Hypertension

HypertensionHypertension

Hypertension is much more than a Hypertension is much more than a "cardiovascular disease" because it "cardiovascular disease" because it affects other organ systems of the affects other organ systems of the body such as kidney, brain, and eyebody such as kidney, brain, and eye..

Most peopol are not even aware of Most peopol are not even aware of being hypertensive because it is being hypertensive because it is usually asymptomatic until the usually asymptomatic until the damaging effects of hypertension damaging effects of hypertension (such as stroke, myocardial infarction, (such as stroke, myocardial infarction, renal dysfunction, etc.) are observedrenal dysfunction, etc.) are observed . .

Path physiologyPath physiology::Arterial blood pressure reflects the force exerted on Arterial blood pressure reflects the force exerted on arterial walls by blood flowarterial walls by blood flow . .

--Blood pressure normally stays relatively constant because Blood pressure normally stays relatively constant because of homeostatic mechanisms that adjust blood flow to of homeostatic mechanisms that adjust blood flow to meet tissue needsmeet tissue needs..

- - The two major determinants of arterial blood pressure The two major determinants of arterial blood pressure areare::

11--cardiac output (systolic pressure)cardiac output (systolic pressure) 22--peripheral vascular resistance (diastolic pressure)peripheral vascular resistance (diastolic pressure) . .

--Regardless of the cause, arterial pressure becomes Regardless of the cause, arterial pressure becomes elevated either due to an increase in cardiac output, an elevated either due to an increase in cardiac output, an increase in systemic vascular resistance, or bothincrease in systemic vascular resistance, or both . .

B.P.=C.O x P.RB.P.=C.O x P.R..

S.V. H.RS.V. H.R..

Neurohumoral Neurohumoral blood volumeblood volume Neurohumoral Neurohumoral activation   Kidney diseaseactivation   Kidney disease activationactivation

V.C. of Bl.V. Excretion +v chronotropicV.C. of Bl.V. Excretion +v chronotropic

Urine output Blood volume H.RUrine output Blood volume H.R..

S.VS.V . .

C.OC.O..

B.PB.P..

HYPERTENSIONHYPERTENSIONHypertension is persistently high blood pressure that results Hypertension is persistently high blood pressure that results from abnormalities in regulatory mechanisms. It is defined from abnormalities in regulatory mechanisms. It is defined as a systolic pressure above 140 mm Hg or a diastolic as a systolic pressure above 140 mm Hg or a diastolic pressure above 90 mm Hg on multiple blood pressure pressure above 90 mm Hg on multiple blood pressure measurementsmeasurements..

ClassificationClassificationSystolicSystolic(mmHg)(mmHg)

DiastolicDiastolic(mmHg)(mmHg)

NormalNormal<<120120<<8080

PrehypertensionPrehypertension120-139120-13980-8980-89

MildMild140-159140-15990-9990-99

ModerateModerate>>160160>>110110

SeverSever>>180180

>>120120

HypertensionHypertension

Primary Hypertension Secondary Primary Hypertension Secondary HypertensionHypertension

( ( idiopathicidiopathic( )( )secondary to a secondary to a diseasedisease))

Primary HypertensionPrimary Hypertension It represent 90% to 95 % of high blood pressure casesIt represent 90% to 95 % of high blood pressure cases , ,

as there's no identifiable cause. This type of high blood as there's no identifiable cause. This type of high blood pressure is called pressure is called Essential hypertensionEssential hypertension or primary or primary hypertension which tends to develop gradually over hypertension which tends to develop gradually over yearsyears..Risk factors that may lead to hypertension includeRisk factors that may lead to hypertension include::

• •Age & RaceAge & Race • •ObesityObesity

• •Elevated serum cholesterol (total and low-density Elevated serum cholesterol (total and low-density lipoprotein) and triglycerideslipoprotein) and triglycerides

• •Cigarette smokingCigarette smoking••Excessive alcohol, Xanthenes& Sodium intakeExcessive alcohol, Xanthenes& Sodium intake

• •Family history of hypertension or other cardiovascular Family history of hypertension or other cardiovascular diseasedisease

••StressStress..

Secondary HypertensionSecondary HypertensionSecondary hypertension accounts for about 5-10% of all cases of hypertension. Secondary hypertension accounts for about 5-10% of all cases of hypertension. Patients with this hypertension are best treated by controlling or removing the Patients with this hypertension are best treated by controlling or removing the underlying pathologyunderlying pathology, although they may still require antihypertensive drugs, although they may still require antihypertensive drugs..These diseases may beThese diseases may be: :

11 . .Renal disordersRenal disorders cases of glomerulonephritis, and other permanent damage of the kidneys, where cases of glomerulonephritis, and other permanent damage of the kidneys, where salt and water retention dominates. Renal artery stenosis (atherosclerosis) salt and water retention dominates. Renal artery stenosis (atherosclerosis) sufficient to reduce the glomerular pressure leads to rennin release from the sufficient to reduce the glomerular pressure leads to rennin release from the juxtaglomerular apparatus and finally aldosterone release and thus juxtaglomerular apparatus and finally aldosterone release and thus increased increased salt-water retention . All of the previous salt-water retention . All of the previous can lead to secondary systemic can lead to secondary systemic

hypertensionhypertension. .

22 . .HyperaldosteronismHyperaldosteronism has a primary and a secondary form. This condition is has a primary and a secondary form. This condition is characterised by an isolated rise in serum aldosterone that leads to characterised by an isolated rise in serum aldosterone that leads to increased increased

salt-water retention & finallysalt-water retention & finally secondary systemic hypertension secondary systemic hypertension. .

33 . .Cushing’s syndrome Cushing’s syndrome describes clinical conditions with increased glucocorticoid describes clinical conditions with increased glucocorticoid concentration in the blood plasma concentration in the blood plasma increased salt-water retention ,that increased salt-water retention ,that can lead can lead

to secondary systemic hypertensionto secondary systemic hypertension. .

and prevent high blood pressureand prevent high blood pressure::

44..Cardiovascular disorderCardiovascular disorder - as coarctation of the aorta - is the cause of - as coarctation of the aorta - is the cause of hypertension in a few young patients. hypertension in a few young patients. Atherosclerosis Atherosclerosis is characterised by a is characterised by a special systolic hypertension frequently found in the elderly without any special systolic hypertension frequently found in the elderly without any

diastolic hypertension. These patients do not have any arteriolar diseasediastolic hypertension. These patients do not have any arteriolar disease   

55 . .Phaeochromocytoma. Phaeochromocytoma. This is a tumour of the sympathetic nervous system This is a tumour of the sympathetic nervous system releasing both noradrenalin and adrenaline. The signs are intermittent or releasing both noradrenalin and adrenaline. The signs are intermittent or constant systemic hypertension, tachycardia with other arrhythmias, constant systemic hypertension, tachycardia with other arrhythmias, orthostatic hypertension and flushingorthostatic hypertension and flushing..

66 . .In the last three months of pregnancy some females develop hypertension, In the last three months of pregnancy some females develop hypertension, oedema and proteinuria (oedema and proteinuria (pre-eclampsia pre-eclampsia or or toxaemia of pregnancytoxaemia of pregnancy). If this ). If this condition develops into severe hypertension with fits and lung oedema, it is condition develops into severe hypertension with fits and lung oedema, it is called called eclampsiaeclampsia. This is a life threatening condition, which must be treated . This is a life threatening condition, which must be treated immediately with immediately with intravenous hydralazine or minoxidil, and if necessary intravenous hydralazine or minoxidil, and if necessary

termination of pregnancytermination of pregnancy..

77..Drugs Drugs such as steroids or oral contraceptives with high oestrogen, such as steroids or oral contraceptives with high oestrogen, sympatomimetics, aldosterone, and vasopressin all cause severe systemic sympatomimetics, aldosterone, and vasopressin all cause severe systemic hypertension.Monoamineoxidase-inhibitors combined with tyramine hypertension.Monoamineoxidase-inhibitors combined with tyramine (cheese) or wine sometimes cause hypertension. A careful medical history (cheese) or wine sometimes cause hypertension. A careful medical history is helpfulis helpful..

        

88--Sleep ApneaSleep ApneaSleep apnea is a disorder in which people repeatedly stop breathing for Sleep apnea is a disorder in which people repeatedly stop breathing for short periods of time short periods of time ((10-30 seconds10-30 seconds) ) during their sleepduring their sleep. . This condition This condition is often associated with obesity, although it can have other causes such is often associated with obesity, although it can have other causes such as airway obstruction or disorders of the central nervous systemas airway obstruction or disorders of the central nervous system. . These individuals have a higher incidence of hypertensionThese individuals have a higher incidence of hypertension. . The The mechanism of hypertension may be related to sympathetic activation mechanism of hypertension may be related to sympathetic activation and hormonal changes associated with repeated periods of apneaand hormonal changes associated with repeated periods of apnea--induced hypoxia and hypercapnea, and from stress associated with the induced hypoxia and hypercapnea, and from stress associated with the loss of sleeploss of sleep

99--HyperHyper- - or hypothyroidismor hypothyroidismExcessive thyroid hormone induces systemic vasoconstriction, an increase Excessive thyroid hormone induces systemic vasoconstriction, an increase in blood volume, and increased cardiac activity, all of which can lead in blood volume, and increased cardiac activity, all of which can lead to hypertensionto hypertension..  It is less clear why some patients with   It is less clear why some patients with hypothyroidism develop hypertension, but it may be related to hypothyroidism develop hypertension, but it may be related to

decreased tissue metabolismdecreased tissue metabolism. . ..

Symptoms and SignsSymptoms and SignsHypertension is usually asymptomatic until complications develop in target Hypertension is usually asymptomatic until complications develop in target organsorgans..

Dizziness, flushed faces, headache, fatigue, sweating, and nervousness are caused Dizziness, flushed faces, headache, fatigue, sweating, and nervousness are caused by uncomplicated hypertensionby uncomplicated hypertension..

• •Eventually, signs and symptoms occur as target organs are damagedEventually, signs and symptoms occur as target organs are damaged::--Heart damage is often reflected as angina pectoris, myocardial infarction, or Heart damage is often reflected as angina pectoris, myocardial infarction, or

heart failure( Chest pain, tachycardia, dyspnea, fatigue, and edema may heart failure( Chest pain, tachycardia, dyspnea, fatigue, and edema may occur)occur)..

- - Brain damage may be indicated by transient ischemic attacks or strokes of Brain damage may be indicated by transient ischemic attacks or strokes of varying severityvarying severity..

--Renal damage may be reflected by proteinuria, increase in (BUN), and increased Renal damage may be reflected by proteinuria, increase in (BUN), and increased serum creatinineserum creatinine..

--Ophthalmoscopic examination may reveal hemorrhages, sclerosis of arterioles, Ophthalmoscopic examination may reveal hemorrhages, sclerosis of arterioles, and inflammation of the optic nerve (papilledema). Because arterioles in the and inflammation of the optic nerve (papilledema). Because arterioles in the eye be visualized in the retina of the eye, damage to retinal vessels may eye be visualized in the retina of the eye, damage to retinal vessels may indicate damage to arterioles in the heart, brain, and kidneyindicate damage to arterioles in the heart, brain, and kidney..

DiagnosisDiagnosisHypertension is diagnosed and classified by Hypertension is diagnosed and classified by sphygm-omanometrysphygm-omanometry . .

- - HistoryHistory

- - Physical examinationPhysical examination..

- - Other tests (to identify etiology and determine Other tests (to identify etiology and determine whether target organs are damaged .Tests whether target organs are damaged .Tests include urinalysis, albumin: creatinine ratio, include urinalysis, albumin: creatinine ratio, blood tests (creatinine, K, Na, fasting plasma blood tests (creatinine, K, Na, fasting plasma glucose, lipid profile), and ECG. Thyroid-glucose, lipid profile), and ECG. Thyroid-stimulating hormone is often measured. chest stimulating hormone is often measured. chest x-ray, screening tests for pheochromocytomax-ray, screening tests for pheochromocytoma....

--BP must be measured twice, first with the BP must be measured twice, first with the patient supine or seated, then after the patient patient supine or seated, then after the patient has been standing for ≥ 2 min (on 3 separate has been standing for ≥ 2 min (on 3 separate days)days). .

Treatment goalsShort term goal

reduce blood pressure

Long term goal

•reduce mortality due to hypertension-induced disease as:

•stroke

•congestive heart failure

•coronary artery disease

•nephropathy

•retinopathy

Treatment of hypertensionTreatment of hypertensionNon–Pharmacological Non–Pharmacological

Treatment Treatment Lifestyle changes can help controlLifestyle changes can help controland prevent high blood pressureand prevent high blood pressure::

Diet low in sodiumDiet low in sodium.. . .Diet that promotes weight lossDiet that promotes weight loss . .Regular exercise programRegular exercise program.. . .

Quitting smokingQuitting smoking..Avoiding stressAvoiding stress.. . .

Pharmacological TreatmentPharmacological Treatment Mono-(Tailored) TherapyMono-(Tailored) Therapy

ANDAND Stepped TherapyStepped Therapy

--In monotherapy if the initial drug In monotherapy if the initial drug (and dose) does not produce (and dose) does not produce the desired effect, options for the desired effect, options for further management further management include :Increasing the drug include :Increasing the drug dose or substituting with dose or substituting with another druganother drug . .

- -In stepped therapy : treatment In stepped therapy : treatment begin with one drug then begin with one drug then adding second drug from a adding second drug from a different group if there is no different group if there is no good responsegood response..

If the response is still inadequate, If the response is still inadequate, a third drug may be addeda third drug may be added..

Principally, systemic hypertension is Principally, systemic hypertension is treatable through one or more of the treatable through one or more of the following strategiesfollowing strategies::

  11 . .Reduction of the Reduction of the total blood volumetotal blood volume (and thus the (and thus the stroke volume) with diuretics results in stroke volume) with diuretics results in reduction of the driving pressurereduction of the driving pressure..

22   .   .Reduction of the Reduction of the Heart rate Heart rate reduces cardiac reduces cardiac output and thus the driving pressure (as with output and thus the driving pressure (as with ββ

blockers and calcium channel blockers)blockers and calcium channel blockers). .

33   .   .Reduction of Reduction of TPRTPR with vasodilatator, with vasodilatator, alpha1 adrenergic receptor antagonists and ACE inhibitors reduces the driving pressure reduces the driving pressure..

Drug SelectionDrug SelectionHypertension: an elevation of arterial blood pressure

above an arbitrarily defined normal valueMild Moderate

Next slide

Cont. :Drug SelectionCont. :Drug Selection

Angiotensin-converting enzyme inhibitors(ACEI) & angiotensin receptor blockers (ARB)Angiotensin-converting enzyme inhibitors(ACEI) & angiotensin receptor blockers (ARB)::- - They are recommended for hypertensive adults with diabetes mellitus and heart failureThey are recommended for hypertensive adults with diabetes mellitus and heart failure

--Avoided with renal artery stenosis ,acute renal failure & pregnancyAvoided with renal artery stenosis ,acute renal failure & pregnancy . .

Beta blockers(BB)Beta blockers(BB):: These drugs are first choice for clients younger than 50 years of age with high-rennin These drugs are first choice for clients younger than 50 years of age with high-rennin hypertension, tachycardia, angina pectoris, myocardial infarction and with hypertension, tachycardia, angina pectoris, myocardial infarction and with thyrotoxicosis (Why??)..Contraindicated for patients who have asthma,COPD, peripheral vascular diseaseContraindicated for patients who have asthma,COPD, peripheral vascular disease , ,

diabetes mellitus, or second or third degree heart blockdiabetes mellitus, or second or third degree heart block..

Calcium channel blockers (CCB)Calcium channel blockers (CCB): : Ca channel blocker is preferred to a β-blocker in patients with variant angina (with Ca channel blocker is preferred to a β-blocker in patients with variant angina (with coronary spasms and a bronchospastic disorder, coronary spasms and a bronchospastic disorder, certain arrhythmias or with or with Raynaud's diseaseRaynaud's disease..Contraindicated in patients with heart failureContraindicated in patients with heart failure. .

DiureticsDiuretics are preferred for patients with heart failure are preferred for patients with heart failureAvoided with D.M. & gouty patientsAvoided with D.M. & gouty patients..

VasodilatorsVasodilatorsThey are used in combination with a beta blocker and a diuretic to prevent hypotension-They are used in combination with a beta blocker and a diuretic to prevent hypotension-induced compensatory mechanisms (stimulation of the SNS and fluid retention) that induced compensatory mechanisms (stimulation of the SNS and fluid retention) that raise blood pressureraise blood pressure

Summary of Drug Targets

CCB

e.g. ; αα 2 2 agonist

DIURETICSDIURETICSThey decrease blood volume and thus cardiac output is decreased. They decrease blood volume and thus cardiac output is decreased. With long-term administration of diuretic, cardiac output returns to With long-term administration of diuretic, cardiac output returns to normal, but there is a persistent decrease in peripheral vascular normal, but there is a persistent decrease in peripheral vascular resistance. This is because ofresistance. This is because of

11--A persistent small reduction in extracellular water and plasma A persistent small reduction in extracellular water and plasma volumevolume..

22--Decreased receptor sensitivity to vasopressor substancesDecreased receptor sensitivity to vasopressor substances..33--Arteriolar vasodilatation secondary to electrolyte (mainly Na) Arteriolar vasodilatation secondary to electrolyte (mainly Na)

depletion in the vessel walldepletion in the vessel wall..

Loop diuretics:Loop diuretics: ( (furosemide, bumetanide, torsemide)furosemide, bumetanide, torsemide)They are the most effective diuretics mainly used inThey are the most effective diuretics mainly used in

emergency as in hypertensive crisisemergency as in hypertensive crisis.. Thiazide diureticsThiazide diuretics ( (chlorothiazid & Hydrochlorothiazidechlorothiazid & Hydrochlorothiazide))They act on the distal tubules and are less effective thanThey act on the distal tubules and are less effective than

loop diuretics. loop diuretics. MMonotherapy for mild to moderate hypertension.

Potassium sparing diureticsPotassium sparing diuretics: : (Aldosterone antagonists :Spironolactone & Sodium channel (Aldosterone antagonists :Spironolactone & Sodium channel blockers : Amiloride and Triamtereneblockers : Amiloride and Triamterene))

not effective antihypertensive drugs because they have not effective antihypertensive drugs because they have weak diuretic effectweak diuretic effect . However they are . However they are used with other diuretics to decrease their hypokalemic effectused with other diuretics to decrease their hypokalemic effect..

ADVERSE EFFECTS OF ADVERSE EFFECTS OF LOOPLOOP

DIURETICSDIURETICS

Hypomagnesemia

MetabolicAlkalosis

Hypokalemia

Profound ECFVDepletion

Hyperglycemia

Hyperuricemia

Ototoxicity

Hypocalcaemia

ADVERSE EFFECTS OF ADVERSE EFFECTS OF THIAZIDE DIURETICSTHIAZIDE DIURETICS

Hypomagnesaemia

MetabolicAlkalosis

Hypokalemia

ECFVDepletion

Hyperglycemia

Hyperuricemia

Hyponatremia

Hypocalcaemia

Impotence Increased LDL

ββ blockers blockers

11 . .Block Block ββ 1 receptors of the heart: reducing contractility and cause bradycardia 1 receptors of the heart: reducing contractility and cause bradycardia (-ve inotropic ,-ve chronotropic )(-ve inotropic ,-ve chronotropic )

22 . .Blocking Blocking ββ receptors in the kidney: decrease the release of rennin receptors in the kidney: decrease the release of rennin

Non selective Non selective ββ1 & 1 & ββ2 blocker: Propranolol2 blocker: Propranolol. . ββ1 selective:1 selective: Atenolol , Metoprolol , Atenolol , Metoprolol , Esmolol, Betaxolol & Timolol & Timolol

Adverse effectsAdverse effects::--Cold extremities (NA effect on BV. will be mainly on Cold extremities (NA effect on BV. will be mainly on αα1 receptors) so NOT taken 1 receptors) so NOT taken

by patients with PVDby patients with PVD.(.(--BronchospasmBronchospasm. .

--heart failureheart failure..--insomnia & depressioninsomnia & depression. .

--ImpotenceImpotence..- - Increased triglycerides & decrease HDLIncreased triglycerides & decrease HDL..

--They are contraindicated in insulin dependent diabetic patients because they They are contraindicated in insulin dependent diabetic patients because they mask symptoms of hypoglycemia (tachycardia)& also can themselves produce mask symptoms of hypoglycemia (tachycardia)& also can themselves produce hypoglycemia by inhibiting glycogenolysis (by blocking hypoglycemia by inhibiting glycogenolysis (by blocking ββ receptors in liver) receptors in liver)..

--Withdrawal syndrome :may result in tachycardia if it is removed suddenlyWithdrawal syndrome :may result in tachycardia if it is removed suddenly.. - -Do not use in conjunction with Ca2+ channel blockers, conduction effects in

heart

Calcium Channel BlockersCalcium Channel BlockersThe depolarization of vascular smooth muscle relies on the influx of The depolarization of vascular smooth muscle relies on the influx of Ca2+ (rather than Na+ ). These drugs relax arteriolar smooth Ca2+ (rather than Na+ ). These drugs relax arteriolar smooth muscle by reducing calcium entry via L type calcium channels muscle by reducing calcium entry via L type calcium channels (which are also present in the heart)· There are various types of (which are also present in the heart)· There are various types of Ca2+ channels blockersCa2+ channels blockers::

· ·Nifedipine: arterioselectiveNifedipine: arterioselective · ·Amlodipine: arterioselectiveAmlodipine: arterioselective

· ·Diltiazem: cardioselectiveDiltiazem: cardioselective · ·Verapamil: cardioselectiveVerapamil: cardioselective

Adverse effectsAdverse effects::..Reflex tachycardia (Reflex tachycardia (Verapamil and Diltiazem do not cause

reflex tachycardia …Why?) …Why?) · ·FlushingFlushing

· ·EdemaEdema · ·DizzinessDizziness

. .Bradycardia ,AV blockade (Bradycardia ,AV blockade (with cardioselective agentswith cardioselective agents)) · · . .Verapamil must also never be used in conjunction with a Verapamil must also never be used in conjunction with a ββ blocker blocker

because of their additive effects on depressing the heart leading to because of their additive effects on depressing the heart leading to complete heart blockcomplete heart block..

Angiotensin Converting Enzyme InhibitorsAngiotensin Converting Enzyme Inhibitors .1.1Ex.: Ex.: Active : Captopril (Capoten) & Lisinopril.

Prodrugs: must be biotransformed for activity by esterase :Enalapril (Vasotec) &Fosinopril.Adverse effectsAdverse effects::

· ·Dry cough (due to bradykinin)Dry cough (due to bradykinin) · ·Loss of tasteLoss of taste · ·HypotensionHypotension

· ·RashRash · ·Angioedema (due to bradykinin)Angioedema (due to bradykinin)..

. .Hyperkalemia (due to decreased aldosterone)Hyperkalemia (due to decreased aldosterone).. . .RRenal insufficiency & proteinuria (protein in urine).

.Teratogenic.

Angiotensin II receptor antagonistsAngiotensin II receptor antagonists Ex. Lorsatan & valsartanEx. Lorsatan & valsartan

· ·It is selective for AT1 receptorsIt is selective for AT1 receptors · ·It inhibits the cardiovascular effects of angiotensin IIIt inhibits the cardiovascular effects of angiotensin II

· ·Similar efficacy to ACE inhibitors but without the bradykinin associated side Similar efficacy to ACE inhibitors but without the bradykinin associated side effects: There is no cough and no chance of angioedema is no cough and no chance of angioedemaHowever, other side effects may beHowever, other side effects may be::

· ·Pathological effects on the fetusPathological effects on the fetus · ·GI adverse effectsGI adverse effects

α1-blockersSelective: Prazosin, Doxazosin, Terazosin

inhibit vasoconstriction

decrease total peripheral resistance

Selective α-blockers used as monotherapy or adjunct therapy in resistant

patients

Side Effects:•First dose phenomenon•hypotension•tachycardia•baroreceptor reflex•GI effects•Fluid retention•use with diuretic

Vasodilator (Vasodilator (not used as monotherapy….WHY??)11--HydralazineHydralazine

Mechanism of actionMechanism of action The mechanism is unknown. It dilates arterioles· It can cause The mechanism is unknown. It dilates arterioles· It can cause reflex stimulation of the sympathetic reflex stimulation of the sympathetic

nervous systemnervous system, since the vasodilatation causes sever transient drop in blood pressure. This reflex , since the vasodilatation causes sever transient drop in blood pressure. This reflex stimulation causes increased heart rate and contractility, and also rennin release (causes marked stimulation causes increased heart rate and contractility, and also rennin release (causes marked fluid retention and edema)fluid retention and edema)..In order for hydralazine to be useful, it needs to be combined with a In order for hydralazine to be useful, it needs to be combined with a ββ blocker (to prevent the cardiac blocker (to prevent the cardiac effects) and a diuretic (to overcome the fluid retention)effects) and a diuretic (to overcome the fluid retention)..

Side effectsSide effects:: · ·Headache (due to vasodilatation)Headache (due to vasodilatation)

· ·NauseaNausea · ·Tachycardia & edema (reflex stimulation of sympathetic)Tachycardia & edema (reflex stimulation of sympathetic)

SO; Need to be used in conjunction with SO; Need to be used in conjunction with ββ blockers and diuretics blockers and diuretics . . · ·A systemic lupus like conditionA systemic lupus like condition..

22--MinoxidilMinoxidil Relaxes blood vessels by opening K+ channels· This causes K+ to rush out of the cell, hyperpolarizing Relaxes blood vessels by opening K+ channels· This causes K+ to rush out of the cell, hyperpolarizing

the smooth muscle and so making it less excitablethe smooth muscle and so making it less excitable..Adverse effectsAdverse effects::

It can cause reflex stimulation of the sympathetic nervous system which leads to reflex tachycardia & It can cause reflex stimulation of the sympathetic nervous system which leads to reflex tachycardia & salt and water retentionsalt and water retention..SO: Need to be used in conjunction with SO: Need to be used in conjunction with ββ blockers and diuretics blockers and diuretics..

· ·Causes hair growth Causes hair growth ((hypertrichosis)· Another therapeutic use of this drug is in the treatment )· Another therapeutic use of this drug is in the treatment of baldnessof baldness

3-DiazoxideDiazoxide (Hyperstat) is chemically similar to the thiazide diuretics. It is devoid of diuretic activity, but it is a very potent vasodilator.

It produces direct relaxation of arteriolar smooth muscle with little effect on capacitance beds .

Side effects Increased workload on the heart, which may precipitate myocardial ischemia and

Na and water retention.These undesirable effects can be controlled by concurrent therapy with a -blocker and a diuretic.

Diazoxide may cause hyperglycemia, especially in diabetics, so if the drug is used for several days, blood glucose levels should be measured.

44--Sodium nitroprussideSodium nitroprusside--It releases NO which directly relaxes smooth muscle in blood vesselsIt releases NO which directly relaxes smooth muscle in blood vessels··

--Reserved for acute use only(i.e.) It is Reserved for acute use only(i.e.) It is used in emergencyused in emergency situations where a rapid situations where a rapid drop in blood pressure is requireddrop in blood pressure is required··

- -The drug metabolism lead to release of CN, The drug metabolism lead to release of CN, cyanide poisoning may developcyanide poisoning may develop

Centrally acting antihypertensiveCentrally acting antihypertensive

- - The 2 drugs which are used are both The 2 drugs which are used are both αα2 agonists2 agonists · As · As αα2 receptors are located 2 receptors are located presynaptically and centrally, once stimulated they will inhibit the release of NA from presynaptically and centrally, once stimulated they will inhibit the release of NA from the sympathetic nerve terminal & reduce sympathetic outflow from CNSthe sympathetic nerve terminal & reduce sympathetic outflow from CNS . .

αα--methyldopamethyldopaEnters the CNS via active transport into the brain· Converted to a methyl NA by the same Enters the CNS via active transport into the brain· Converted to a methyl NA by the same enzymes (dopadecarboxylase) which are involved in NA synthesis & form enzymes (dopadecarboxylase) which are involved in NA synthesis & form αα-methyl -methyl NA which is a false transmitterNA which is a false transmitter. .

Selective Selective αα2 agonist causes reduced sympathetic outflow to the blood vessels and heart2 agonist causes reduced sympathetic outflow to the blood vessels and heartAdverse effectsAdverse effects::

Sedation, depressionSedation, depressionDry mouth (due to inhibition of the medullary areas controlling salivation)Dry mouth (due to inhibition of the medullary areas controlling salivation)Postural hypotensionPostural hypotension

ClonidineClonidine Selective Selective αα2 agonist ,it causes reduced sympathetic outflow & NA release2 agonist ,it causes reduced sympathetic outflow & NA release

It can cause rebound hypertension on cessation, therefore the patient needs to be titrated off the drug slowly

Both drugs have weak postural hypertensive effectBoth drugs have weak postural hypertensive effect

--Adrenergic neuron blockersAdrenergic neuron blockers ( (rarely used)11 - -Guanethidine; (inhibits NA release)Guanethidine; (inhibits NA release)

Highly polar, therefore does not get into the CNS, acts peripherallyHighly polar, therefore does not get into the CNS, acts peripherallyTaken into secretory vesicles (by the same uptake mechanism as NA) and displace NA from Taken into secretory vesicles (by the same uptake mechanism as NA) and displace NA from its storage granules . Then, it prevents NA release from the presynaptic terminal its storage granules . Then, it prevents NA release from the presynaptic terminal (stabilize the nerve membrane)- hence no NA release with gradual depletion of NA (stabilize the nerve membrane)- hence no NA release with gradual depletion of NA

storesstores . .Decrease blood pressure by vasodilatation, thus reducing venous return and afterload Decrease blood pressure by vasodilatation, thus reducing venous return and afterload hence reducing cardiac outputhence reducing cardiac output

Side effectsSide effects:: Postural hypotensionPostural hypotension

WeaknessWeaknessImpotence & DiarrheaImpotence & Diarrhea

22 - -Reserpine (inhibits NA storage)Reserpine (inhibits NA storage)Blocks NA transport into synaptic vesicles. May also interfere with NA uptake mechanisms Blocks NA transport into synaptic vesicles. May also interfere with NA uptake mechanisms ( but it enters the CNS)( but it enters the CNS)..

Blocks dopamine transport into storage vesicles, so decrease synthesis of NABlocks dopamine transport into storage vesicles, so decrease synthesis of NADecrease blood pressure by vasodilatation, thus reducing venous return and afterload Decrease blood pressure by vasodilatation, thus reducing venous return and afterload hence reducing cardiac outputhence reducing cardiac outputSide effectsSide effects::

Postural hypotensionPostural hypotensionSedation& DepressionSedation& Depression

ParkinsonismParkinsonismPeptic ulcerPeptic ulcer

Caution

Contra-indication

Indication

Adverse effects