Summary of Drugs for CVS - part 1 PDF

Cardiovascular system F ‫كليــة الصيدلة‬  Hypertension Classification of HTN According to Etiology Essential (primary) HTN Secondary HTN (in  5-10 %) due to: - in 90-95 % & of unknown - Secondary to...

Cardiovascular system F ‫كليــة الصيدلة‬  Hypertension Classification of HTN According to Etiology Essential (primary) HTN Secondary HTN (in  5-10 %) due to: - in 90-95 % & of unknown - Secondary to another cause cause. - Such as hypertension due to disease, - Predisposing factors are or the use of certain drug. risk factors. 27/5/2024 3  HTN Risk Factors A) Influenceable factors: 1. Cigarette smoking. 2. Elevated LDL. 3. Stress. 4. Obesity. 5. Increased Na intake. B) Non- Influenceable factors: 1. Family history 2. Insulin resistance (DM) 3. Age 27/5/2024 4 Hypertensive crisis: Is a sudden and severe increase in blood pressure to 180/120 mm Hg or greater. A hypertensive crisis is a medical emergency. It can lead to a heart attack, stroke or other life-threatening health problems. Non-pharmacological management of HTN: Weight reduction Diet rich in fruits, vegetables, and low-fat dairy products with a reduced content of saturated and total fat Dietary sodium restriction: reduce daily dietary sodium intake Physical activity: regular aerobic physical activity Stop alcohol consumption Stop smoking Avoid Stress Control diabetes mellitus and atherosclerosis.  Classification of Antihypertensive Drugs 1) Diuretics 2) Renin-Angiotensin-Aldosterone System (RAAS) Inhibitors = a- Angiotensin Converting Enzyme Inhibitors (ACEI( b- Angiotensin Receptor Blockers (ARB( c- Renin inhibitors: inhibit renin enzyme as aliskiren 3) Calcium Channel Blockers (CCBs) 4) Sympatholytic Drugs 5) Direct Vasodilators (DVD) 27/5/2024 8  Classification of Antihypertensive Drugs Also Antihypertensive Drugs are classified into: A) First line or primary drugs used alone or in combination: Angiotensin Converting Enzyme Inhibitors (ACEIs) & Angiotensin Receptor Blockers (ARBs). Calcium Channel Blockers. Diuretics. B) Second line or Alternative drugs that may be used in selected patients: Alpha blockers, Beta Blockers. Central α2 agonists. Vasodilators. 9 27/5/2024  A. ACE inhibitors and angiotensin receptor blockers (ARBs) Mechanism of action: ACEIs: 1- Inhibit Angiotensin II: prevent vasoconstriction 2- Increase bradykinin: vasodilatation 3- Diuresis: inhibit aldosterone.  ACEIs decrease BP by decreasing PR, without affecting CO or HR.  Unlike direct vasodilators, they do not cause reflex tachycardia thus can be used safely in patients with ischemic heart disease PR= peripheral resistance CO= Cardiac output BP= blood pressure HR= heart rate  A. ACE inhibitors and angiotensin receptor blockers (ARBs) Examples:  ACE-inhibitors: Enalapril, Ramipril and Captopril  AT1 receptor antagonists (ARBs): Losartan and Valsartan Pharmacokinetics:  Eliminated primarily by the kidneys; (adjust dose in renal insufficiency). Adverse effects:  Dry cough (5-30%)  Angioedema  Hyperkalemia  Teratogenic (not used in pregnancy)  B. Diuretics Mechanism of action: Diuretic Action → decrease Blood Volume → decrease Cardiac output →decrease Blood pressure. Classification  Thiazide diuretics: Hydrochlorothiazide  Loop diuretics: Frusemide  Potassium-sparing diuretics: Spironolactone, Triamterene  B. Diuretics Adverse effects:  Hypokalemia  Hypomagnesemia  Hyperkalemia in case of potassium sparing diuretics  Hyponatremia and hypercalcemia (Thiazide) (not in hyperparathyroidism). While Hypocalcemia with loop diuretics  Hyperurecemia  Hyperglycemia  C. Calcium channel blockers Mechanism of action:  Block calcium channels  In heart decrease heart rate and contractility thus decrease CO  In blood vessels: vasodilation (decrease PR) Examples:  Non-Dihydropyridine: Diltiazem and Verapamil (more selective to the heart).  Dihydropyridine: Nifidipine and Amlodipine (more selective to blood vessels) Adverse effects:  Flushing, headache and tachycardia (can worsen angina).  Ankle swelling (edema) is common  Negative inotropic effect of verapamil (can worsen heart failure).  Constipation is common with verapamil. Interactions:  Intravenous verapamil can cause circulatory collapse in patients treated concomitantly with β- adrenoceptor antagonists. Clinical Use:  Amlodipine is used mainly as antihypertensive, while verapamil and diltiazem as antiarrhythmic and antianginal  D. Beta blockers Mechanism of action:  Act mainly by blocking β1 receptors: decrease heart rate Examples:  Non-selective β-blockers: Propranolol and Carvedilol  Selective β1-blockers: Atenolol and Bisoprolol Adverse effects:  Bradycardia  Fatigue,  Cold extremities,  Erectile dysfunction  Bronchospasm specially non selective Interactions:  Increased toxicity with other –ve inotropic drugs such as verapamil or lidocaine  E. α adrenergic blockers Examples: Prazosin, Doxazosin, Terazosin Produce a competitive block of ɑ1-adrenoceptors. Tamsulosin, an ɑ1a- blocker with greater selectivity for prostate muscle, has been used in the treatment of benign prostate hyperplasia (BPH). F. Centrally acting adrenergic drugs This ɑ2 -agonist diminishes central adrenergic outflow, example: Clonidine ɑ-Methyldopa: another ɑ2 Is specially valuable in treating pregnant hypertensive patients  H. Direct vasodilators 1) Arteriodilators: Hydralazine Minoxidil Diazoxide 2) Venodilators: Nitroglycerine I.V. infusion in hypertensive emergencies. 3) Arteriovenodilators: Sodium Nitroprusside  Definition Angina Pectoris is defined as sudden pain beneath the sternum, often radiating to the left shoulder and arm Anginal pain is precipitated when the oxygen supply to the heart is insufficient to meet oxygen demand Most often, anginal pain occurs secondary to atherosclerosis of the coronary arteries  Anti-angina drugs Anti-Anginal Drugs: 1. Nitrites & Nitrates 2. Calcium Channel Blockers(CCB) 3. Β Blockers Adjuvant Drugs: 4. Anti-Platelet: Aspirin, Clopidogrel & Ticlopidine. 5. Drug treatment of Risk & Precipitating factors e.g. Anxiolytic, Antihypertensive, Anti- hyperlipidemic, Anti-diabetic, etc.  Organic nitrates e.g. glyceryltrinitrate (nitroglycerin) Mechanism of action:  Generation of NO leading to vasorelaxation Cardiovascular Effects: Increase O2 supply and decrease cardiac work (decrease O2 demand) by VD Side Effects:  Venodilation → Postural hypotension, reflex tachycaria, dizzness & syncope  Arteriodilation → Throbbing headache & flushing  Tolerance  β- Blockers Cardiovascular Effects: β-blockers reduce anginal pain by ↓ cardiac O2 demand Primarily through blockade of β1 receptors Side Effects: most common Dizziness, weakness, headache, impotence β2 blocking → bronchospasm (asthma), disturb blood glucose and lipid levels Mask hypoglycemic coma, bradycardia Refer to hypertension lecture for more details  Ca++ Channel Blockers In classic angina: Ca channel blockers reduce anginal pain by decreasing cardiac oxygen demand – Decrease heart rate and contractility – Decrease arterial pressure (afterload) In variant angina: Ca channel blockers promote relaxation of coronary artery spasm, thereby increasing cardiac O2 supply  Ca++ Channel Blockers Side Effects Arterial dilation → headache, flushing, dizziness & ankle edema (not respond to diuretics especially nifedipine) ↓ Contractility → poor left ventricular filling Heart Block (especially with β- blockers & digoxin) Refer to hypertension lecture for more details Heart Failure  What is congestive heart failure? Definition: Symptoms: Congestive heart failure (CHF) is a condition Shortness of breath: occurs that occurs when the heart is unable to pump enough blood to meet the needs of the during activity, rest, or sleeping body's tissues. Persistent coughing /wheezing Edema: swelling in extremities Causes includes: Tiredness/fatigue (1) Artery disease Increased heart rate, Heart (2) High blood pressure (hypertension) enlargement (3) Heart defects present at birth (Congenital heart disease) (4) Past heart attacks (myocardial infarction) (5) Heart muscle disease Compensatory Mechanisms  Treating heart failure The main aims being (1) Decrease the symptoms. (2) Slow disease progression, (3) Improve survival. Six Classes of drugs have been shown to be effective (1) ACE inhibitors, (2) -adrenergic blocking agents (3) Diuretics (4) Aldesterone antagonist. (5) Direct vasodilators (6) Inotropic agents  Cardiac Glycosides Derived from plant (digitalis) Example: Digoxin Mechanism of action and effects: Inhibitor of Na+/K+ ATPase pump leading to increased Ca2+ influx with subsequent increased cardiac contractility, decreased heart rate and decreased cardiac size  Side Effects Extremely low therapeutic index (~2) CNS: malaise, confusion, depression, vertigo GI: anorexia, nausea, intestinal cramping, diarrhea Cardiac: bradycardia, arrhythmia Yellow spots in vision Contraindications: AV block Hypokalemia (increases toxicity)