By Dr Gillian Strube, Dr George Strube (auth.)
ACE inhibitors are probably the most intriguing and fascinating of modern clinical advancements. They healthy the patho-physiologica1 procedures of heart problems with attention-grabbing precision and are a continuing stimulus to the purchase of better realizing of the mechanisms concerned and of the mode of motion of the medication themselves. there's nonetheless a lot to be discovered, specially concerning the wider results of the medication, their designated mode and placement of motion and approximately alterations among the various arrangements. ACE inhibitors are of confirmed gain to sufferers with power congestive center failure and are the most recent within the sequence of substances utilized in the therapy of high blood pressure. curiosity within the therapy of high blood pressure has paralleled the improvement of hypotensive medicines and the realisation that long term analysis may be considerably greater. The remedy of high blood pressure has stepped forward in phases following the improvement of a succession of more and more potent medications, each one permitting a better share of sufferers to be taken care of with fewer and less side-effects. First, the ganglion-blocking brokers corresponding to hexamethonium and guan ethidine reworked the outlook for sufferers with malignant high blood pressure yet proved too disagreeable for regimen use in other kinds of hypertension.
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Parasympathetic contractilityt activity J. -------.. Angiotensin II Blood volume t --... " ~ z ~ § ~ tTl > (') HISfORY AND PHARMACOLOGY Angiotensin-converting enzyme (ACE) ACE is widely distributed in the body, and is found in high concentrations in the lung, kidneys, adrenals, brain and vascular and cardiac tissue. As well as promoting vasoconstriction by the formation of angiotensin II, it degrades the vasodilator bradykinin. Function of the RAA system The renin-angiotensin-aldosterone system is a sensitive physiological mechanism which helps to maintain blood pressure and blood volume.
If other causes are excluded, it is important to discover the degree of target organ damage and to identify the presence of complicating conditions. The history, examination and investigations are designed to do this. 37 ACE INHIBITORS IN HYPERTENSION Routine BP >200/120 ~ /~ <200'120 I < 140/90 > 140/90 j /oor mean = HIT' / History. T* I non-drug treatment I repeat in 6 months j follow-up Figure 4,4 Protocol for hypertension screening * depends on age 38 ~~:tin 5 mean < 140'90 ~ repeat in 1 year DIAGNOSIS AND ASSESSMENI' Conditions causing secondary hYPertension: • coarctation of the aorta (delayed femoral pulses, normal blood pressure in legs, rib notching on CXR); • renal disease (proteinuria); • Conn's syndrome (primary aldosteronism: low serum potassium); • Cushing's syndrome (appearance, raised serum sodium and cortisol); • phaeochromocytoma (very rare: intermittent symptoms, raised VMA) Conditions and factors which may complicate hypertension: • • • • • • • diabetes ischaemic heart disease peripheral vascular disease asthma stress factors smoking alcohol History This may provide clues to an underlying cause of the hypertension and forms the basis of the changes in life-style necessary for the non-drug treatment of the condition.
3 Mode of action of ACE inhibitors L",.. I Inhibition of angiotensin II production The predominant clinical effect of ACE inhibitors is inhibition of angiotensin II synthesis. The immediate hypotensive response is therefore directly related to the pre-treatment levels of angiotensin II in plasma, and hence to pre-treatment plasma renin activity (PRA). However, during long-term use, ACE inhibitors control blood pressure in patients with low, as well as high, PRA. The possible explanation for this is discussed later.