The Pharmacological Management of Hypertension

1. The Pharmacological Management of Hypertension Altaz Dhanani Medicines Management Pharmacist, Supplementary Prescriber

2. What's Covered • Drug Treatment of Hypertension • General points on treating Hypertension • Questions???

3. Hypertension – Key Points • A modifiable risk factor • Do not view in isolation • Don’t forget lifestyle advice

4. Effect for Lifestyle Interventions

5. When to treat • BP consistently ≥ 160/100 • BP consistently ≥ 140/90 AND • with existing CVD or • target organ damage or • raised CVD Risk of 20% or more

6. Targets NICE • 140/90 • 140/80 for type 2 diabetics • 135/75 for type 2 diabetics with microalbuminuria or proteinuria • 135/85 for type 1 diabetics (130/80 with nephropathy)

7. Drug Treatment <55 years ≥55 years or Black Step 1 A C or D Step 2 A + C or A + D Step 3 A + C + D Step 4 A + C + D + Further diuretic therapy or α-blocker or β-blocker Consider specialist advice A=ACEi (ARB if intolerant), C= calcium channel blocker, D = thiazide diuretic

8. ACEi’s • Ramipril, lisinopril, perindopril and others • Works by manipulating the renin-angiotensin system • Renin to angiotensin to angiotensin 2 via angiotensin converting enzymes • Angiotensin 2 = potent vasoconstrictor Hence • ACEi’s inhibit the action of the angiotensin converting enzymes and prevent the conversion of angiotensin to angiotensin 2

9. ACEi’s

10. ACEi’s – Adverse Effects • Persistent dry cough • Hyperkalaemia • Worsening renal failure • Angiodema • Hypotension (1st dose) • Rash, neutropenia....

11. ACEi’s – Contra-indications • Hypersensitivity to ACEi (incl. Angiodema) • Pregnancy • Renal insufficiency • Hyperkalaemia

12. ACEi’s – Drug Interactions • K+ sparing diuretics and aldosterone antagonists (spironolactone) – severe hyperkalaemia • Lithium – lithium excretion ↓ • Ciclosporin - ↑ risk of hyperkalaemia • K+ salts - ↑ risk of severe hyperkalaemia

13. ACEi’s – Points to Note • Generally recommended for people < 55 yrs and Caucasian • In diabetes, ACEi’s are an appropriate 1st line choice • Caution when initiating, 1st dose hypotension esp. with pts on concomitant diuretic therapy first dose at night • Monitor U&E’s before initiation and regular monitoring during treatment • Preferred Rx’ing drugs......

14. ARB’s (or A2RA’s or ATII’s) • Losartan, Valsartan, Irbesartan etc • Effects similar to ACEi’s • Works by blocking angiotensin 2 (potent vasoconstrictor) from entering receptors in the smooth muscles of blood vessels • Primarily SHOULD only be considered where an ACEi is indicated but not tolerated

15. ARB’s – Adverse Effects • Hyperkalaemia • Angiodema • Symptomatic hypotension – dizziness or light-headedness Contra-indications • Pregnancy • Hepatic impairment for some agents

16. ARB’s – Drug Interactions • Much the same as the ACEi’s • Telmisartan ↑ plasma concentration of digoxin

17. ARB’s – Points to Note • SHOULD only used where an ACEi is indicated but not tolerated • NO compelling evidence to suggest they offer any clinical advantage over ACEi’s • No compelling evidence that there are differences between individual agents • Considerably more costly than ACEi’s • Monitoring as per ACEi’s • Preferred Rx’ing drugs.....

18. Calcium Channel Blockers • Amlodipine, Felodipine, Nifedipine etc • Can be split into 2 groups dependant on their properties: • Dihydropyridines (e.g. amlodipine) • Non-dihydropyridines (diltiazem, verapamil) • Dihydropyridines potent vaso-dilators, relax the vascular smoothe muscle and dilates the arteries

19. CCB’s

20. CCB’s – Adverse Effects • Flushing • Headache • Dizziness • Ankle swelling

21. CCB’s – Drug interactions • Theophylline - ↑ plasma conc of theophylline • Ciclosporin – plasma conc ↑ • Digoxin – plasma conc ↑ • Antifungals - ↑ plasma conc of dihydropyridines • Grapefruit Juice - ↑ plasma conc of dihydropyridines (though not as significant an interaction as with simvastatin)

22. CCB’s – Points to Note • Equal 1st line choice with thiazide diuretics for pts ≥ 55yrs or pts who are of African or Caribbean descent • What about previous concerns over CCB’s re: that CCB’s increase risk of CV events independent of their BP lowering effect? • Immediate release formulations should be avoided (e.g. Non m/r nifedipine) • m/r formulations should be Rx’ed by brand name (nifedipine and diltiazem versions)

23. Thiazide Diuretics • Bendroflumethiazide, Indapamide e.t.c. • Stop the resorption of sodium hence promoting its excretion leading to more urine being produced. Flushes excess fluids and minerals from the body • Act within 1-2 hours of administration and generally have a duration of action of 12-24 hours

24. Diuretics

25. Diuretics – ADR’s • Hypokalaemia • Postural hypotension • Impotence • Mild GI effects

26. Diuretics – Drug Interactions • Cardiac glycosides – hypokalaemia caused by diuretics increases cardiac toxicity • Ciclosporin - ↑ risk of nephrotoxicity • Lithium - ↑ plasma conc.

27. Diuretics – Points to Note • Considered as equal first line choice with CCB’s for black pts or aged 55 yrs and over • Due to low acquisition costs of these drugs, may be used preferentially over CCB’s • Low doses of thiazides produce maximal or near-maximal BP lowering with little biochemical disturbance (higher doses confer little advantage in BP control but disturbs plasma concs of K+, Na+, uric acid, glucose and lipids!)

28. Beta-Blockers • Atenolol, metoprolol e.t.c. • Not exactly known how they work in hypertension – but they ↓ cardiac output, and block the action of stress hormones that constrict the blood vessels in the heart, brain and body

29. BB’s – ADR’s • Bradycardia • Shortness of breath • Coldness of extremities • CNS effects with lipid soluble drugs (propranolol) • Impotence

30. BB’s – Contra-Indications • Asthma/severe COPD • Marked bradycardia • Severe peripheral artery disease • Heart Block

31. BB’s – place in Therapy • No longer recommended first line treatment • BUT they are an option for: • Younger patients with C/I’s for ACEi’s or ARB’s • Women of child bearing potential • Pts with compelling indications for their use (e.g. ischaemic heart disease) • Best avoided in combination with thiazide diuretics

32. Those that are already receiving a BB NICE • If BP controlled....no absolute need to replace the BB with an alternative • If BP not controlled, revise treatment according to treatment algorithm • When a BB is withdrawn, step the dose down gradually • Do not withdraw if there are compelling indications for being treated with one

33. Hypertension – Points to Note • NICE guidance on drug treatment NOT based on large clinical outcome studies – based on sound pathophysiological grounds and expert opinion • Do not forget lifestyle advice – to be offered on an ongoing basis • If drug intervention is needed, follow NICE algorithm unless there are compelling indications to do otherwise • Most patients will need more than 1 drug to control BP?? • Β-Blockers do have a role in hypertensive therapy, but in limited circumstances

34. Hypertension – Points to Note 2 • Remember treatment targets – but bear in mind it won’t be possible for all pts to achieve • Any lowering of BP is beneficial – esp. those at highest baseline CVD risk • Account for patients’ tolerability and concordance when reviewing treatment response • All patients should have at least an annual review of care

35. 3 Steps to Hypertension Heaven - NPC • Does the pt really need drug therapy • Check your measuring technique • Measure several readings over a period of time • Review all potential drug causes and try non-drug therapies first (unless BP really high) • Attend to other risk factors – smoking, lipids etc • If treatment is necessary, getting the pressure down is more important than worrying too much about which drug to use • Thiazides are first choice for most people, CCB’s probably less so, doxazosin (α-blocker) first choice for almost no one! • Treat the patient, not the blood pressure • A drug that is not taken will not work and is the most expensive medication • Potential benefits of aggressive therapy with multiple drugs must be weighed against the acceptability to the patient of such therapy