L 33 Therapeutic Control of Hypertension Lecture Notes 2023 PDF

L 33: Therapeutic control of Hypertension ILOs At the end of this session, the student will be able to:  Classify drugs used for treatment of hypertension.  Explain mechanism of action of different classes of antihypertensive drugs.  Distinguish differences between their antihypertensive classes....

L 33: Therapeutic control of Hypertension ILOs At the end of this session, the student will be able to:  Classify drugs used for treatment of hypertension.  Explain mechanism of action of different classes of antihypertensive drugs.  Distinguish differences between their antihypertensive classes.  Discuss their major adverse effects and drug interactions  Recommend appropriate pharmacotherapy for hypertensive patients in different clinical scenarios. According to the international society of Hypertension (Figure-1), the optimal blood pressure (BP) is 120/80 mmHg. To define hypertension, blood pressure is >140/90 mmHg, during 2–3 office visits at 1–4-week intervals at resting state. Figure-1: Classification of hypertension If hypertension is Essential, treatment will be directed towards decreasing the elevated BP. If hypertension is Secondary, treatment will be directed to the cause.  The Goals of treatment of hypertension are: A. Short term: decrease BP depending on the grade of hypertension B. Long term: decrease morbidity & mortality of END ORGAN DAMAGE  Lines of treatment of Hypertension: Choice of the lines of treatment for hypertension depends on the degree of hypertension together with comorbidities of other diseases in the hypertensive patient. Hypertension is treated by: I. Non-Pharmacological treatment: A. Life Style & Risk Factors Modification: - Change the sedentary life by Exercising; Brisk Walking 30 min / 3 times week - Dietary Changes; decrease intake of Salt & Fats & increase intake of Fruits &Vegetables - Habits; No Alcohol, No smoking, Caffeine - Decrease stress B. Control of Comorbidities: Obesity, Diabetes, hyperlipidaemia, hyperuricemia and atherosclerosis II. Pharmacological treatment (Anti-hypertensive treatment) A : Angiotensin Converting Enzyme Inhibitors (ACEIs) Angiotensin Receptor Blockers (ARBs) B : B-Blockers (Unless CVS comorbidities: Ischemic HD & HF) C : Ca++ Channel Blockers D : Diuretics Others: a2-Agonists, vasodilators and a-Blockers  What are the possible ways by which antihypertensive agents reduce the elevated BP? A : ACEIs & (ARBs) ACEIs (Ramipril) inhibits the angiotensin (Ag) converting enzyme thus; 1- Decreasing the synthesis of Ag II. As a result, decrease the stimulation of angiotensin receptor-1 (AT-1) leading to decrease in vasoconstriction (VC), decrease PVR and blood pressure. Also, it inhibits cardiac work and contractility. 2- Decrease degradation of bradykinin. As a result, increase vasodilatation (VD), decrease PVR and blood pressure 3- End result of inhibition of RAAS, decrease release of Aldosterone, decreasing salt and water retention and blood volume. ARBs (Valsartan) blocks angiotensin receptors (AT1) thus; 1- Block AT1 receptors ( VC) but Ag level is not affected. 2- Ag synthesis is not inhibited  act on AT2 synthesis ( VD) 3- End result of inhibition of RAAS, decrease release of Aldosterone, decreasing salt and water retention and blood volume.  Other Pharmacological actions and Therapeutic indications: 1-  Adrenergic activity   reflex tachycardia: Can replace other antihypertensives that induce tachycardia 2-  Fibrosis & myocyte hypertrophy   LVH & Remodeling: used in treatment of hypertension with heart Failure 3- Is Reno-protective   progression of Chronic Kidney Disease: used in treatment of hypertension with CKD. Drug of Choice in treatment of hypertension in Diabetic patients  Adverse drug reactions: 1- Dry cough or Angioedema in some patients due to accumulation of bradykinin in patients taking ACEIs. Replace by ARBs 2- Hyperkalemia; secondary to inhibition of Aldosterone. Give Ca gluconate (Antagonize K on heart) + Insulin (shifts K intracellular) 3- Acute renal Failure; in patients with End Stage Renal Disease (excessive decrease in intraglomerular pressure). B : B-Blockers: They act by blocking the beta receptors. They are either: A. Non-cardio-selective (B1 & B2): Propranolol B. Cardio-selective (B1 only): Metoprolol, Atenolol, Bisoprolol, Nebivolol. (They are preferred over non-cardio-selective)  Pharmacological actions of all B-Blockers in lowering the BP are: 1. Decreasing cardiac work, contractility and conduction thus decreasing cardiac output and BP. 2. Inhibition of renin release from the kidney 3. Inhibition of higher central autonomic control [only that cross BBB ]  Other pharmacological actions that add to lowering the BP with some B-Blockers: - Propranolol: Controls anxiety & stress (cross BBB). It controls CV manifestations & tremors of hyperthyroidism - Nebivolol; increase NO synthesis by stimulating NOS enzyme - Carvedilol has also an 1 blocking action so can decrease peripheral resistance N.B. All beta-blockers have no vasodilating action, and non-selective B-blockers block the B2 effect which is: -Dilator to some blood vessels that is why they cause intermittent claudication. - Dilator to bronchi, that is why they cause bronchoconstriction Indications: A- IT IS NO LONGER USED AS FIRST LINE TREATMENT OF HYPERTENSION, but can be used ONLY if hypertension is associated with other CV diseases such as IHD, Chronic HF or Arrhythmia. B- In anxiety and tremors induced by hyperthyroidism (propranolol). ADRs: (Generally less with the cardio-selective B-Blockers) 1- Masking hypoglycemic manifestations in Diabetic patients 2- Claudication and cold extremities. 3- For lipid soluble B-Blockers, may develop nightmares Contraindication; In hypertension with bronchial asthma, diabetes, bradycardia or heart block C : Calcium Channel Blockers (CCBs): Dihydropyridines (The BV) Nifedipine Retard & Amlodipine Mechanism of Blocking of Voltage gated Ca++ Action channels (L-Type) in Vascular smooth muscles Pharmacological Vascular dilatation effect  PVR  mean BP Indications ADRs Combination with B-Blockers Contraindications Non-Dihydropyridines (The Pump) Verapamil > Diltiazem Blocking of Voltage gated Ca++ channels (L-Type) in Myocardium Suppression of all cardiac properties  Cardiac work and contractility  Heart rate  mean BP Vascular Cardiac In hypertension & angina In myocardial ischemia/ arrhythmia Hypotension, Headache & Hypotension, Bradycardia & Ankle edema Heart Block Can be combined with beta Never combine with beta blocker Blocker (Protect against reflex (Severe Bradycardia and heart tachycardia block) Not to be combined with other Not given in patient with vasodilators, for fear of reflex bradycardia tachycardia D : Diuretics: 1- Thiazide diuretics: blocks the Na/Cl cotransporters in DCT (5%) to decrease salt and water reabsorption, thus ending in reduction of cardiac output and BP. It is a moderate ceiling diuretic. Main side effect is hypokalemia. Thus, it should be avoided in patients taking digitalis for risk of arrhythmia. 2- Aldosterone antagonists (Spironolactone): Blocks the aldosterone receptors in the collecting ducts that acts on Na/K pump & H/K exchange to end in loss of Na & H2O and retention of K. So, it is a K-sparing low ceiling diuretic. Used mainly in patients with heart failure to reduce cardiac remodeling and avoid the risk of hypokalemia. D :Others: I) In pregnancy, methyldopa is the standard therapy (having stood the test of time) in not causing any teratogenicity. Currently others can be used. The only group of antihypertensives that are absolutely contraindicated are those antagonizing RAAS System as they are teratogenic. II) In emergency hypertension, Clonidine (centrally acting -agonist) or parenteral (IV) antihypertensives as Na nitroprusside (Nitroso VD) and Hydralazine that could be easily titrated are used for better control over the reduction in blood pressure. GENERAL CONSIDERATION WHEN USING ANTIHYPERTENSIVES The main objective of treatment is to control and maintain BP to prevent long term ENDORGAN DAMAGE. Decreasing blood pressure by antagonizing the RAAS has the most beneficial effect on the end-organ damage. INon-pharmacological treatment is a constant line in all cases IIPharmacological treatment (aim is to decrease 5-15 mmHg gradually) - According to the patient comorbidities, first line treatment is either ACEIs/ARBs, Thiazide diuretics or CCBs. - If target blood pressure is not reached within one month of initiating therapy we either; a) Increase the dosage of the initial medication OR b) Add a second medication (combination therapy/ Add on therapy, for a synergistic effect)