Antihypertensives | Classes of Drugs | Baro Receptor

This Presentation provides a knowledge about Antihypertensives, types of blood pressure, hypertension types, normal blood pressure regulation, baro receptors, classes of antihypertensive drugs,recent discovery on hypertension. This is an assignment for the subject, Advanced Pharmacology-I, 1st year M.Pharm, 1st semester.

1. ADVANCED PHARMACOLOGY - I “ Hypertensives ” By Chetan A., M.Pharm 1 st Year (Pharmacology) K.K. College of Pharmacy Chennai, TamilNadu

2. Learning Objective Definition Types of Blood Pressure Types of Hypertension Antihypertensives Definition Normal Blood Pressure Regulation Baro Receptors Classes of Antihypertensives Recent Discovery Facts Reference

3. Hypertension It is defined as a physiologic condition where there is an increase in the arterial blood pressure above normal. It is a multifactorial disease. Normal B.P is 120/80 mm Hg. An individual is hypertensive when B.P is >140/90 mm Hg. It is one of the leading causes of mortality & Morbidity due to stroke, heart attack & kidney failure.

4. Types of Blood pressure Normal blood Pressure 120mmhg _80mmHg Pre Hypertension B.P Stage 1 : 150_160mmHg to 100_110mmHg Stage 2 : 180_200mmHg to 120_140mmHg Post/Chronic B.P More than 200mmHg to more than 150mmHg

5. Types of hypertension Essential or primary Hypertension - a disorder of unknown origin Contributors include: salt sensitivity, insulin resistance, genetics, environmental factors,others Secondary Hypertension - Caused by other disorders R enal, adrenal, coarctation of the aorta, steroids, pregnancy

6. Antihypertensives These a re the class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction.

7. Normal Blood Pressure Regulation Blood Pressure = Cardiac output (CO) X Resistance to passage of blood through precapillary arterioles (PVR) Physiologically CO and PVR -is maintained by – Arterioles, postcapillary venules heart and kidney Baroreflex, humoral mechanism and renin- angiotensin- aldosterone system regulates the above 4 sites Local agents like Nitric oxide In hypertensives – Baroreflex and renal blood - volume control system – set at higher level All antihypertensives act via interfering with normal mechanisms

8. Baro Receptor Baro reflexes are responsible for minute to minute regulation of blood pressure. Central sympathetic neurons in vasomotor area are tonically active. When there is stretch in vessel wall, baro receptor stimulation occurs & inhibits sympathetic activity Reduction in stretch increases baro receptor activity.

9. Classes of Antihypertensives Diuretics Adrenergic receptor antagonists Benzodiazepines Calcium channel blockers Renin Inhibitors ACE inhibitors Angiotensin II receptor antagonists Aldosterone receptor antagonists Vasodilators α 2 agonists Endothelin receptor blockers

10. Hydrochlorothiazide, a popular thiazide diuretic Loop diuretics: Furosemide Thiazide diuretics: Thiazide-like diuretics: Potassium-sparing diuretics: spironolactone Diuretics

11. Action Act on kidney Remove more sodium and water from water Relax blood vessel walls Lower blood pressure

12. Thiazide diuretics are recommended as the first line of treatment for high blood pressure. They are usually recommended as one of at least two medicines to control high blood pressure. Loop diuretics are prescribed for people who also have heart failure, kidney problems, or swelling in their legs (edema) Diuretics

13. Furosemide , like other loop diuretics, acts by inhibiting NKCC2, the luminal Na-K-2Cl symporter in the thick ascending limb of the loop of Henle. By inhibiting the transporter, the loop diuretics reduce the reabsorption of NaCl and also diminish the lumen- positive potential that derives from K + recycling Diuretics

14. Spironolactone is used primarily to treat heart failure, edematous conditions such as nephrotic syndrome or ascites in patients with liver disease, essential hypertension, hypokalemia. spironolactone is only a weak diuretic because it primarily targets the distal nephron (collecting tubule), where only small amounts of sodium are reabsorbed, but it can be combined with other diuretics to increase efficacy. The antihypertensive effect of spironolactone may exceed that of complex combined regimens of other antihypertensives since it targets the primary cause of the elevated blood pressure. Diuretics

15. Adrenergic receptor antagonists Beta blockers atenolol Metoprolol Alpha blockers Mixed Alpha + Beta blockers : labetalol

16. Beta Bloc k e r s Inhibits the effect of nor epinephrine and epinephrine And lessens the feedback mechanism G protein receptor kinase inhibits receptor activity Increase in cyclic Adenosine mo n o p ho s p h at e Improves c ont r acti o n s Decrease heart rate, Calcium entry into failing myocytes

17. Labetalol combines both selective, competitive, alpha-1-adrenergic blocking and nonselective, competitive, beta-adrenergic blocking activity in a single substance. Stimulation of beta receptors within myocardium Stimulation of alpha receptors within vascular smooth muscles Decrease in systemic arterial blood pressure and systemic vascular resistance Without a reduction in heart rate, cardiac output or stroke volume.

18. Be n z o d ia z epines They work as an agonist of the GABA-a receptors in the brain, thus slowing down neurotransmission and dilating blood vessels. benzodiazepines inhibit the re-uptake of a nucleoside chemical called Adenosine, which serves as an inhibitory chemical mentioned above. It also serves as a coronary vasodilator, allowing the cardiac muscle to relax and dilating cardiac arteries.

19. Calcium channel blockers Peripheral arterial dilatation Stimulation of renin and formation of angiotensin Decrease systemic vascular resistance Decrease in blood pressure Amlodipine, Nifedipine & Diltiazem block the entry of calcium into muscle cells in artery walls.

20. Diltiazem Diltiazem is a potent vasodilator , increasing blood flow and variably decreasing the heart rate via strong depression of A-V node conduction. Because of its negative inotropic effect , diltiazem causes a modest decrease in heart muscle contractility and reduces myocardium oxygen consumption. Its negative chronotropic effect results in a modest lowering of heart rate, due to slowing of the sinoatrial node . It results in reduced myocardium oxygen consumption. Because of its negative dromotropic effect , conduction through the AV (atrioventricular) node is slowed , which increases the time needed for each beat. This results in reduced myocardium oxygen consumption

21. Renin Inhibitors Renin inhibitors bind to the active site of renin and inhibit the binding of renin to angiotensinogen. renin inhibitors prevent the formation of Ang I and Ang II A reduction in Ang II levels or blockade of angiotensin receptors suppress the feedback loop increased plasma renin concentrations (PRC) and plasma renin activity (PRA)

22. ACE Inhibi t o r s Blocks the conversion of angiotensin I to angiotensin II Lower arteriolar resistance Increase venous capacity Normally Angiotensin II causes vasoconstriction and hence hypertension . Decrease cardiac output Stimulates adrenal gland to release aldosterone which causes sodium retention and hence increase in blood pressure. Stimulates post. Pituitary to release vasopressin which also increases water retention With ACE inhibitors, the production of angiotensin II is decreased, leading to decreased blood pressure. C a ptopril Enalapril Ramipril Increase excretion of sodium in the urine

23. Angio t ensin II receptor antagonists These substances are AT 1 -receptor antagonists; that is, they block the activation of angiotensin II AT 1 receptors. vasodilatation. reduces secretion of vasopressin. reduces production and secretion of aldosterone. The combined effect reduces blood pressure. olmesart an telm i sart an

24. Vasodilators Vasodilators act directly on the smooth muscle of arteries to relax their walls so blood can move more easily through them; only used in hypertensive emergencies. Vasodilatation works to decrease TPR and blood pressure through relaxation of smooth muscle cells in the tunica media layer of large arteries and smaller arterioles . TPR: total peripheral resistance

25. α 2 agonists Stimulate alpha receptors in the brain Open peripheral arteries For treating hypertension, these drugs are usually administered in combination with a diuretic. Adverse effects of this class of drugs include sedation, drying of the nasal mucosa and rebound hypertension.

26. Endothelin receptor blockers By blocking this interaction, bosentan decreases pulmonary vascular resistance. Under normal conditions, endothelin-1 binding of ET-A or ET-B receptors causes constriction of the pulmonary blood vessels. Bosentan is a competitive antagonist of endothelin-1 at the endothelin-A (ET-A) and endothelin-B (ET-B) receptors.

27. Side Effects of Diuretics Potassium-sparing diuretics retain the potassium that other diuretics cause the body to excrete. Common side effects of these diuretics include nausea, headache and stomach upset. The most common side effect of loop diuretics, such as Lasix, is hypokalemia, or low potassium. Other side effects include dry mouth, weakness , diarrhea and headache. difficulty urinating, gout, a nd hives are severe side effects and should be addressed immediately. Thiazide diuretics can cause orthostatic hypotension.

28. Side Effects of ACE Inhibitors Common side effects of ACE inhibitors are diarrhea, headache and joint pain. Fever and chills, trouble breathing or jaundice requires immediate attention.

29. May include fatigue, dizziness and weakness. Side Effects of Beta Blockers

30. Regular check-Up

31. Recent Discovery Central Corneal Thickness in the Ocular Hypertension Treatment Study (OHTS) ( James D. Brandt MD 2001) Central corneal thickness influences intraocular pressure (IOP) measurement. Results: Mean central corneal thickness was 573.0 ± 39.0 μm. Twenty-four percent of the OHTS subjects had central corneal thickness > 600 μm. Mean central corneal thickness for African American subjects (555.7 ± 40.0 μm; n = 318) was 23 μm thinner than for white subjects (579.0 ± 37.0 μm; P < 0.0001). Other factors associated with greater mean central corneal thickness were younger age, female gender, and diabetes. Conclusions OHTS subjects have thicker corneas than the general population. African American subjects have thinner corneas than white subjects in the study. The effect of central corneal thickness may influence the accuracy of applanation tonometry in the diagnosis, screening, and management of patients with glaucoma and ocular hypertension.

32. Facts More than 10 million cases per year in India. Hypertension can last for years or be lifelong. High blood pressure may be linked to dementia. High B.P causes thickening of a part of heart (Left Ventricle). Blood pressure is normally lower at night while you're sleeping. Our blood pressure starts to rise a few hours before you wake up, peaking in the middle of the afternoon and drop in the evening. Anxiety can rise and lower blood pressure. Losartan Potassium Tablets, USP and Losartan Potassium/Hydrochlorothiazide Tablets if stopped immediately may harm the patient. Sweaty workouts can lower B.P in Hypertension.

33. Reference Google Search Shareslide Wikipedia Elsevier Inc.

34. Quote ~ “An idiot with a plan can beat a Genius without an plan”