CVS Pharmacology Final Summary Part 1 PDF

Heart Failure What do I expect from treating a patient with Heart Failure? The main aims being: o Decrease the symptoms (use diuretics i.e. Loop diuretics) The very high levels of angiotensin II and...

Heart Failure What do I expect from treating a patient with Heart Failure? The main aims being: o Decrease the symptoms (use diuretics i.e. Loop diuretics) The very high levels of angiotensin II and o Slow disease progression (ACE-I/ARBs/ Beta-blockers) aldosterone, increases remodeling (myocyte death & fibrosis) as well as hypertrophy. o Improve survival. Drugs used in Heart Failure Six Classes of drugs have been shown to be effective 1. ACE inhibitors (↓ Mortality) 2. β adrenergic blocking agents (↓ Mortality) 3. Aldosterone antagonist (I.e Spironolactone) ➔ (↓ Mortality) 4. Diuretics (↓ Symptoms & Reduces Hospitalizations) 5. Inotropic agents (I.e digoxin) ➔ Reduces Hospitalizations 6. Direct vasodilators (hydralazine & isosorbide dinitrate) ACE Inhibitors Beta Blockers Mechanism of action Mechanism of action o Decrease vascular resistance ➔ Decrease blood pressure & o Medium-long term effect: increase CO ▪ prevent sympathetic activation of the heart ➔ inhibit o Decrease Adrenaline & Aldosterone ➔ Decreased Cardiac apoptosis, necrosis, fibrosis, hypertrophy & remodeling desensitization of beta receptors Uses: ▪ Prevent cardiac remodeling o ACEls & ARBs are the drugs of choice in symptomatic and o The benefit is attributed in part to their ability to prevent asymptomatic HF patients changes of the sympathetic system, include decreasing the o These agents show a significant decrease in the mortality and heart rate and inhibiting renin secretion. morbidity. Uses: o May be considered as a single-agent therapy in patients who o Bisoprolol (cardioselective), carvedilol (non-selective) or have mild dyspnea on exertion, and do not have signs of volume nebivolol (increases NO) should be the beta blocker of first overload. choice for the treatment of patients with chronic heart failure Side effects due to left ventricular systolic dysfunction. o Dry irritating-persistent cough, Hyperkalemia, Angioedema & o These agents show a significant decrease in the mortality and Fetal toxicity (teratogenic), Hyponatremia, Hyperkalemia. morbidity. Notes Notes o Patients with heart failure due to left ventricular systolic o In the short term they can produce decompensation with dysfunction who are still symptomatic despite therapy with an worsening of heart failure and hypotension. ACE inhibitor and a beta blocker may benefit from the addition of ▪ They should be initiated at low dose and only candesartan. gradually increased with monitoring up to the target ▪ It is relatively contraindicated because there are other dose. pathways to produce angiotensin II and to stop or o Should be used with caution in those with low initial blood decrease any angiotensin response, we combine the pressure (ie systolic BP Sodium retention, myocardial hypertrophy, Uses: and hypokalemia. o Diuretic therapy should be considered for heart failure patients o Spironolactone —> Sodium loss, less myocardial remodeling, with dyspnea or Edema. and Hyperkalemia Side effects o Loop diuretics —> Hypovolemia & Hyponatremia Uses: o Spironolactone ACE-Inhibitors / ARBs —> Hyponatremia o Spironolactone should be preserved for the most advanced o Mixing loop diuretics with ACE-Inhibitors / ARBs ➔ Hyponatremia cases of HF can become worse. o Loop diuretics and thiazides cause hypokalemia. Side effects: ▪ Potassium sparing diuretics help in reducing the o Main side effects include CNS effects, such as confusion, hypokalemia due to these diuretics. endocrine abnormalities, and gastric disturbances like peptic o ACE-Inhibitors / ARBs —> Hyperkalemia ulcer. o Mixing loop diuretics with ACE-Inhibitors / ARBs ➔ Balanced o Spironolactone increases estrogen ➔ Gynecomastia effect on potassium levels. o Patients are usually started on spironolactone, whether they Notes are men or women, but if gynecomastia develops in men, we o Loop diuretics like furosemide and bumetanide are the most switch to eplerenone, although in Jordan we start with effective and commonly used. Eplerenone anyway. ▪ Ethacrynic acid is used instead in cases of sulfur Notes hypersensitivity o The dose of spironolactone should be no more than 25-50 o The dose of diuretic should be individualized to reduce fluid mg/day, and it is only recommended in those with moderate to retention without over-treating, which may produce dehydration severe heart failure due to LVSD. or renal dysfunction. o If you might not be able to monitor and control potassium levels in a patient; you should not give aldosterone antagonists Inotropic agents (Digitalis) Mechanism of action Inotropic agents (Dobutamine) o Inhibits the sodium-potassium ATPase of the myocyte ➔Increased intracellular Ca2+ ➔ positive inotropic effect ➔ increasing cardiac Mechanism of action contractility. o Dobutamine is a B1 adrenergic agonist that has positive o increases the vagus activity and increases the acetylcholine action inotropic effect and is the most used inotropc agent after on the M2 receptors on the heart, thus resulting in the negative digoxin. chronotropic activity Uses: Uses: o Digoxin is indicated with severe left-ventricular systolic failure o As mentioned, must be given by intravenous infusion (not after initiation of ACE inhibitors, diuretics, and β Blocker. oral) and is used in the treatment of acute HF in a hospital Side effects setting. o Digoxin toxicity (common) ➔ due to chronic use of drug, low Side effects: levels of K+ (due to a diuretic use for example) & drug o Hypotension (May also -yet with less affinity- bind to Beta-2 interactions. receptors ➔ Vasodilation & Hypotension) ❖ Anorexia, nausea and vomiting and diarrhea Notes ❖ Vision changes (xanthopsia) (yellow and white rings obscuring o Dobutamine increases the rate of mortality, but we use it in vision), fatigue and headache. one condition, if the ejection fraction is too low or ❖ cardiac effects that include premature ventricular contraction, cardiogenic shock (heart is very weak). and ventricular tachycardia and fibrillation. Arrhythmia and atrial tachycardia. Notes Hydralazine and Isosorbide Dinitrate o Digoxin has a low therapeutic index or window ➔ must be “ monitored The addition of a combination of hydralazine and a nitrate is o Digoxin interaction reasonable for patients with reduced LVEF who are already taking an ▪ Quinidine, verapamil, and amiodarone can cause digoxin intoxication, ACEI and beta- blocker for symptomatic HF and who have persistent both by replacing digoxin from tissue protein binding sites, and by symptoms competing with digoxin for renal secretion. ▪ Macrolide and tetracycline antibiotics should be avoided because they A combination of hydralazine and a nitrate might be reasonable in elevate digoxin serum concentration and enhance the risk for digoxin patients with current or prior symptoms of HF and reduced LVEF who toxicity. cannot be given an ACEI or ARB because of drug intolerance, o Good things about digoxin hypotension, or renal insufficiency ▪ No good oral inotropic agents exist other than digoxin. African American patients with advanced heart failure due to left ▪ Digoxin also has a rapid onset of action, making it useful in ventricular systolic dysfunction should be considered for treatment emergency condition, in which the drug in given intravenously, and the onset of action will be within 5-30 minutes. with hydralazine and isosorbide dinitrate in addition to standard ▪ DG Fab (also known as Digoxin-specific antibody fragments or Digoxin Immune Fab) is therapy. antidote for digoxin.  Anti-Hyperlipidemia type Ib hyperlipidemia Summary. > - S. all have equal efficacy 1. Statins = HMG CoA Reductase Inhibitors (-statin) “most potent” Rosuvastatin is the most potent. MOA ↳ a. Inhibit HMG CoA Reductase —> less Mevalonate is formed —> Less cholesterol b. Increase hepatic LDL receptors —> increase uptake of LDL from blood by the liver —> Less LDL is circulating in blood —> lower cholesterol. Side effects: headache- H: Hepatotoxicity —> check liver enzymes & funcGon before giving staGns (they may rise liver enzymes) daytime & statins at night. fenofibrate< , By binding to & inhibiting CoQ10 ⑭ M: Myopathy —> Dose dependent (also using fibrates concomitantly worsens myopathy).. may progress into Rhabdomyolysis. —— ↳ more in women. WitWarfarin]44 When & ↑ abnorma - · with statins Creatine Kinase given -. GI upset G: Good for Coronary Artery Disease (CAD) … staGns were shown to reduce morbidity & mortality in paGents with CAD Dose. CYP2C9 —> breaks down fluvastatin, Rosuvastatin. I CYP3A4 —> breaks down Atorvastatin, Lovastatin, Simvastatin. required Not to 2. Niacin (Vitamin B3): used to treat IIb & IV hyperlipoproteinemia, severe hypercholesterolemia for exam lipase) VLDL is high.. sensitive Thormone MOA 2 a. Inhibits Lipolysis in adipose tissue —> Less VLDL is synthesized and released by the liver —> less LDL in ! b. Increases synthesis of HDL (most effective drug to increase HDL) Side effects: AvoidPeUerds a FBI: Flushing, Burning, Itching. ·Prevented by aspirin/Ibuprofen. GI disturbances: GI irritation Nausea & Vomiting Peptic ulcer activation , ,. B3: 3 Bees ! are elevated in the sky just like: o ↑ Liver enzymes o ↑ Uric acid levels how > Do not use in gout patients o ↑ Glucose Levels ? Inhibit insulin release from the pancreas. Slides & 3. Fibrates: (-fibrate)/ Gemfibrozil: used to treat hypertriglycerolemia. Special · to those with 24 VLDL) ① Useful in treating type I ↳ Unlike fenofibrate , Gemfibrozil not be with statin can given MOA hyperlipidemia. a. Activate PPAR-α —> increase synthesis of LPL —> More TGs are broken down (main mechanism) Doctor said b. Increase HDL ↳ type I GV c. Decrease LDL Side effects: Mild GI disturbances —> most common Gallstones (lithiasis) = Gallbladder stones m most important. Myositis & risk of bleeding When taken with warfarin it displaces , as it from its binding sites) 4. Bile Acid Resins ‫ ﺻﻣﻎ‬: Cholestyramine , Colestipol MOA ↳ Drug of Choice (along with diet/niacin) a hyperlipidemia a. Sticks to Bile acids in the intestine and doesn’t allow them to get reabsorbed into the liver forcing the liver to synthesize bile acids, which is made of cholesterol —> less cholesterol in the plasma. Note : Taken with food Side effects S GI disturbances —> constipation & nausea. Less absorption of vitamins D,E,K,A. Less absorption of some drugs (I.e. digoxin, warfarin). Take them 1-6 Hrs after. + Tetracycline , Aspirin 5. Cholesterol absorption inhibitor: Ezetimibe > NPCIL/ Receptor Eze$mibe selec$vely inhibits intes$nal border absorp$on of dietary and biliary cholesterol in the small intes$ne.. headache..diarrhea effect combined with statins (not used has Synergetic when alone as it has very mild activity)