Pharmacotherapy of hypertension

Pharmacotherapy of hypertension

Hypertension

according to WHO and Joint National Committee,hypertension is defined as SBP>140 and DBP>90

Blood pressure

It’s the lateral pressure exerted by the flowing column of blood

On the vessel walls.

Normal value : 120/80 mmHg

HYPERTENSION IS NOT A DISEASE, BUT ITS AN IMPORTANT RISK FACTORFOR MANY UNDERLYING DISEASES

Types of hypertension

• Essential hypertension ( primary ) -patients with arterial hypertension & no definable

cause

• Secondary hypertension -Individuals in whom a specific structural organ or a

genetic defect is responsible for hypertension

Essential hypertensionFactors causing are 1.Genetic factors 2.Foetal factors 3.Environmental factors(Risk factors)

-Smoking -Alcohol consumption -Na+ intake -Stress

Obesity leads to Insulin resistance

-Hyper insulinemia causes vaso constriction

-Modified ion transport mechanisms

Secondary hypertension

Causes:- 80% of the cases are renal -Diabetic nephropathy -Chronic

glomerulonephritis -Renovascular

disease Endocrine causes

-cushings syndrome -Pheochromocytoma -Acromegaly -Cohn’s syndrome

CVS -Coarctation of aorta Drug effects -oral contraceptive pills -Steroids

-vasopressins -MAO- inhibitor

CLINICAL ASPECTS OF HYPERTENSION

APPROACH TO THE PATIENT

When hypertension is suspected , BP should be

Measured at least twice during two separate

Examinations after initial screening

OPTMAL <120 <80

NORMAL <130 <85

HIGH NORMAL 130-139 85-89

HYPERTENSION STAGE 1

140-159 90-99


160-179 100-109


>180 >110

ISOLATED HYPERTENSION

>140 <90

CATOGORY SBP DBP

Signs & symptoms

• Most patients have no signs & symptoms .• When symptoms are present they fall into three

categories 1 . symptoms related to elevated BP 2 . symptoms related to hypertensive vascular disease 3 . symptoms related to underlying disease, in the

case of secondary hypertension

1. Symptoms related to elevated BP

• Headache – localised to occipital region

• Dizziness • Easy fatigability• Palpitations

2 . symptoms related to vascular disease

• Epistaxis• Blurring of vision• Episodes of dizziness• Angina pectoris• Dyspnoea – due to

cardiac failure

3 . symptoms related to underlying disease

• Polyuria, polydypsia, muscle weeknes - in patients with primary aldosteronism

• Weight gain – in patients with Cushings syndrome• Episodic headache, palpitations, postural dizziness –

in patients with pheochromocytoma

Physical examination

• General appearance• Fundoscopic findings• Examination of heart• Abdominal examination• Compare BP and pulse in two upper extremeties and

in supine and standing positions

Management

I- non pharmacological therapy If SBP < 140 mmhg DBP < 90 mm hg It includes • wt reduction , BMI <25 kg /m2

• Low fat & saturated fat diet• Low sodium diet < 6 gms daily• Limited alcohol consumption• Dynamic exercise• Increased fruit & vegetable

consumption

• Decreased smoking

II- drug therapy

Lifestyle ModificationsLifestyle Modifications

Reduce weight to normal BMI Reduce weight to normal BMI (<25kg/m(<25kg/m22): 5-20 mmHg/10kg loss): 5-20 mmHg/10kg loss

DASH eating plan: 8-14 mmHgDASH eating plan: 8-14 mmHg

Dietary sodium reduction: 2-8 mmHgDietary sodium reduction: 2-8 mmHg

Increase physical activity: 4-9 mmHgIncrease physical activity: 4-9 mmHg

Reduce alcohol consumption: 2- 4 Reduce alcohol consumption: 2- 4 mmHgmmHg

DASH Diet

Dietary

Approaches

to

Stop

Hypertension

• Fruits, vegetables, low fat dairy foods, and reduced sodium intake

• Includes whole grains, poultry, fish, nuts

• Reduced amounts of red meat, sugar, total and saturated fat, and cholesterol

Anti hypertensive drugs

1. Diuretics1. Thiazides

• Hydrochlorothiazide, chlorthalidone

• Indapamide2. High ceiling diuretics

• Furosemide3. K+ sparing diuretics

• Spironolactone, amiloride2. ACE inhibitors

• Captopril , enalapril, ramipril , lisinopril, perindopril , fosinopril

3. Angiotensin receptor blockers ( at 1 blockers )

• losartan , valsartan , irbesartan , telmisartan

4. Calcium channel blockers• Verapamil , diltiazem ,

nifedipine , amlodipine , felodipine , nitrendipine

5. Α+β adrenergic blockers• Labetelol , carvedilol

6. Α adrenergic blockers• Prazosin , terazosin ,

doxazosin , phentolamine , phenoxybenzamine

7. Central sympatholytics• Clonidine , methyl dopa

8. Vasodilators– Arteriolar

• Hydralazine , minoxidil , diazoxide

– Arteriolar plus venous • Sodium nitroprusside

DIURETICS

•

Classification

1. Thiazide diuretics - Hydrochlorthiazide -Chlorthalidone -Indapamide2. High ceiling diuretics -Furosemide3. K+ sparing -spironolactone -Amiloride

Diuretics (water pills)

• Diuretics are the drugs that have the ability to increase urinary excretion of salt and water by acting over different parts of nephron.

• Alcohol, caffeine, digoxin, theophylline water intake increase urine output. But these are not classical diuretics, they are called physiological diuretics.

• Getting rid of excess salt and fluid helps lower blood pressure and can make it easier for your heart to pump.

• Diuretics may be used to treat a number of heart-related conditions, including high blood pressure, heart failure, kidney and liver problems, and glaucoma.

Classification of diuretics according to efficacy/potency

• High efficacy/high ceiling diuretics- Prevents 15-25% reabsorption of salt & water, e.g; Loop

diuretics• Moderate efficacy diuretics- Prevents 5-10% reabsorption of salt & water, e.g; Thiazide

diuretics• Low efficacy diuretics- Prevents 5% (maximum) reabsorption of salt & water, e.g;

K+ sparing diuretics, Osmotic diuretics, Carbonic anhydrase inhibitors.

. Thiazide diuretics• Thiazides are the most widely used of the diuretic

drugs. They are called “celling diuretics” because increasing the dose above normal does not promote a further diuretic response.

• Mechanism of action of thiazide: In the distal convoluted tubule thiazides cause secretion of waterDecrease blood volume Decrease BP.

• In prolonged use may cause vasodilation Decrease peripheral resistance Decrease BP

All thiazides are secreted by the organic acid secretory system in the proximal tubule and compete with the secretion of uric acid by that system. As a result, thiazide use may decrease uric acid secretion and elevate serum uric acid level.

Not effective at low glomerular filtration rates.- Although hydrochlorothiazide is the most widely

used diuretic for hypertension, chlorthalidone may be more effective because of its much longer half-life.

Thiazides - Pharmacokinetics

Clinical Indications of thiazide• Hpertension: They reduce blood pressure and

associated risk of CVA/stroke and MI in hypertension

- They should be considered first-line therapy in hypertension (effective, safe and cheap)

• Heart failure• Nephrolithiasis due to idiopathic hypercalciuria

- Condition characterized by recurrent stone formation in the kidneys due to excess calcium excretion

- Thiazide diuretics used to prevent calcium loss and protect the kidneys

• Nephrogenic diabetes insipidus.• Thiazides allow increased solute excretion in the urine,

breaking the Polydipsia-Polyuria cycle.

ADVERSE EFFECTS OF THIAZIDES• HYPOKALEMIAHYPONATREMIA DEHYDRATION (particularly in the elderly) leading to

POSTURAL HYPOTENSIONHYPERCALCEMIAHYPERGLYCEMIA possibly because of impaired insulin

release secondary to hypokalemia.HYPERURICEMIA HYPERLIPIDEMIA HYPERSENSITIVITY - may manifest as interstitial nephritis,

pancreatitis, rashes, blood dyscriasis (all very rare)METABOLIC ALKALOSIS due to increased sodium load at

the distal convoluted tubule which stimulates the sodium/hydrogen exchanger to reabsorb sodium and excrete hydrogen

IMPOTENCE

Dosage of thiazide

Contraindications: Excessive use of any diuretic is dangerous in patients with hepatic cirrhosis, borderline renal failure, or heart failure

. Loop diuretics• furosemide and ethacrynic acid. bumetanide and

torsemide are sulfonamide loop diuretics. They are called high celling diuretics

• The loop diuretics acts promptly, even among patients who have poor renal function or have not responded to thiazides or other diuretics.

• Mechanism of action:• Loop diuretics inhibit Sodium-Potassium-Chloride Transporter 2

(NKCC2), in the thick ascending limb of Henle’s loop. • By inhibiting this transporter, the loop diuretics (TAL) reduce

the reabsorption of NaCl • It also diminish the lumen-positive potential that comes from

K+ recycling. This positive potential normally drives divalent cation reabsorption in theTAL and by reducing this potential, loop diuretics cause an increase in Mg2+ and Ca2+ excretion.

LOOP DIURETICS - PHARMACOKINETICSRapid GI absorption. Also given i.m. and i.v.Extensively protein bound in plasmaShort half-lives in general

CLINICAL USES OF LOOP DIURETICSEdema due to congestive heart failure , nephrotic syndrome

or cirrhosisAcute pulmonary edema *Acute hypercalcemia

• Hyperkalemia, acute renal failure, and anion overdose. ADVERSE EFFECTS OF LOOP DIURETICSHypokalemia, hyponatremia & hypocalcemia (in contrast to

thiazides)Dehydration and postural hypotensionmetabolic alkalosis hypercholesterolemia, hyperuricemia, hyperglycemia, HypersensitivityOTOTOXICITY (especially if given by rapid IV bolus)

Typical dosages of loop diuretics

Contraindications:Furosemide, bumetanide, and torsemide may exhibit allergic cross-reactivity in patients who are sensitive to other sulfonamides, but this appears to be very rare

. POTASSIUM-SPARING DIURETICS• They act in the collecting tubule to inhibit Na+

reabsorption and K+ excretion. • The major use of potassium-sparing agents is in

the treatment of hypertension, most often in combination with a thiazide.

• Types: - Aldosterone antagonist: (spironolactone,

eplerenone) - Na+ channel inhibitor: (amiloride, triamterene).• Spironolactone is a weak diuretic because most of

the filtered Na+ is reabsorbed before reaching the CT.

• *Aldosterone normally stimulates the Na+/K+-exchange sites of the collecting tubule

CLINICAL USES OF POTASSIUM- SPARING DIURETICS

ADVERSE EFFECTS OF POTASSIUM-SPARING DIURETICS

• Hyperaldosteronism - Primary hypersecretion (Conn’s syndrome) - Secondary hyperaldosteronism (evoked by heart failure, hepatic cirrhosis,

nephrotic syndrome).• In combination with K+ loosing diuretics (loop & thiazide) to prevent K+

excretion.• Eplerenone can slow the progression of albuminuria in diabetic patients.• Eplerenone has been found to reduce myocardial perfusion defects after

myocardial infarction.

A. HyperkalemiaB. Hyperchloremic Metabolic Acidosis C. GynecomastiaD. Acute Renal FailureE. Kidney Stones

Potassium-sparing diuretics and combination preparations

Contraindications:Potassium-sparing agents can cause severe, even fatal, hyperkalemia in susceptible patients. Patients with chronic renal insufficiency are especially vulnerable and should rarely be treated with these diuretics.

V. Carbonic Anhydrase Inhibitors

• . Acetazolamide

Mechanism of action:

H+ + HCO3- H2CO3 Carbonic anhydrase_> H2O + CO2

• Accumulation of H+ in the lumen which impairs the transport

action of Na+/H+ exchanger

• The decreased ability to exchange Na+ for H+ in the presence

of acetazolamide results in a mild diuresis.

• Additionally, HCO3 is retained in the lumen, with marked

elevation in urinary pH. The loss of HCO3- causes a

hyperchloremic metabolic acidosis and decreased diuretic

efficacy following several days of therapy ( set-off).

• Glaucoma (most common indication) - The reduction of aqueous humor formation by carbonic anhydrase

inhibitors decreases the intraocular pressure.

• Urinary Alkalinization• Metabolic Alkalosis• Acute Mountain Sickness: Acetazolamide, a mild diuretic, works by

stimulating the kidneys to secrete more bicarbonate in the urine, thereby acidifying the blood. This change in pH stimulates the respiratory center to increase the depth and frequency of respiration, thus speeding the natural acclimatization process. An

CLINICAL USES OF CARBONIC ANHYDRASE INHIBITORS

ADVERSE EFFECTS OF CARBONIC ANHYDRASE INHIBITORS

• Hyperchloremic Metabolic Acidosis• Renal Stones• Renal Potassium Wasting

CONTRAINDICATION: - Hyperammonemia - Hepatic encephalopathy in patients with cirrhosis.

Carbonic anhydrase inhibitors used orally in the treatment of glaucoma

Changes in urinary electrolyte patterns and body pH in response to diuretic drugs

V. Osmotic Diuretics (AQUARETICS)

• Hydrophilic chemical substances that are filtered through the glomerulus, such as mannitol and urea . •Diuresis is due to their ability to carry water with them into the tubular fluid. •M/A: •The presence of a non-reabsorbable solute such as mannitol prevents the normal absorption of water. As a result, urine volume increases.

•Osmotic diuretics used to maintain urine flow & save the patient from dialysis e.g treatment for patients with increased intracranial & intraocular pressure or acute renal failure due to shock, drug toxicities, and trauma.

•ADVERSE EFFECTS OF OSMOTIC DIURETICS- Extracellular Volume Expansion, Dehydration, Hyperkalemia, Hypernatremia, and Hyponatremia (When used in patients with severe renal impairment)

Class Adverse Side Effects Drug Interactions

Thiazide

• Hypokalemia• Metabolic alkalosis• Dehydration leading to hypotension• Hyponatremia• Hyperglycemia in diabetics• Hypercholesterolemia; hypertriglyceridemia• Increased low-density lipoproteins• Hyperuricemia (at low doses)• Azotemia (in renal disease patients)

•hypokalemia potentiates digitalis toxicity•non-steroidal anti-inflammatory drugs: reduced diuretic efficacy•beta-blockers: potentiate hyperglycemia, hyperlipidemias•corticosteroids: enhance hypokalemia

Loop

• Hypokalemia• Metabolic alkalosis• Hypomagnesemia• Hyperuricemia• Dehydration leading to hypotension• Dose-related hearing loss (ototoxicity)

•hypokalemia potentiates digitalis toxicity•non-steroidal anti-inflammatory drugs: reduced diuretic efficacy•corticosteroids: enhance hypokalemia•aminoglycosides: enhance ototoxicity, nephrotoxicity

K+-sparing

• Hyperkalemia• Metabolic acidosis• Gynecomastia (aldosterone antagonists)• Gastric problems including peptic ulcer

• ACE inhibitors: potentiate hyperkalemia• Non-steroidal anti-inflammatory drugs: reduced diuretic efficacy

Carbonic anhydrase inhibitors

• Hypokalemia• Metabolic acidosis

Central sympatholytics

• Clonidine– Moderately potent antihypertensive– High affinity and intrinsic activity for α2a subtype .

MechanismCLONIDINE

IMIDIZOLINERECEPTORS

α2A RECEPTORS

METHYL DOPA

• Alpha methyl analouge of dopa• Precursors of dopamine & noradrenaline• Alphamethyl noradrenaline (na) in the brain

acts on central alpha 2 receptors to decrease efferent sympathetic activity

• Methyl dopa inhibits enzyme dopa decarboxylase and decreases production of na

• Inhibition of postural reflexes is mild

ADVERSE EFFECTS

• Sedation• Lethargy• Dryness of mouth• Nasal stuffiness• Headache• Impotence• Postural hypotension lesser than clonidene

Calcium channel blockers

MECHANISM OF ACTION• MEMBRANE

POTENTIAL DROPS TO -40mv

• Inward movement of ca2+

• Depolarisation of smooth muscle

• Smooth muscle contraction

So ccbs blocks ca2+

entry and thus Cause smooth muscle

relaxation

MEMBRANE POTENTIAL = -40 mV

Classification

• Phenyl alkylamine – verapamil• Dihydropyridine – nifedipine • Benzothiazepine – diltiazem

VERAPAMIL

• HAS SOME α ADRENERGIC BLOCKING ACTIVITY

• Cardiac effects (myocardial depression)• DOSE – 40 -160 mg TDS

• Adverse effects• Nausea , constipation , bradycardia• Flushing , headache & ankle oedema

• Contraindications• 2nd and 3rd degree heart block• CHF• Sick sinus

• Interactions• Should not be given with β blockers• It increases plasma digoxin level• Should not be used with other

cardiac depressants

DILTIAZEM

• Less potent vasodilator than nifedipine & verapamil

NIFEDIPINE

• Most potent vasodilator• Direct depressent effect on heart requires higher

dose• It does not depress SA node or Av node condution .

• Adverse effects• Nausea, hypotension ,palpitation , flushing, ankle edema ,

headache and drowsiness

uses• Angina pectoris• Cardiac arrhythmias• Hypertrophic cardio-myopathy• Premature labour

ADRENERGIC BLOCKERS IN ANTIHYPERTENSIVE THERAPY

MODE OF ACTION

• Β1 ACTIVATION CAUSES CARDIAC STIMULATION , INCREASED HEART RATE , INCREASED FORCE & INCREASED CONDUCTION VELOCITY . INCREASED RENIN RELEASE ALSO OCCURS => ↑ BP

Thus β1 blockers produce an opposing action, there by

reducing bp.

• Αlpha1 & α2 causes constriction of blood vessels. And thus α blockers produces an opposing

action ,thereby reducing the bp.

β ADRENERGIC BLOCKERS• MILD ANTI HYPERTENSIVES • NON SELECTIVE

– PROPRANOLOL• MECHANISM OF ACTION

–HEART - ↓ HEART RATE , FORCE OF CONTRACTION & CO

–BLOOD VESSEL - TPR ↓–↓ RENIN –↓ SYMPATHETIC OUTFLOW

• DRAWBACKS– REBOUND HYPERTENSION, PRECIPITATES CHF ,

BRADYCARDIA , WORSENS COPD

OTHER NON SELECTIVE DRUGS

• Pindolol • Labetalol• Carvedilol

• Pindolol has more bioavailabily than propranalol .

USES

• Angina pectoris• M i• Chf • Thyrotoxicosis• Pheochromocytoma• Migraine

β + α BLOCKERS

• LABETALOL PHARMACOLOGICAL ACTION

• Β1 + β 2+ α1 • ↓ SBP & ↓ DBP

DRAWBACK• POSTURAL HYPOTENSION

• OTHER DRUG - CARVEDILOL

ACE-inhibitors

α ADRENERGIC BLOCKERS• Selective - prazosin• Pharmacological action

• Vasodilatation• Drawbacks

• First dose effects may lead to Orthostatic hypotension , syncope (start with small dose)

• Nasal congestion• Headache , palpitation, blurred vision

• Other drugs – • Terazosin• Doxazosin

•Angiotensin converting enzyme inhibitors

Captopril

• Sulphydryl containig dipeptide

• Orally active • Mechanism

• Competitive inhibition of ACE

• Decreased metabolism of bradykinin

Adverse effects

• Hypotension• Hyperkalemia• Cough• Rashes , urticaria• Acute renal failure• Angio-oedema , feto-

pathic• Headache , dizziness

and GI- problems

uses of ACE inhibitors

• CHF• MI• Diabetic nephropathy

Angiotensin antagonists

(AT1 receptor blockers)

LosartanValsartan

CandesartanIrbesartan

Telmisartan

Mechanism of action

• Competative antagonist of AT1

• Blockade of AT1 receptors• Vasodilation• Reduce secretion of

vasopressin• Reduce production &

secretion of aldosterone

» Leads to reduction of blood pressure

Advantages

• Alternative to ACE- inhibitors• No cough & no angioedema • effective in portal hypertension due to cirrhosis

Vasodilators

• Arteriolar – hydralazine / dihydralazine,

minoxidil,diazoxide

• Arteriolar+venous - sodium nitroprusside

HYDRALAZINE / DIHYDRALAZINE

• First orally active antihypertensive drug to be marketed.

• Directly acting arteriolar vasodilator.

• Decrease total peripheral resistance (t.P.R), decreases

• Diastolic (dbp) than systolic (sbp)

(Mode of Action (MOA• Cause fall in intracellular calcium conc. • Direct relaxation of arteriolar smooth

muscle • Arteriolar vasodilation.• Partly endothelium dependent and

involve generation of NO and cGMP.• No action on coronary arteries.• Hydralazine induced hypotension

evokes reflex compensatory mechanisms (Sympathetic stimulation), so given with diuretics and beta blockers.

NO , cGMP

↓ Ca 2+

PHARMACOLOGICAL EFFECTS

• Decrease in B.P.• No postural hypotension.• Reduces B.P equally in supine and up right positions.

ADVERSE EFFECTS2 types of adv effects:-1. Extension of pharmocological effects of drug.

a. Headache ,nausea, flushing, palpitation, tachycardia ,nasal stuffiness.

b. Angina and ischaemia may be ppted.2. Due to immunological reaction.

a. Drug induced systemic lupus erythematosis (SLE)-syndrome on prolonged use-common in females and slow acetylators.

b. Serum sickness , hemolytic anaemia , vasculitis, rapidly progressive glomerulonephritis.

THERAPUTIC USES

Not a 1st line drug in treatment of hypertension.Usually given in low doses along with other drugs.Oral dosage:25-100mg twice daily.1) Used in patients with renal involvement.2) Used in pregnancy.3) Used parenterally in hypertensive emergencies.

MINOXIDIL: K+ CHANNEL OPENERSUsed for severe and drug resistant forms of hypertension.

Moa:It’s a prodrug.

Hepatic sulfotransferase

Minoxidil ---------→ minoxidil n-o sulfateMinoxidil sulfate activates the ATP modulated k + channel →

k + efflux in smooth muscles → hyperpolarisation and smooth muscle relaxation


• Arteriolar vasodilation.• Blood flow to skin, skeletal muscles,

GIT, heart, more than to CNS.• Myocardial contractility

(adrenergically mediated) and CO.

ADVERSE EFFECTS

1. Fluid and salt retention.2. Cardiovascular effects.3. Hypertrichosis

THERAPEUTIC USES

1. Treatment of severe hypertension (htn) , esp in patients with renal insufficiency.

2. Use in alopecia –topical application.

SODIUM NITROPRUSSIDE

Rapidly and constantly acting vasodilator,used in short term control.

Moa:It’s a nitrovasodilator.Release NO→activates guanylylcyclase

– cGMP pathway→ vasodilation

NO


1. Arteriolar + venous dilation.2. Myocardial work is reduced, ↓ oxygen demand, no ischaemia.3. It’s a non selective vasodilator , so regional

distribution of blood flow affected. But renal blood flow (R.B.F) maintained.

4. Only moderate increase in heart rate.

PHARMACOKINETICS

• Iv route effective.• Rapid onset of action-30 sec.• Duration of action less.• Decomposes in alkaline pH and

exposure to light.

ADVERSE EFFECTS

• TOXICITY

NITROPRUSSIDE → CYANIDE/THIOCYANATE

LEADS TO LACTIC ACIDOSIS.• SIDE EFFECTS DUE TO VASODILATOR ACTION-

PALPITATION, NERVOUSNESS,PERSPIRATION,PAIN IN ABDOMEN,WEAKNESS,DISORIENTATION.

THERAPEUTIC USES

• Used in hypertensive emergencies.• To lower B.P in acute aortic dissection.• To improve CO in CHF,in hypertensive

patients.• To induce controlled hypotension during

anaesthesia.

Hypertension in pregenecyA sustained BP reading over 140/90

mmHg during pregnancy.2 types:-

1. Pregnant woman with preexisting htn.

2. Pregnancy induced htn-preeclampsia, eclampsia etc.

•

140 / 90 mmHg

Drugs unsafe in pregnancy

• Diuretics, ACE inhibitors, AT1 antagonists, reserpine,non selective β blocker, sodium nitroprusside.

DRUGS SAFE IN PREGNANCY• hydralazine, methyldopa, dihydropyridine

CCBs, cardioselective β blocker, prazosin & clonidine.

abc

Hypertensive emergencies and urgencies

Emergency: controlled reduction of bp over minutes.

Urgency: over hours.Indications:-1. Hypertensive encephalopathy.2. Hypertensive acute LVF

&pulmonary edema.3. Unstable angina or MI with raised

BP.4. Dissecting aortic aneurysm.5. Eclampsia.6. Hyprtensive episodes in

pheochromocytoma, cheese reaction & clonidine withdrawal.

Drugs usedParenteral drugs with controllable action used. Mean BP should be lowered by no more than 25% over

min or few hrs & then gradually to not lower than 160/100 mmhg.

1. Sodium nitroprusside-drug of choice. Need infusion pump & constant monitoring.2. Glyceryl trinitrate-iv route,venodilator action.3. Esmolol-given as bolus followed by slow iv inj.4. Phentolamine-drug of choice for hyperadrenergic

states.5. Diazoxide6. Hydralazine7. Labetalol8. Furosemide

Hypertension in diabetics

# The presence of hypertension doubles the already elevated risk of heart disease in diabetics

# Increases the risk for strokes, retinal damage, and peripheral vascular disease

# Accelerates the progression of kidney disease in diabetics.

• At an early stage these problems can be treated by following diet, exercising, and taking medications as directed.

• At a later stage treatment it is often more difficult. For example, end-stage kidney disease may require dialysis, or heart disease may require bypass surgery.

• Current recommendations are to maintain a pressure below 130/90 in diabetics

• Treatment is also recommended if any signs of kidney damage are present

• If the blood pressure is elevated from the patient’s previous readings. For example, if the blood pressure has generally been 100/70 and then consistently becomes 120/80, treatment should be started

• Medications should be started to protect the kidneys in diabetics if microalbuminuria is found to be present

• Choosing medications

# ACE inhibitors are effective at the amount of microalbumin in urine and appears to be the most effective at reducing the progression of kidney disease.

# These drugs can also improve sensitivity to insulin and improve blood sugar and cholesterol levels.

# They also protect the heart from changes that cause congestive heart failure, another complication of hypertension.

• It is necessary to monitor blood work frequently for possible side effects of these medications.

• # Some (but not all) calcium of channel blockers may also reduce microalbuminuria

• # Another choice is the use alpha blockers. • These also improve sensitivity to insulin with

improvements in blood sugar and cholesterol. • They reduce the size of the prostate, reducing the need

for prostate surgery in men. • It is necessary to increase the dosage of these

medications slowly, otherwise dizziness is common. • Caution , they may cause postural hypotension in

diabetics who are already at risk of this due to autonomic neuropathy.

• Taking these medications at bed time.• # Diuretics (water pills) can increase sugar and

cholesterol. These side effects can be reduced by using lower doses

• # Beta-blockers can also increase blood sugar and

cholesterol . another side-effect is that they can mask some of the earliest symptoms of a hypoglycemic reaction, increasing the risk of more serious reactions. Because of these problems, beta-blockers were avoided in the past for diabetics.

• Beta-blockers are now used more commonly in diabetics due to their benefits in reducing the risk of heart attacks. They are generally used in people who have had a heart attack to reduce the risk of subsequent heart attacks.

• As both hypertension and diabetes increase the risk of heart disease, it is necessary to control other risk factors as well as possible. This includes avoiding tobacco and controlling cholesterol to maintain the LDL portion of the cholesterol below 100.

Documents

Pharmacotherapy of hypertension