Hypertension Ph.Alaa A Khojah

Hypertension Ph.Alaa A Khojah

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 TPR1-Neural Sympathetic & parasympathetic nervous system.2. Hormonal Renal: Ang IIAdrenal: Catecholamine’s& Aldosterone.3-Local factor artery & vein. CRITICAL POINTS!1. These organ systems and mechanisms control physical factors of CO and TPR2. 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 Agents1-Diuretics2-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 systemOften 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 1st line

1. Thiazideshydrochlorothiazide (HydroDIURIL, Esidrix);chlorthalidone (Hygroton)

2. Loop diureticsfurosemide (Lasix); bumetadine (Burmex);ethacrynic acid (Edecrin)

3- K+ Sparingamiloride (Midamor); spironolactone (Aldactone);triamterene (Dyrenium)

drug properties initial dose rangechlorothizide thiazide diuretic 500mg po daily 125-1000

hydrochlorothizide thiazide diuretic 12.5 mg po daily 12.5-50

benzthizide thiazide diuretic 25 mg po bid 50-100

chlorothalidone thiazide diuretic 25mg po daily 12.5-0

bumetanide loop diuretic 0.5 mg po daily /iv 0-5-5

furosemide loop diuretic 20mg po daily / iv 20-100

torsemide loop diuretic 5 mg po daily /iv 5-10

ethacrynic acid loop diuretic 50 mg po daily/iv 25-100

amiloride K sparing diuretic 5 mg po daily 5-10

triamterene K sparing diuretic 50 mg po bid 50-200

Eplerenone K sparing diuretic 25mg po daily 25-100

spironolactone K sparing diuretic 25 mg po daily 25-100

Diuretics (cont)

4. Adverse Reactionsdizziness.electrolyte imbalance/depletion.hypokalemia.(thiazide)

hyperkalemia (k sparing )hyperlipidemia.(thiazide)hyperglycemia (Thiazide).gout.(Thizide)

gynecomastia (k sparing )

5. Contraindicationshypersensitivity.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 muscle2- 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 antagonist initial dose dosage rane

doxazosin (Cardura) 1mg PO daily 1-16

prazosin 1mg PO bid-tid 1-20

terazosin 1mg PO at bedtime 1-20

5. Contraindications Hypersensitivity

Peripheral -1 Adrenergic Antagonists, con.

4. Adverse effectsnausea; 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 release3-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 dose doasage range

clonidine *catapres* 0.1 mg PO bid 0.1-1.2

clonidine path TTS/WK ~ O.1 mg/d release

0.1-0.3

guanfacine 1mg PO daily 1-3

guanabenz 4mg PO bid 4-46

methyldopa*aldomet* 250 mg PO bid-tid 250-2.000

4. Adverse Effectsdry mouth; sedation;

impotence;

Central Sympatholytic (-2 Agonists); cont.

6. Therapeutic Considerationsthird 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

drug properties initial dose range

atenolol selective 50 mg po daily 25-100

bisprolol selective 5 mg po daily 5-40

metroprolol selective 50-100 mg po daily 2.5-20

nadolol Non selective 40 mg po daily 20-240

propranolol Non selective 40 mg po daily 40-240

timolol Non selective 10 mg po daily 20-40

pindolol ISA 5 mg po daily 10 -60

carvidilol a & B antagonist 6.25mg po daily 12.5-50

labetalol a & B antagonist 100mg po bid 200-1200

acebutolol selective, 200mg po bid 200-1200

-Adrenergic Antagonists, cont

6. Therapeutic ConsiderationsSelectivity

nadolol (Corgard) non selective, but 20 hr 1/2 life metoprol (Lopresor) -1 selective, 3-4 hr 1/2 life

Risky in pulmonary disease even selective -1 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. Contraindicationsasthma; diabetes; bradycardia; hypersensitivity

5-Anti-Angiotensin II DrugsAngiotensin II Formation

2. Ang II Receptor Antagonists losartan (Cozaar); candesartan (Atacand); valsartan (Diovan)

1. Angiotensin Converting Enzyme- Inhibitors)

Ang I

Ang II

ACE

ACE

Ang II

Renin

Angiotensinogen

Ang IAT1

AT2

LungVSMBrainKidneyAdr Gland

quinapril (Accupril); fosinopril (Monopril); moexipril (Univasc); lisinopril (Zestril, Prinivil); benazepril (Lotensin); captopril (Capoten

. Effects on Cardiovascular System a. Renal

1. Maintenance of normal GFR2. Reduces plasma vasopressin

and aldosterone Decreased CO

b. Cardiac1. Decreased Ang II and

Norepinephrine effects Decreased SymNS influence;

Decreased CO c. Vascular

1. Decreased Ang II Decreased TPR- due to Ang II

ACEI initial dose dosage range

captopril 25mg PO bid 50-450

benazepril 10mg PO bid 10-40

Enalapril 5mg PO daily 2.5-40

Fosinopril 10 mg Po daily 10-40

Angiotensin 11 receptor blocker

initial dose dosage form

Candesartan 8mg PO daily 8-32

Losartan 50mg PO daily 25-100

Valsartan 80 mg PO daily 80-320

Omlesartan 20mg PO daily 20-40

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 / prostaglandinsa.

5. Contraindicationspregnancy; 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++ channeldecreases/prevents contraction

3- Effect on Cardiovascular systemVascular relaxationDecreased TPR

Ca++ Channel Blockers, cont.

5. ContraindicationsCongestive heart failure; pregnancy and lactation;Post-myocardial infarction

6. Therapeutic Considerationsverapamil >interactions w/ cardiac

glycosides

4. Adverse Effects

a. most associated with excessive vasodilation1. mild to moderate edema2. flushing3. tachycardia- Nifedipine- due to reflex SymNS activation

aggravates angina4. bradycardia- Diltiazem, verapamil

drug initial dose range

amlodipine 5mg po daily 2.5-10

diltiazim 30 mg po daily 90-360

nifedipiene 10 mg po daily 30-120

verapamil 80 mg po pid 80-480

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 dose dosage range

Hydralazine 10 mg PO qid 50-300

Minoxidil 5 mg PO qid 2.5-100

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 PointsHypertensive 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 EmergencyA 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.

• http://www.heart.org/HEARTORG/Conditions/HighBloodPressure/AboutHighBloodPressure/Hypertensive-Crisis_UCM_301782_Article.jsp

• The Washington manual of medical therapeutic /

• Clinical pharmacy and therapeutic /