ANTIHYPERTENSIVE

AGENTS & ANESTHETIC

IMPLICATIONSDr. Vaibhav Tulsyan

Hypertension

High Blood Pressure

JNC 8 Recommendations:

Patient Subgroup Target SBP (mm Hg) Target DBP (mm Hg)≥ 60 years < 150 < 90

< 60 years < 140 < 90

≥ 18 years with CKD < 140 < 90

≥ 18 years with Diabetes < 140 < 90

1st line antihypertensives:Thiazide diureticsAngiotensin-converting enzyme inhibitors (ACEI)Angiotensin receptor blockers (ARB)Calcium channel blockers (CCB)

Other antihypertensives:Loop (high ceiling) diureticsPotassium sparing diuretics -blockersβα-blockersCombined α & β blockersCentrally acting sympathomimetic agentsVasodilatorsDirect renin inhibitorAdrenergic neuron blockers – Reserpine, guanethidine

Thiazide Diuretics 1st line antihypertensives. Mild (average fall in MAP ~ 10 mm Hg) Potentiate other antihypertensives (except DHPs) and

prevent tolerance to them Antihypertensive action is attenuated by NSAIDS They act on the early segment of the DCT by inhibiting

Na+ and Cl− reabsorption causing net loss of Na+ and water in urine

Have maximal antihypertensive effect at low dose i.e. increasing the dose increases only diuretic effect

Thiazide Diuretics Chlorthalidone, Hydrochlorthiazide, Indapamide Mechanism of antihypertensive action:

Initially: Diuresis → depletion of Na+ and body fluid volume → decrease in cardiac output

Subsequently after 4 - 6 weeks, Na+ balance and CO is regained by 95%, but BP remains low!

There is reduction in total peripheral resistance (TPR) due to deficit of little amount of Na+ and water (Na+ causes vascular stiffness) similar to that seen in diets with sodium restriction.

Thiazide diuretics – other effects

Renal – decrease renal blood flow & GFR Metabolic:

Hypokalemia causing muscle pain & fatigue, dangerous arrhythmias in those taking digoxin, sudden cardiac death

Hyperglycemia - ↓ K+ → ↓ Insulin release Hyperlipidemia - ↑ risk of stroke Hyperuricemia These metabolic side effects occur at higher doses (50-100

mg per day) Low dose (12.5-25 mg per day) is recommended for HTN K+ sparing diuretic (spironolactone, amiloride, eplerenone)

usually added in elderly to combat hypokalemia.

Loop Diuretics inhibit Na+ and Cl− reabsorption in the thick

ascending limb of the loop of Henle and in the early part of the DCT.

Weaker antihypertensive Na+ deficient state is temporary, not maintained round-

the-clock and TPR is not reduced antihypertensive efficacy does not parallel diuretic

potency Used only when HTN complicated by CRF, CHF,

marked fluid retention. Furosemide, Torsemide, Bumetanide

Diuretics – Anesthetic Implications Chronic diuretic therapy hypokalemia (more with

thiazides) potentiation of the effects of muscle relaxants used during anesthesia, as well as predisposition to cardiac arrhythmias and paralytic ileus.

Thiazides cause hyperuricemia → may precipitate or worsen gout during anesthesia when uric acid excretion is reduced

Thiazide diuretics taken for hypertension should be continued on the day of surgery.

RAAS AT II :

potent vasoconstriction and stimulation of aldosterone → increased systemic vascular resistance and increased afterload → increased BP

Aldosterone: stimulates water and

sodium reabsorption → increased blood volume, increased preload, and increased BP

Cardiac hypertrophy and cardiac remodeling

ACE Inhibitor 1st line antihypertensive Captopril – active drug, metabolized to active metabolites Enalapril, Ramipril – prodrugs, become active following hepatic

metabolism Lisinopril – active drug, not metabolized Control HTN in ~ 50% patients when used alone Other uses of ACEI:

Congestive Heart Failure Myocardial Infarction Prophylaxis of high CVS risk subjects Diabetic Nephropathy Scleroderma crisis

ACEI – Advantages No postural hypotension Safe in asthmatics and diabetics Prevention of secondary hyperaldosteronism and K+ loss

due to diuretics Reverse the left ventricular hypertrophy and increased

wall-to-lumen ratio of blood vessels that occurs in hypertensive patients

No hyperuricaemia or deleterious effect on plasma lipid profile

No rebound hypertension on withdrawal Minimal worsening of quality of life parameters DOC in hypertensive patients with CHF Renal protective effects in patients with diabetes

AT1 Receptor Blockers (ARBs) Losartan, Telmisartan, Olmesartan Most of the physiological actions of angiotensin II are

mediated via AT1 receptor

Competitive antagonist and inverse agonist of AT1 receptor

Does not interfere with other receptors except TXA2

Blocks all the actions of Angiotensin II – vasoconstriction, sympathetic stimulation, aldosterone release and renal actions of salt and water reabsorption

ACEI and ARB should not be given concurrently

Superiority of ARB over ACEI Blockade of the AT1-receptor is the most specific way

of preventing the adverse effects of angiotensin II seen in heart failure and hypertension, especially as angiotensin II may be synthesized by alternative non-ACE pathways.

The AT2 receptor is not blocked, which may possess cardioprotective properties.

There is a much lower incidence of cough and angioedema (no ACE inhibition) and therefore improved compliance.

ACEI & ARB - Anesthetic Implications Can theoretically blunt the compensatory activation

of the renin-angiotensin system during surgery → prolonged hypotension.

For patients undergoing procedures with major fluid shifts, or for patients who have medical conditions in which hypotension is particularly dangerous, it may be prudent to discontinue them before surgery.

Calcium Channel Blockers

CCB 1st line antihypertensive agents Block L-type of voltage gated Ca+2 channels. These channels admit Ca+2 and cause depolarization →

excitation-contraction coupling through phosphorylation of myosin light chain → contraction of vascular smooth muscle → elevation of BP

DHPs have maximum smooth muscle relaxation and vasodilator property followed by verapamil and diltiazem

Verapamil is an anti-arrhythmic agent

CCB - Advantages Do not compromise haemodynamics No sedation or other CNS effects Not contraindicated in asthma, angina (especially variant)

and PVD patients: may benefit these conditions. Do not impair renal perfusion. Do not affect male sexual function. No deleterious effect on plasma lipid profile, uric acid level

and electrolyte balance. Shown to have no/minimal effect on quality of life. No adverse fetal effects; can be used during pregnancy (but

can weaken uterine contractions during labour). Effective in low renin hypertension

CCB – Anesthetic Implications Patients receiving calcium channel blockers may have

an increased incidence of postoperative bleeding, probably due to inhibition of platelet aggregation. The multiple benefits of these drugs probably outweigh the small risk of continued therapy.

Potentiate volatile anesthetics and Neuromuscular Blocking Drugs

It is recommended to continue them on the day of surgery

Beta adrenergic blockers Non selective: Propranolol, nadolol, timolol Cardioselective: Metoprolol, atenolol, esmolol, betaxolol All beta-blockers have similar antihypertensive effects Reduction in CO but no change in BP initially Resistance vessels adapt to chronically reduced CO –

antihypertensive action Other mechanisms – decreased renin release from kidney (β1

mediated), Reduced NA release and central sympathetic outflow reduction

Non-selective ones – reduction in GFR Drugs with intrinsic sympathomimetic activity may cause

less reduction in HR and CO  

β Blockers – Contd. Advantages:

No postural hypotension No salt and water retention Low incidence of side effects Low cost Once a day regime Preferred in young non-obese patients, prevention of sudden

cardiac death in post infarction patients and progression of CHF

Drawbacks (side effects): Fatigue, lethargy – decreased work capacity Loss of libido – impotence Cognitive defects – forgetfulness Rebound hypertension Therefore cardio-selective drugs are preferred now

β blockers – Anesthetic implications Anesthetic indications:

Premedication in a patient of β blocker therapy Deliberate hypotensive anesthesia – better control of heart rate Obtund hypertensive response to laryngoscopy and intubation Thyrotoxic crisis – Propranolol 0.01-0.1 mg/kg iv (max 2 mg) Antiarrhythmic Phaeochromocytoma – to counter tachycardia due to α blocker

Muscarinic effect of succinylcholine is exaggerated by βblockade

Reversal of neuromuscular blockade with neostigmine should be avoided if intraoperative bradycardia cannot be increased with atropine

β blockers – Anesthetic Implications Normal sympathetic response to blood loss, acute hypovolemia

may be obtunded They are associated with acute withdrawal syndromes that can

lead to adverse perioperative events. should not be stopped ∴abruptly.

Withdrawal can also lead to accelerated angina, myocardial infarction, or sudden death.

It is recommended that patients with 3 or more risk factor for CHD be given β blocker perioperatively as they decrease mortality

Esmolol is used in the short-term management of tachycardia and hypertension in the perioperative period, and for acute supraventricular tachycardia.

α blockers Non-selective – Phenoxybenzamine, Phentolamine used in hypertensive emergencies, phaeochromocytoma Selective α1 blockers – Prazosin, Terazosin Used in chronic hypertension Reduction in TPR and mean BP, also reduction in venous

return & CO Do not produce tachycardia as presynaptic α2 receptors

are not inhibited – autoregulation of NA release remains intact

Postural hypotension, fluid retention Also used in management of severe CHF along with

cardiac glycosides and diuretics

α + β blockers Labetalol:

α1 + β blocker used to treat hypertensive crises and to facilitate

hypotension during anesthesia used to treat hypertension associated with angina and

during pregnancy

Centrally acting sympathomimetics α2 agonists – Methyldopa, Clonidine

Methyldopa – Used in hypertension during pregnancy Clonidine: Moderately potent antihypertensive Rapid i.v. injection of clonidine raises BP transiently due to activation of

peripheral postsynaptic vasoconstrictor α2B receptors at the high concentrations so attained

Exhibits therapeutic window phenomenon i.e. optimum lowering of BP occurs between blood levels of 0.2–2.0 ng/ml. At higher concentrations fall in BP is less marked.

Sedation, mental depression, disturbed sleep, constipation, impotence, postural hypotension.

Clonidine withdrawal – Alarming rise in BP, in excess of pretreatment level, with tachycardia, restlessness, anxiety, sweating, headache, nausea and vomiting occur in some patients when doses of clonidine are missed for 1–2 days. T/t is α+β blocker, or clonidine itself

Clonidine – Anesthetic implications ↓ anesthetic requirements (contributes to MAC via ↓ in

sympathetic activity and arousal) Premedication for sedation (useful in pediatrics), decreases

hemodynamic lability, and potential cardioprotection (studies have suggested greater effect than perioperative beta-blockers)

Regional and neuraxial anesthesia as adjunct to local anesthetics (Additive analgesic effect and duration without some of the side effects seen with opioids)

Detoxification aid to suppress unpleasant sympathetic responses during withdrawal from narcotics, alcohol, nicotine

Neuropathic pain

Vasodilators Nitroglycerin, Sodium nitroprusside: For hypotensive anesthesia, hypertensive episodes intraoperatively,

attenuation of pressor response to laryngoscopy and intubation Causes reflex tachycardia, flushing, shock. Tolerance to NTG – dose dependent and duration dependent. A

drug free interval of 12-24 hrs is recommended to reverse tolerance

NTG causes resistance to anticoagulative effect of heparin SNP causes coronary steal phenomenon Hydralazine: used in severe, refractory or malignant hypertension,

pregnancy induced hypertension, pre-eclampsia, eclampsia

Direct renin inhibitor Aliskiren Blocks the production of Angiotensin I Causes fall in BP which is more marked in the Na+

depleted subjects with high basal PRA Antihypertensive efficacy of aliskiren is equivalent to

that of ACE inhibitors or ARBs Renoprotective effect as well in hypertension and

diabetes mellitus

Post-operative hypertension Causes:

History of hypertension preoperatively Pain, hypervolemia, and bladder distention Excitement on emergence from anesthesia Hypercarbia

Usually begins within 30 minutes of the completion of surgery and lasts approximately two hours.

SBP > 180 mm Hg or DBP > 110 mm Hg should be treated immediately

Patients on chronic antihypertensive therapy should resume their usual medications postoperatively

With the exception of beta blockers and clonidine, it is not necessary for patients receiving chronic antihypertensive therapy who are unable to resume oral medications to continue the same class of drugs postoperatively

Hypertensive emergencies Cerebrovascular accident or head injury with high BP Left ventricular failure with pulmonary edema due to hypertension Hypertensive encephalopathy Angina or MI with raised BP Acute renal failure with high BP Eclampsia Phaeochromocytoma, cheese reaction and clonidine withdrawal Drugs:

Sodium Nitroprusside (0.5-10 mcg/kg/min) NTG (0.5-10 mcg/kg/min) – cardiac surgery, LVF, MI, unstable angina. Hydralazine (10-20 mg i.m. or slow i.v.)– eclampsia. Avoided in MI or

aortic dissection. Esmolol (0.5 mg/kg bolus and 50-100 mcg/kg/min) - useful in reducing

cardiac contractility and cardiac work. Phentolamine (5-10 mg IV) – phaeochromocytoma, cheese reaction

and clonidine withdrawal Labetalol – Phaeochromocytoma, MI, unstable angina, eclampsia

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