Drugs used to treat hypertension

1. Drugs used to treat hypertension 2006

2. Hypertension • risk factor for: ischemic heart disease, stroke, renal failure and heart failure Classification of BP • Category • Normal • High normal • Hypertension • Stage 1 • Stage 2 • Stage 3 • Stage 4 • Systolic Diastolic • <130 <85 • <139 <89 • 140-159 90-99 • 160-179 100-109 • 180-209 110-119 • >210 >120

3. Arterial blood pressure (BP) is determined by cardiac output (MV) and peripheral vascular resistance (PR). BP = CO x PR Peripheral resistance is determined by the caliber and total cross-sectional area of the resistance vessels (small arteries and arterioles) in the various tissues. - Influence of predisposing factors Cardiac output may be increased in children or young adults during the earliest stages of essential hypertension

4. Hypertension • Essential (primary) • - most (90-95 %) patients with persistent arterial hypertension • genesis of hypertension unknown • predisposing factors: • Secondary • is secondary to some • distinct disease: • Renal + renovascular desease • (artery stenosis) • Hormonal defects • (Cushing´s syndrome, • phaeochromocytoma) • Mechanical defect • (coarctation of aorta) • Hypertension in pregnancy • Drug-induced hypertension • (sympatomimetics, • glucocorticoids) • Neurologic desease susceptive (obesity, stress, salt intake, lack of Mg2+, K+, Ca2+, ethanol  dose, smoking) non-susceptive (positive family history, insulin resistance, age, sex, defect of local vasomotoric regualtion)

5. Baroreceptors • - they are responsible for rapid adjustment in blood pressure • Kidney • - plays a key role in long-term control of blood pressure and in • the pathogenesis of hypertension • - excretion of salt and water controls intravascular volume, • which influences the force of contraction of the heart by the • Starling mechanism • - secretion of renin (1/3 of patients) increases production of angiotensin II causes direct constriction of resistance vessels and stimulation of aldosterone synthesis in the adrenal cortex  increases renal sodium absorption and intravascular volume • - renal disease (vascular, parenchymal or obstructive) is a • cause of arterial hypertension

6. Non-renal mechanisms –neuronal mechanisms sympathetic nervous system(continual background of vasoconstrictor tone), and – endocrine and autocrine/paracrine mechanisms (NO vs, endothelin) Clinically important consequences of hypertension („end organ damage“) include damage both to large and small blood vessels as well as left-ventricular hypertrophy (increased arterial pressure causes an increased risk of arterial rupture and bleeding from a weak spot in the arterial wall) !

7. THERAPY OF HYPERTENSION Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society 2004—BHS IV. J Hum Hypertens 2004; 18: 139–85.* • Non-pharmacological - lifestyle • - decrease of salt intake • - reduction of body weight • - restriction of smoking and drinking excessive amounts of alcohol • - regular physical activity and relaxation, lack of stress • - increased intake of Mg2+, K+, Ca2+ - fruit, vegetables *BNF 51th edition, 2006

8. The following thresholds for treatment are recommended: Accelerated (malignant) hypertension (with papilloedema or fundal haemorrhages and exudates) or acute cardiovascular complications, admit for immediate treatment; Where the initial blood pressure is systolic ≥ 220 mmHg or diastolic ≥ 120 mmHg, treat immediately; Where the initial blood pressure is systolic 180–219 mmHg or diastolic 110–119 mmHg, confirm over 1–2 weeks then treat if these values are sustained; Where the initial blood pressure is systolic 160–179 mmHg or diastolic 100–109 mmHg,and the patient has cardiovascular complications, target-organ damage (e.g. left ventricular hypertrophy, renal impairment) or diabetes mellitus (type 1 or 2), confirm over 3–4 weeks then treat if these values are sustained; Where the initial blood pressure is systolic 160–179 mmHg or diastolic 100–109 mmHg, but the patient has no cardiovascular complications, no target-organ damage, or no diabetes, advise lifestyle changes, reassess weekly initially and treat if these values are sustained on repeat measurements over 4–12 weeks; *BNF 51th edition, 2006

9. Where the initial blood pressure is systolic 140–159 mmHg or diastolic 90–99 mmHg and the patient has cardiovascular complications, target-organ damage or diabetes, confirm within 12 weeks and treat if these values are sustained; • Where the initial blood pressure is systolic 140–159 mmHg or diastolic 90–99 mmHg and no cardiovascular complications, no target-organ damage, or no diabetes, advise lifestyle changes and reassess monthly; treat persistent mild hypertension if the 10-year cardiovascular disease risk is ≥ 20%. • An optimal target systolic blood pressure < 140 mmHg and diastolic blood pressure < 85 mmHg is suggested. • In some individuals it may not be possible to reduce blood pressure below the suggested targets despite the use of appropriate therapy. *BNF 51th edition, 2006

10. Drug treatment of hypertension No consistent or important differences have been found between the major classes of antihypertensive drugs in terms of antihypertensive efficacy, side-effects or changes to quality of life. The choice of antihypertensive drug will depend on the relevant indications or contra-indications for the individual patient: 1. Diuretics 2. Drugs influencing sympathetic nerves 3. Vasodilators 4. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 receptor *BNF 51th edition, 2006

11. Thiazides — particularly indicated for hypertension in the elderly; a contra-indication is gout; Beta-blockers — indications include myocardial infarction, angina; compelling contra-indications include asthma, heart block; ACE inhibitors — indications include heart failure, left ventricular dysfunction and diabetic nephropathy; contra-indications include renovascular disease and pregnancy; when thiazides and beta-blockers are contra-indicated, not tolerated, or fail to control blood pressure Angiotensin-II receptor antagonists are alternatives for those who cannot tolerate ACE inhibitors because of persistent dry cough, but they have the same contra-indications as ACE inhibitors; Calcium-channel blockers. a) Dihydropyridine calcium-channel blockers are valuable in isolated systolic hypertension in the elderly when a low-dose thiazide is contra-indicated or not tolerated. b) ‘Rate-limiting’ calcium-channel blockers (e.g. diltiazem, verapamil) may be valuable in angina; contra-indications include heart failure and heart block; Alpha-blockers — a possible indication is prostatism; a contra-indication is urinary incontinence. *BNF 51th edition, 2006

12. A single antihypertensive drug is often not adequate and other antihypertensive drugs are usually added in a step-wise manner until control is achieved. Unless it is necessary to lower the blood pressure urgently, an interval of at least 4 weeks should be allowed to determine response. Where two antihypertensive drugs are needed → 1.an ACE inhibitor or an angiotensin-II receptor antagonist or a beta-blocker may be combined with → 2.either a thiazide or a calcium-channel blocker. If control is inadequate with 2 drugs, a thiazide and a calcium-channel blocker may be added. In patients at high risk of diabetes it is best to avoid a combination of a beta-blocker and a thiazide. In patients with primary hyperaldosteronism, spironolactone is effective. Response to drug treatment for hypertension may be affected by the patient’s age and ethnic background. A beta-blocker or an ACE inhibitor may be the most appropriate initial drug in younger Caucasians; Afro-Caribbean patients respond less well to these drugs and a thiazide or a calcium-channel blocker may be chosen for initial treatment. *BNF 51th edition, 2006

13. 1. DIURETICS - preferable (to loop diuretics) for the treatment of uncomplicated hypertension- given by mouth as a single morning dose- begin to act within 1-2 hours and work for 12-24 hours- treatment should be started using a low dose • drugs of first choice for treating patients with mild hypertension • often combined with another drug in treatment of more severe • hypertension THIAZIDES hydrochlorothiazide, clopamid, chlorthalidone indapamid, metipamid

14. Lumen – urine Distal convoluted tubule Interstitium - blood Thiazides

15. Mechanism of action: • = lower blood pressure by reduction of blood volume and by direct • vascular effect • inhibition of sodium chloride transport in the early segment of the distal • convoluted tubule  natriuresis, decrease in preload and cardiac • output - renal effect • slow decrease of total peripheral resistance (raised initially) during • chronic treatment, suggesting an action on resistance vessels - • extrarenal effects • compensatory responses to pressor agents including angiotensin II and • noradrenaline are reduced during chronic treatment with thiazides • used with loop diuretic - synergistic effect occurs

16. Adverse effects: - Idiosyncratic reactions (rashes - may be photosensitiv, purpura) - Increased plasma renin (which limits the magnitude of their effect on BP) - Metabolic and electrolyte changes Hyponatremia Hypokalemia (combine with potassium-sparing diuretics) Hypomagnesemia Hyperuricemia (most diuretics reduce urate clearance) Hyperglycemia Hypercalcemia (thiazides reduce urinary calcium ion clearance  precipitate clinically significant hypercalcemia in hypertensive patients with hyperparathyroidism) Hypercholesterolemia (a small  in plasma cholesterol concentration)

17. LOOP DIURETICS furosemid - useful in hypertensive patients with moderate or severe renal impairment, or in patients with hypertensive heart failure. - relatively short-acting (diuresis occurs over the 4 hours following a dose)  used in hypertension if response to thiazides is inadequate Mechanism of action: - they inhibit the co-transport of Na+, K+ and Cl- - of Ca2+ and Mg2+ excretion - they have useful pulmonary vasodilating effects (unknown mechanism)

18. Lumen – urine Thick ascending limb Interstitium - blood Furosemide

19. Toxicity: - hypokalemic metabolic alkalosis (increased excretion of K+) - ototoxicity (dose dependent, reversible) - decrease of Mg2+ plasma concentration (hypomagnesemia) - hyperuricemia (competition with uric acid about tubular secretion) - sulfonamide allergy - risk of dehydration (> 4 L urine/ 24 h) Imporatant drug interaction may occurs if loop diuretic is given with Li+ (thymoprofylactic drug). Decrease of Na+ reabsorption can lead to increase of Li+ reabsorption  toxicity.

20. 2. Drugs influencing sympathetic nerves a) a -adrenoreceptor antagonists Mechanism of action: - vasodilatation (reduce vascular resistence) and decreased blood pressure by antagonizing of tonic action of noradrenaline on a1 receptors (vascular smooth muscle) competitive with: a.short-term action: a blockers with ISA - ergot alcaloids a non-selective - phentolamine a1selective - prazosin, uradipil, b. long-acting a1antagonists- doxazosin, terazosin non-competitivewith long-term action, non-selective - phenoxybenzamin

21. 2. Drugs influencing sympathetic nerves Toxicity: the most important toxicities of the alpha-blockers are simple extensions of their a-blocking effects – type A adverse effects - the main manifestations are: - drowsiness, weakness, orthostatic hypotension(first dose – bedtime administration) -and for the nonselective agents, reflex tachycardia- in patients with coronary disease, angina may beprecipitated by the tachycardia (less frequent in selective alpha1-blockers) - oral administration of any of these drugs can causenausea, vomiting, diarrhoea - urinary incontinece - priapism, nasal congestion

22. 2. Drugs influencing sympathetic nerves Phaeochromocytoma Long-term management of phaeochromocytoma involves surgery. Alpha-blockers are used in the short-term management of hypertensive episodes in phaeochromocytoma. Once alpha blockade is established, tachycardia can be controlled by the cautious addition of a beta-blocker; a cardioselective beta-blocker is preferred. Phenoxybenzamine, a powerful alpha-blocker, is effective in the management of phaeochromocytoma but it has many side-effects. Phentolamine is a short-acting alpha-blocker used mainly during surgery of phaeochromocytoma; its use for the diagnosis of phaeochromocytoma has been superseded by measurement of catecholamines in blood and urine.

23. 2. Drugs influencing sympathetic nerves b) b -adrenoreceptor antagonists • Mechanism of action: • the fall in cardiac output   BP • - theyreduce renin secretion • CNS-effects ??? • additional mechanisms involve baroreceptors or other homeostatic • adaptations • Possible mechanisms include: • b-adrenoceptors located on sympathetic nerve terminals can promote • noradrenaline release, and this is prevented by b-receptor • antagonists • local generation of angiotensin II within vascular tissues is stimulated • by b2-agonists.

24. 2. Drugs influencing sympathetic nerves b-adrenoreceptor antagonists cardio-selective: b1blockersatenolol, metoprolol b1blockers with ISAacebutol b1 + a1blockerslabetalol, carvedilol cardio non-selective: b1 + b2blockersmetiprolol, propranolol, nadolol b1 + b2blockers with ISApindolol, bopindolol Note: Partial agonist activity (intrinsic sympathomimetic activity – ISA) - may be an advantage in treating patients with asthma because these drugs will cause bronchodilation; they have moderate (lower) effect on lipid metabolism, cause lesser vasospasms and negative inotropic effect

25. 2. Drugs influencing sympathetic nerves • Adverse effects • Cardiovascular adverse effects, which are extension of the beta • blockade, include: • bradycardia • antrioventricular blockade • congestive heart failure (unstable) • asthmatic attacks(in patients with airway disease) • premonitory symptoms of hypoglycemia from insulin overdosage • (eg, tachycardia, tremor and anxiety, may be marked) • CNS adverse effects - sedation, fatigue, and sleep alterations.

26. 2. Drugs influencing sympathetic nerves c) Centrally acting drugs a2-agonist actions Methyldopa false transmitter Clonidine, Moxonidine direct a2-agonist, imidazol receptor agonists - limited use in the treatment of hypertension. - methyldopa  hypertension during pregnancy - methyldopa causes symptoms of drowsiness and fatigue that are intolerable to many adult patients in long-term use - they are seldom used to treat essential hypertension - clonidine is potent but poorly tolerated (rebound hypertension, if it is discontinued abruptly, is an uncommon but severe problem)

27. 2. Drugs influencing sympathetic nerves Adverse effects: - drowsiness, fatigue (esp. methyldopa), depression, nightmares (methyldopa - rarely extrapyramidal features) – driving!! - nasal congestion, anticholinergic symptoms (constipation, bradycardia) – clonidine - dry mouth - hepatitis, drug fever (with methyldopa) - sexual dysfunction, salt and water retention - hypertensive rebound associated with anxiety, sweating, tachycardia and extrasystoles (rarely hypertensive crisis)

28. 3. Vasodilators • drugs which dilate blood vessels (and decrease peripheral vascular • resistance) by acting on smooth muscle cells through non-autonomic • mechanisms: • * release of nitric oxide • (NO stimulates guanylyl cyclase and increase cGMP in smooth • muscles  reduction of cytoplasmic Ca2+ by causing Ca2+ • sequestration in the endoplasmic reticulum  relaxation of both • arterioles and venous capacitance vessels, lowering peripheral • vascular resistance and reducing cardiac pre- as well as afterload) • * opening of potassium channels • (leads to hyperpolarization and relaxation of vascular smooth muscle) • * blockade of calcium channels • (reduce intracellular calcium concentration relax aretriolar smooth • muscle, reduce peripheral vascular resistance)

29. 3. Vasodilators • compensatory responses are preserved (may include salt retention • and tachycardia)  suitable combination with diuretics or b-blockers A) DIRECT ACTING minoxidil, diazoxide, sodium nitroprusside, hydralazine Minoxidil - therapy of severe hypertension resistant to other drugs - prodrug its metabolite (minoxidil sulfate) is a potassium channel opener ( repolarization + relaxation of vascular smooth muscle) - more effect on arterioles than on veins - orally active - Adverse: Na+ and water retention → coadministration with beta-vlocker and diuretic is mandatory for this drug, oedemas, hypertrichosis, breast tenderness

30. 3. Vasodilators • Diazoxide • - given by rapid iv. injection (less than 30 seconds)* in hypertensive emergencies • - potassium channel opener • glucose intolerance due to reduced insulin secretion (used in patients with inoperableinsulinoma) • - adverse: Na+ and water retention, hyperglycaemia, hirsutism • Hydralazine • - rapidly and fairly absorbed after oral administration • - arteriolar resistance • useful for hypertensive crisis during pregnancy • AE: Na+ and water retention,systemic lupus erythematosus – suspected if there is unexplained weight loss, arthritis *BNF 51th edition, 2006

31. 3. Vasodilators Sodium nitroprusside - short-acting agent (few minutes)  administrated by infusionin hypertensive emergencies (hypertensive encephalopathy, shock, cardiac dysfunction) for max 24 hours (risk of cumulation of cyanide toxicity) - Releases NO - the stock solution should be diluted and covered with foil to prevent photodeactivation - adverse effects: too rapid reduction of BP, nausea, palpitation, dizziness cyanide metabolite accumulation – tachycardia, hyperventilation, arrhythmias, acidosis

32. 3. Vasodilators B) INDIRECT ACTING - CALCIUM CHANNEL-BLOCKING AGENTS 1. dihydropyridine (nifedipine, nicardipine, amlodipine) 2. diltiazem, verapamil • they block voltage-dependent „L-type“ calcium channels  relaxation • of smooth muscle vasodilation  reduce peripheral vascular resistance reduction of BP • negatively inotropic drugs • they differ in selectivity for calcium channels in vascular smooth • muscles and cardiac tissues • - orally active suitable for long-term use

34. 3. Vasodilators • DIHYDROPYRIDINES(nifedipine, nicardipine) • - evoke vasodilatation resulting in sympathetic reflex activation, • - relatively selective for vascular smooth muscle (arterial) • amlodipine,lacidipine, isradipine, felodipine– 2nd generation • - longer duration of action – once daily • - do not reduce myocardial contractility – do not produce clinical • deterioration in heart failure • nimodipine – preferentially acts on cerebral arteries – prevention of vascular spasm following aneurysmal subarachnoid haemorrhage • Indication:all grades of essential hypertension • alone (nifedipine, amlodipine) in patients with mild hypertensionfor patients in whom thiazide diuretics and b-blockers are contraindicated • combinations • angina (with beta-blockers)

35. 3. Vasodilators • verapamil, diltiazem • - effects on the voltage-dependent channels in cardiacconductingtissue • - vasodilatation • it also blocks Ca2+ entry in gastrointestinal smooth muscle and • consequently causes constipation

36. 3. Vasodilators Adverse effects of calcium channel-blocking agents Calcium channel blockers do not affect concentrations of plasma cholesterol or triglycerides, or extracellular calcium homeostasis.

37. 4. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 rc. ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEI) Captopril, enalapril, quinapril, lisinopril, perindopril, ramipril Indications • - hypertension where thiazide diuretics and beta-blockers are • contraindicated • useful in hypertensive patients with heart failure (beneficial effect) • can limit the size of myocardial infarction • diabetic nephropathy

38. 4. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 rc. • Mechanism of action • - ACEI regulates balance between bradykinin (vasodilatation, natriuresis) and angiotensin II (vasoconstriction, Na+-retention) • AT1 receptors - widely distributed in the body (lung - huge surface area of endothelial cells, heart, kidney, striated muscle and brain) and present on the luminal surface of vascular endothelial cells • Angiotensin II • vasoconstriction • noradrenaline release from sympathetic nerve terminals • aldosterone secretion from the zona glomerulosa of the adrenal cortex • - ADH • is agrowth factorfor vascular smooth muscle and some other cells = remodelling

39. 4. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 rc. Angiotensin I (inactive) Bradykinin (active vasodilator) angiotensin- converting enzyme Inactive metabolites Angiotensin II (active vasoconstrictor) ACE inhibitors

40. 4. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 rc. Mechanism of action: Converting enzyme inhibitors lower blood pressure by reducing angiotensin II, and also by increasing vasodilator peptides such as bradykinin. Dilatation of arteriol  reduction of peripheral vascular resistance, blood pressure and afterload Increase of Na+ and decrease of K+ excretion in kidney Decrease noradrenaline release  reduction of sympathetic activity (use is not associated with reflex tachycardia despite causing arterioral and venous dilatation) Inhibition of aldosterone secretion from the zona glomerulosa contributes to the antihypertensive effects of ACEI Influence on the arteriolar and left ventricular remodelling that are believed to be important in the pathogenesis of human essential hypertension and post-infarction state

41. 4. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 rc. • Pharmacokinetics: • active when administered orally • most of ACEIs are highly polar, eliminated in the urine, without CNS • penetration • fosinopril - metabolized by the liver • captopril, lisinopril - active per se • enalapril, quinapril - prodrugs  require metabolic conversion to • active metabolites • enalapril, quinapril and lisinopril - given once daily • captopril - administered twice daily • However, ACE inhibitors are effective in many patients with low renin as well as those with high renin hypertension and there is only a poor correlation between inhibition of plasma-converting enzyme and chronic antihypertensive effect, possibly because of the importance of converting enzyme in various key tissues rather than in the plasma.

42. 4. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 rc. ACE inhibitors

43. 4. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 rc. • Adverse effects and contraindications of ACEI: • are generally well tolerated. Adverse effects include: • First dose hypotension - particularly in those receiving diuretic • therapy; the first dose should preferably be given at bedtime. • Dry cough • - the most frequent (5-30%) symptom; could be reduced by treatment • with sulindac (inhibits prostaglandin biosynthesis) • Urticaria and angioneurotic edema • -  kinin concentrations  urticarial reactions and angioneurotic • edema) • Functional renal failure • - occurs predictably in patients with hemodynamically bilateral renal • artery stenosis, and in patients with renal artery stenosis in the vessel • supplying a single functional kidney (though they protect the diabetic • kidney) - !!! renovascular disease !!! • Fetal injury • -results in oligohydramnios, craniofacial malformations • - contraindication in pregnancy

44. 4. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 rc. Hyperkalemia – monitor !! - ACEIs cause a modest increase in plasma potassium as a result of reduced aldosterone secretion. This may usefully counter the small reduction in potassium ion concentration caused by thiazide diuretics. Potassium accumulation may be marked, especially if the patient is consuming high-potassium diet and/or potasssium- sparing diuretics. Under these circumstances, potassium concentrations may reach toxic levels (hazardous in patients with renal impairment). Therapeutic combination: - useful interaction ACEIs with diuretics: Converting enzyme inhibitors interrupt by diuretics increased plasma renin activity (and the consequent activation of angiotensin II and aldosterone) and enhance the antihypertensive efficacy of diuretics, as well as reducing thiazide-induced hypokalemia. - adverse interaction ACE inhibitors with potassium-sparing diuretics and potassium supplements, leading to hyperkalemia especially in patients with renal impairment !!! NSAID – ↑ renal damage

45. 4. Angiotensin-converting enzyme inhibitors (ACEI), blockers of AT1 rc. B) BLOCKERS OF AT1 RECEPTOR losartan, valosartan, irbesartan • - the receptor blockers - competitively inhibit angiotensin II at its AT1 • receptor site • most of the effects of angiotensin II - including vasoconstriction and aldosterone release - are mediated by the AT1 receptor • AT1-blockers do not block AT2 receptor, which is exposed to high concentration of angiotensin II during treatment with AT1- blockers • they influence RAS more effective because of selective blockade (angiotensin II synthesis in tissue is not completely dependent only on renin release, e.g. in heart, but could be promote by serin- protease - stronger influence on the myocard remodelling)

46. angiotensinogen renin nonrenin proteases cathepsin t-PA angiotensin I chymase CAGE ACE angiotensin II

47. - these drugs lower blood pressure as the ACE inhibitors and have the advantage of much lower incidence of adverse effects resulting from accumulation of bradykinin (cough, angioneurotic oedema) - they cause fetal renal toxicity (like that of the ACE inhibitors) - these drugs reduce aldosterone levels and cause potassium accumulation (attainment of toxic levels - hazardous in patients with renal impairment).

48. Clinical pharmacology of hypertension Hypertension in the elderly Benefit from antihypertensive therapy is evident up to at least 80 years of age, but it is probably inappropriate to apply a strict age limit when deciding on drug therapy. Elderly individuals who have a good outlook for longevity should have their blood pressure lowered if they are hypertensive. The thresholds for treatment are diastolic pressure averaging ≥ 90 mmHg or systolic pressure averaging ≥ 160 mmHg over 3 to 6 months’ observation (despite appropriate non-drug treatment). A low dose of a thiazide is the clear drug of first choice, with addition of another antihypertensive drug when necessary.

49. Isolated systolic hypertension Isolated systolic hypertension (systolic pressure ≥ 160  mmHg, diastolic pressure < 90 mmHg) is associated with an increased cardiovascular disease risk, particularly in those aged over 60 years. Systolic blood pressure averaging 160 mmHg or higher over 3 to 6 months(despite appropriate non-drug treatment) should be lowered in those over 60 years, even if diastolic hypertension is absent. Treatment with a low dose of a thiazide, with addition of a beta-blocker when necessary is effective; a long-acting dihydropyridine calcium-channel blocker is recommended when a thiazide is contra-indicated or not tolerated. Patients with severe postural hypotension should not receive blood pressure lowering drugs. Isolated systolic hypertension in younger patients is uncommon but treatment may be indicated in those with a threshold systolic pressure of 160 mmHg (or less if at increased risk of cardiovascular disease).

50. Hypertension in diabetes For patients with diabetes, the aim should be to maintain systolic pressure < 130 mmHg and diastolic pressure < 80 mmHg. However, in some individuals, it may not be possible to achieve this level of control despite appropriate therapy. Low-dose thiazides, beta-blockers, ACE inhibitors (or angiotensin-II receptor antagonists) and long-acting dihydropyridine calcium-channel blockers are all beneficial. Most patients require a combination of antihypertensive drugs. Hypertension is common in type 2 (non-insulin-dependent) diabetes and antihypertensive treatment prevents macrovascular and microvascular complications. In type 1 (insulin-dependent) diabetes, hypertension usually indicates the presence of diabetic nephropathy. An ACE inhibitor (or an angiotensin-II receptor antagonist) may have a specific role in the management of diabetic nephropathy; In patients with type 2 diabetes, an ACE inhibitor (or an angiotensin-II receptor antagonist) can delay progression of microalbuminuria to nephropathy.