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Pharmacology Lecture 2 Hypertension I have only written the extra info that haven’t been mentioned in the slides, due to lack of time. Slide one : 1. Very common disease in individuals over 50 years of age. 2. Since it’s a silent disease with no obvious symptoms, dealing with hypertensive patients will be difficult in terms of making sure that they take their medications. 3. Chronic hypertension leads to congestive heart failure, MI, renal damage, or cerebrovascular accidents mainly because it alters the perfusion to these organs. How ? Altered kidney perfusion : changes glomerulus filtration. Altered perfusion to the heart : changes in pre and after load in the heart. This is particularly important because when you change the BP in a patient, you change homeostasis in his whole body. 4. Uncontrolled hypertension is more prevalent and common than the controlled one. Slide two : 1. 2ndry hypertension makes about 10-15% of total hypertension 2. Regarding sodium intake and Its effect on hypertension, it’s a very controversial issue and still needs more studies. Slide three : 1. Cholesterol is the most important factor affecting hypertension by increasing it’s incidence by a 4.5 factor. 2. LVH : Left ventricular hypertrophy. Slide Four : 1. Reflex response to bring the BP back to normal is basically dependent on changing the TPR ( vasculature), and inotropic and chronotropic effects on the heart. Slide Five : 1. Long-term regulation of BP depends on maintaining a particular blood volume. Slide Six : 1. Five groups of drugs are mainly used to control hypertension : the most important one is diuretics, and the least used one is the ablockers. 2. 1st line therapy : Diuretics or B- Blockers. Diuretics are known worldwide to be used in mild hypertension. 3. B- blockers may cause MI, and are prescribed only in cases where the patient isn’t responsive to diuretics. 4. 2nd line therapy are ACEI and Ca antagonists. Sometimes they might be used as the 1st line therapy. 5. a -blockers : vasodilators and used in prostate hypertrophy. So it might be used in old men as 1st line therapy. 6. In people who are resistant to the usual therapy, we give patients other drugs like Reserpine, Clonidine, Prazosine, etc.. ( the drugs in the box at the bottom of the figure). These drugs and combinations of them are reserved to patients with severe cases of hypertension and/or patients who aren’t responsive to usual therapy. 7. Clonidine is kind of dangerous to use because you decrease the sympathetic activity in the whole body, plus some CNS inhibition. Slide Seven : Antihypertensive drugs work on many levels, which are : 1. a. Kidney : Diuretics >> Thiazide, loop diuretics. b. ACEI c. Aliskiren ( Renin antagonist). d. Angiotensin II receptor blockers >> Losartan ( more powerful regarding control of ACE than ACEI ) 2. Parasympathetic and sympathetic systems related drugs : a. B-receptors blocking agents : reduce heart activity and reduce BP >> Propranolol. b. a-receptor blockers : vasodilation >> Prazosin ( blocks a 1 receptors ) c. centrally acting agents : a 2 receptor agonists >> Methyldopa , clonidine, etc .. d. Ganglion nerve terminals : 1st to be used but is very rarely used now. 3. Vascular smooth muscle : decrease depolarization > decrease tone >> vasodilation. Calcium channel blockers are used here. Slide Eight 1. Low dose of diuretics are as effective as a high dose, but with less side effects. ( 40 gm in comparison to 200 gm ) 2. Thiazides : Hydrochlorothiazide or Chlorothiazide 3. Reduction in peripheral vascular resistance : in general, when you first give a patient with hypertension a diuretic, they tend to urinate more than usual during the first week, which is then followed by adjustment of the body to the drug called the reduction in peripheral vascular resistance. Slide Nine : 1. The combination of drugs used with patients suffering from moderate to severe hypertension is usually manufactured as one tablet ; Lasortan and ACEI for example. 2. Thiazides don’t cause orthostatic hypotension. Slide Ten : 1. All diuretics cause hypokalemia, but it’s tolerable. Hypokalemia is caused by excretion of K along with Na. 2. Hyperurecemia : caused by competition between diuretics and uric acid in the body, causing uric acid retention. ( may lead to gout ) Slide Eleven : 1. Severe electrolyte imbalance ( 25% in comparison to 5-7 % with thiazides ). So, we don’t prescribe loop diuretics to patients with hypertension unless they have impaired renal function, because thiazides need more than 30% glomerulus filtration rate. 2. Loop diuretics don’t cause hyperglycemia as much as thiazides. 3. Ototoxicity of loop diuretics when used with aminoglycosides is irreversible. ( synergistic activity.) Slide Twelve : 1. B- Selective and non-selective blockers : in non-selective blockers they cause problems in asthmatic and diabetic patients. ( Bronchoconstriction and decreased glucose levels specially in diabetic patients taking insulin ) 2. B- selective blockers are better to use in hypertension. Slide thirteen 1. Metoprolol and Atenolol are the best and most prescribed B-blocking agents for hypertensive patients. ( Metoprolol has a longer half life than Atenolol and therefore is better) 2. Pindolol and Acebutolol have intrinsic activity : are antagonists with partial agonist activity. Heart rate doesn’t drop in these drugs due to the partial agonism. Used in patients who have bradychardia or bradyarrythmia. Acebutalol is used more than Pindolol because it’s cardioselective. 3. Esmolol : used in hypertension crisis accompanied with tachycardia. It’s a drug that is ideally used in emergencies because its action is very fast to happen and very short lived. Has a vasodilation effect and reduces heart rate. Now the doctor talks about a slide that isn’t included in the slides we have. Non-Selective adrenergic blocking agents: 1. Labetolol, Cardidolol ( not sure about this one ) 2. Block both B and a receptors. 3. Used in patients suffering from hypertension along with high peripheral resistance. 4. Used also in Ryanaud’s disease. 5. Never stop using B-Blocking agents abruptly; it has to be gradual to avoid precipitated arrhythmia because hypersensitivity of Breceptors towards NE develop in patients taking these drugs. Done By : Aseel Sbeih