20 Hypertension Learning objectives: • To understand regulation of blood pressure and • To understand management goals significance of hypertension • To appreciate use of drug therapy, patient • To familiarise oneself with blood pressure monitoring and follow-up required monitoring • To identify principles of drug therapy in • To identify drugs used in hypertension and hypertensive emergency. appreciate their characteristics • To review current guidelines for the management of hypertension Background • drug-induced factors (e.g. oral contraceptives, corticosteroids). Hypertension is a chronic condition characterised by a sustained diastolic reading greater than or equal to 80 mmHg and a systolic reading greater than or Regulation of blood pressure equal to 120 mmHg (120/80 mmHg). Occurrence can damage blood vessels and increase probability of • Peripheral vascular resistance (depends on development of atheromatous disease. Treatment is arteriolar volume) aimed to decrease morbidity and mortality. • Cardiac output (depends on heart rate, Factors implicated in primary hypertension contractility, filling pressure, blood volume) include: • Blood pressure ϭ cardiac output ϫ peripheral vascular resistance. • age • genetics • environment Sympathetic nervous system • weight Baroreceptors present in the aorta and carotid sinus: • race. Causes of secondary hypertension include: • increase cardiac output • increase peripheral resistance. • renal disease • pregnancy The renin–angiotensin–aldosterone system is shown • hormonal factors in Figure 20.1. Sample chapter from Lecture Notes in Pharmacy Practice 108 | Lecture Notes in Pharmacy Practice Renin–angiotensin–aldosterone system Vasoconstriction Angiotensinogen from liver Renin from kidney Aldosterone from Sodium adrenal cortex retention Angiotensin I Angiotensin II Sodium retention in kidney Figure 20.1 Renin–angiotensin–aldosterone system. Risk factors Occurrence of hypertension may exacerbate: • Family history • Age • atherosclerosis • Obesity • coronary artery disease • Smoking • congestive heart failure • Lifestyle: stress, sedentary, diet • diabetes mellitus • Diabetes mellitus • insulin resistance • Hyperlipidaemia. • stroke • renal disease • retinal disease. Target organ damage due to hypertension Blood pressure measurement • Cardiovascular: constriction of arterioles and insufficient blood flow to coronary vasculature Using a sphygmomanometer (see also leads to angina, myocardial infarction; left Chapter 11) ventricular hypertrophy may occur due to increased cardiac output leading to heart • Patient should be relaxed, sitting down with arm failure. at about the level of the heart; check pressure in • Renal: arteriolar nephrosclerosis leads to both arms. polyuria, nocturia, protein and red blood cells in • Three consecutive elevated readings taken on urine, elevated serum creatinine, renal three separate occasions should be documented insufficiency. before the diagnosis of ‘hypertension’ is applied • Cerebral: decreased blood flow and decreased to a patient. oxygen supply lead to transient ischaemic • Interpretation of results: systolic reading is more attacks, cerebral thromboses, haemorrhage. important than diastolic reading; patient history • Retinal: damage to arterioles of retina leads to and family history are taken into consideration haemorrhage, visual disturbances. when deciding on line of action. Sample chapter from Lecture Notes in Pharmacy Practice Hypertension | 109 Management goals When to refer European Guidelines for the management of • • High blood pressure (more than hypertension were issued in June 2007 by the 180/110 mmHg with signs of European Society of Hypertension jointly with papilloedema and/or retinal haemorrhage) the European Society of Cardiology.1 • Suspected phaeochromocytoma (signs Overall goal to achieve blood pressure (BP) of • include labile or postural hypotension, 140/90 mmHg. headache, palpitations, pallor and Goal takes into consideration comorbidities • diaphoresis) (e.g. in diabetes the goal is to achieve • Unusual signs and symptoms or 130/80 mmHg). symptoms that suggest a secondary cause Pharmacotherapy should consider the five • of high blood pressure. important drug classes: ACE inhibitors, angiotensin receptor antagonists, beta-blockers, calcium channel blockers and diuretics. Management of hypertension • Choice of drug therapy should depend on: – comorbidities (e.g. diabetes mellitus – ACE • Confirm diagnosis through repeated blood inhibitors or angiotensin receptor antagonists; pressure measurement metabolic syndrome – angiotensin-converting • Patient assessment for underlying cause(s) and enzyme (ACE) inhibitors, angiotensin receptor comorbidities antagonists, calcium antagonists) • Assess occurrence of target organ damage – history of clinical events (e.g. myocardial • Review treatment options infarction – beta-blockers, ACE inhibitors, • Establish treatment goals angiotensin receptor antagonists; angina • Identify and manage other risk factors (e.g. pectoris – beta-blockers, calcium channel hyperlipidaemia) blockers (avoiding short-acting • Patient follow-up. dihydropyridines); heart failure – diuretics, beta-blockers (particularly carvedilol), Reviewing treatment options ACE inhibitors, angiotensin receptor antagonists) • Pharmacotherapy or non-pharmacological – organ damage (e.g. renal dysfunction – ACE measures only? inhibitors, angiotensin receptor antagonists; • Which drug(s)? left ventricular hypertrophy – ACE inhibitors, Diagnosis and management of hypertension are shown angiotensin receptor antagonists, calcium in Figure 20.2. channel blockers). • Regardless of which drug therapy is used, monotherapy achieves blood pressure goal Cardiovascular risk assessment in only a limited number of patients. Majority of • Urine test for proteinuria and albuminuria patients require multiple drug therapy. • Blood tests: glucose, electrolytes, creatinine, • Lifestyle measures are relevant for all serum total cholesterol and high-density patients: smoking cessation, weight reduction lipoprotein (HDL) cholesterol and maintenance, reduction of excessive • ECG. alcohol intake, physical exercise, reduction of salt intake, increased fruit and vegetable Lifestyle changes intake, decreased saturated and total fat intake. • Weight reduction • Exercise Sample chapter from Lecture Notes in Pharmacy Practice 110 | Lecture Notes in Pharmacy Practice Diagnosis of hypertension Medical history Physical exam, diagnostic tests High blood pressure and identified cardiovascular risk/comorbidities Modify lifestyle Pharmacotherapy Patient monitoring Continuing treatment Figure 20.2 Diagnosis and management of hypertension. • Diet (low-salt diet) blood pressure. (Note use of ambulatory blood • Smoking cessation pressure monitors to detect variation of blood • Alcohol restriction. pressure control.) See Figure 20.3 for decision-making in management Factors influencing choice of drug of hypertension. • Contraindications to drug • Presence of target organ damage, renal disease, Potential indications for the use of diabetes or cardiovascular disease • Other coexisting disorders ambulatory blood pressure • Interactions with drugs used for other conditions monitor by the patient • Age • Unusual blood pressure variability • Occupation • White coat hypertension • Lifestyle. • Evaluation of nocturnal or drug-resistant hypertension Determining efficacy of treatment over 24 hours Use of antihypertensive drugs • • Diagnoses and treatment of hypertension in • Initiate drug therapy at a low dose pregnancy. • Consider multiple drug therapy • Change to different class of drugs if drug is not producing effect on blood pressure levels or if Drug therapy side-effects are a significant problem • Use formulations that provide a 24-hour control: • Diuretics: reduce blood volume better adherence and ensure control of blood • Sympatholytics: reduce ability of sympathetic pressure in early morning when there is surge of system to raise blood pressure Sample chapter from Lecture Notes in Pharmacy Practice Hypertension | 111 Overall cardiovascular Decision about drug therapy risk of the patient Examples c alculation of risk Computer programs/algorithms, e.g. Coronary Risk Prediction Charts Family history, (British Hypertension Society)a other conditions Figure 20.3 Decision-making in management of hypertension. aTo be found in the BNF.2 • Calcium channel blockers: reduce peripheral • Act in the distal convoluted tubule resistance • Are weak diuretics and in fact may be found in • ACE inhibitors, angiotensin II antagonists: combination products with thiazides. reduce peripheral resistance Table 20.1 Comparison of bendroflumethiazide Diuretics and indapamide Create a negative sodium balance resulting in a • Bendroflumethiazide Indapamide reduction of blood volume • Thiazides (e.g. bendroflumethiazide, indapamide) Half-life (hours) 3–4 14 Loop diuretics (e.g. furosemide) are used mainly • Duration of effect 6–12 24–36 in pulmonary oedema due to ventricular failure, (hours) chronic heart failure (see also Chapter 22). a • Potassium-sparing diuretics (e.g. amiloride Dose (mg) 2.5 2.5 ( hydrochlorthiazide), spironolactone) aTo be administered in the morning to reduce nocturnal need for • Caution: hypokalaemia. urination. Thiazide diuretics O • Reduce sodium and water retention in the distal O O O S S H convoluted tubule in the kidney resulting in a N H2N reduction of the peripheral resistance F C N Cause loss of potassium and magnesium salts 3 • Bendroflumethiazide • Potassium supplementation