholamines = Decreased HR & contractility & Dec. BP (AF) = Decreased O2 demand!!! |
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BETA-BLOCKERS
- SEs - similar drugs - clinical use *fatigue & sex issues are main reasons for stopping* |
SEs: SNS depression
- Brady - hypotn - peripheral vasospasm - claudication - WORSENING OF HEART FAILURE - bronchospasm (worse asthma); esp in Beta1 blockers - Metabolic effects: insulin weirdness, less HDL, increase triglycerides - NEURO: fatigue, lethargy, memory loss, hallucinations, sleep distrubance - Sexual dysfxn: impotence, libido probs OTHER DRUGS: - High lipid sol = more CNS (like fatigue) - Intrinsic agonist activity: less dec in HR - Membrane stabilizing activity: maybe more effective in tx-ing arrhythmias clinical: MOST EFFECTIVE - use in CAD - for EVERYONE post-MI - start low & monitor HR & BP - careful in asthmatics & conduction problems |
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CALCIUM CHANNEL ANTAGONISTS & M. ISCHEMIA
(Amlodipine, Nifedipine, Diltiazem, Verapamil) - indications - mech |
INDICATION: Reduce chest pain in..
- Stable Angina - Unstable Angina - Variant angina (NO GOOD for MI) - Nifedipine actually INCREASES mortality post-MI MECH: Stops extracell Ca2_ - Bind a1-subunit of L-type Ca2+ channels - Reduced Ca influx - Decreased contractility & - Slows conduction & automaticity (in AV, SA nodes) & - Vasodilation (smooth mm. relax) **Dif drugs have variable effects on certain parts** |
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CALCIUM CHANNEL ANTAGONISTS
- USES OF EACH PARTICULAR DRUG - Amlodipine (norvasc) & felodipin (plendil) - Nifedipine (adalat, procardia) - Diltiazem (cardizem, dilacor-XR) - Verapamil (calan, isoptin, verelan) |
1. Amlodipine & Felodipine
- Potent Vasodilators - No big effect on <3 conduction or contractility 2. Nifedipine: - Potent vasodilator - medium suppression of contractility *only sustained release* 3. Diltiazem & Verapamil - Moderate vasodilator - POTENT suppression of contractility & automaticity/conduction *Bradycardia can be a SE* *Diltiazem must be sustained release* |
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CA2+ CHANNEL ANTAGS
- metab - SEs clinical use: - HR monitor is mandatory in Diltiazem & verapamil, esp in combo w/ beta-blockers |
METAB'D in LIVER
SEs: - Hypotn (--> reflex SNS activity) - Bradycardia - Peripheral edema - wORSE CHF (except for amlodipine & felodipine) - Reflex catecholamine release (can worsen ischemia) *Peripheral edema: caused by direct vasodilation of peripheral vessel & NOT reduction in contractility |
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RANOLAZINE
(RANEXA) - indication in m. ischemia - mech |
INDICATION
- Chronic tx of stable angina (2nd line drug; only if others don't work or SEs too bad) MECH: UNKNOWN! - No real effect on BP or HR - probably alters cardiac metabolism *Blocking Late Na+ channel = decreased contractility |
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ranolazine (ranexa)
- side effects - drug interactions - clinical use |
1. QT prolongation = major
2. bRADY 3. Palpitations 4. hypoTN 5. Syncope 6. GI side effects: nausea, vomiting, abd pain 7. CNS: vertigo, dizzy, headache, blurry DURG INTERAXNS: Inhibitors of hepatic CYP3A4: increase serum levels - Grapefruit - diltiazem & verapamil - HIV protease inhibitors - ketoconazole - macrolide abx **Drugs that prolong QT interval can ^ chance of v-arrhythmias |
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ANTI-PLATELET DRUGS & MYOCARDIAL ISCHEMIA
- indication - mech - clinical use |
PREVENTION
- aspirin & clopidogrel ACUTE TX: - UNSTABLE angina - acute MI MECH: 1. Aspirin: COX inhibitor - prevents TX-A2 formation & platelet activation 2. Thienopyridines: inhbit P2Y12-R - inhibit ADP mediated platelet activation 3. Abciximab, Eptifibatide, Tirofiban - Inhibit Glyoprotein2b/3a-R - inhibits platelet aggreg; even with platelet activation - noncompetitive & comp. inhibitors = INHIBITION OF CLOT FORMATION --> inhibit symptoms assc'd with clots CLINICAL: - Daily prophylactic use in CAD pts or many risk factors - Monitor for occult bleeding |
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anti-platelet drugs & m. ischemia
- metab - side effects |
METAB:
1. Aspirin: irrev inhib of COX 2. Ticlopidine: irrev inhib of P2Y12 - clopidogrel is a prodrug 3. Abciximab: Fab Fragment of Ab - noncompetitive inhib - works many hours after stopping drug SIDE EFFECTS: #1. BLEEDING 2. Irritated gastic mucosa 3. severe neutropenia (ticlopidine - 2.4%) 4. Thromboyctopenia (abciximab - 2%) UNIQUE SE: - Severe hypersensitivy to aspirin - more common in pts w/ asthma, nasal polyps, or chronic urticaria |
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MECHANICOPHARMACOLOGICAL TX
- DRUG-ELUTING ENDOVASCULAR STENTS - clinical use - mech - duration - common SE |
CLINICAL USE:
- Coat the stents w/ drugs - prevents re-stenosis (smooth m. proliferation 2' injury of stent placement) MECH: - Paclitaxel: binds polymerized microtubules - Sirolimus & Everolimus: bind cytosolic FKBP12 --> inhibits mTOR (cell cycle prog) DURATION: couple years SE: - Inhibit growth of endothelium also - Risk of thrombosis (bare emtal) --> MI (minimize w/ aspirin & clopidogrel) |
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ANTI-PLATELETS & MYOCARDIAL ISCHEMIA
- DRUGS? |
1. Acetylsalicylic acid (aspirin)
2. Ticlodipine (ticlid) 3. Clopidogrel (plavix) 4. Abciximab (reopro) |
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ERYTHROPOIETIN
- Epoetin alfa (Epogen, procrit, exprex) - Darabapoetin alfa (aranaesp) (longer half life) - NESP 1. indication 2. mech *Highly effective when given w/ adequate iron intake - med. 1/2 life, but only give 3x/week |
INDICATION: tx anemia assc'd with:
- Chronic kidney disease - Sx - AIDS - CA chemo - Prematurity - chronic inflamm MECHANISM: - nearly identical to endog. EP - Bind to a R on committed erythroid progenitor in marrow --> Cell survival, proliferation, & maturation |
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ERYTHROPOIETIN & FRIENDS
1. adverse effects 2. Drug interactions 3. Clinical use |
SIDE EFFECTS:
- Thromboembolic events (Risk increases w/ higher Hb levels) - Increase BP (hypertensive encephalopathy & seizures) - Headache, tachy, edema, SOB, nausea, vomit, diarrhea, flu-ish, etc DRUG INTERAXNS: - Absolute or functional iron deficiency (use it up!) - will need iron supp. CLINICAL USE: - Check HCT 1-2x/wk until stabilized - don't let it increase >4 pts/2 wks |
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GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR
(GM-CSF) Sargramostim (Leukine) 1. Indication 2. Mech 3. SEs |
INDICATION: fights neutropenia in
- Autologous BMT - Allogeneic transplatnation - Intensive chemo - Mylodeysplasia, aplastic anemia - AIDS-assc'd neutropenia MECH: = GM-CSF - increase neutrophils & monocytes - Enhances migration / phag / superoxide production / ADCC METAB: works in about 1 week SEs: - bone pain, malaise, flu, fever, diarrhea, dyspnea, rash - Sensitivity: flushing, hypotn, nausea, vmoit, dyspnea (ganulocyte sequestraction in pulmonary circulation = SOB) - Supravent. Arrhythmias - High BUN & creatinine & hepatic enzymes |
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GRANULOCYTE COLONY STIMULATING FACTOR
(G-CSF) Filgrastim (neuopogen) - Pegfilgrastim is similar (pegylated), but cleared by neutrophils (not kidneys) 1. inidcation 2. mech 3. admin 4. metab 5. SE |
INDICATION: severe neutropenia
- post-autologous hematopoetic stem cell transplant - High dose chemo MECH: stimulate CFU-G - increase production, enhance phag & cytotoxic fxns Parenteral admin; fast absorption SEs: - bone pain & local skin rxns - Splenomegaly = long term tx - RARE: cutaneous necrotizing vasculitis |
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oprelvekin (neumega)
- indication - mech - adverse - clinical |
INDICATION: Fights rpt thrombocytopenia in CHEMO
MECH: Recombinant IL-11 = enhanced megakaryocyte maturation in vitro - increases platelets in you ADVERSE: - Fluid retention - tachy & palpitations - edema, SOB - blurred vision, paresthesias CLINICAL: - monitor platelets - d/c when > 100k - monitor Heart failure pts close |
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Thrombopoietin
- rHuMGDF (Recombinant human megakaryoctye growth & dev. factor) - rHuTPo (Recombo human thrombopoietin) 1. indications 2. mech 3. adverse |
INDICATION: fights thrombocytopenia in
- chemo - radiation (myelosuppression) MECH: - Stimulates stem cell diff into megakaryocyte progenitors - Selectively stimulates megakaryocytopoiesis to increase platelet ADVERSE: - Develop anti-recombo TP Abs -->Cross-react w/ native TP --> Thrombocytopenia! end up getting/worsening what you're trying to stop! |
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DRUGS USED IN IRON DEFICIENCY
1. Oral iron preps 2. Parenteral iron |
ORAL IRON PREPS
1. Ferrous sulfate (feosol) 2. Ferrous fumarate (feostat) 3. F. gluconate (fergon) 4. Polysacc iron complex (Niferex) PARENTERAL IRON 1. Sodium ferric gluoconate complex (Ferrlecit) - in sucrose 2. Iron sucrose (Saccharate) 3. Iron dextran (Infed, Dexferrum) |
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ORAL IRON PREPS
- indication - adverse -clinica use |
INDICATION: Fe-def anemia (and no absorption problems)
Adverse: - Heart burn - nausea - upper GI discomfort - Diarrhea - Constipation - RARE: HEMOCHROMATOSIS (iron overload; usu. genetic) CLINICAL: - See increase retic in ~4-7 days - longer delay in Hb rise - wait 3-4 weeks for full effect |
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PARENTERAL IRON
- indication - CLEARance - adverse |
INDICATION:
- oral fe absorption sucks/intolerant Clearance is via reticuloendothelial cells if given in high doses ADVERSE: - Generalized symptoms (fever, malaise, lymphoadenopathy) - rare: anaphylactic rxn (higher in iron dextran) |
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TX OF MEGALOBLASTIC ANEMIA
- what types of drugs? |
1. Vit B12 (Cyanocobalamin)
2. Folic acid |
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VIT B12
(cyanocobalamin) - indication - abs - adverse - clinical |
INDICATION: anemia 2' vit B12 def
(megaloblastic anemia) *Oral abs is very variable* - depends on IF - >100 micrograms is just cleared, so don't up it more than that ADVERSE: - rare: anaphylaxis (mostly w/ IV) --> give IM or deep SC CLINICAL: - only give prophylactically in SEVERE cases |
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FOLIC ACID
- indication - mech - abs - adverse |
INDICATION:
- megaloblastic anemia 2' folate def. - Prophylactic: Pregnancy, breastfeeding, TPN, hemolytic anemia - Elevated homocysteine MECH: - Purine synthesis Abs: proximal SI --> enterohepatic circ - daily intake required ADVERSE: - rare: rxns to parenteral injxns - HIGH DOSES: counteract anti-epileptic effect of phenobarb, phenytoi, primidone (pills are 1 mg or less to avoid this) clinical: - Careful not to misdx Vit B12 def as folate def. (Neuro symptoms will NOT improve, even if anemia might) |
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HEPARIN
- indication - mech - metab/elim |
INDICATION: (clot-buster)
- initial tx of Venous Thrombosis, PE, acute coronary syndromes, acute MI - used in angioplasty, stent procedures - sx requiring <3/lung bypass - tx DIC sometimes - prevention/prophylactic MECH: - Catalyzed the inhibition of coag via antithrombin - Antithrombin inhibits coag factors (Thrombin, factor 10a, 9a) METAB: immediate onset in IV - cleared by RE system |
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HEPARIN
- ADVERSE EFFECTS - UNIQUE SEs - clinical considerations |
ADVERSE:
- MC = Bleeding (1-5%) - Rare: weird liver fxn, osteoporosis (long term), hyperK+ (inhibit aldosterone) UNIQUE: HIT (heparin-induced thrombocytopenia) 0.5% pts 5-10 days post-tx start = THROMBOSIS/coag - Lower incidence in low MW heparin - IgG Abs against heparin-factor 4 complexes --> platelet activation --> thrombin generation *HIT can be more severe w/ prior heparin exposure* - TX: stop heparin; use other anticoag CLINICAL USE: - monitor 2 prevent bleeding - use PTT & ACT (activated coag time - bleeding time?) - LMWH dosage monitored by factor X activity |
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HEPARIN
- SIMILAR DRUGS - antag |
Low MW Heparin (LMWH)
- Enoxaparin (Lovenox) - Dalteparin (fragmin) - Tinzaparin (Innohep) - Ardeparin (normiflo) - Nadroparin (fraxiparine) - Raviparin (Clivarine) *INHIBITS Factor Xa activity* Fondaprinux (aristra) = factor 10a inhibitor - synthetic pentasacc HEPARIN ENEMY: Protamine sulfate: mix of polypeptides from salmon sperm - binds tight to heparin - Neutralizes its anti-coag effecs - give minimal amounts (anaphylaxis can occur; esp in DM pts) *Protamine is sometimes in insulin* **NOT USED IN RENAL CLEARANCE** |
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OTHER PARENTAL ANTICOAGULANTS
(other than heparin) - Lepirudin |
1. Lepirudin (Refludan)
- recombinant hirudin - Direct thrombin inhibitor (leech saliva) - for HIT pts - Kidney excretion - Rarely develop antihirudin Abs |
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PARENTERAL ANTICOAGULANTS
*Protamine sulfate NEUTRALIZES heparin* |
1. Heparin
2. LMWH 3. Lepirudin (Refludan) 4. Bivalirudin (angiomax) 5. Argatroban 6. Danaparoid (orgaran) 7. Drotrecogin alfa (Xigris) |
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OTHER PARENTAL ANTICOAGULANTS
(other than heparin) - BIVALIRUDIN - ARGATROBAN |
BIVALIRUDIN
- synthetic protein - direct inhibitor of thrombin; similar to lepirudin - ALT. to heparin in pts w/ coronary angioplasty - renal clearance Argatroban - synthetic L-Arg compound - competitive inhibitor of Thrombin - Tx/prophylaxis of HIT - cytochrome P450 liver clearance - excreted in bile |
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OTHER PARENTAL ANTICOAGULANTS
(other than heparin) - Danaparoid - Drotrecogin alfa |
DANAPAROID:
- nonheparin GAGs from procine SI - Prophylaxis of DVT, & HIT tx - like heparin; activates antithrombin to do its dirty work (inhbit factor 10a) DROTRECOGIN ALFA - recombinant human activated protein C - INactivates factors Va & VIIIa - used in pts with severe sepsis (improves mortality) |
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ORAL ANTICOAGULANTS
- WARFARIN (coumadin) - indications - mech - CLINICAL |
INDICATIONS: thrombosis
- Prevents progression or recurrence of DVT & PE - Pts w/ prosthetic valves, chronic a-fib, intracardiac thrombus MECH: Vit K antagonist - decrease total amt. of Vit-K dep. coagulation factors made by liver - made factors have diminished activity = FACTORS 2,7,9,10 clinical: - start: 2-5 mgs/day - monitor PT in INR - monitor monthly |
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ORAL ANTICOAGULANTS
WARFARIN (coumadin, others) - metab - adverse effects |
METAB:
- completely absorbed - 99% is bound to plasma proteins - SUPER LONG HALF LIFE - Does NOT affect factors already made --> Takes a while to see effects (3-5 days) & vice versa ADVERSE: - MC = Bleeding, < 5% / yr - Birth defects of kids born to moms - Skin necrosis, purple toe syndrome, alopecia, urticaria, dermatitis, fever, anusea, diarrhea, abd cramps, anorexia - Precipitates venous limb gangrene & multicentric skin necrosis (assc'd w/ HIT) |
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ORAL ANTICOAGULANTS
WARFARIN (coumadin, others) - DRUG INTERACTIONS - POTENTIATION / INHIBITION |
INTERACTIONS;
1. Altered uptake or metab of oral anticoag or Vit K 2. Altered synthesis/fxn/clearance of hemostatic factors 3. Agents that alter epithelial integrity = increased bleeding 4. Drugs that reduce absorption (like cholestyramine) 5. Increased metabolic clearance- induction of hepatic enzymes (and vice versa) 6. Agents taht displace warfarin from binding sites of plasma proteins |
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WARFARIN
- Potentiation - inhibition |
POTENTIATION
1. Alcohol (if + liver dz) 2. Amiodarone - abx & anabolic steroids 3. Tylenol; aspirin 4. heparin 5. Indomethacin LOTS OF THINGS INHIBITION - Barbiturates - Carbamazepine - Cholestyramine - griseofulvin - more and more and more |
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FIBRINOLYTIC DRUGS
1. Streptokinase (Streptase) 2. Recombinant t-PA = Alteplase (activase) 3. Reteplase (Retavase) - indications - mech - adverse - contraindications |
INDICATIONS: ACUTE tx
- of acute MI - Non-hemorrhagic stroke - dissolve pathologic thrombi MECH: Activate plasminogen --> PLASMIN POWER!! - lyses fibrin & dissolve thrombi - streptokinase needs to bind plasminogen - t-PA types are MORE CLOT specific |
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ANTI-FIBRINOLYTICS
- streptokinase + t-PA types - adverse - contraindications |
ADVERSE:
- MC = Bleeding 1.) Lysis of fibrin in thrombri PRIOR to vasc injury 2.) Systemic lytic state (activating plasmin?) **INTRACRANIAL HEMORRHAGE** - Streptokinase can cause allergies via previous exposure CONTRAINDICATIONS - Recent major sx - Serious recent re-bleeding - sever uncontrolled hTN - recent cerebral vasc accident - other Intracranial dz - aortic dissection - acute pericarditis |
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AMINOCAPROIC ACID
- indications - mech - elimination - SEs |
INHIBITS FIBRINOLYSIS
(pro-clot) INDICATION Reduce bleeding after prostate sx or tooth extraction in HEMOPHILIACS mech: - Competitive inhib of plasminogen & plasmin - blocks fibrinolysis ELIM: 50% excreted in urine unchanged SE: - Excessive THROMBOSIS - rarely: myopathy & muscle necrosis |
