losocor co training south africa dr saurav deka
DESCRIPTION
Losacar co contain losartan and hydrochlorothiazide . This presentation give you brief about basics of hypertension and its treatment with losartan hydrochlorothiazide .TRANSCRIPT
Losacar Co
CONTENT • INRODUCTION • BASICS OF HYPERTENSION • DIFFERENT GUIDELINES • LOSARTAN CO
INTRODUCTION
Introduction : What is Blood Pressure ?
Blood Pressure Classification
BP Classification SBP mmHg* DBP mmHg
Normal <120 and <80
Prehypertension 120-139 or 80-89
Stage 1 Hypertension 140-159 or 90-99
Stage 2 Hypertension ≥ 160 or ≥ 100
JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314
Hypertension even today is a triple paradox which is :
Easy to diagnose OFTEN remains undetected
Simple to treat OFTEN remains untreated
Despite availability of potent drugs, treatment all too OFTEN is ineffective
Hypertension
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 SA
2.Herediatary: -Risk of hypertension is higher in white & indian men
than coloured and African men- African women had lowest risk of hypertension
3. 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 Killer
Heart AttackStroke
Kidney Failure
CRITICAL 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 South Africa since 1995 – 2005 ,chapter 8
BASICS OF HYPERTENSION
Heart
HR
Arteries
SVR
Veins
Stroke Volume
Physiologic Components of BP
Determinants of Blood Pressure
Mean Arterial Pressure = X Arteriolar
Diameter
BloodVolume
StrokeVolume
HeartRate
Filling PressureContractility
Blood Volume Venous Tone
CRITICAL POINT!Change any physical factors controlling
CO and/or TPR and MAP can be altered.
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.
5. Pharmacological treatment by Anti hypertensive drugs
4. If primary, initiate lifestyle changessmoking cessationweight lossdietstress reductionless alcohol etc.
Classes of Antihypertensive Agents
1. ACE inhibbitor Captopril,ramipril ,lisinopril,enalpril,Perindopril,imidapril etc
2 . AT1 blocker (ARB) Losartan,candesartan,irbesartan,valsartan,telmesartan,olmesartan
3.Calcium channel blocker
Amlodipine ,Nifedipine ,verapamil,diltiazem,felodipine , etc
4. Diuretics Hydrochlorothiazide,Chlorthalidone,Indapamide, furosemide,spirinolactone
5.Beta blockers Propanolol,metoprolol,atenelol, labetelol,carvedilol
6.Alpha blockers Prazocin ,Terazocin ,Doxazosin,phentolamine,
7.Central Sympatholytics
Clonidine, methyldopa
8. Vasodilator Hydralazine,minoxidil,Diazoxide,Sodium Nitroprusside
Diuretics as anti hypertensive
2. Mechanism of Action
Urinary Na+ excretionUrinary water excretion
Extracellular Fluid and/or Plasma Volume
3. Effect on Cardiovascular System
Acute decrease in CO
Chronic decrease in TPR, normal COMechanism(s) unknown
1. Site of Action Renal Nephron
Diuretics (cont)4. Adverse Reactions
dizziness, electrolyte imbalance/depletion,hypokalemia, hyperlipidemia,hyperglycemia (Thiazides)gout
5. Contraindicationshypersensitivity, compromised kidney functioncardiac glycosides (K+ effects)hypovolemia,hyponatremia
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 reachedbefore maximum diuresis- 2nd agent indicated
Anti-Angiotensin II DrugsAngiotensin II Formation
2. Ang II Receptor Antagonists losartan (Cozaar); candesartan (Atacand); valsartan (Diovan)
1. Angiotensin Converting Enzyme- Inhibitors enalopril (Vasotec); quinapril (Accupril); fosinopril (Monopril); moexipril (Univasc); lisinopril (Zestril, Prinivil); benazepril (Lotensin); captopril (Capoten)
Ang I
Ang II
ACE
ACE
Ang II
Renin
Angiotensinogen
Ang IAT1
AT2
LungVSMBrainKidneyAdr Gland
Effect on Cardiovascular System
Anti-Angiotensin II Drugs, cont
Volume Aldosterone Vasopressin
CO
Angiotensin II
Vasoconstriction
TPR
SymNS
HR/SV Angiotensin II Norepinephrine
CO
SymNS
GUIDELINE -JNC 7- ISH WHO- South African Hypertension guideline 2011
Blood Pressure Treatment in NutShell
BP Classification SBP mmHg* DBP mmHg Lifestyle Modification
Drug Therapy**
Normal <120 and <80 Encourage No
Prehypertension 120-139 or 80-89 Yes No
Stage 1 Hypertension 140-159 or 90-99 Yes Single
Agent
Stage 2 Hypertension ≥ 160 or ≥ 100 Yes Combo
JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314
*Treatment determined by highest BP category; **Consider treatment for compelling indications regardless of BP
Algorithm for Treatment of Hypertension
Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)
Initial Drug Choices
Drug(s) for the compelling indications
Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB)
as needed.
With Compelling Indications
Lifestyle Modifications
Stage 2 HTN (SBP >160 or DBP >100 mmHg)
2-drug combination for most (usually thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)
Stage 1 HTN (SBP 140–159 or DBP 90–99 mmHg)
Thiazide-type diuretics for most. May consider ACEI, ARB, BB,
CCB, or combination.
Without Compelling Indications
JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314
Not at Goal Blood Pressure
Optimize dosages or add additional drugs until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
With any single drug, not more than 25–50% of hypertensives achieve adequate blood pressure control
J Hum. Hypertens 1995; 9:S33–S36For patients not responding adequately
to low doses of monotherapy
Increase the dose of drug. This, however, may lead to
increased side effects
Substitute with another drug from a different class
Add a second drug from a different class
(Combination therapy)
Add second drug from different class (Combination therapy)
If inadequate response obtained
Combination therapy for hypertension
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
LOSARCO Losartan plus Hydrochlorothiazide
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
Losartan
· Significant antiproteinuric effects in diabetic nephropathy- Renoprotective effects
· Has significant fibrinolytic activity which reduces the risk of ischaemia
· Good Urocosuric amongst ARB s· Once daily dose offers convenience
ANGIOTENSINOGEN
ANGIOTENSIN 1
ANGIOTENSIN 2
VASOCONTRICTIONSYMPATHETIC STIMULATIONALDOSTERONE RELEASE
AT1 AT2
GOOD EFFECTS
LEADING TO NORMALISING BLOOD PRESSURE WITHOUT COUGH AND IT IS A COMPLETE RAAS BLOCKER
CARDIACCHYMASE
CATHEPS INELASTIN
ACE
LOSARTAN
BRADYKININ
INACTIVE FRAGMENTS
NO COUGH
MECHANISM OF ACTION : LOSARTAN
HIGHEST COMPLIANCE
64%58%
50%43%
38%
0%
10%
20%
30%
40%
50%
60%
70%
LosartanPotassium
ACE Inhibitors CaAntagonists
Beta blockers ThiazideDiuretics
% P
ATIE
NTS
LOWEST INCIDENCE OF GOUGH
29.20% 34.10%
71.70%
0.00%10.00%20.00%30.00%40.00%50.00%60.00%70.00%80.00%
LOSARTAN
POTASSIUM
Hydrochlorthiazide lisinopril
% PA
TIENT
S
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
K id n e yNa loss
Arteriolar relaxation
BV
TPR
A P
Thiazides
R e f l e x e s
S y m p a t h o a c t i v a t io nR e n in re le a s e
T P RC a r d ia cco n tra c t i l i t yV e n o u s t o n e
CO Then
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 drug
Epstein M, et al. Arch Intern Med. 1996;156:1969–1978.
Losartan-Hydrochlorothiazide Combination: Advantages
Synergistic Anthihypertensive effectLOSARTAN HYDROCHLOROTHIAZIDE
¯RAAS ¯ SNS
Inhibits effects of ANG II
¯ Blood Pressure
¯ Plasma volume and natriuresis
¯ Cardiac output
¯ Peripheral resistance
Blood Pressure
RAAS SNS
¯BP
ANG II
+
(–) (–)
Losartan-Hydrochlorothiazide Combination:
Potassium AdvantagesLOSARTAN
¯ RAAS
¯ Aldosterone
Serum Potassium
Serum potassium levelsremain within normal limits
Hydrocholorothiazide
¯ Plasma volume and natriuresis
RAAS
Aldosterone
¯ Serum Potassium
+
Losartan-Hydrochlorothiazide Combination: Gout Advantages
Hydrochlorothiazide
¯ Uric acid excretion
Gout
No Gout
Losartan
Serum uric acid¯ Serum Uric Acid
+
Improved Safety
Serum uric acid excretion
n = 39
0
10
20
30
40
50
60
70
80
n = 63
With HCTZ Without HCTZ
Response = SBP < 140 mm HgP = .002
SBP Response to Two-drug Combinations That Include or Do Not Include a Diuretic
Per
cen
t R
esp
on
se
Materson BJ, et al. J Hum Hypertens. 1995;9:791–796.
Losacar-CO: Indications
Losacar-H is indicated for the treatment of hypertension in patients who do not respond to monotherapy alone.
LOSACAR-HDosing Considerations
A patient whose blood pressure is not adequately controlled with losartan monotherapy may be switched to Losacar-H (losartan potassium 50mg/ hydrochlorothiazide12.5mg) once daily. If blood pressure remains uncontrolled after about 3 weeks of therapy, the dose may be increased to two tablets 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-CoContraindications
Losartan-Hydrochlorothiazide are contraindicated in patients who are hypersensitive to any of their components.
Due to the thiazide component, Losartan -Hydrochlorothiazide is contraindicated in patients with anuria or hypersensitivity to 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