Blood Pressure Classification BP Classification SBP mmHg* DBP mmHgNormal <120 and <80Prehypertension 120-139 or 80-89Stage 1Hypertension 140-159 or 90-99Stage 2Hypertension ≥ 160 or ≥ 100 JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314
HypertensionHypertension even today is a tripleparadox which is : Easy to diagnose OFTEN remainsundetected Simple to treat OFTEN remainsuntreated Despite availability of potent drugs,treatment all too OFTEN is ineffective
Hypertension In South Africa• Around 25% of all men and 15% of adult women are thought to be suffering from hypertension• Black hypertensive patients in South Africa are prone to cerebral haemorrhage, malignant hypertension, kidney disease leading to uraemia and congestive heart failure, whereas coronary heart disease (CHD) is relatively uncommon.• In contrast, CHD is the major outcome related to hypertension in the white and Indian communities.
Factors for Hypertension in SA 1. Food : HIGH SALT INTAKE-High amount of salt used to preserve food or to make food tastier .-Bread is staple food for many people in SA containing high salt.-Low potassium intake due to less consumption of Fruit- Average salt intake 7.8 gm by black ,8.5 gm by colored and 9.5 g in white South Africans
Factors for Hypertension in SA2.Herediatary:-Risk of hypertension is higher in white & indian men than coloured and African men- African women had lowest risk of hypertension3. Genetic :-In European ancestry :ACE gene contributing in male & angiotensinogen (AGT) gene contributing in female-In African 217G-AAGT variant gene contributing BP-β2 receptor gene not associated with HTN in African ancestry
Hypertension is the Silent KillerHeart Attack Kidney Failure StrokeCRITICAL POINT for SA• Death risk increased by 60 % with increase in 20mmHg of diastolic BP in African population• The African Health Report 2007 deaths from CVD were 37% and 21% of years of life lost due to premature death in SA
South Africans are different!!!! • Black patients are poor responder to beta blocker & ACE inhibbitors • Above agents are need to combined with a thiazide diuretic to increase efficiency** Krisela Steyn “ Hypertension in South Africa “Chronic Diseases of Lifestyle in SouthAfrica since 1995 – 2005 ,chapter 8
Physiologic Components of BP Heart HR VeinsStroke Volume Arteries SVR
Determinants of Blood Pressure Blood VolumeMean Arterial Pressure = X Arteriolar Diameter Stroke Heart Volume Rate CRITICAL POINT! Change any physical factors controlling CO and/or TPR and MAP can be altered. Contractility Filling Pressure Blood Volume Venous Tone
Algebra of Blood Pressure BP = Cardiac Output x SVR CO = HR x Stroke Volume ↓BP = HR x Stroke Volume x SVR
General Treatment Strategy of Hypertension 1. Diagnosis- 3- 6 independent measurements. 2. Determination of primary vs. secondary hypertension. 3. If secondary, treat underlying pathology. 4. If primary, initiate lifestyle changes smoking cessation weight loss diet stress reduction less alcohol etc. 5. Pharmacological treatment by Anti hypertensive drugs
Diuretics as anti hypertensive1. Site of Action Renal Nephron2. Mechanism of Action Urinary Na+ excretion Urinary water excretion Extracellular Fluid and/or Plasma Volume3. Effect on Cardiovascular System Acute decrease in CO Chronic decrease in TPR, normal CO Mechanism(s) unknown
Diuretics (cont)6. Therapeutic Considerations -Thiazides (most common diuretics for HTN) -Generally start with lower potency diuretics -Generally used to treat mild to moderate HTN - Use with lower dietary Na+ intake, and K+ supplement or high K+ food -K+ Sparing (combination with other agent) - Loop diuretics (severe HTN, or with CHF) Osmotic (HTN emergencies) - Maximum antihypertensive effect reached before maximum diuresis- 2nd agent indicated
Anti-Angiotensin II Drugs Angiotensin II Formation1. Angiotensin Converting Enzyme- 2. Ang II Receptor Antagonists Inhibitors losartan (Cozaar); enalopril (Vasotec); candesartan (Atacand); quinapril (Accupril); valsartan (Diovan) fosinopril (Monopril); moexipril (Univasc); lisinopril (Zestril, Prinivil); benazepril (Lotensin); captopril (Capoten) Angiotensinogen ACE Ang I Lung Ang I VSM AT1 Brain Ang II Kidney ACE AT2 Adr Gland Ang II Renin
Anti-Angiotensin II Drugs, cont Effect on Cardiovascular SystemVolume HR/SV Angiotensin II Aldosterone Angiotensin II Vasopressin Vasoconstriction Norepinephrine SymNSCO SymNS TPR CO
GUIDELINE-JNC 7- ISH WHO- South African Hypertension guideline 2011
Blood Pressure Treatment in NutShell Lifestyle DrugBP Classification SBP mmHg* DBP mmHg Modification Therapy**Normal <120 and <80 Encourage NoPrehypertension 120-139 or 80-89 Yes NoStage 1 SingleHypertension 140-159 or 90-99 Yes AgentStage 2Hypertension ≥ 160 or ≥ 100 Yes Combo*Treatment determined by highest BP category; **Consider treatment for compellingindications regardless of BP JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314
Algorithm for Treatment of Hypertension Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease) Initial Drug Choices Without Compelling With Compelling Indications IndicationsStage 1 HTN (SBP 140–159 or Stage 2 HTN (SBP >160 or DBP Drug(s) for the compelling DBP 90–99 mmHg) >100 mmHg) indicationsThiazide-type diuretics for most. 2-drug combination for most Other antihypertensive drugs May consider ACEI, ARB, BB, (usually thiazide-type diuretic and (diuretics, ACEI, ARB, BB, CCB) CCB, or combination. ACEI, or ARB, or BB, or CCB) as needed. Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved. Consider consultation with hypertension specialist. JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314
Combination therapy for hypertension 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 monotherapyIncrease the dose of drug. Substitute with another Add a second drug from aThis, however, may lead to drug from a different class different class increased side effects (Combination therapy) If inadequate response obtained Add second drug from different class (Combination therapy)Recommended by JNC-7 guidelines and 1999 WHO-ISH guidelines
South African Hypertension Guideline 2011-First Step for uncomplicated hypertension : low dose thiazide or ACEI / ARB (CCB in black patients)-Second step If still uncomplicated, then ACEI or ARB OR CCB . -Beta-blockers, such as atenolol, are no longer considered as routine step one to step three therapies due to their risk of inducing diabetes and relative ineffectiveness.- Stroke ,Diabetis with protein uria,CKD : ARB or ACEI with diuretics
Losartan• Prototype angiotensin II receptor antagonist• Particularly valuable in patients who are intolerant to ACE inhibitors• Prevents and regresses LVH• Offers advantage in CHF by increase in exercise tolerance
LosartanSignificant antiproteinuric effects indiabetic nephropathy- RenoprotectiveeffectsHas significant fibrinolytic activity whichreduces the risk of ischaemia Good Urocosuric amongst ARB sOnce daily dose offers convenience
MECHANISM OF ACTION : LOSARTAN ANGIOTENSINOGENCATHEPS IN BRADYKININELASTIN ANGIOTENSIN 1 CARDIAC CHYMASE ACE NO COUGH ANGIOTENSIN 2 INACTIVE FRAGMENTS AT1 LOSARTAN AT2 GOOD EFFECTSVASOCONTRICTIONSYMPATHETIC STIMULATIONALDOSTERONE RELEASE LEADING TO NORMALISING BLOOD PRESSURE WITHOUT COUGH AND IT IS A COMPLETE RAAS BLOCKER
LOWEST INCIDENCE OF GOUGH 80.00% 71.70% 70.00%% PATIENTS 60.00% 50.00% 40.00% 29.20% 34.10% 30.00% 20.00% 10.00% 0.00% LOS ARTAN Hy dr oc hlor t hia z ide lisinopr il P OTAS S IUM
Hydrochlorothiazide• Prototype thiazide diuretics• Commonly the first line treatment in mild-moderate hypertension• Often used in combination with other antihypertensive agents• Proven benefit in stoke and myocardial infarction reduction
Hydrochlorothiazide• Used at doses lower than those used to obtain a diuresis• Full antihypertensive effect may take 10-12 weeks• At the doses used diabetes and hypercholesterolaemia are not problems
Thiazide diuretics: mechanism of action AP Reflexes TPR Cardiac contractility Sympathoactivation Renin release Venous tone TPR Arteriolar relaxation KidneyCO Then Na loss Thiazides BV
Why combination therapy• Multiple mechanisms involved in the pathogenesis of hypertension• Effectiveness of monotherapy limited by stimulation of counter-regulatory mechanisms• Effective BP control seen in only 50% of patients on monotherapy; combination therapy results in a much higher responder rate (>80%)• BP goals difficult to attain with monotherapy in patients with diabetes or target organ damage
Combination Therapy: Rationale • Improved BP reduction – Increased efficacy of two drugs in combination compared to either as monotherapy, due to their additive and/or synergistic effects • Broader spectrum of response – Effective response over a wider range of patient groups • Improved tolerability – Reduced likelihood of dose-dependent side effects, clinical and metabolic, by combining smaller doses of two drugs vs high doses of a single agent – Side effects associated with a particular drug may be modified by the pharmacologic properties of the second drugEpstein M, et al. Arch Intern Med. 1996;156:1969–1978.
Losartan-Hydrochlorothiazide Combination: Advantages Synergistic Anthihypertensive effect LOSARTAN + HYDROCHLOROTHIAZIDE RAAS SNS Plasma volume Cardiac and natriuresis outputInhibits effects (–) (–) of ANG II RAAS SNS Peripheral resistance Blood Pressure ANG II Blood Pressure P
Losartan-Hydrochlorothiazide Combination: Potassium AdvantagesLOSARTAN + Hydrocholorothiazide RAAS Plasma volume and natriuresisAldosterone RAAS Serum Aldosterone Potassium Serum Potassium Serum potassium levels remain within normal limits
SBP Response to Two-drug CombinationsThat Include or Do Not Include a Diuretic 80 n = 39 P = .002 70 Response = SBP < 140 mm Hg 60 Percent Response 50 n = 63 40 30 20 10 0 With HCTZ Without HCTZMaterson BJ, et al. J Hum Hypertens. 1995;9:791–796.
Losacar-CO: IndicationsLosacar-H is indicated for the treatment ofhypertension in patients who do not respond tomonotherapy alone.
LOSACAR-H Dosing ConsiderationsA patient whose blood pressure is not adequatelycontrolled with losartan monotherapy may beswitched to Losacar-H (losartan potassium 50mg/hydrochlorothiazide12.5mg) once daily. If bloodpressure remains uncontrolled after about 3 weeksof therapy, the dose may be increased to twotablets once daily
Losacar -Co: Adverse Effects• Generally well tolerated• Amongst the commonly reported adverse effects include : dizziness, abdominal pain, edema, palpitations, back pain, cough, sinusitis, upper respiratory infection and skin rash.
LOSACAR-Co ContraindicationsLosartan-Hydrochlorothiazide arecontraindicated in patients who arehypersensitive to any of theircomponents.Due to the thiazide component, Losartan-Hydrochlorothiazide is contraindicatedin patients with anuria or hypersensitivityto other sulfonamide-derived drugs.
CONCLUSION• Better blood pressure control• Lesser incidence of individual drug’s side- effects like potassium inbalance ,gout.• Neutralisation of side-effects• Increased patient compliance• Effective response over a wider range of patient groups