antihypertensive iv

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  • Presenter : Dr Isvaran SubramaniamModerator : Dr Nizar

  • CONTENTIntroduction



  • IntroductionDiagnosis of Hypertension

    the average of two or more DBP measurements on at least two subsequent visits is 90 mm Hg or moreor when the average of multiple SBP readings on two or more subsequent visits is consistently greater than 140 mm Hg

  • Classification of blood pressure levels

    Optimal =

  • Classified into

    Primary or Essential HPT : 95%

    Secondary HPT :

  • Regulation of Normal BP magnitude of the arterial pressure depends on two fundamental hemodynamic variables:

    cardiac outputtotal peripheral resistance

  • *

  • Uncontrolled BPIHDCVARenal impairmentHypertension RetinopathyHypertension Crisis

  • Management of HypertensionThe goal of antihypertensive therapy is to reduce overall cardiovascular risk and thus cardiovascular morbidity and mortality

    This may be achieved by maintaining SBP < 140 mmHg and DBP < 90 mmHg

    Management includesNon Pharmacologic InterventionsLifestyle ModificationsPharmacologic Therapy

  • Lifestyle Modificationsreduced dietary sodium and increased calcium and potassium from food sourcesweight loss for overweight patients

    *Other lifestyle modifications, including relaxation and stress reduction, caffeine restriction, magnesium supplementation, changing the fat content of the diet, and garlic and onion consumption, have not been shown to produce sustained benefits in BP control.

  • regular physical activitymoderation of alcohol consumption smoking cessation

  • ANTI HYPERTENSIVES 6 classes of drugs;SympatholyticsVasodilatorsAngiotensin Converting Enzyme InhibitorsAngiotensin-II Receptor BlockersCalcium Channel BlockerDiuretics

  • Sympatholytics

  • Sympatholytics

    1. Adrenergic-receptor blockersAlpha PrazosinBeta Atenolol, Propanolol, EsmololAlpha-Beta Labetalol

    2.Central Alpha-2 agonistClonidine, Methldopa

    3. Postganglionic BlockersReserpine, Guanethidine

  • Adrenergic-receptor blockers

  • ORGANACTIONRECEPTORHeart Heart rate AV nodal conduction Contractility

    Vascular Smooth Muscle Skin; Splanchnic Skeletal muscle Skeletal muscle

    Bronchial Tree

    Gastrointestinal tract Smooth muscle, wall Smooth mucle sphincter Saliva secretion Gastric acid secretion Pancreatic secretionIncreaseIncreaseIncrease






    1 2 1


    1 21


  • What are alpha blockers?Alpha blockers work by dilating blood vessels.Therefore reduces afterload.Alpha blockers include: Doxazosin (brand name Cardura) Prazosin (Minipress) Terazosin (Hytrin)

  • What are beta blockers?Beta blockers lower high blood pressure by slowing down the heart rate and decreasing the force of contraction of the heart.Increase coronary blood flow due to increase diastolic filling time

    Some common beta blockers include: Atenolol (Tenormin) Betaxolol (Kerlone) Metoprolol (Lopressor) Propranolol (Inderal) Timolol (Blocadren)

  • What are alpha-beta blockers?Alpha-beta blockers relax blood vessels and slow down the heart.

    Alpha-beta blockers include labetalol (brand name Normodyne)

  • Alpha Blockers

  • PRAZOSIN( Alpha 1 -blocker )quinazoline derivative Highly selective alpha-1-blockerproduces peripheral vasodilation; vascular tone in both resistance (arterioles) and capacitance (veins) vessels is reducedresulting in decreased Vascular Resistance, CO and BPnot associated with reflex tachycardia

  • Pharmacokinetics Prazosinadministered orally 60% bioavailability protein binding 90%nearly completely metabolized by the liverEliminated in bile and faeceselimination half-time is about 3 hours (prolonged by cardiac failure)

  • Side Effects Prazosinfirst dose phenomenon ; dizziness, faintness, syncope soon after the administration of the first dosevertigofluid retentionorthostatic hypotensiondryness of the mouth, nasal congestion, nightmares, urinary frequency, lethargy, and sexual dysfunction

  • Phentolaminecompetitive antagonism3-5 times more active at alpha-1 compared to alpha-2, with some Beta adrenergic agonist and anti-serotoninergic activityCauses marked reduction in BP with reflex tachycardiaPositive inotropic action probably due to indirect action via noradrenaline release due to alpha-2-blockadeSide effects : palpitation, vomitting

  • PhenoxybenzamineIrreversible alpha-adrenergic blockerNon-competitiveChemically related to nitrogen mustardsUsed mainly for control of Hypertension due to phaeochromocytomaMore alpha-1 effect than alpha-2Onset : 1 hour, duration : several days

  • Side effects :

    Postural hypotensionTacycardiaRetrograde ejaculationNasal congestionmiosis

  • Beta Blockers

  • Some beta-blockers, when they bind to the beta-adrenoceptor, partially activate the receptor while preventing norepinephrine from binding to the receptor. These partial agonists therefore provide some "background" of sympathetic activity while preventing normal and enhanced sympathetic activity. These particular beta-blockers (partial agonists) are said to possess intrinsic sympathomimetic activity (ISA).

    Some beta-blockers also possess what is referred to as membrane stabilizing activity (MSA). This effect is similar to the membrane stabilizing activity of sodium channel blockers that represent Class I antiarrhythmics. Usually at high concentrationReduce phase 0 and phase 4 slope

  • The first generation of beta-blockers were non-selective, meaning that they blocked both beta1 (b1) and beta2 (b2) adrenoceptors.

    Second generation beta-blockers are more cardioselective in that they are relatively selective for b1 adrenoceptors.

    Note that this relative selectivity can be lost at higher drug doses


  • Clinical Effectnegative inotropic and chronotropic effectsconduction speed (AVN) is sloweddecreased the rate of spontaneous phase 4 depolarization antidysrhythmic effect

  • Side Effects increased airway resistanceunmask the signs of hypoglycaemiaprecipitate cardiac failurePeripheral Vascular Disease and Raynauds phenomenonhyperkalaemiamemory loss and mental depressionwithdrawal hypersensitivity

  • PROPANOLOLnon-selective blockerequal antagonism at beta-1 and beta-2lacks of ISA; pure antagonist the first beta-antagonist introduced

  • Pharmacokinetics Propanololrapidly and almost completely GIT absorptionextensive hepatic first-pass metabolism (70%); poor bioavailabilityextensively bound to plasma proteins (90% to 95%) clearance is by hepatic metabolism to active metabolite, 4-hydroxypropranolol

    (equivalent in activity to propanolol)

  • Used in :

    HypertensionPortal HypertensionAnginaMigraineArrhytmiasAnxietythyrotoxicosis

  • ESMOLOLselective beta-1 blocker; lacks of ISAPure antagonistrapid-onset and short-acting preventing or treating haemodynamic instability intraoperatively in response to noxious stimulation, e.g. during intubation

  • Pharmacokinetics EsmololIntra-venousrapid metabolism in blood by hydrolysis of the methyl ester in RBCinactive acid metaboliteselimination half-time 10 minutes in urinepoor lipid solubility; limits transfer into the CNS or across the placenta

  • Alpha-Beta Blocker

  • LABETOLOLselective alpha-1 antagonist nonselective beta-1 and beta-2 antagonist Beta : AlphaOral = 3 : 1IV = 7 : 1Some intrinsic sympatomimetic activityuseful in management of PIH

  • Pharmacokinetics Labetololextensive first pass metabolism30-40% bioavailabilitymetabolism is by conjugation to glucuronic acid< than 5% excreted unchanged in the urineelimination half-time is 5 to 8 hours (prolonged in liver disease and unchanged in renal dysfunction)

  • Side Effects LabetololOrthostatic hypotension (most common) Beta-antagonists effects BronchospasmCongestive heart failureHeart blockFatigueMental depressionFluid retention

  • Central Alpha-2 agonist

  • CLONIDINE centrally acting alpha-2 agoniststimulates alpha-2 inhibitory neurons in the medullary vasomotor centerresulting in reduction of SNS outflow from the CNS to peripheral tissuesmanifested as decreases in BP, HR and COLicensed in the US as a extradural route for pain therapyUsed as a migraine prophylaxis

    *-reduction of SNS outflow also causes reduced plasma renin activity (beta R)-stimulation of alpha2 R at presynaptic junction also inhibits catecholamine release

  • Pharmacokinetics Clonidine well absorbed after oral administration60% of the drug excreted unchanged in the urineduration of action; 8 hours

  • Side Effects Clonidine dry mouthsedationwithdrawal syndrome; hyperadrenergic states resembling phaechromocytomaretention of Na+ and waterskin rashesconstipation



    inhibits SNS from the vasomotor center to the peripheryresulting in decrease SVR and BP

  • Pharmacokinetics Methyldopaoralincomplete absorption (25-50%)low protein binding 15%maximal effect within 4 to 6 hours after an oral dose and persists for as long as 24 hrs

  • Side Effects MethyldopaSedation / confusionHepatic dysfunction, necrosis; maybe fatal

    Rebound hypertension Retention of Na + and water Sexual dysfunctionBradycardiaSLE like symptoms

    *-In animals, anesthetic requirements (MAC) for volatile drugs are decreased 20% to 40% -Elevations of plasma concentrations of transam