PATHOPHYSIOLOGY OF HYPERTENSION- AS PER 2ND SEMESTER BPHARM SYLLABUS

Pathophysiology of Hypertension in brief for 2nd semester BPHARM students.

1. HYPERTENSION Ms. FATHIMATH RAIHANA ASSISTANT PROFESSOR P A COLLEGE OF PHARMACY

2. Hypertension is defined as the clinical condition where a persistent elevation of arterial blood pressure observed in more than 2 consecutive recordings. Normal = 120/80mmHg. Blood pressure – the pressure exerted by the blood on the walls of the arteries. Classification : According to JNC ( Joint National Committee ), based on extent of elevation in blood pressure, hypertension is classified as : Pre - Hypertension Stage I Hypertension Stage II Hypertension

3. Classification Systolic blood pressure ( mmHg) Diastolic blood pressure (mmHg) Normal <120 <80 Pre-Hypertension 120-129 80-89 Stage –I Hypertension 140-159 90-99 Stage – II Hypertension >=160 >=100

4. Epidemiology : It affected 1 billion individuals among worldwide . It is a major health problem in India and other developing countries. More prevalent in adults upto 10%. 57% of death occur due to stroke. 24% of death occur due to coronary heart disease secondary to hypertension. In India, hypertension is more in urban 25% than in rural 10% population. Aged more than 60 years, 60% of individuals have hypertension.

5. Etiology : Based on etiological factors, Hypertension is classified into 2 types : Primary hypertension / Essential hypertension Secondary hypertension Primary Hypertension : There is no specific cause identified. But there can be certain risk factors that may contribute for development of hypertension. About 90-95% of hypertension cases belong to this type and usual onset of primary hypertension is at the age of 36 years.

6. Risk factors include : Family history : Hypertension is common in subjects who have hypertensive parent. Environmental factors : Stress Obesity Physical inactivity Heavy consumption of salt Alcohol consumption Cigaratte smoking High cholesterol Age

7. Secondary Hypertension : About 5-10% of hypertensive patients. The usual onset of disease is after 55 years. The common causes of hypertension are : Renal diseases like chronic renal failure renal artery disease Endocrine disorders like Diabetes Mellitus, thyroid disorders. Pregnancy Drugs : Steroids, NSAIDs, Estrogen

8. PATHOGENESIS : Blood pressure is the mathematical product of cardiac output and Total Peripheral Resistance (TPR). Hence, increase in either cardiac output or TPR results in hypertension. Blood pressure = Cardiac Output * Total Peripheral Resistance BLOOD VOLUME Sodium Mineralocorticoids Atriopeptin HUMORAL FACTORS Constrictors Angiotensin II, Endothelin, Catecholamines , Thromboxane, Leukotrienes Dilators Prostacyclin Bradykinin Nitric oxide LOCAL FACTORS Autoregulation Hypoxia NEURAL FACTORS Constrictors Dilators α - Adrenergic receptors β -Adrenergic receptors CARDIAC FACTORS Heart rate Contractility

9. 1. Abnormal neural function : Both ANS and CNS controls blood pressure. Any change in normal BP Stimulates baroreceptor cells and Impulses passes to brain Alters negative feedback mechanism Vasoconstriction BP increase Baroreceptors are receptors seen in heart that monitors the level of blood and give signals. MECHANISMS :

10. 2. Defect in autoregulation : Increase in renal reabsorption Increase blood volume Increase BP

11. 3. Alterations in vascular epithelial cells : Nitric oxide, prostaglandin Angiotension II Vasoconstriction Increase BP

12. 4. Dietary consumption of sodium, potassium , calcium : Level of sodium, potassium, calcium Blood volume BP

13. KIDNEY play an important role in regulating arterial blood pressure. It is activated when kidney/renal perfusion decrease or decreased renal blood flow. The kidney release an enzyme Renin – located in the juxtaglomerular cells. RAAS - RENIN ANGIOTENSION ALDOSTERONE SYSTEM :

14. Angiotensinogen Angiotensin - I Angiotensin - II Aldosterone Kidney Adrenal cortex Sodium reabsorption Blood volume BP Vasoconstriction Sodium reabsorption Increase sympathetic nervous system Increase vascular resistance BP + + Release Renin ACE Angiotensin C onverting E nzyme Bind to the receptor Potent vasoconstrictor that directly acts on arteriolar smooth muscles .

15. When blood pressure falls, your kidneys release the enzyme, Renin . Renin splits angiotensinogen, a protein made in your liver and converts to angiotensin I. Angiotensin I which is inactive, flows through your bloodstream and gets converted into Angiotensin II by the help ACE in your lungs and kidneys. Angiotensin II is a hormone that causes vasoconstriction. Angiotensin II - also triggers adrenal glands to release aldosterone. Aldosterone cause your kidneys to retain sodium . The increase in sodium causes water retention . Aldosterone also causes kidney to release renin. Increases blood volume BP increase

16. Headache Blurred vision Sleepiness Difficulty in breathing Tingling and numbness of hands and feet. Confusion Fatigue Irregular heart beat Elevated blood pressure measured using sphygmomanometer. SIGNS AND SYMPTOMS :

17. CVS – Angina, myocardial infarction, heart failure Brain – Stroke Renal system – Renal failure, chronic kidney disease Ophthalmic - Retinopathy COMPLICATIONS :

18. NON-PHARMACOLOGICAL TREATMENT : Lifestyle changes : Physical activity Weight loss if over weight. Adoption of the (DASH) diet - Dietary Approaches to Stop Hypertension. Avoid alcohol consumption Smoking cessation Dietary sodium restriction. TREATMENT :

19. PHARMACOLGICAL TREATMENT : ACE inhibitors : Captopril Enalapril Ramipril 2. Angiotensin Receptor blockers (ARBs) : Losartan Telmisartan Olmesartan 3 . Direct renin inhibitor : Aliskiren

20. 4. Calcium channel blockers : Diltiazem Verapamil Nifedipine 5. Diuretics : Thiazides – Hydrochlorthiazide Loop diuretics – Furosemide, bumetanide Potassium sparing diuretics – Amiloride , triamterene, spirolonolactone 6. Sympatholytic agents : Centrally acting sympatholytics : Clonidine, methyldopa b. β -adrenergic blockers : Atenelol Propranolol

21. c. α + β - blockers: Labetalol Carvedilol d. α- adrenergic blockers : Selective – Prazosin, terazosin Non-selective – phenoxybenzamine , phentolamine 7. Vasodilators : Arteriolar dilators : Hydralazine, minoxidil Primary venodilator : Nitroglycerin Arteriolar and venodilator : Sodium nitroprusside