therapy of systemic hypertension by dr.mohamed abd almoneim

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Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

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Page 1: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Therapy of systemic hypertension

By Dr.Mohamed Abd Almoneim

Page 2: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Treatment of hypertension:The aim of treatment is to reduce blood pressure to normal levels i.e below 140/90 mmHg with minimal side effects.Benefits of treatment:

Control of hypertension reduces the excess risk of stroke and congestive heart failure associated with high blood pressure .Lines of treatment:

A) Non pharmacological therapy:B) Antihypertensive drug therapy.C) Treatment of hypertensive emergencies.D) Treatment of the cause in secondary hypertension:

E.g. surgical removal of pheochromocytoma or renal artery stenosis.

Page 3: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Treatment:Lifestyle Recommendations To reduce the possibility of becoming

hypertensive: Avoid stress.

1-Healthy diet; High in fresh fruits, vegetables and low fat dairy products, low in saturated fat and salt.

2. Regular physical activity: 30-60 minutes of moderate intensity dynamic exercise 4-7/week at least 4/week

3. Decrease alcohol consumption 4. Maintenance of ideal body weight (BMI 18.5-24.9 kg/m2) *Waist Circumference:

< 102 cm for men < 88 cm for women

5. Restriction of salt intake to less than 100 mmol/day in individuals considered salt-sensitive, such as: age over 45, individuals with impaired renal function or with diabetes.

6.Smoke free environment

Page 4: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Lifestyle Recommendations for the Treatment of Hypertension (Non drug therapy)

Avoid stress.

Page 5: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

1-Weight reduction: recommended in overweight patients:1.0 kg decrease in body weight was accompanied by an average reduction of

1.6 / 1.3 mm Hg in blood pressure ,this appears at a threshold around 4kg decrease in body weight to observe an effect in reduction in blood pressure.

*Weight reduction reduces C.V.S risks even without control of blood p. *Drug therapy can be reduced if weight reduction is successful.2-ExerciseEndurance exercise (aerobic exercise) may reduce many of the major C.V.S. risk

factors including blood pressure, serum cholesterol, and weight and glucose tolerance.

*Some antihypertensive drugs can interfere with exercise. e.g.diuretic induced hypokalemia and decrease muscle blood flowB-Blocker and CCBs, can reduce performance by inhibiting exercise induced

increase in heart rate and cardiac output Patients on a regular exercise program should be prescribed drug that allows

them to continue long-term therapy. Efforts should be made to reduce antihypertensive therapy.

Page 6: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

3-Dietary sodium restrictionDo not add sodium chloride to food during cooking or at the

table.Avoid or minimize the use of fast foods (contain high sodium

content). 4-potassium supplementation High potassium intake may reduce blood pressure by increasing

excretion of sodium, suppressing renin secretion, arteriolar dilatation.and impairing responsiveness to endogenous vasoconstrictors.

5-Magnesium supplementation: Is needed in patients who are hypomagnesmia due to diuretic

therapy.

Page 7: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

• Stop alcohol .• Tea and caffeine restriction • Stress reduction • Stop smoking.• Avoid drugs as……..

• Patients failing to normalize blood pressure after 2 weeks of non-pharmacological therapy should be considered for drug treatment.

Page 8: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Drug Therapy :1-For secondary hypertension (curable hypertension): all can

be treated except bilateral renal failure. 2-For primary hypertension: Indications for PharmacotherapyStrongly consider prescription if:

1-Average DBP equal or over 90 mmHg and:Hypertensive Target-organ damage (or CVD) orOther cardiovascular risk factors

Elevated systolic BPCigarette smokingAbnormal lipid profileStrong family history of premature CV diseaseTruncal obesitySedentary Lifestyle

2-Average DBP equal or over 80 mmHg in a patient with diabetes

Page 9: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Drug therapy (antihypertensive drugs):•

►First choice groups (commonly used drugs): ABCDAngiotensin-converting enzyme inhibitors (ACEIs).Beta-blockers.Calcium channel blockers.Diuretics.►Second choice groups:α1-adrenergic blockers: e.g. prazosin and doxasosin.

Combined α and β-blockers: e.g. labetalol. Adrenergic neuron blockers: e.g. α-methyldopa and reserpine.Direct vasodilators: e.g. hydralazine and diazoxide.Central α2 stimulants: e.g. clonidine and guanfacine.

Serotonin receptor blockers: e.g. ketanserine.Dopamine (D1) receptor agonists: e.g. fenoldopam.

Page 10: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Beta blockers (LoL)* PharmacokineticsMost of beta-blockers are absorbed orally:1-Lipophilic (fat-soluble) beta-blockers:They are well absorbed, but undergo extensive hepatic metabolism

(first pass effect). They are preferred in patients with renal failure. They can also cross the BBB and produce CNS effects.e.g. propranolol, …….

2-Hydrophilic (water-soluble) beta-blockers:They are less well absorbed and slowly eliminated by the kidney. They are not preferred in patients with renal failure and cannot

cross to CNS.e.g. atenolol, ………………etc.

Page 11: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Mechanism of Action1-Beta blocking action: 2-Intrinsic sympathomimetic action (ISA):= -

stimulate action.3-Local anaesthetic, or quinidine-like action or

membrane stabilizing activity. 3-CNS depressant action.4-Direct vasodilator action.(recent drugs only)

Not all beta-blockers have the above-mentioned actions but they differ in their mechanism of action.

Page 12: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Classification1- NON SELECTIVE BETA-BLOCKERS (1st

GENERATION)=block 1, 2, 3Liable to cause side effects.(propranolol) 2- BETA-1 SELECTIVE BLOCKERS

"CARDIOSELECTIVE" (2nd GENERATION)= block 1 only (atenolo)

3- BETA-BLOCKERS WITH V.D. ACTION (3rd

GENERATION)e.g carvidelol

Page 13: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Pharmacological EffectsCardiovascular system*Decreases heart rate and myocardial contractility.(B1)**Slow A-V conduction because the vagal action on the A.V. node predominates(B1). * Decreases total coronary blood flow(B2) and oxygen consumption(B1).*Quindine like action suppresses ectopic foci in the heart.*Decrease blood flow to most tissues by the unopposed alpha effect in response to

reduced COP.*Decrease platelet aggregation.

Lowers blood pressure by:********1-Negative inotropic and chronotropic effects lead to decreased COP2-Decrease renin release3-Blocks presynaptic 2 receptors lead to decreased NE release.4-Decrease central sympathetic outflow.5-Resetting of baroreceptors downwards.6-May act through vascular prostaglandins.7-Some blockers have vasodilator properties.

Page 14: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Respiratory systemBronchospasm and increased airway resistance in susceptible patients

EyeDecreases aqueous humor formation and reduce intra-ocular pressure. Metabolic effects:1-In normal individual : no effect on blood glucose. But:Augment hypoglycemic effects of insulin by blocking glycogenolsis and gluconeogenesis.Mask the hypoglycemic symptoms except sweating.2-Increase triglycerides and decrease H.D.L. CNSAntianxiety effectInsomnia, lethargy, night mares, vivid dreams and depression Others Salt and water retention secondary to the decrease in COP.

Page 15: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

• Therapeutic UsesA- Cardiovascular1-Treatment of hypertension with a diuretic.2-Ischaemic heart diseases :(angina and infarction) 3-Cardiac arrhythmias:*Supraventricular arrhythmias especially those

produced by exercise, thyrotoxicosis and pheochromocytoma.

*Digitalis induced arrhythmias.*Arrhythmias induced during surgery (I.V. esmolol).4-Hypertrophic obstructive cardiomyopathy: by their negative inotropic action.

Page 16: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

GITCases of gastrointestinal bleeding by decreasing COP and enhancing splanchenic

vasoconstriction.

EndocrineHyperthyroidism. Pheochromocytoma. (Must be combined with alpha-blockers).

C- EyeOpen angle glaucoma. (Timolol)

D- CNSProphylaxis of migraine Anxiety and essential tremors.

Carvedilol is nonselective beta blocker with antioxidant and alpha mediated vasodilator properties used in CHF, postinfarct LV Dysfunction and hypertension not for angin

Page 17: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Combined alpha and beta-blockers: labetalol It is selective 1 blocker and non-selective beta-

blocker.It has rapid onset of action.It is used to control severe hypertension

associated with pheochromocytoma and hypertension in pregnant patient.

Page 18: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Adverse EffectsHeart failure, bradycardia, hypotension.Bronchospasm in susceptible patients.Potentiation of the hypoglycaemic effect of insulin and oral hypoglycemic

drugs and masking of the hypoglycaemic symptoms.Peripheral ischaemia, intermittent claudication and cold extremities.Reduced blood flow to the liver and kidney reducing metabolism of

drugs.Hyperkalaemia..Nightmares, vivid dreams and depression.Nausea, vomiting, diarrhea or constipation.Increased plasma triglycerides and decrease HDL.Allergic reactions (rash fever)Sudden withdrawal leads to aggravation of the disease under treatment

due to up regulation of beta-receptors.Decrease sexual function.

Page 19: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

ContraindicationsCongestive heart failure.Heart block.Variant angina.Hypotension.Peripheral vascular diseases.Bronchial asthma.With verapamil (Negative chronotropic and inotropic).Alone in pheochromocytoma (Severe hypertension).Never stopped suddenly (Especially in case of angina)Diabetes mellitus.

Page 20: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

►Indications of beta-blockers in hypertension: 1-Hypertension associated with: IHD, cardiac

arrhythmia, or thyrotoxicosis.2-Hypertension associated with high plasma

renin (hyperreninemic hypertension).3-In patients with increased sympathetic

overactivity e.g. young age, hyperkinetic circulation, etc.

4-As a part of combined therapy.

Page 21: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

What are the criteria of ideal beta-blocker in hypertension? It should be:

(1) β1-cardioselective, (2) Has long duration of action; and (3) Has improved pharmacokinetic profile e.g.

atenolol.

Page 22: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Alpha blockers :PRAZOSIN Mechanism of Action (Selective 1 blocker and Direct V.D. at high doses).Pharmacological EffectsV.D. of arteries and veins lowering the blood pressure.It does not produce any change in C.O.P., renal blood flow and GFR thus; it could be used in

renal failure.Salt and water retention. Therapeutic UsesTreatment of mild to moderate hypertension.Treatment of acute congestive heart failure (decreases pre- and after-load).Impaired bladder emptying due to prostate obstruction (decreased the tone of trigone) leads

to decreased resistance to flow of urine. Adverse EffectsFirst dose effect: 1-The initial dose especially if large can produce postural hypotension and syncope.It occurs most commonly in salt and water depleted patients (start with a small dose and at

bedtime).2-Dizziness, headache, drowsiness, and palpitation (disappears with continued treatment).3-False positive tests for antinuclear factor.4-Salt and water retention. TERAZOSIN and TRIMAZOCIN Similar to prazosin but it does not produce first-dose syncope.

Page 23: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Centrally acting antihypertensive drugs 1-Adrenergic neuron blockers: reserpine .

Reserpine :*Adrenergic neurone blocking action by preventing the granular uptake of

catecholamines where it stays outside the granules (in the cytoplasm) to be inactivated by MAO enzyme. Now, the nerve has to synthesize more and more NE to keep the stores constant. As this process is limited, with frequent sympathetic stimulation the granules are depleted and the released NE becomes less, leading to decreased sympathetic tone. This process of depletion needs about seven days to be completed.

Depletion of tissues e.g. brain, heart, and adrenal medulla from their catecholamine and 5HT content.

*Parasympathomimetic action.

The hypotension effect is due to:Adrenergic neurone blocking action.Central action (inhibition of VMC and tranquilization)Depletion of suprarenal medulla.

Page 24: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Adverse Effects:1-Bradycardia, flushing and nasal stuffiness.2-Hyperacidity, peptic ulceration, salivation and diarrhea.3-Loss of libido and impotence in males.4-Salt and water retention.5-Psychic depression, suicidal attempts, parkinsonian-like rigidity

and nightmares, cancer breast. Uses : Less common nowadays due its side effects.Not alone but as part of combination therapy for treatment of

hypertension.

Page 25: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

2-Alpha methyl dopa:Pharmacological actions1-In the CNS it is transformed to alpha methyl NE. which

activates inhibitory 2 receptor in the medullary region leading to inhibition of the sympathetic outflow.

2-Inhibits plasma renin activity.3-Adrenergic neurone blocking action by:*Inhibition of dopa decarboxylase enzyme.*Competes with dopa for dopa decarboxylase enzyme

leading to formation of alpha methyl norepinephrine (false chemical transmitter) ineffective on the adrenergic receptors.

Page 26: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Pharmacological effects Antihypertensive.Therapeutic UsesTreatment of hypertension. (in pregnant female and in chronic renal failure) because

it does not affect the heart rate, COP, renal, cerebral or myocardial blood flow. Adverse effectsDrowsiness (common and disappears with continued treatment).Depression (Less than reserpine).Nasal stuffiness.Drug fever.Salt and water retention.Liver damage.Bone marrow depression.Positive Commb's test. 3-Beta-Blockers: propranolol .

Page 27: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

4-Central α2 stimulants: Clonidine and guanfacine.

Mechanism: It stimulates presynaptic α2 receptors → inhibition of NA release.

It inhibits dopamine hydroxylase enzyme → inhibition of NA synthesis. Inhibition of central sympathetic outflow.It inhibits renin release and plasma renin activity. Therapeutic uses: 1-Moderate to severe hypertension.2-Prophylaxis of migraine.3-In opiate withdrawal to decrease symptoms of sympathetic overactivity.4-As a sedative to reduce anxiety in preanesthetic medication.

Page 28: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Side effects: Sedation and dry mouth (xerostomia).Severe hypertension can occur with overdoses

due to stimulation of α1 receptors as a result of loss of selectivity.

Sudden withdrawal can lead to hypertensive crisis (treated by combined α & β blockers), so it must be stopped gradually.

Salt and water retention.

Page 29: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Guanfacin: it has a mechanism of action and

side effects similar to clonidine.

Page 30: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Serotonin receptor blockers: KetanserineMechanism: It blocks vascular α1 receptors and platelet 5-HT2

receptors → VD and ↓ platelet aggregation.Uses: Treatment of hypertension.Treatment of peripheral vascular disease.Thrombophlebitis and pulmonary embolism. Side effects: dizziness and fatigue.

Page 31: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Dopamine (D1) receptors agonists: Fenoldopam Mechanism: It stimulates D1 receptors in peripheral arteries leading to VD

and diuresis. Uses: it is given by continuous i.v. infusion Treatment of hypertensive emergencies. Treatment of post-operative hypertension. Side effects: Hypotension and reflex tachycardiaIncrease IOP so it should be avoided in patients with glaucoma.

Page 32: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

LOOP DIURETICS (High-Ceiling Diuretics) Loop diuretics include: furosemide, bumetanide, ,,,,, Pharmacokinetics They are rapidly absorbed from GIT and can be given i.v.General characteristics 1-Efficacy: are the most potent diuretics.They are effective at low GFR even below 10 ml/minute. 2-Onset: They have rapid onset of action, ½ - 1 hour after oral

administration and 5-10 min. following i.v. injection. 3-Duration: They have short duration of action up to 4

hours.

Page 33: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Mechanism of action A.Renal mechanism:1-Diuretic : see renal pharmacology………………..2-The loop diuretic furosemide produces stimulation of

cyclooxygenase activity resulting in increased synthesis of vasodilator prosta-glandins PGE2 and PGI2. These prostaglandins may contribute to furosemide increased glomerular filtration and promoting water and sodium excretion.

B. Extra-renal mechanism: Furosemide has actions on the vascular system (venodilator action)

that occur before its diuretic and is mediated by PGs.These effects produces changes in renal blood flow and a reduction

in LV filling pressure.

Page 34: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Uses 1-Acute pulmonary edema.2-All types of Na+ salt and water retention including

edema, ascites and pleural effusion especially severe cases.

3-Hypertensive emergencies (by i.v. route) and in some cases of renal hypertension.

4-Oliguria due to acute renal failure.5-Hyperkalemia; they can significantly enhance

urinary K+excretion. 6-Drug poisoning to produce forced diuresis and

enhance renal excretion of the offending drug.

Page 35: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Side Effects Hypokalaemia metabolic alkalosis:Hypomagnesaemia:Hyovolaemia and hyponatraemia: Hyperuricaemic: Ototoxicity (more with ethacrynic acid): It is common with impaired renal functions and in patients receiving other ototoxic

drugs such as aminoglycoside antibiotics.Glucose intolerance (hyperglycemia): this is due to inhibition of insulin release from B cells of pancreas (by opening K+

channels) and/or diminishes peripheral glucose utilization. This is less common than with thiazides.Hypersensitivity and idiosyncrasy: allergic reactions in the form of skin rash, oesinophilia or allergic interstitial nephritis

occur with furosemide and are usually reversible. Hyperlipidemia:increase LDL & TG and decrease HDL.

Page 36: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Interactions 1-The diuretic induced K+ deficiency increases the sensitivity of

myocardium to digitalis.2-Glucocorticoid treatment produces additive decrease in serum

potassium level.4-Ethacrynic potentiates ototoxicity of aminoglycosides.5-Furosemide potentates nephrotoxicity of cephalosporins.6-Non-steroidal anti-inflammatory drugs which are potent inhibitors of

prostaglandin synthesis, reduce the diuretic effects of furosemide because these effects may be mediated through furosemide induced increase in synthesis of PGE2 and PGI2.

7-Organic acid such as probenicid and indomethacin which are secreted by the active organic acid secretory system in the PCT could inhibit tubular secretion of loop diuretic competitively and thus prevent them to reach their site of action and reduce their diuretic activity.

Page 37: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

THIAZIDES e.g. chlorothiazide and hydrochlorothiazide

Widely used diuretics because they are effective orally and have moderate diuretic efficacy (prevents reabsorption of about 10% of Na+ in the filtrate).

Pharmacokinetics Thiazides are well absorbed one hour after oral administration.They are widely distributed in the body and can cross the

placenta Thiazides are excreted by the renal organic acid secretory system

at the PCT.

Page 38: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

General Characteristics Site: They act principally at proximal part of DCT. Efficacy: They have moderate diuretic efficacy

(prevents reabsorption of about 10% of Na+ in the filtrate. They should be avoided in renal impairment.

Onset: They act within one hour after oral administration.

Mechanism of Action: • See renal pharmacology

Page 39: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Pharmacological Effects 1-They increase renal excretion of Na+ and Cl- accompanied with water.2-They increase K+ excretion.3-They may decrease uric acid excretion leading to hyperuricaemia.4-They decrease renal blood flow through a direct action on renal vasculature.7-Antihypertensive effect (zhe mechanism of antihypertensive action is):*Decrease peripheral vascular resistance due to vasodilator action possibly

through: A- Direct V.D B- Decreased vascular receptor sensitivity to vasopressor agents

(adrenaline, angiotensin...) by decreasing Na+ content in the cells of vascular wall.

C- Increase synthesis of the vasodilator PGs.*Decreased cardiac output due to decrease blood volume by the diuretic action

Page 40: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Uses Essential hypertension:they may be used alone as initial monotherapy

or as a part of combined antihypertensive regimen.

They are used in treatment of edema and ascites (i.e. all types of Na+ and H2O retention) due to mild or moderate congestive heart failure, hepatic disease and renal disease.

Page 41: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Side Effects Hypokalaemia metabolic alkalosis.Hypovolaemia and hyponatraemia. Hypotension Hyperuricaemia.Hyperglycaemia: produced by the same mechanisms mentioned with

loop diuretics.Hyperlipidaemia: thiazides increase serum cholesterol, triglycerides and

LDL. This is possibly due to decreased insulin activity or release.Hypersensitivity: hypersensitivity reactions are related to sulfonamide

moiety and there is cross sensitivity with other sulfonamides.Deterioration of patients with hepatic or renal failure.Other side effects: parethesia, drowsiness, fatigability and impotence

are dose-related side effects.

Page 42: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

POTASSIUM - SPARING DIURETICSAldosterone antagonists: Spironolactore and eplerenone.Direct Na+- channel inhibitors: Triamterene and

amiloride. General Characteristics Site: Distal part of DCT or cortical part of collecting ducts.Efficacy: weak since the fraction of filtered Na load

reabsorbed at thus site is only 2-5% of the filtered Na+ load.

Page 43: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Mechanism of action 1-Block of aldosterone receptors

(spironolactone &eplerenone):2-Direct inhibition of Na+ transport though

specific Na+ channels in late part of the DCT and the collecting tubules. e.g. triamterene and amiloride.

Page 44: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Uses of K+ Sparing Diuretics1-Commonly given with loop acting or thiazide

diuretics to balance the excessive K+ loss and to limit the incidence of metabolic alkalosis that occurs at the same setting during use of loop acting or thiazide diuretic.

2-Cases of hyperaldosteronism either primary (Conn's syndrome) or secondary (CHF, hepatic cirrhosis, nephrotic syndrome) especially spironolactone.

3-Refractory edema (with potent diuretics to potentate their diuretic action).

Page 45: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

Side Effects of K+ Sparing Diuretics 1-It may cause hyperkalemia due to decrease k+ secretion. This occurs especially in

patients on high K+ intake or in patients with severe renal insufficiency or in-patient treated with other drugs that cause potassium-sparing effect e.g. beta-blockers, non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors or angiotensin receptor blockers.

2-Hyperchloraemic metabolic acidosis. 3-Nausea, abdominal pain, drowsiness and mental confusion.4-Spironolactone, lead to gynecomastia and impotence in males and menstrual

disordersin females. Contraindications of K+ Sparing Diuretics In presence of hyperkalemiaIn combination with other K+ sparing drugs or with K+ supplements.In-patient with chronic renal insufficiency. Drug interactions Administration with ACE inhibitors and other agents causing hyperkalemia or

potassium supplements may cause hyperkalemia.

Page 46: Therapy of systemic hypertension By Dr.Mohamed Abd Almoneim

►Indications of diuretics in hypertension:

1-Thiazides are given as initial therapy in most cases of essential hypertension.

2-Loop diuretics are given in hypertensive emergencies.

3-Hypertension associated with salt and water retention: e.g.Congestive heart failure (CHF). Chronic renal failure (give loop diuretics).Liver cirrhosis (give spironolactone).Primary hyperaldosteronism (give spironolactone).