26/08/2013 Learning Objectives: After completing this chapter you should able to: •Name categories of cardiovascular drugs •Describe the therapeutics effects of drugs •Identify the side effects 2 26/08/2013 Heart & Blood Circulation 3 functional parts: • • • Cardiac muscle Conduction system Nerve supply Main Diseases ?

CHF – Congestive heart failure ? CAD – Coronary artery disease ( arteriosclerosis, angina pectoris, myocardial infarction) 3 26/08/2013 Cardiac drugs • • • • • Used in hypertension angina pectoris and MI Shock Arrhythmias CHF I. Anti-hypertensive drugs ? for treatment of hypertension (high blood pressure).

II. Anti-anginal drugs ? for treatment of angina III. Anti-arrhythmic drugs ? for treatment of arrhythmia IV. Cardiotonic drugs (e. g. , digoxin) ? for treatment of heart failure CARDIAC GLYCOSIDES Treatment for congestive heart failure 4 26/08/2013 Cardiac Glycosides ? Plant leaves of Digitalis purpurea & lanata ? Consists of chains of glucose sugars 5 26/08/2013 Mode of Action • Increase the force of myocardial contractions • Inhibits the enzyme ATP, which energizes the sodium /potassium pump. • stimulate an exchange mechanism.

• They increases level of CALCIUM inside the cell • More calcium will accumulate inside the cell during cellular depolarization • Positive inotropic effect • Negative chronotropic effect Clinical pharmacokinetics • Digitalization – produce an effective blood level • Maintenance – maintain therapeutic level • Digoxin and digitoxin • Both can administered orally and IV. The t 1/2 life of digoxin is normally 1. 5 to 2. 0 days. The t1/2 life of digitoxin is normally 5 to 7 days 6 26/08/2013 Therapeutic uses • Atrial fibrillation • Congestive heart failure.

Adverse effects • Hypokalemia or hypercalcemia increases the risk of digitalis toxicity. • Gastrointestinal effects: anorexia, nausea, vomiting, diarrhea • Neurological effects: malaise, fatigue, depression, altered color vision. • Cardiovascular effects: any cardiac arrhythmia may occurs Drug Interaction • Antacid – decrease the absorption of glycosides • Antiarrythmic drug increase glycoside plasma levels 7 26/08/2013 Treatment of digoxin toxicity: 1. 2. 3. 4. Withdraw drug Correct low serum K+ Treat ventricular arrhythmias Digoxin specific antibodies. Evaluation.

• Increased in urine output • Normal heart rate in arrhythmia NITRATES 8 26/08/2013 Nitrates • Previously known as coronary dilators • Used in two ways : –During attacks –Prophylactic drugs Mode of Action • Relax vascular smooth muscle • By nitrate & nitrite ions • A decrease in venous return to the heart & decrease in blood pressure. Clinical Pharmacokinetics • Nitroglycerin, Isosorbide Dinitrate, Amyl Nitrate • Can be administered in several different forms 9 26/08/2013 Therapeutic uses • Angina pectoris • Congestive heart failure • Myocardial Infarction.

Adverse Effect • Headache • Facial flushing • Hypotension BETA BLOCKERS 10 26/08/2013 Mode of Action • Blocks the ? – adrenoceptors in the heart and reduce cyclic AMP. They slow the heart and reduce its force of contraction. • Reduce cardiac output by diminishing the sympathetic nervous system response Clinical pharmacokinetics • Beta – blockers may be lipophilic or hydrophilic • Selective & nonselective • The 3 beta-blockers most widely used are: – Propranolol, Atenolol, Metoprolol Clinical indication • Hypertension • Angina pectoris • Myocardial infarction 11 26/08/2013 Adverse effect.

• Bradycardia • Bronchospasm • Fatigue, depression Contraindication • Bradycardia • Chronic obstructive pulmonary disease • Diabetic CALSIUM CHANNEL BLOCKER 12 26/08/2013 Calcium –channel blockers Mode of action • Inhibit the entrance of calcium into cells- altering action potential-blocking muscle contraction • Reduce the force of contraction of the heart.

• The blocking of CALCIUM will interfere with the muscle cell ability to contract • This effects will decrease blood pressure, cardiac workload and myocardial O2 consumption • 3 types of calcium channel blocker ? Dihydropyridines (e.g. nifedipine) intense arterial vasodilatation and lower the blood pressure and the afterload on the heart.

Well absorbed orally and is metabolized by liver. 13 26/08/2013 ?Verapamil tend to have less effect on the peripheral circulation and more effect on the heart, slowing the heart and reducing the force of contraction. It can be given orally or IV. It is metabolized by liver. ?Diltiazem has more effect on the heart than nifedipine and more effect on the peripheral circulation CCB Site of Action diltiazem & verapamil nifedipine (and other dihydropyridines) Therapeutic uses.

• Angina • Hypertension 14 26/08/2013 Adverse effects • Nifedipine: facial flushing band ankle swelling, headache, dizziness • Verapamil: headache, dizziness, constipation, • Diltiazem: constipation, ankle oedema, headache. Contraindication • Renal and hepatic dysfunction • pregnancy ACE INHIBITOR 15 26/08/2013 ACE inhibitor Mode of Action • Prevent the formation of angiotensin II, preventing its vasoconstrictor effects as well as decreasing aldosteron production and fluid retention RAAS ACE Inhibitors . Angiotensin I ACE Angiotensin II 1. potent vasoconstrictor – increases BP 2. stimulates Aldosterone.

– Na+ & H2O reabsorbtion Clinical pharmacokinetics • Captopril is given orally and is cleared by kidney. • Enalapril is also given orally 16 26/08/2013 Therapeutic uses • Cardiac failure • Hypertension • Diabetic Adverse effects • • • • Severe hypotension Hyperkalaemia Impairment of renal function Cough Contraindication • Renal failure • Pregnant woman 17 26/08/2013 Drug interaction • With K+ sparing diuretics and K+ supplements, there is a risk of dangerous hyperkalaemia There are two ways of spreading light to be the candle or the mirror that reflects it. Edith Wharton 18.

Drugs are classified into various categories primarily for the purpose convenience. All similar drugs, be it in terms of their mechanism of actions or their pharmacological action are grouped in a single category. This is done because drugs in the …

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Take-home Quiz 5. 1 Renal and Respirator Chapter 28 Diuretic Drugs Drug FAMILY PROTOTYPE DRUG LOCATION ON NEPHRON PHYSIOLOGIC EFFECT, e. g. reabsorption of Na++ Typicallly USED FOR EFFECT ON H2O Na++ K+ Cl- Mg+ + Ca+ Drug interactions (food …

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1. Protamine sulfate: antidote for heparin (use is when patient’s aPTT is very high) Vitamin K: antidote for coumadin (uses PT/INR); both work slowly. 2. Why are Coumadin and Heparin given together? If you have DVT treatment, it can keep …

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