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

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

Hypertension – Key Points A modifiable risk factor Do not view in isolation Don’t forget lifestyle advice CVD – 30% of all deaths; 4 mill bed days/annum Major modifiable RF Statins, Aspirin – based on CVD risk or pts h/o CVD Estimating CVD risk – JBS Lifestyle Advice – to all pts on ongoing basis; support & guidance to amke approp changes Healthier lifestyle may reduce or delay - even remove the need for long term drug therapy in some

Effect for Lifestyle Interventions Avg reduction in SBP & DBP % with 10mmHg reduction in SBP (<1 year) Other Comments (from NICE 2006) Diet (Healthy, Low calorie) 5-6mmHg ~40% Avg wt changes 2-9Kg Exercise (Aerobic, 30-60mins, 3-5x/week) 2-3mmHg ~30% Relaxation Therapy (Structured) 3-4mmHg ~33% Cost & availability to PCO unknown Multiple Interventions 4-5mmHg ~25% Education alone unlikely to be effective Alcohol Reduction Salt Reduction (<6g/day) Effects diminish over time (2-3yrs) Other: Caffeine (> 5cups/day inc BP by ~2-1mmHg, Smoking (per se) no effect on BP.

When to treat BP consistently ≥ 160/100 BP consistently ≥ 140/90 AND with existing CVD or target organ damage raised CVD Risk of 20% or more These thresholds consider overall CVD risk in addition to the absolute BP level

Targets 140/80 for type 2 diabetics 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) 140/90 – non-diabetics – (note old BP targets for BHS) Lower targets for diabetics Evidence base for optimal BP incomplete – primarily base on HOT study and UKPDS in pts with diabetes

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 - updated NICE guidance on HT treatment Recomm based following systematic review of RCT AND a health economic analysis Limitations & uncertainties of the available evidence so many recommendations based on pathophysiological groungs and expert concensus Explain algorithm CCB’s and thiazides 1st line for afro/caribbean descent (not mixed race) Ace’is for pts < 55 yrs - arb if intolerance Compare with old BHS guidelines and NICE guidelines Step 2 explanation – add drugs in a sequential manner; May get some pts responding better to switch in drug class – NOT recommended by NICE Treatment algo for pts with HT ONLY – not diabetics. A=ACEi (ARB if intolerant), C= calcium channel blocker, D = thiazide diuretic

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

ACEi’s

ACEi’s – Adverse Effects Persistent dry cough Hyperkalaemia Worsening renal failure Angiodema Hypotension (1st dose) Rash, neutropenia.... Bradykinin build up: 5-10% affected Hyperkaleamia - arrythmias

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

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

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......

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

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

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

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.....

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

CCB’s

CCB’s – Adverse Effects Flushing Headache Dizziness Ankle swelling

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)

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) Concerns prior to 2000 ASCTO, ALLHAT and others alleviated these concerns; incidence of death or CV events were fewer or no different to other classes of drugs Standard relese forms assoc with large variations in BP

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

Diuretics

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

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

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!)

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

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

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

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

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

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 More than one drug – ALLHAT 40-60% controlled on one drug

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

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