Altaz DhananiMedicines Management Pharmacist, Supplementary Prescriber

Drug Treatment of Hypertension

General points on treating Hypertension

Questions???

A modifiable risk factor

Do not view in isolation

Don’t forget lifestyle advice

Intervention 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 3-4mmHg ~30%

Salt Reduction (<6g/day)

2-3mmHg ~25% Effects diminish over time (2-3yrs)

Other: Caffeine (> 5cups/day inc BP by ~2-1mmHg, Smoking (per se) no effect on BP.

BP consistently ≥ 160/100

BP consistently ≥ 140/90 AND ◦ with existing CVD

or◦ target organ damage

or◦ raised CVD Risk of 20% or more

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)

<55 years ≥55 years or BlackStep 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-blockerConsider specialist advice

A=ACEi (ARB if intolerant), C= calcium channel blocker, D = thiazide diuretic

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

Persistent dry cough Hyperkalaemia Worsening renal failure Angiodema Hypotension (1st dose) Rash, neutropenia....

Hypersensitivity to ACEi (incl. Angiodema)

Pregnancy

Renal insufficiency

Hyperkalaemia

K+ sparing diuretics and aldosterone antagonists (spironolactone) – severe hyperkalaemia

Lithium – lithium excretion ↓ Ciclosporin - ↑ risk of hyperkalaemia K+ salts - ↑ risk of severe hyperkalaemia

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......

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

Hyperkalaemia Angiodema Symptomatic hypotension – dizziness or

light-headedness

Contra-indicationsContra-indications PregnancyHepatic impairment for some agents

Much the same as the ACEi’s

Telmisartan ↑ plasma concentration of digoxin

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.....

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

Flushing Headache Dizziness Ankle swelling

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)

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)

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

Hypokalaemia Postural hypotension Impotence Mild GI effects

Cardiac glycosides – hypokalaemia caused by diuretics increases cardiac toxicity

Ciclosporin - ↑ risk of nephrotoxicity

Lithium - ↑ plasma conc.

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!)

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

Bradycardia Shortness of breath Coldness of extremities CNS effects with lipid soluble drugs

(propranolol) Impotence

Asthma/severe COPD Marked bradycardia Severe peripheral artery disease Heart Block

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

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

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

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

1. 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

2. 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!

3. 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