ANTI-HYPERTENSIVE DRUGS

DR-MAYURI GOLHAR

CONCERN WHILE ADMINISTERING ANESTHESIA TO PATIENTS ON ANTI-HYPERTENSIVE MEDICATIONS•Attenuation of sympathetic nervous

system activity.•Modification of response to

sympathomimetic drugs.•Sedation.

•Due to attenuation of sympathetic nervous system activity.

•Orthostatic hypotension.•Exaggerated systemic BP decrease blood

loss body position

change decrease venous return

due to PPV

DRUGSSYMPATHOLYTICS-B-BLOCKERSLABETELOLPRAZOSINTERAZOSINCLONIDINE

CCB-DILTIAZEMVERAPAMILNIFIDIPINENICARDIPINEISRADIPINE

ACE-I-CAPTOPRIL RAMIPRILENALAPRIL FOSINOPRILLISINOPRILBENZEPRILQUINAPRIL

VASODILATING DRUGS-HYDRALAZINEMINOXIDIL

ANGIOTENSIN RECEPTOR BLOCKER-LOSARTAN

DIURETICS-THIAZIDES.LOOP DIURETICS(bumetanide, ethacranic acid, furosemide)K SPARING( amiloride, spirinolactone. Triamterene)

SYMPATHOLYTICS

•B- ADRENERGIC BLOCKERS-•Young & middle aged•Coronary artery disease•Action-classified as selective, non-

selective, with intrinsic sympathomimetic activity.

•B1- selective ( cardiac), -less

bradycardia,vasospasm,bronchospasm,. does not mask hypoglyemia - in pulmonary disease, PVD,IDDM•B1+B2- nonselective( cardiac, bronchial

& vascular sm)

•SIDE EFFECTS—•Bradycardia•Bronchospasm•Claudication•Congestive cardiac failure•Masking of hypoglycemia•Precipitation of angina

LABETALOL

•a1 + b adrenergic blocking properties•Vasodilatation•Produces less bradycardia & negative

inotropic effect.•SIDE EFFECTS- orthostatic hypotension-bronchospasm-increases aminotransferase level-paresthesia( scalp numbness)- Urinary rention

PRAZOSIN

•Selective postsynaptic a1 blocker.•Vasodilatation of arteries & veins.•When used with a thiazide diuretic its

effect to treat moderate to severe HTN in young.

•Does not cause reflex increase in CO & renin

•USES-to reduce afterload in pts of CCF.•Pre-op in pts of pheochromocytoma.•To relieve vasospasm of raynauds•In pts with BPH to reduce the size of

gland.

•Pharmacokinetics-- 60% bioavailability-elimination ½- 3hours-first pass hepatic metabolism.•CVS-- reduces systemic vascular resistance.-dilatation of veins & arteries & reduces

venous return

Side -effects•Vertigo•Fluid retention•Dryness of mouth•Urinary retention•Sexual dysfunction, lethargy, nasal

congestion•Increases hypotension in patients given

epidural block treated with this drug as it inhibits the vasoconstriction at the unblock portion.

•When given along with b-blocker produces refractory hypotension during regional anesthesia

CLONIDINE

•Centrally acting a2 agonist.•It reduces the sympatheticNS output from

the CNS.•Used in severe HTN or renin dependant

disease .•Daily dose- 0.2-0.3mg orally.•Transdermal patch who cannot take oral

dose.•USES-Analgesic: given in epidural/ SAB (150-450

ug) produces dose dependant analgesia.

•Acts at the substanstia gelatinosa of spinal cord & activates post-sympathetic a2 receptors.

•Side effects-hypotension, sedation & dryness of mouth.

•Pre-medication: orally 5ug/kg-blunts taccycardia associated with

laryngoscopy & intubation.-decreases increase in HR & BP intra-op- Reduces plasma catecholeamines- Reduces anesthetic requirements of

inhaled & injected drugs

•In patients with coronary art disease a small dose of 2ug/kg reduces chances of ischaemic episodes without affecting hemodynamic stability.

•It supress pressor response of ephedrine so dose of ephedrine should be considered while using clonidine intra-op.

•Prolonging the effect of regional anesthesia:-

- Dose 75-150ug added with teracaine/ bupivacaine prolongs motor & sensory blockage

- Not used in obstetric pt as it causes foetal bradycardia.

•Orally 150-200 1-1.5 hours prior spinal anesthesia increases the sensory block with teracaine/bupivacaine.

•Side effect- bradycardia & hypotension•Used in the diagnosis of

pheochromocytoma--orally o.3 mg decreases plasma

catecholeamine level in normal pts but not of pheochromocytoma.

•Treatment of opioid withdrawal:-as it reduces sym NS output it is used in

nicotine & smoking withdrawal•Treatment of shivering- 75ug iv-it inhibits thermoregulatory control

•Attenuates hemodynamic responses of ketamine-

5ug/kg orally given 90min before induction reduces BP&HR increase after ketamine administration.

•Mech of action--stimulates the a2 adrenergic inhibitory

neurons in the medullary vasomotor centre.

Decreases sympathetic outflow from CNS.

Decreases syst BP, HR, Cardiac output.-it also modifies the function of K channels

in CNS & makes the cell memb hyperpolerised & decreases the requirement of anesth agents

•PK- rapidly absorbed after oral administration

- Peak plasma conc 80-90 min- elimat ½- 9-10 hours- 50% metabolism occurs in liver.•CVS EFFECTS- It decreases the systolic BP more than the

diastolic BP- Initially there is decrease in the Cardiac

output but it returns to pre-drug level- Homeostatic reflexes are maintained so

problems of orthostatic hypotension & hypotension during exercise are less.

- It does not affect the renal Bld flow & GFR.

•SIDE EFFECTS- -sedation & xerostonia- bradycardia & hypotension.- Retention of Na & water- Skin rashes,- Impotence, orthostatic hypotension - Rebound hypotension

- Rebound hypotension patient on daily t/t with >1.2mg with sudden withdrawal.

- It occurs early-8hrs or late-36hrs- Taccy,diphoresis,nervousness,headache,

abdominal pain,- It also exaggerates catecholamine conc &

perp vasoconstriction.- Also seen with b-blockers & TTCA

depressants.- t/t- reinstitute clonidine- B-blocker- labetolol- Withdrawal should be gradual over 7days- Transdermal patch.- * Atipamezole a2 receptor antagonist.

DEXMEDETOMIDINE•Selective potent a2 agonist.•Active dextro isomer of medetomidine.•Dose dependant analgesia, hypnosis

&sedation•Shorter duration of action than clonidine•Uses- to decrease hemodynamic

responses to laryngoscopy & intubation•Reduces catecholamines & requirement of

anesthetic agents•Reduces hemodynamic responses of

ketamine.• t/t for shivering

•1ug/kg dose – TIVA•0.5ug/kg used along with lidocaine for

regional anesthesia.•200-700ug/kg/hr-post op sedation. •Side effects-- hypotension- Mild depression of ventilation.

ACE-INHIBITORS

•Used as 1st line therapy for-t/t of syst HTN-CCF( regress LVH)-Mitral regurgitation-HTN in diabetic ptsMech of action ANG1---X--- ANG2Prevents vasoconstriction & stimulation of

SNS.Side effects-cough, rhinorrhoea,URTI,allergy.- due to

inhibition of peptidyl dipeptidase.

- angioedema-proteinurea occurs in pts with previous

renal disease-ACE I are contraindicated in renal arterial

stenosis as renal perfussion is highly dependant on ANGII in these patients.

-In case of respiratory depression-epinephrine 0.3-0.4mg(1:1000) s.c.

Pre-op management-They should be continued until surgery &

reinitiated soon post-op.

•As it causes hypotention in the peri-op period.

•It shd be sustituted with a short acting anti-HTN if need arises.

•If there is hypotension it shd be t/t with crystalloids & sympathomimetics.

•These drugs increases sensitivity to insulin & hypoglycemia in pts with DM+HTN.

CAPTOPRIL•Orally- 12.5-25mg, 8-12hrly•Competitive inhibition of ANGIANGII.•Increase in ANGI & renin levels & loss of

negative feedback control.•Aldosteron increase results in slight increase

in K conc•PK- well absorbed orally. 30% bound to protein,

inhibition DD enzyme occurs after 15min•Elm ½- 2hrs•Oxidized to dimer& sulfideskidneys

•CVS--decreases the systemic vascular resistance-reduces Na & water retention particularly

prominent to kidneys( coronary& cerebral bF remains autoregulated)

- No orthostatic hypotension as it does not interact with SNS activity.

- - compensatory rise in HR due to changes in baroreceptor sensitivity.

- Useful in pts with CCF as it improves the efficacy of vasodilators in t/t of CCF

- It also reverse the vascular & renal effects of sleroderma.

•Side-effects--rash,pruritis,loss of taste-hyperkalemia specially in pts with

impaired renal functions/ on t/t with diuretics.

-granulocytopenia-angioedma- due to inhibition of bradykinin.

ENALAPRIL•Tightly binds to the enzyme so a single dose is

effective.•It is a prodrug, metabolized in liver to active

form enalaprilate.•Used in pts who are chronically t/t with ACE-I

& cannot tolerate oral medications can be give IV enalapril.

•Rash, pruritis granulocytopenia is less.

ANGIOTENSIN RECEPTOR BLOCKER•LOSARTAN Act at ANGII receptor.•ANGII is a vasoactive hormone•This drug and its active metabolite carboxylic

acid blocks vasoconstriction & aldosteron secretion by selective inhibition.

•Acts on ANT1 receptor on vascular smooth ms.•The active metabolite is 10-20 times more potent•After oral administration 1st pass hepatic

metabolism by cyto p450 enzyme •Doze- 25-50mg OD•S/E –same as ACE-I but lesser cough.•Drugs acting on renin ang system causes foetal

& neonatal morbidity so shd be avoided in preg

CALCUIM CHANNEL BLOCKERS

•Causes vasodilatation.•Elderly, black & salt sensitive patients.•It can be successfully used in pts in

whome salt restriction is unacceptable.•Incidence of ischemia can increase when

treated with high doss of short acting CCB.

VASODILATING DRUGS

•HYDRALAZINE•Phthalazine derivative•Relaxation of vascular sm•Increases dilatation of art more than veins•Increases dilatation of coronary, cerebral,

renal, & splanchnic circulation.•It interferes with Ca transport in smooth

ms•Used in chronic sys HTN•Used with a diuretic& b blocker

•Doze- 2.5-10mg iv- BP reduces in (10-20min)•Effect lasts for 3-6 hrs•Undergoes hepatic 1st pass metabolism•Elm ½ 3hrs, metabolised be acetylation•CVS- Reduces diastolic BP-red syst vascular resistance.-increase in HR, CO, stroke vol as it inceeases the

baroreceptor mediated sympathetic activity.•Causes less orthostatic hypotension.•Renin activity is increased

•Side effects- Na & water retention•Vertigo, diphoresis, nausea & taccycardia•Angina pectoris•Tolerance•Drug induced fever, urticaria,polyneuritis

anemia,pancytopenia•Defluorination of enflurane( hydrazine)•SLE in 10-20% ( t/t .6month > 200mg)

MINOXIDIL

•Orally active, causes direct relaxation of art sm muscles

•Used with B Blockers & diuretic•Used in severe form of HTN (with renal

failure, transplant rejection, venovascular disease)

•Plasma levels are attained after 1 hr & metabolised to inactive minoxidil glucoronide

•Elm ½ 4hrs

•CVS- increases HR & CO- Increases norepinephrine + renin conc- Na + water retention- s/e- fluid retention- Pulmonary HTN- Pericardial effusion- Cardiac tamponade- hypertrichosis

DIURETICS

•Less commanly used- high cost, shorter duration of action

• used in pts of renal insufficiency & in whom thiazides are ineffective

•Used in pts who have allergy to thiazides, ethacrinic acid is the diuretic of choice.

•S/E- hypokalemia- seen with longer actingProlonged hypokalemia impairs glucose

metabolism & increases ventricular irritability.

•It is avoided in pts with coronary art disease & pts on digitalis

•K sparing diuretics are less potent & used in pts with increased risk of hypokalemia

•These drugs should be used with caution in pts with impaired renal function & those on t/t with ACEI as there is a risk of drug induced hyperkalemia.

THANK YOU…