Hypertension Dr.Hassan H Alwafi MBBS, Demonstrator Department of Clinical Pharmacology UQU

Hypertension The Silent Killer Hypertension is the term used to describe high blood pressure. Blood Pressure: is a measurement of the force against the walls of your arteries as the heart pumps blood through the body. Blood pressure management includes systolic and disystolic components, and both are important determining an individual’s cardiovascular risk.

Determinants of Arterial Pressure Mean arterial pressure = CO X TPR (blood volume & arterial diameter). Mechanisms of Controlling CO and TPR 1-Neural Sympathetic & parasympathetic nervous system. 2. Hormonal Renal: Ang II Adrenal: Catecholamine’s& Aldosterone. 3-Local factor artery & vein. CRITICAL POINTS! 1. These organ systems and mechanisms control physical factors of CO and TPR 2. Therefore, they are the targets of antihypertensive therapy.

Etiology : Primary hypertension (90-95%) *Essential hypertension. SECONDARY HYPERTENSION *Renal disease. *Endocrine disease. *Vascular disease. *Drug. Sympathomimetic Amine- Estrogen-Cyclosporine-Erythropoietin,NSAID- and steroid

Hypertension Complications: (The risk of complication is related to the level of BP elevated) Aneurysm: Hypertension symptoms weaken blood vessel walls, which can result in an aneurysm. This bulge in the blood vessel can rupture, causing internal bleeding. A ruptured aneurysm is a life-threatening event. Atherosclerosis. Coronary Artery Disease. Heart Failure. Kidney Complications: total renal failure, Kidney aneurysms and renal tissue scarring. cerebral hemorrhage /infarction. Vision Loss: The small blood vessels in the eyes can be damaged as a result of high blood pressure, causing nerve damage or bleeding. Blurred vision can occur, as can -

Symptom: Most of the time, there are no symptoms. Symptoms that may occur include: -Confusion -Fatigue -Headache -Irregular heartbeat -Nose bleeding -Vision changes

Diagnoses: 1.Blood pressure should be measured by using sphygmomanometer. 2. Check for possible secondary cause by (Taking history, blood Test, Echo, ECG, Urinalysis,& Ultrasound of the kidney )

Treatment: The goal of treatment is to reduce blood pressure to lower risk of complications. Treatment of hypertension includes both pharmacological and Non-pharmacological treatment.

General Treatment Strategy of Hypertension 1-Diagnosis. 2-Primary or secondary hypertension. 3-Secondary > treat underlying cause. 4-Primary> initiate life style modification. 5->Pharmacological treatment

Pharmacological Treatment: A large selection of antihypertensive drug is available. It’s important to use drug that minimize patient Side effects. Many patient need combination of drug to achieve adequate blood pressure.

Antihypertensive Medication Classes of Antihypertensive Agents 1 -Diuretics 2-Peripheral a-1 adrenergic antagonist. 3-Central sympatholytic (a-2Agonist). 4-B-Adrenergic Antagonists. 5-Anti-angiotensin Drugs. 6-Ca++ Channel Blockers. 7-Vasodilator. CRITICAL POINTS: Each designed for specific control system Often used in combination.

1-Diuretics 1-Site of Action: Renal Nephron. 2-Mechanism of action: Increase (urine excretion & Na excretion). Decrease (extracellular fluid and plasma volume). 3-Effect on Cardiovascular System: Acute decrease in CO. Chronic decrease in TPR.

1-Diuretics 1 st line 1. Thiazides hydrochlorothiazide (HydroDIURIL, Esidrix); chlorthalidone (Hygroton) 2. Loop diuretics furosemide (Lasix); bumetadine (Burmex); ethacrynic acid (Edecrin) 3 - K+ Sparing amiloride (Midamor); spironolactone (Aldactone); triamterene (Dyrenium )

drugpropertiesinitial doserange chlorothizidethiazide diuretic500mg po daily hydrochlorothizidethiazide diuretic12.5 mg po daily benzthizidethiazide diuretic25 mg po bid chlorothalidonethiazide diuretic25mg po daily bumetanideloop diuretic0.5 mg po daily /iv0-5-5 furosemideloop diuretic20mg po daily / iv torsemideloop diuretic5 mg po daily /iv5-10 ethacrynic acidloop diuretic50 mg po daily/iv amilorideK sparing diuretic5 mg po daily5-10 triamtereneK sparing diuretic50 mg po bid EplerenoneK sparing diuretic25mg po daily spironolactoneK sparing diuretic25 mg po daily25-100

Diuretics (cont) 4. Adverse Reactions dizziness. electrolyte imbalance/depletion. hypokalemia.(thiazide) hyperkalemia (k sparing ) hyperlipidemia.(thiazide) hyperglycemia (Thiazide). gout.(Thizide) gynecomastia (k sparing ) 5. Contraindications hypersensitivity. compromised kidney function. cardiac glycosides (K+ effects). hypovolemia. hyponatremia

Therapeutic Considerations : Thiazides (most common diuretics for HTN). Generally start with lower potency diuretics. Generally used to treat mild to moderate HTN. Use with lower dietary Na+ intake. and K+ supplement or high K+ food. K+ Sparing (week diuretic >combination with other agent). Loop diuretics (severe HTN, or with CHF ) Osmotic (HTN emergencies ). Diuretics (cont)

2-Peripheral a-1 Adrenergic Antagonists Drugs: prazosin (Minipres); terazosin (Hytrin) 1-Site of Action-:- Peripheral arterioles, smooth muscle 2- Mechanism of Action Competitive antagonist at a-1 receptors on vascular smooth muscle.. 3- Effects on Cardiovascular System Blocking  -receptors on vascular smooth muscle allows muscle relaxation, dilation of vessel, and reduced resistant

a- adrenergic antagonistinitial dosedosage rane doxazosin (Cardura)1mg PO daily1-16 prazosin1mg PO bid-tid1-20 terazosin1mg PO at bedtime1-20

5. Contraindications Hypersensitivity Peripheral  Adrenergic Antagonists, con. 4. Adverse effects nausea; drowsiness; postural hypotension; 1st dose syncope 6. Therapeutic Considerations -useful with diabetes, asthma, and/or hypercholesterolemia -use in mild to moderate hypertension -often used with diuretic,  antagonist

3-Central Sympatholytic (a-2 Agonists) Drugs: clonidine (Catapres), methyldopa (Aldomet) 1. Site of Action: CNS medullary cardiovascular centers” 2-Mechanism of Action : CNS a-2 adrenergic stimulation >Decreased norepinephrine release 3-Effects on Cardiovascular System : Stimulation of a-2 receptors in the medulla decreases peripheral Sympathetic activity reduces tone, vasodilation and decreases TPR

Centrally acting adrenergic agent initial dosedoasage range clonidine *catapres*0.1 mg PO bid clonidine pathTTS/WK ~ O.1 mg/d release guanfacine1mg PO daily1-3 guanabenz4mg PO bid4-46 methyldopa*aldomet*250 mg PO bid-tid

4. Adverse Effects dry mouth; sedation; impotence; Central Sympatholytic (  -2 Agonists); cont. 6. Therapeutic Considerations third line; methyldopa drug of choice for pregnancy prolonged use--salt/water retention, add diuretic

4- B- Adrenergic Antagonists. Drugs: propranolol (Inderal); metoprolol (Lopressor) atenolol (Tenormin); nadolol (Corgard); pindolol (Visken) 1-Site of action: 2-Mechanism of Action competitive antagonist at b- adrenergic receptors..3-Effects on Cardiovascular System. Cardiac--  HR,  SV   CO. Renal--  Renin   Angiotensin II   TPR

drugpropertiesinitial doserange atenololselective50 mg po daily bisprololselective5 mg po daily5-40 metroprololselective mg po daily nadololNon selective40 mg po daily propranololNon selective40 mg po daily timololNon selective10 mg po daily20-40 pindololISA5 mg po daily carvidilola & B antagonist6.25mg po daily labetalola & B antagonist100mg po bid acebutololselective,200mg po bid

 drenergic Antagonists, cont 6. Therapeutic Considerations Selectivity nadolol (Corgard) non selective, but 20 hr 1/2 life metoprol (Lopresor)  selective, 3-4 hr 1/2 life Risky in pulmonary disease even selective  Use post myocardial infarction- protective Use with diuretic to prevent reflex tachycardia. Mixed  blocker available (labetalol)(Trandate, Normodyne) decreases TPR (  ), prevents reflex tachycardia (  ) 4. Adverse Effects oadema ; postural hypotension fatigue; exercise intolerance; 5. Contraindications asthma; diabetes; bradycardia; hypersensitivity

5-Anti-Angiotensin II Drugs Angiotensin II Formation 2. Ang II Receptor Antagonists losartan (Cozaar); candesartan (Atacand); valsartan (Diovan) 1.Angiotensin Converting Enzyme- Inhibitors ) Ang I Ang II ACE   Ang II Renin Angiotensinogen Ang I AT1 AT2 Lung VSM Brain Kidney Adr Gland quinapril (Accupril); fosinopril (Monopril); moexipril (Univasc); lisinopril (Zestril, Prinivil); benazepril (Lotensin); captopril (Capoten

. Effects on Cardiovascular System a. Renal 1. Maintenance of normal GFR 2. Reduces plasma vasopressin and aldosterone Decreased CO b. Cardiac 1. Decreased Ang II and Norepinephrine effects Decreased SymNS influence; Decreased CO c. Vascular 1. Decreased Ang II Decreased TPR- due to Ang II

ACEIinitial dosedosage range captopril25mg PO bid benazepril10mg PO bid10-40 Enalapril5mg PO daily Fosinopril10 mg Po daily10-40 Angiotensin 11 receptor blocker initial dosedosage form Candesartan8mg PO daily8-32 Losartan50mg PO daily Valsartan80 mg PO daily Omlesartan20mg PO daily20-40

Anti-Angiotensin II Drugs, cont 4. Adverse Effects a. hyperkaelemia b. altered gustatory sensation c. angioedema- sudden edema skin/ mucous membranes; etiology unknown d. cough- increase bradykinin / prostaglandins a. 5. Contraindications pregnancy; hypersensitivity; bilateral renal stenosis 6. Therapeutic Considerations a. use with diabetes or renal insufficiency 1. Ang II contributes to decreased renal function b. use in heart failure 1. Ang II contributes to ventricular remodeling c. usually used with diuretic, additive with thiazide 1. Decreases sodium retention by reducing aldosterone d. used where diuretic or  -blocker contraindicated or ineffective Enalapril, iv for hypertensive emergency

6- Ca++ Channel Blockers 1-Site of Action- Vascular Ca++ Channel Blockers smooth muscle 2-Mechanism of Action- Blocks Ca++ channel decreases/prevents contraction 3- Effect on Cardiovascular system Vascular relaxation Decreased TPR

Ca++ Channel Blockers, cont. 5. Contraindications Congestive heart failure; pregnancy and lactation; Post-myocardial infarction 6. Therapeutic Considerations verapamil >interactions w/ cardiac glycosides 4. Adverse Effects a. most associated with excessive vasodilation 1. mild to moderate edema 2. flushing 3. tachycardia- Nifedipine- due to reflex SymNS activation aggravates angina 4. bradycardia- Diltiazem, verapamil

druginitial doserange amlodipine5mg po daily diltiazim30 mg po daily nifedipiene10 mg po daily verapamil80 mg po pid80-480

7- Vasodilators Drugs: hydralazine (Apresoline); minoxidil (Loniten); nitroprusside (Nipride); diazoxide (Hyperstat I.V.); fenoldopam (Corlopam) 1-Site of Action: vascular smooth muscle 2-Effect on cardiovascular system :vasodilation > decrease TPR

direct acting vasodilator initial dosedosage range Hydralazine10 mg PO qid Minoxidil5 mg PO qid

Vasodilators, Cont 4. Adverse Effects reflex tachycardia Increase SymNS activity (hydralazine, minoxidil,diazoxide) lupus (hydralazine) hypertrichosis (minoxidil) cyanide toxicity (nitroprusside) 5. Therapeutic Considerations Nitroprusside- IV only Hydralazine- safe for pregnancy diazoxide- emergency use for severe hypertension.

Summary Important Points Hypertensive Agents Each class of antihypertensive agent: 1. has as specific mechanism of action, 2. acts at one or more major organ systems, 3. on a major physiological regulator of blood pressure, 4. reduces CO and/or TPR to lower blood pressure, 5. has specific indications, contraindications, and therapeutic advantages and disadvantages associated with the mechanism of action.

Treatment of hypertensive emergencies Goal: produce a rapid but well controlled fall in BP. Context: hypertensive encephalopathy, eclampsia, pheo, hypertension with pulmonary oedema, aneurism, subarachnoid hemorrhage etc.. Labetalol iv (alpha & beta blocker) I.v nitroprusside I.v. nitroglycerine hydralazine iv or im (eclampsia) iv phentolamine or phenoxybenzamine po (pheo)

hypertensive emergency Hypertensive Emergency A hypertensive emergency exists when blood pressure reaches levels that are damaging organs. Hypertensive emergencies generally occur at blood pressure levels exceeding 180 systolic OR 120 diastolic, but can occur at even lower levels in patients whose blood pressure had not been previously high.

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