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Hypertension is defined as systolic blood pressure (SBP) of 140 mmHg or greater, diastolic blood pressure (DBP) of 90 mmHg or greater, or taking antihypertensive medication. VI JNC, 1997. Types of hypertension. Essential hypertension 90% No underlying cause Secondary hypertension
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Hypertension is defined as systolic blood pressure (SBP) of 140 mmHg or greater, diastolic blood pressure (DBP) of90 mmHg or greater, or taking antihypertensive medication. VI JNC, 1997
Types of hypertension • Essential hypertension • 90% • No underlying cause • Secondary hypertension • Underlying cause
Causes of Secondary Hypertension • Renal • Parenchymal • Vascular • Others • Endocrine • Neurogenic • Miscellaneous • Unknown
Hypertension: Predisposing factors • Age > 60 years • Sex (men and postmenopausal women) • Family history of cardiovascular disease • Smoking • High cholesterol diet • Co-existing disorders such as diabetes, obesity and hyperlipidaemia • High intake of alcohol • Sedentary life style
1999 WHO-ISH Guidelines :Definitions and Classifications of BP Levels SBP DBP Category* (mm Hg) (mm Hg) Optimal < 120 < 80 Normal < 130 < 85 High-normal 130-139 85-89 Grade 1 hypertension (mild) 140-159 90-99 Borderline subgroup 140-149 90-94 Grade 2 hypertension (moderate) 160-179 100-109 Grade 3 hypertension (severe) > 180 > 110 ISH > 140 < 90 Borderline subgroup 140-149 < 90 WHO-ISH Guidelines Subcommittee J Hypertens 1999; 17:151
1999 WHO-ISH Guidelines:Stratification of risk to Quantify Prognosis Degree of hypertension (mm Hg) Risk factors and Grade 1-mild Grade 2-moderate Grade3-severe disease history (SBP 140-159 (SBP 160-179 (SBP > 180 or DBP 90-99) or DBP 100-109) or DBP > 110) I No other risk Low risk Med risk High risk factors II 1-2 risk factors Med risk Med risk Very high risk III > 3 risk factors or High risk high risk Very high risk target organ disease or diabetes IV Associated Very high risk Very high risk Very high risk Clinical conditions WHO-ISH Guidelines Subcommittee J Hypertens 1999;17:151
Diseases Attributable to Hypertension Left Ventricular Hypertrophy Heart Failure Gangrene of the Lower Extremities Myocardial Infarction Hypertensive Encephalopathy Aortic Aneurym HYPERTENSION Coronary Heart Disease Blindness Cerebral Hemorrhage Chronic Kidney Failure Preeclampsia/Eclampsia Stroke Adapted from Dustan HP et al. Arch Intern Med. 1996; 156: 1926-1935
1999 WHO-ISH Guidelines: Desirable BP Treatment Goals • Optimal or normal BP (< 130/85 mm Hg) for • Young patients • Middle-age patients • Diabetic patients • High-normal BP (< 140/90 mm Hg) desirable for elderly patients • Aggressive BP lowering may be necessary in patients with nephropathy, chronic renal failure, particularly if proteinuria is • < 1 g/d - 130/80 mm Hg • > 1 g/d - 125/75 mm Hg
Significant benefits from intensive BP reductionin diabetic patients Major CV events / 100 patient-yr Lancet 1998, 351, 1755
Relative risks of specific types of clinical complicationsrelated to tight and less tight BP Control Patients with Absolute risk aggregate (events/1000 and points patients-yr) Tight Less tight Less RR for control control Tight tight tight control Clinical end point (n=758) (n=390) control control p (95% Cl) Any diabetes-related 259 170 50.9 67.4 0.0046 0.76 (0.62-0.92) end point Deaths related to 82 62 13.7 20.3 0.019 0.68 (0.49-0.94) diabetes All cause mortality 134 83 22.4 27.2 0.17 0.82 (0.63-1.08) Myocardial infarction 107 69 18.6 23.5 0.13 0.79 (0.59-1.07) Stroke 38 34 6.5 11.6 0.013 0.56 (0.35-0.89) Peripheral vascular 8 8 1.4 2.7 0.17 0.51 (0.19-1.37) disease Microvascular disease 68 54 12.0 19.2 0.0092 063 (0.44-0.89) Ref : UK Prospective Diabetes Study Group BMJ 1998; 317:703
Life style modifications • Lose weight, if overweight • Limit alcohol intake • Increase physical activity • Reduce salt intake • Stop smoking • Limit intake of foods rich in fats and cholesterol
Factors affecting choice of antihypertensive drug • The cardiovascular risk profile of the patient • Coexisting disorders • Target organ damage • Interactions with other drugs used for concomitant conditions • Tolerability of the drug • Cost of the drug
Drug therapy for hypertension Class of drugExample Initiating dose Usual maintenance dose Diuretics Hydrochlorothiazide 12.5 mg o.d. 12.5-25 mg o.d. -blockers Atenolol 25-50 mg o.d. 50-100 mg o.d. Calcium Amlodipine 2.5-5 mg o.d. 5-10 mg o.d. channel blockers -blockers Doxazosin 1 mg o.d. 1-8 mg o.d. ACE- inhibitors Lisinopril 2.5-5 mg o.d. 5-20 mg o.d. Angiotensin-II Losartan 25-50 mg o.d. 50-100 mg o.d. receptor blockers
Diuretics Example:Hydrochlorothiazide • Act by decreasing blood volume and cardiac output • Decrease peripheral resistance during chronic therapy • Drugs of choice in elderly hypertensives Drawbacks • Hypokalaemia • Hyponatraemia • Hyperlipidaemia • Hyperuricaemia (hence contraindicated in gout) • Hyperglycaemia (hence not safe in diabetes) • Not safe in renal and hepatic insufficiency
Beta blockers Example:Atenolol • Block b1 receptors on the heart • Block b2 receptors on kidney and inhibit release of renin • Decrease rate and force of contraction and thus reduce cardiac output • Drugs of choice in patients with co-existent coronary heart disease Drawbacks • Adverse effects: lethargy, impotency, bradycardia • Not safe in patients with co-existing asthma and diabetes • Have an adverse effect on the lipid profile
Calcium channel blockers Example:Amlodipine • Block entry of calcium through calcium channels • Cause vasodilation and reduce peripheral resistance • Drugs of choice in elderly hypertensives and those with co-existing asthma • Neutral effect on glucose and lipid levels Drawbacks • Adverse effects: Flushing, headache, Pedal edema
ACE inhibitors Example:Lisinopril, Enalapril • Inhibit ACE and formation of angiotensin II and block its effects • Drugs of choice in co-existent diabetes mellitus Drawbacks • Adverse effect: dry cough, hypotension, angioedema
Angiotensin II receptor blockers Example:Losartan • Block the angiotensin II receptor and inhibit effects of angiotensin II • Drugs of choice in patients with co-existing diabetes mellitus Drawbacks • Adverse effect: dry cough, hypotension, angioedema
Alpha blockers Example:Doxazosin • Block a-1 receptors and cause vasodilation • Reduce peripheral resistance and venous return • Exert beneficial effects on lipids and insulin sensitivity • Drugs of choice in patients with co-existing hyperlipidaemia, diabetes mellitus and BPH Drawbacks • Adverse effects: Postural hypotension
Antihypertensive therapy:Side-effects and Contraindications Class of drugs Main side-effects Contraindications/ Special Precautions Diuretics Electrolyte imbalance, Hypersensitivity, Anuria(e.g. Hydrochloro- total and LDL cholesterol thiazide) levels, ¯ HDL cholesterol levels, glucose levels, uric acid levels b-blockers Impotence, Bradycardia, Hypersensitivity, (e.g. Atenolol) Fatigue Bradycardia, Conduction disturbances, Diabetes, Asthma, Severe cardiac failure
Antihypertensive therapy: Side-effects and Contraindications (Contd.) Class of drug Main side-effects Contraindications/ Special Precautions Calcium channel blockers Pedal edema, Headache Non-dihydropyridine(e.g. Amlodipine, CCBs (e.g diltiazem)– Diltiazem) Hypersensitivity, Bradycardia, Conduction disturbances, Congestive heart failure, Left ventricular dysfunction. Dihydropyridine CCBs– Hypersensitivity a-blockers Postural hypotension Hypersensitivity(e.g. Doxazosin) ACE-inhibitors Cough, Hypertension, Hypersensitivity, Pregnancy,(e.g. Lisinopril) Angioneurotic edema Bilateral renal artery stenosis Angiotensin-II receptor Headache, Dizziness Hypersensitivity, Pregnancy,blockers (e.g. Losartan) Bilateral renal artery stenosis
Choosing the right antihypertensive Condition Preferred drugs Other drugs Drugs to be that can be used avoided Asthma Calcium channel a-blockers/Angiotensin-II b-blockers blockers receptor blockers/Diuretics/ ACE-inhibitors Diabetes a-blockers/ACE Calcium channel blockers Diuretics/mellitus inhibitors/ b-blockers Angiotensin-II receptor blockers High cholesterol a-blockers ACE inhibitors/ Angiotensin-II b-blockers/levels receptor blockers/ Calcium Diuretics channel blockers Elderly patients Calcium channel -blockers/ACE- (above 60 years) blockers/Diuretics inhibitors/Angiotensin-II receptor blockers/- blockers BPH a-blockers b-blockers/ ACE inhibitors/ Angiotensin-II receptor blockers/ Diuretics/ Calcium channel blockers
Limitations on use of antihypertensives in patientswith coexisting disorders Coexisting Diuretic b-blocker ACE All CCB a1-blockerDisorder inhibitor antagonist Diabetes Caution/x Caution/x Dyslipidaemia x x CHD Heart failure 3/Caution Caution Asthma/COPD x /Caution Peripheral Caution Caution Caution vasculardisease Renal artery x x stenosis
Effect of various antihypertensives on coexisting disorders Total LDL- HDL- Serum Glucose Insulin cholesterol cholesterol cholesterol triglycerides tolerance sensitivity Diuretic ¯¯¯ b-blockers - ¯¯ - - ACEinhibitors - - - - Allantagonists - - - - CCBs - - - - - - a-blockers ¯¯¯
Combination therapy for hypertension – Recommended by JNC-VI guidelines and 1999 WHO-ISH guidelines With any single drug, not more than 25–50% of hypertensives achieve adequate blood pressure control J Hum. Hypertens 1995; 9:S33–S36 For patients not responding adequately to low doses of monotherapy Substitute with another drug from a different class Increase the dose of drug. This, however, may lead to increased side effects Add a second drug from a different class (Combination therapy) If inadequate response obtained Add second drug from different class(Combination therapy)
Advantages of fixed-dosecombination therapy • Better blood pressure control • Lesser incidence of individual drug’s side-effects • Neutralisation of side-effects • Increased patient compliance • Lesser cost of therapy
Fixed-dose combinations as recommended byJNC-VI (1997) guidelines and 1999 WHO-ISH guidelines • Calcium channel blocker and b-blocker(e.g. Amlodipine and Atenolol) • Calcium channel blocker and ACE-inhibitor (e.g. Amlodipine and Lisinopril) • ACE-inhibitor and Diuretic (e.g. Lisinopril and Hydrochlorothiazide) • b-blocker and Diuretic (e.g. Atenolol and Hydrochlorothiazide)
Efficacy and Tolerability of a fixed-dose combination of amlodipine andatenolol (Amlopres-AT) in Indian Hypertensives (n=369) Reduces BP effectively 80.5% 175.4+19.4 143.8+ 13.2 Blood Pressure (mm Hg) 106.8+ 10.5 % responders 88.2+ 7.6 • Safe and well tolerated • Adverse events were reported in 7.9% of patients • Common side effects included edema, fatigue and headache • Indian Practitioner 1997; 50: 683-688.
Efficacy and Tolerability of combined amlodipine andlisinopril (Amlopres-L) in Indian hypertensives (n=330) Reduces BP effectively 77.65 175.4+19.4 143.8+ 13.2 Blood Pressure (mm Hg) 106.8+ 10.5 % responders 88.2+ 7.6 • Safe and well tolerated • Adverse events were reported in 9.7% of patients • Side effects commonly reported included cough and edema • Only 1.76% of patients withdrew from the study. • Indian Practitioner 1998; 51: 441-447.
Condition Pregnancy Coronary heart disease Congestive heart failure Preferred Drugs Nifedipine, labetalol, hydralazine, beta-blockers, methyldopa, prazosin Beta-blockers, ACE inhibitors, Calcium channel blockers ACE inhibitors,beta-blockers Drugs in special conditions 1999 WHO-ISH guidelines
Summary • Hypertension is a major cause of morbidity and mortality, and needs to be treated • It is an extremely common condition; however it is still underdiagnosed and undertreated • Hypertension is not controlled with monotherapy in at least 50% of patients; in these patients combination therapy is required