Hypertension Therapeutics Lecture Semester 6

Lesson Outcomes: Therapeutics of Hypertension Semester 6 ContentsIMU Domain Review of the cardiovascular risk factors1,4 Non-pharmacological measures to reduce blood pressure1,2 The common classes of anti-hypertensive drugs1 Adverse effects of anti-hypertensive drugs1 Selecting an anti-hypertensive drug1,2,7 Influence of co-morbid factors in drug selection2,7 Monitoring drug therapy2,7 Resistant hypertension1,2 Hypertensive urgencies/emergencies1,2 Hypertension and pregnancy1,2 (Not covered: Detection and evaluation of hypertension)

Case Study 1 Mr. C, a 64-year-old ex-banker, is found on routine medical check up to have a BP of 170/100. He is asymptomatic and is usually in good health. He does not smoke and stopped drinking alcohol 4 years ago. There is no known family history of hypertension but his father died in his 50’s possibly from acute MI. On examination: BMI 27. BP 170/90. Otherwise physical examination is unremarkable. Investigation: Total cholesterol: 6.5 mmol/L, LDL 4.8 mmol/L, HDL 1.3mmol/L. ECG: sinus rhythm with no signs of LVH. How would you advice him?

Non-Pharmacological measures to reduce BP Weight Reduction: BMI < 23 Sodium Intake (< 100 mEq/L of Na or 6g NaCl a day) Diet Plan Physical Exercise (aerobic exercise ≥ 30 minutes ≥ 3 times/wk) Avoid/Reduce Alcohol (<21 units/wk ♂ ; < 14 units/wk ♀: 1 unit = 9 g of alcohol) Stop Smoking

Case Study 1 Mr. C’s BP is found on follow-up to be persistently in the range of / He is diagnosed to have hypertension. Before commencing drug treatment what else would you discuss with the patient? Explain the diagnosis Explain risk of not treating Explain need for long-term treatment Discuss medication to be used and possible side-effects Inform need for regular follow-up Ensure continuation of non-pharmacological measures

Case Study 1 Mr. C was started on a thiazide diuretic (other drug choices also possible) Thiazide Diuretics (eg. hydrochlorothiazide, chlorothiazide) What are the possible side-effects of thiazide diuretics? Hypokalaemia Hyperuricaemia ( can precipitate gout) Hyperglycaemia (can worsen diabetes in high doses) Hyponatremia Alkalosis Monitor renal profile Monitor diabetes

Case study 1 After one month Mr. C is reviewed in the clinic. His BP is 160/90. Renal profile and serum uric acid are normal. It is decided to add a second drug to his treatment regimen. An angiotensin-converting enzyme inhibitor (ACEI) is added What are the possible side-effects of ACEIs? Dry cough Hyperkalaemia (care with K supplements, spironolactone) Worsen/precipitate renal failure (contraindicated in bilateral renal artery stenosis) First dose hypotension (care in dehydrated patients) Allergic rashes Angioedema Contraindicated in pregnancy Monitor renal function

Case Study 1 Mr. C develops cough with the ACE Inhibitor and is changed to an angiotensin-receptor blocker (ARB) What are the possible side-effects of ARBs? Hyperkalaemia Renal impairment Hyponatremia Hypotension Contraindicated in pregnancy Monitor renal function Avoid in bilateral renal artery stenosis

Case Study 1 If Mr. C’s blood pressure is still not controlled what would you do? 1. Check adherence to medication 2. Check if carrying out non-pharmacological measures 3. Check if there are any drug interactions: alcohol, NSAIDS 4. Recheck for causes of secondary hypertension If Mr. C requires a third drug to achieve target BP what would you add? A calcium channel blocker (CCB) is used. Possible side-effects: Headaches, dizziness, flushing Oedema Constipation (Short-acting CCBs should be avoided because of the higher risk of adverse cardiac events; long-acting or sustained release preparations preferred)

Case Study 2 A 43-year-old woman with diabetes for 10 years and hypertension for 5 years is seen in the MOPD for follow-up. Her current medication is metformin 500 mg tds, gliclazide 80 mg od, simvastatin 40 mg on, hydrochlorothiazide 12.5 mg od, telmisartan 80 mg od and amlodipine 5 mg od. Her BP is 150/90 and the medical officer decides to add metoprolol 50 mg bd. Questions for discussion: Can thiazide diuretics be used in diabetic patients? Can beta-blockers be used in diabetics?

Case Study 2  Thiazide diuretics may worsen diabetes by causing hyperglycaemia.  However in clinical trials, there is no difference in cardiovascular outcomes between different anti-hypertensive drugs as long as BP control is achieved.  Many guidelines recommend that in diabetics, diuretics may be added to the anti- hypertensive regime to achieve target BP 1,2. Low doses recommended. RAS blockers is the first-line treatment unless contraindicated. 1. ASH Position Paper: Treatment of Hypertension in Patients with Diabetes. The Journal of Clinical Hypertension 2008; 10: (issue 9) The JNC 7 Report. JAMA. 2003; 289:

Case Study 2 Beta-blockers in uncomplicated hypertension:  In hypertensive patients without diabetes, starting β-blockers (especially if combined with diuretics) results in a higher incidence of new-onset diabetes 1.  β-blockers are not recommended as first-line treatment of hypertension unless there is a compelling indication 2. In diabetes with hypertension:  Cardiovascular outcomes are improved by achieving target BP.  β-blockers can be added on to the treatment regime to achieve target BP 3,4.  Newer generation β-blockers (those with ‘vasodilating’ effects: carvedilol) preferred over older β-blockers (atenolol, metoprolol) 1. Diabetes Care. 2006; 29(5); NICE clinical guideline 34. Hypertension: management of hypertension in adults in primary care. June The JNC 7 Report. JAMA. 2003; 289: The Journal of Clinical Hypertension. 2008; 10: (issue 9)

Case Study 2 Possible side-effects if a β-blocker is used: Fatigue Bradycardia, heart block Bronchospasm (avoid in asthma) Impotence in males Metabolic: Hyperglycaemia Adverse lipid profile changes (↑TG ↓HDL-C) May mask symptoms of hypoglycaemia/hyperthyroidism β-blockers should not be stopped suddenly; tail off over 1-2 weeks

Choice of drug treatment There is no ‘fixed rule’ as to which drug to start a particular patient on Choice is best ‘individualized’ based on: Type and severity of hypertension Age Presence of co-morbid medical conditions Cost/economics Ethnicity (more research needed)

Initial Treatment of Hypertension ( without other co-morbid risk factors ) A = ACE Inhibitor (or ARB) C = Calcium-Channel Blocker D = Thiazide-Type Diuretic British Hypertension Society / NICE clinical guideline 34 (2006) Younger than 5555 Years Or Older AC or D A + C or A + D A + C + D

Co-morbid Conditions and Choice of Drugs in Hypertension Diabetes/Chronic Renal Disease ACEIs or ARBs StrokeACEIs ± Diuretics IHD/Anginaβ-blockers CCBs (long-acting) Post-AMI/Heart Failureβ-blockers and ACEIs Elderly/Isolated Systolic Hypertension Diuretics or CCBs The JNC 7 Report. JAMA. 2003; 289:

Starting hypertension treatment Drug therapy is often initiated with a single drug at a low dose. Monitor for response and side-effects. Monotherapy lowers BP to target levels in only about half of patients with mild to moderate hypertension. If target BP is not achieved it may be preferable to add a second drug from another class rather than to keep increasing the dose of the first. For those with moderate/severe hypertension (BP > 160/100) consider starting with a 2 drug combination. Diabetics often require more than one drug and often up to 3 or 4 to achieve target BP levels. Clinical Practice Guidelines: Management of Hypertension (3 rd Edition) 2008 Academy of Medicine Malaysia

Targets Patient GroupTarget BP Most PatientsBP < 140/85 DiabeticsBP <130/80 (Proteinuria >1g/day BP <125/75) Clinical Practice Guidelines: Management of Hypertension (3rd Edition) 2008 Academy of Medicine Malaysia

Resistant Hypertension Consider : Compliance Drug Interactions/Excessive Sodium Intake/Alcohol Renovascular Disease Secondary Hypertension

Hypertensive Urgencies and Emergencies Usually BP > 220/120 Urgencies Asymptomatic or symptomatic Usually admit: oral treatment Emergencies: (acute LVF, dissecting aortic aneurysm, hypertensive encephalopathy, acute renal failure) Admit IV treatment: labetalol, nitrates, hydrallazine, sodium nitroprusside

Hypertension and Pregnancy Differentiate between: 1. Pregnancy-induced hypertension / pre-eclampsia. 2. Pre-existing / chronic hypertension (hypertension that is present before pregnancy or diagnosed before 20 th week of gestation or first diagnosed in pregnancy and persists beyond D42 post-partum). Suitable drugs: α-Methyldopa Labetalol Nifedipine (ACEIs are contraindicated because of foetal abnormalities and death) For pregnancy-induced hypertension, long term follow up is advised because of the higher likelihood of developing hypertension. For pre-existing hypertension, pregnancy is best planned and BP well controlled before conceiving.

“The most effective treatment prescribed by the most careful clinician will control hypertension only if the patients are motivated. Motivation improves when patients have positive experiences with, and trust in, the clinician. “ JNC VII 2003

End of lecture Thank you