Antihypertensive drugs

anti hypertensive drugs and use in anesthesia

1. ANTIHYPERTENSIVE DRUGS By- Dr Isha Bhagat No of slides : 53 Date: 24/02/2020 1 1) STOELTING’S PHARMACOLOGY & PHYSIOLOGY IN ANESTHESIA PRACTICE- 5 TH EDITION ((PG: 480-513) 2) K D TRIPATHI MEDICAL PHARMACOLOGY – 7 TH EDITION ( CHAPTER 40 )

2. Contents : JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension 2

3. JNC-8 classification : 3 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hyptertension

4. 4 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hyptertension

5. Factors effecting BP: 5 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hyptertension

6. 6 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hyptertension

7. ANTIHYPERTENSIVE AGENTS 7 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

8. ANTIHYPERTENSIVE AGENTS 8 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

9. ACE INHIBITORS 9 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

10. ACE INHIIBTORS 10 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

11. ACE INHIBITORS 11 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

12. ACEINHIBIOTES 12 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

13. ACE INHIBITORS 13 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

14. ARB’S 14 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

15. Angiotensin Receptor Blockers (ARBs) - Losartan 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 salt and water reabsorption No inhibition of ACE 15 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

16. Losartan Theoretical superiority over ACEI’s : Cough is rare – no interference with bradykinin and other ACE substrates Complete inhibition of AT1 – alternative remains with ACEs Result in indirect activation of AT2 – vasodilatation (additional benefit) However , losartan decreases BP in hypertensive which is for long period (24 Hrs ) HR remains unchanged and CVS reflexes are not interfered. no significant effect on plasma lipid profile, insulin sensitivity and carbohydrate tolerance. Mild uricosuric effect 16 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S-losartan B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

17. Beta-adrenergic blockers 1/3: Non selective : Propranolol  (others: nadolol , timolol , pindolol , labetolol ) Cardioselective : Metoprolol  (others: atenolol, esmolol , betaxolol ) All beta-blockers have similar antihypertensive effects – irrespective of additional properties: Reduction in C.O but no change in BP initially Adaptation by resistance vessels to chronically reduced CO – antihypertensive action Other mechanisms – decreased renin release from kidney Reduced NA release and central sympathetic outflow reduction Non-selective ones – reduction in g.f.r but not with selective ones   17 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

18. Beta-adrenergic blockers 2/3 JNC 8 recommends - 1 st line of antihypertensive along with diuretics and ACEIs Advantages: No postural hypotension No salt and water retention Once a day regime Preferred in young non-obese patients Drawbacks : Fatigue, lethargy – decreased work capacity Loss of libido – impotence Cognitive defects – forgetfulness Therefore cardio-selective drugs are preferred now 18 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

19. CENTRALLY ACTING ADRENERGIC DRUGS :- 19 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension CLONIDINE : It is a selective partial α 2- adrenergic agonist that acts as an antihypertensive because of its ability to decrease sympathetic output from the CNS. Adult dose: 0.2-0.3 mg orally. Reaches peak plasma concentration- 60-90 mins. Elimination half life : 9-12 hours. 50% metabolized in liver and remaining excreted unchanged in urine. Duration of hypotensive effect after a single dose is 8 hrs. The Transdermal patch requires about 48 hrs to produce steady state therapeutic plasma concentrations.

20. 20 METHYLDOPA: Moderate efficacy. Circulating levels of NA and renin tend to fall due to reduction in sympathetic tone. Partly metabolized and partly excreted unchanged in urine. Antihypertensive effect develops over 4-6 hrs and lasts for 12-24hours . Used to treat hypertension during pregnancy. DEXMEDETOMIDINE : Selective α 2 agonist. Administered IV as an infusion from 0.1 – 1.5 mcg/kg/min with elimination half life of 2 hrs. Large IV boluses (0.25-1 mcg/kg ) over 3-5 mins results in paradoxical HTN with a decrease in HR . CENTRALLY ACTING ADRENERGIC DRUGS :- JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

21. VASODILATORS 21 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

22. 2) SODIUM NITROPRUSSIDE-1/2 : Direct acting, non selective peripheral vasodilator that causes relaxation of arterial and venous vascular smooth muscle. Relaxes both capacitance and resistance vessels. Onset of action is immediate, and its duration is transient , requiring continuous IV administration to maintain a therapeutic level. Recommended initial dose : 0.3 mcg/kg/min IV titrated to a maximum rate of 10 mcg/kg/min IV with maximum rate not to be infused for more than 10 mins. In patients with heart failure and ventricular dilatation, Nitroprusside improves ventricular function and C.O mainly by reducing aortic impedance (afterload), but also by lowering atrial filling pressure (preload) . 22 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

23. Used in hypertensive emergency ; 50 mg is added to a 500 ml bottle of saline/ glucose solution. The infusion is started at 0.02 mg/min and titrated upward with the response: 0.1-0.3 mg/min if needed. It decomposes on exposure to light and should be covered with black paper. SNP infusion of more than 2mcg/kg/min IV results in dose-dependent accumulation of cyanide -> leading to cyanide toxicity. 23 SODIUM NITROPRUSSIDE-2/2 : JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

24. 3)Nitro-glycerine (NTG) 1/2 : Organic nitrate  acts on venous capacitance vessels and large coronary arteries to produce peripheral pooling of blood and decreased cardiac ventricular wall tension. USE : sublingual / IV administration for the treatment of angina pectoris as a result of either atherosclerosis of the coronary arteries or intermittent vasospasm of these vessels. Controlled hypotension can be achieved with the continuous infusion of NTG. It’ s not recommended in patients with hypertrophic obstructive cardiomyopathy ( HOCM) or in the presence of severe aortic stenosis. 24 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

25. 3)Nitro-glycerine (NTG) -2/2 : Route of administration : oral, sublingual, Buccal, trans-mucosal, transdermal ointment or patch. Elimination half life : 1.5 minutes - Large volume of distribution DOSE : NTG is commonly diluted to a concentration of 100 mcg/ml and administered as a continuous IV infusion (0.5-5mcg/kg/min). In large doses, NTG can produce methemoglobinemia in patients with hepatic dysfunction. Tolerance : is dose –dependent and duration dependent, manifesting in 24 hours. A drug free interval of 12-14 hrs is recommended to reverse tolerance to NTG . 25 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

26. Calcium Channel Blockers – Classification-1/5 26 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

27. Calcium Channel Blockers – Mechanism of action 2/5 Three types Ca+ channels in smooth muscles – Voltage sensitive, receptor operated and leak channel Voltage sensitive are of 3 types  L-Type, T-Type and N-Type Normally, L-Type of channels admit Ca+ and causes depolarization  excitation-contraction coupling through phosphorylation of myosin light chain  contraction of vascular smooth muscle  elevation of BP CCBs block L-Type channel: Smooth Muscle relaxation Negative inotropic and chronotropic effects in heart DHPs > Verapamil > Diltiazem  have highest smooth muscle relaxation and vasodilator action. 27 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

28. Calcium Channel Blockers-3/5 Advantages: Unlike diuretics no adverse metabolic effects but mild adverse effects like – dizziness, fatigue etc. Do not compromise hemodynamics – no impairment of work capacity No sedation or CNS effect Can be given to asthma, angina patients No renal and male sexual function impairment No adverse fetal effects 28 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

29. Calcium Channel Blockers – current status- 4/5 As per JNC 8: CCBs are not 1 st line of antihypertensive unless indicated – ACEI/diuretics/beta blockers However it’s been used as 1 st line by many because of excellent tolerability and high efficacy. Preferred in elderly and prevents stroke. CCBs are effective in low Renin hypertension. They are next to ACE inhibitors in inhibition of albuminuria and prevention of diabetic nephropathy. 29 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

30. Calcium Channel Blockers -5/5 Contraindications: Unstable angina Heart failure Hypotension Post infarct cases Preparation and dosage: Amlodipine – 2.5, 5 and 10 mg tablets (5-10 mg OD) ( Stamlo , Amlopres , Amlopin ). Nimodipine – 30 mg tab and 10 mg/50 ml injection – Vasotop , Nimodip , Nimotide etc. 30 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

31. COMBINED A AND B ADRENERGIC RECEPTOR ANTAGONISTS -1 LABETOLOL: It’s a unique parenteral and oral antihypertensive drug that exhibits selective α 1 and non-selective β 1 and β 2 adrenergic antagonist effects . Metabolism : conjugation by glucoronic acid with 5% drug recovered unchanged in Urine. Elimination half life : 5-8 hrs IV dose of Labetolol (0.1-0.5mg/kg) Is present in 5 to 10 mins. 31 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

32. Uses: Safe and effective in Hypertensive emergencies Large bolus doses of labetalol (2mg/kg) IV administered to treat hypertensive emergencies may result in excessive decrease in BP . Repeated doses ( 20-80 mg IV) may be administered every 10 mins until desired response is achieved. Rebound hypertension after withdrawal of Clonidine and hypertensive responses in patients with pheochromocytoma can be effectively treated with labetalol. Also effective in t/t of angina pectoris. Labetalol 0.1-0.5 mg/kg IV can be administered to Anesthetized patients to attenuate increases in HR and BP that increase due to surgical stimulus. S/E: Orthostatic Hypotension is most common side effect. 32 LABETOLOL-2: JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

33. α lpha – Adrenergic blockers : Prazosin 33 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

34. α lpha – Adrenergic blockers: Prazosin : 34 Not a good 1 st line drug Not good for monotherapy JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

35. DIURECTICS 35 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

36. DIURETICS 36 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

37. LOOP DIURETICS 37 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

38. HIGH CEILING DIURETICS 1/2 : FUROSEMIDE , is a weaker antihypertensive than thiazides. Fall in BP is entirely dependent on reduction in plasma volume and CO. Elimination half life : 1-2 hrs Dose- 0.5-1 mg/kg IV over 1-2 mins, maybe increased to 80mg if inadequate response. In patients with normal renal function , 40 mg of IV furosemide will produce maximal natriuresis. It has a rapid onset of action , producing diuresis within 5 – 10 mins of administration , with a peak effect at 30 mins and duration of action 2-6 hrs . 38 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

39. HIGH CEILING DIURETICS 2/2 : Maximal diuresis can be achieved with an IV bolus of 160-200 mg , administered slowly to avoid occurrence of tinnitus. Doses larger than 200 mg will not result in increased natriuresis . The natriuretic action lasting only 4-6h r after the conventional morning dose is followed by compensatory increase in proximal tubular reabsorption of Na+. They are indicted only when it is complicated by : Chronic renal failure Coexisting refractory CHF Resistance to combination regimens S/E : Hypokalemia 39 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

40. K SPARING 40 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

41. ANTIHYPERTENSIVES AND ITS ANAESTHETIC CONSIDERATIONS There is a concern about the interaction between anaesthetics and antihypertensive drugs. Areas of concern for administration of anaesthetic in patients treated with antihypertensive medication: Reduced sympathetic nervous system activity Orthostatic hypotension Reduced sensitivity to indirectly-acting sympathomimetic agents (caused by antihypertensive drugs that deplete norepinephrine from nerve terminals.) 41 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

42. ANTIHYPERTENSIVES AND ITS ANAESTHETIC CONSIDERATIONS Maintenance of antihypertensive drug treatment during perioperative time frame: F ewer systemic blood pressure and heart rate fluctuations during anesthesia. Decreased likelihood of cardiac dysrhythmias. Conclusion: Previously effective antihypertensive drug therapy should be continued during the perioperative period. The pharmacology of the particular antihypertensive drug should be considered in the development of the anesthesia plan. 42 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

43. ANTIHYPERTENSIVES AND ITS ANAESTHETIC CONSIDERATIONS CCBs interaction with anesthetics: In anaesthetized patients with preexisting left ventricular dysfunction- Verapamil administration results in: Myocardial depression Reduced cardiac output In patients with depressed left ventricular function, anaesthetized with a volatile anaesthetic and underlying open chest surgery: IV verapamil further decreases ventricular function Volatile anaesthetics have blocking actions on CCB’s because of which CCB’s are administered with caution to patients with impaired renal function or hypovolemia. 43 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

44. CCBs interaction with anesthetics: Patients treated with a combination of β - adrenergic blockers + nifedipine  tolerate high dose of Fentanyl anaesthesia. Neuromuscular blocking drugs : CCB’s alone don’t produce a skeletal muscle relaxant effect. These drugs potentiate the effects of depolarizing and non depolarizing muscle relaxant. Antagonism of NMB’s is impaired because of decreased presynaptic release of Ach in the presence of CCB. Verapamil and diltiazem have potent local anaesthetic property which may increase the risk of local anaesthetic toxicity when R.A is given 44 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

45. ANTIHYPERTENSIVES AND ITS ANAESTHETIC CONSIDERATIONS: Administer all anti-hypertensive medications except D iuretics and ACEIs until the day of surgery . Diuretics should not be administered because they induce volume depletion and K+ derangement. RAAS is involved in maintaining normal BP during anaesthesia . Therefore ACEI’s should be discontinued day before surgery. Abrupt withdrawal of beta blocker agents may adversely affect the heart rate and blood pressure and may precipitate MI, so they should be continued till the day of surgery. 45 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

46. ANTIHYPERTENSIVES AND ITS ANAESTHETIC CONSIDERATIONS Adverse effects are seen in patients with chronic use of ACE inhibitors. It is recommended to discontinue the Drugs 12-24 hours prior to surgery. Exaggerated hypotension attributed to continued ACE inhibitor therapy has been responsive to crystalloid fluid infusion and/or administration of a catecholamine or vasopressin infusion They may also increase insulin sensitivity and hypoglycaemia, which is a concern when these drugs are administered to patients with DM. 46 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

47. ANTIHYPERTENSIVES AND ITS ANAESTHETIC CONSIDERATIONS When SODIUM NITROPRUSSIDE is used for controlled hypotension during anaesthesia , the patient’s capacity to compensate for anaemia and hypovolemia may be diminished. (If possible, pre-existing anemia and hypovolemia should be corrected prior to administration of it.) Hypotensive anesthetic techniques may also cause abnormalities of pulmonary V/Q ratio. Patients intolerant of these abnormalities may require higher FiO2 . 47 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

48. Treatment of Hypertension – General principles Stage I: Start with a single most appropriate drug with a low dose. Preferably start with Thiazides. Others like beta-blockers, CCBs, ARBs and ACE inhibitors may also be considered. CCB – in case of elderly and stroke prevention. If required increase the dose moderately Partial response or no response – add from another group of drug, but remember it should be a low dose combination If not controlled – change to another low dose combination In case of side effects lower the dose or substitute with other group Stage 2: Start with 2 drug combination – one should be diuretic 48 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

49. Treatment of Hypertension – combination therapy In clinical practice a large number of patients require combination therapy – the combination should be rational and from different patterns of haemodynamic effects Sympathetic inhibitors (not beta-blockers) and vasodilators + diuretics Diuretics, CCBs, ACE inhibitors and vasodilators + beta blockers (blocks renin release) Hydralazine and CCBs + beta-blockers (tachycardia countered) ACE inhibitors + diuretics 3 (three) Drug combinations: CCB+ACE/ ARB+diuretic ; CCB+Beta blocker+ diuretic; ACEI/ARB+ beta blocker+diuretic 49 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

50. Treatment of Hypertension. Never combine: Alpha or beta blocker and clonidine - antagonism Nifedepine and diuretic -synergism Hydralazine with DHP or prazosin – same type of action Diltiazem and verapamil with beta blocker – bradycardia Methyldopa and clonidine Hypertension and pregnancy: Most drugs are not safe in pregnancy Avoid diuretics, propranolol, ACE inhibitors, Sodium nitroprusside etc Safer drugs : Hydralazine, Methyldopa, cardioselective beta blockers and prazosin 50 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

51. 51 JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

52. HYPERTENSIVE EMERGENCY : 52 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 Pheochromocytoma, cheese reaction and clonidine withdrawal Drugs: Sodium Nitroprusside (20-300 mcg/min) – dose titration and monitoring GTN (5-20 mcg/min) – cardiac surgery, LVF, MI and angina Esmolol (0.5 mg/kg bolus) and 50-200mcg/kg/min - useful in reducing cardiac work Phentolamine – pheochromocytoma, cheese reaction a nd clonidine withdrawal (5-10 mg IV) JNC-8 Classification of HTN Types of HTN Factors effecting BP Risk factors Anti-hypertensive classification: ACE INHIBITORS ARB’S B BLOCKERS CENTRALLY ACTING ADRENERGIC DRUGS VASODILATORS Hydralazine Sodium Nitroprusside NTG CCB’S COMBINED ALPHA AND BETA ADRENERGIC BLOCKERS- Labetolol A BLOCKERS- prazosin DIURETICS Thiazides Loop diuretics High ceiling diuretics K+ sparing Anaesthetic consideration Treatment of hypertension

53. THANKYOU  53