Hypertension-An Overview

INTRODUCTION:

Systemic arterial hypertension is one of the strongest known modifiable risk factors for ischaemic heart disease, stroke, renal failure and heart failure. It remains poorly treated. As an asymptomatic disorder, people are understandably reluctant to accept adverse drug effects in addition to the inconvenience of long-term treatment. In this regard, modern drugs represent an enormous improvement.

PATHOPHYSIOLOGY AND SITES OF DRUG ACTION

Hypertension is occasionally secondary to some distinct disease. However, most patients with persistent arterial hypertension have essential hypertension. Arterial blood pressure is determined by cardiac output, peripheral vascular resistance and large artery compliance. Peripheral vascular resistance is determined by the diameter of resistance vessels (small muscular arteries and arterioles) in the various tissues. One or more of a ‘mosaic’ of interconnected predisposing factors (including positive family history, obesity and physical inactivity among others) are commonly present in patients with essential hypertension, some of which are amenable to changes in diet and other habits. The importance of intrauterine factors (the ‘Barker hypothesis’) is supported by the finding that hypertension in adult life is strongly associated with low birth weight.

Cardiac output may be increased in children or young adults during the earliest stages of essential hypertension, but by the time hypertension is established in middle life the predominant haemodynamic abnormality is an elevated peripheral vascular resistance. With ageing, elastic fibres in the aorta and conduit arteries are replaced by less compliant collagen causing arterial stiffening and systolic hypertension, which is common in the elderly. The kidney plays a key role in the control of blood pressure and in the pathogenesis of hypertension. Excretion of salt and water controls intravascular volume. Secretion of renin influences vascular tone and electrolyte balance via activation of the renin–angiotensin–aldosterone system. Renal disease (vascular, parenchymal or obstructive) is a cause of arterial hypertension.

Conversely, severe hypertension causes glomerular sclerosis, manifested clinically by proteinuria and reduced glomerular filtration, leading to a vicious circle of worsening blood pressure and progressive renal impairment. Renal cross-transplantation experiments in several animal models of hypertension, as well as observations following therapeutic renal transplantation in humans, both point to the importance of the kidney in the pathogenesis of hypertension. The sympathetic nervous system is also important in the control of blood pressure, providing background α receptor mediated vasoconstrictor tone and β receptor-mediated cardiac stimulation. Sympathetic activity varies rapidly to adjust for changes in cardiovascular demand with alterations in posture and physical activity. It is also activated by emotional states such as anxiety, and this can result in ‘white-coat’ hypertension. A vasoconstrictor peptide, endothelin, released by the endothelium contributes to vasoconstrictor tone. Conversely, endothelium-derived nitric oxide provides background active vasodilator tone. Cardiovascular drugs work by augmenting or inhibiting these processes. The main such drugs for treating hypertension can usefully be grouped as:

1. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin AT1 receptor antagonists (sartans);
2. Beta-adrenoceptor antagonists
3. Calcium channel antagonists
4. Diuretics.

Each of these classes of drug reduces clinical end-points such as stroke, but in uncomplicated hypertension B drugs may be less effective than other classes. Other antihypertensive drugs useful in specific circumstances include α-adrenoceptor antagonists, aldosterone antagonists and centrally acting antihypertensive drugs.

GENERAL PRINCIPLES OF MANAGING ESSENTIAL HYPERTENSION

Consider blood pressure in the context of other risk factors: use cardiovascular risk to make decisions about whether to start drug treatment and what target to aim for:

1.  Use non-drug measures (e.g. salt restriction) in addition to drugs. Explain goals of treatment and agree a plan the patient is comfortable to live with (concordance).
2.  Review the possibility of co-existing disease (e.g. gout, angina) that would influence the choice of drug.
3. Use a low dose and, except in emergency situations, titrate this upward gradually.
4. Addition of a second drug is often needed. A drug of the other group is added, i.e. an A drug is added to patients started on a C or D drug, a C or D drug is added to a patient started on an A drug. A third or fourth drug may be needed. It is better to use such combinations than to use very high doses of single drugs: this seldom works and often causes adverse effects. 
5.  Loss of control – if blood pressure control, having been well established, is lost, there are several possibilities to be considered:
6. non-adherence;
7. drug interaction – e.g. with non-steroidal anti-inflammatory drugs (NSAIDs)
8. inter-current disease – e.g. renal impairment, atheromatous renal artery stenosis

Drugs used to treat Hypertension:

1. Angiotensin converting enzyme inhibitors.

Examples: Ramipril, Trandolapril, Enalapril, Lisinopril, Captopril

2. Angiotensin Receptor Blockers.

Examples: Losartan, Candesartan, Irbesartan, Valsartan

3. β-Adrenoreceptor  Antagonists.

Examples: Propranolol, Atenolol, Metoprolol, Esmlol, Sotalol, Labetalol, Oxprenolol

4, Calcium Channel Blockers.

Examples: Nefidipine, Amlodipine

5. Diuretics.

Examples: Thiazide Diuretics