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
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

4. 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.

5. 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

6. 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

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
- 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

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....
Bradykinin build up: 5-10% affected
Hyperkaleamia - arrythmias

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)
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

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

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