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HP 200704 Pharmacological PDF
HP 200704 Pharmacological PDF
For personal use only. Not to be reproduced without permission of the editor
(permissions@pharmj.org.uk)
Hypertension
pharmacological management
By Beth Gormer, MPharm, MRPharmS
SIDNEY MOULDS/SPL
Excellence are also described
H
ypertension is a risk factor for macological treatment, as recommended by absorbed following oral administration,wide-
many coronary events. However, the British National Formulary, is sum- ly distributed and metabolised in the liver.
blood pressure can usually be marised in Panel 1 (p120). The diuretic effect of thiazides occurs
reduced with appropriate treat- Regardless of the severity of hypertension, within one to two hours of administration
ment, reducing the risk of stroke, coronary all patients should be offered lifestyle advice and continues for 1224 hours, allowing
events, heart failure and renal failure. to reduce their blood pressure.This includes once daily administration.
Many different factors are involved in the advice on smoking cessation, weight reduc- The antihypertensive effect occurs at low
pathogenesis of hypertension.These include tion, exercise, alcohol intake and diet. thiazide doses and there is no additional
increased cardiac output, increased periph- benefit to blood pressure from increasing the
eral resistance, vasoconstriction and reduced Drug classes Commonly used classes of dose, although additional diuresis can occur
vasodilation. The kidneys also play a role in antihypertensive drugs are the thiazide at higher doses.
the regulation of blood pressure by control- diuretics (eg, bendroflumethiazide), beta- The effects of thiazides on the renal tubule
ling sodium and water excretion, and the blockers (eg, propranolol, atenolol), depend on the extent of their excretion, so
secretion of renin, which influences angiotensin-converting enzyme inhibitors thiazides may be less effective in patients
vascular tone and electrolyte imbalance. (eg, captopril, enalapril), angiotensin II with renal impairment.
Neuronal mechanisms such as the sympa- antagonists (eg, candesartan, losartan), calcium
thetic nervous system and endocrine systems channel blockers (eg, amlodipine, nifedipine) Side effects Increased urinary excretion
are also involved in blood pressure regula- and alpha-blockers (eg, doxazosin). with thiazide diuretics can lead to
tion. These systems are therefore targets for Less commonly used drugs include hypokalaemia, hyponatraemia and hypo-
drug therapy to reduce blood pressure. vasodilator and centrally acting antihyper- magnesaemia. Hypercalcaemia can occur
tensives and, rarely, guanethidine, which is due to reduced excretion of calcium. Inter-
Target blood pressures The optimal indicated for the treatment of hypertensive ference with the excretion of uric acid can
systolic blood pressure (SBP) is crisis. cause hyperuricaemia, so thiazides should be
<140mmHg and the optimal diastolic used with caution in patients with gout.Thi-
blood pressure (DPB) is <85mmHg. A tar- Thiazide diuretics azide diuretics can also cause
get SBP of 130mmHg and DPB of hyperglycaemia due to impaired glucose tol-
<80mmHg should be considered for Thiazide diuretics are moderately potent erance (insulin resistance) leading to an
patients with established atherosclerotic diuretics which lower blood pressure by increased risk of non-insulin dependent dia-
cardiovascular disease, diabetes or chronic inhibiting sodium reabsorption at the begin- betes mellitus.
renal failure.1 Guidance on initiating phar- ning of the distal convoluted tubule in the Other less common side effects include
kidney, increasing sodium excretion and hyperlipidaemia, causing increases in low
urine volume. Thiazides also have a direct density lipoprotein and triglycerides and a
Beth Gormer is cardiology pharmacist at the
Royal Sussex County Hospital, Brighton
vasodilatory effect on arterioles, sustaining reduction in high density lipoprotein
the antihypertensive effect. They are well (HDL). Up to 25 per cent of men treated
A C or D
A + C or A + D
A+C+D
Add
Further diuretic therapy
or
Alpha-blocker
or
Beta-blocker
Consider seeking specialist advice
H O S P I TA L P H A R M AC I S T APRIL 2007 VO L . 1 4
review, the evidence base for the use of beta- function in patients with unilateral renal References
blockers in the treatment of hypertension artery stenosis. A dihydropyridine calcium
was much weaker than for the other drug channel blocker can be added if further 1. British National Formulary (52). London: British
classes. It was concluded that, in the absence blood pressure lowering is required, but thi- Medical Association and Royal Pharmaceutical
of other compelling indications for a beta- azide diuretics may be ineffective. Society of Great Britain;2006.
blocker (eg, angina), they should not be 2. National Institute for Health and Clinical
recommended as an initial treatment for Systolic hypertension Isolated systolic Excellence. Hypertension. Management of
hypertension. hypertension (ISH) is defined as an SBP of hypertension in adults in primary care.
Beta-blockers were also found to be less greater than 160mmHg with a DBP less London:NICE;2006.
effective than ACE inhibitors or dihydropy- than 90mmHg. Patients with ISH should be 3. Dahlof B, Sever PS, Poulter N, Wedel H, Beevers
ridine calcium channel blockers in reducing offered the same treatment as patients with DG, Caulfield M. Prevention of cardiovascular
the risk of diabetes, especially in patients raised SBP and raised DBP, because ISH car- events with an antihypertensive regimen of
already taking a thiazide diuretic. If a patient ries the same risk of complications.2 amlodipine adding perindopril as required versus
taking beta-blockers requires a second drug, The dihydropyridine calcium channel atenolol adding bendroflumethiazide as required,
an ACE inhibitor or calcium channel block- blockers have been used in the treatment of in the Anglo-Scandinavian Cardiac Outcomes
er should be added, rather than a thiazide. isolated systolic hypertension in the elderly, Trial-Blood Pressure Lowering Arm (ASCOT-BPLA):
especially where a thiazide diuretic is con- a multicentre randomised controlled trial. Lancet
Special considerations traindicated. 2005;366:895906.
4. The National Collaborating Centre for Chronic
Pregnancy Centrally acting agents have a Accelerated hypertension Accelerated or Conditions.Hypertension. Management of
poor CNS profile. However, methyldopa is very severe hypertension, defined as a DBP hypertension in adults in primary care: partial
used in pregnancy, due to its long-term safe- of greater than 140mmHg, requires urgent update. London;Royal College of Physcians:2006.
ty data and beta-blockers are used in the medical attention. Beta-blockers such as 5. Wright JT, Dunn JK, Cutler JA, Davis BR, Cushman
third trimester. Intravenous labetolol is atenolol or labetolol or the dihydropyridine WC, Ford CE. Outcomes in hypertensive black and
reserved for use in pregnancy in a hyperten- calcium channel blockers are indicated for nonblack patients treated with chlorthalidone,
sive crisis. A controlled release formulation this condition. DBP should be reduced to amlodipine and lisinopril. JAMA
of nifedipine has also been used in pregnan- 100110mmHg during the first 24 hours. 2005;293:15951608.
cy but is unlicensed. Blood pressure should be reduced further 6. Dahlof B, Devereux RB, Kjeldsen SE, Julius S,
over the next two to three days using a com- Beevers G, Faire U et al. Cardiovascular morbidity
Ethnic group Thiazide diuretics and the bination of diuretics, vasodilators and ACE and mortality in the Losartan Intervention For
dihydropyridine calcium channel blockers inhibitors, if required. Endpoint reduction in hypertension study (LIFE): a
are more effective than beta-blockers in If intravenous treatment is required then randomised controlled trial against atenolol.
Afro-Caribbean patients. ACE inhibitors sodium nitroprusside or glyceryl trinitrate is Lancet 2002;359:9951003.
and angiotensin II antagonists have been recommended.
shown to increase the risk of stroke in this Further reading
group of patients and are therefore not rec- The cardiology pharmacist
ommended as first line therapy.5,6 i. Yui Y, Sumiyoshi T, Kodama K, Hirayama A, Nonogi
As a member of the multidisciplinary team, H, Kanmatsuse K et al. Comparison of nifedipine
Elderly The new NICE guidance states that the pharmacist has an important role to play retard with angiotensin converting enzyme
thiazide diuretics or dihydropyridine calci- in the treatment of hypertension. inhibitors in Japanese hypertensive patients with
um channel blockers should be the first line To aid concordance or ensure compliance coronary artery disease: the Japan Multicenter
therapy in elderly people.2 However, atten- with a medication regimen the pharmacist Investigation for Cardiovascular Diseases-B (JMIC-
tion should be paid to renal function during can give information about the benefits and B) randomized trial. Hypertension Research
treatment with a thiazide because the elderly side effects of drugs so that patients can 2004;27:44956.
are more at risk of renal impairment. make an informed decision about their ii. Julius S, Kjeldsen SE, Weber M, Brunner HR,
Patients over 80 years old should be offered treatment. This information should include Ekman S, Hansson L et al. Outcomes in
the same treatment as patients aged over 55 why the medicine is needed and the risks of hypertensive patients at high cardiovascular risk
years. not taking it. Practical points, such as ensur- treated with regimens based on valsartan or
ing that the medicine is prescribed once amlodipine: the VALUE randomised trial. Lancet
Diabetes Patients with diabetes may require daily if possible, may also improve 2004;363:202231.
a combination of antihypertensive drugs to adherence.
achieve their optimal target blood pressure. Other medicines that a patient is taking
ACE inhibitors are the initial treatment of should also be reviewed. Concurrent non-
choice because they can delay the progres- steroidal anti-inflammatory drugs, the oral
sion of microalbuminuria to nephropathy. contraceptive pill, glucocorticoids, and sym-
Patients with diabetic nephropathy should pathomimetics can all increase blood
be treated with an ACE inhibitor or an pressure. These medicines, some of which
angiotensin II receptor antagonist to min- can be bought over the counter, should be
imise the risk of further renal deterioration, avoided in patients with high blood
even if their blood pressure is normal. pressure.
It is important to remember that a patient
Renal disease ACE inhibitors can reduce may have additional co-morbidities. The
or abolish glomerular filtration and can pharmacist can advise and review co-
cause severe and progressive renal failure. existing disease states to ensure the most
They are therefore contraindicated in appropriate therapy choice is made.
patients with bilateral renal artery stenosis. To help reduce costs, pharmacists can also
However, ACE inhibitors are unlikely to ensure that non-proprietary drugs are pre-
have an adverse effect on overall renal scribed when appropriate.