HTN_JMI.ppt

7/28/2019 HTN_JMI.ppt

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HTN (Hypertension) is Chronic elevation

in blood pressure > 140/90 mmHg

ANTIHYPERTENSIVE DRUGS are those

drugs used to combat hypertension.

Anti-Hypertensive Drugs


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CLASSIFICATION- Anti hypertensives

1st Line Anti-hypertensive drugs

1. ACEI : CAPTOPRIL, ENALAPRIL,RAMIPRIL

2. ANGIOTENSIN BLOCKERS :

LOSARTAN,CANDESARTAN, VALSARTAN

3. BLOCKERS: PROPANOLOL, ATENOLOL

4. CCBs : VERAPAMIL,DILITIAZEM, NIFEDIPINE

5. DIURETICS

THIAZIDES: HYDROCHLOROTHIAZIDE,CHLORTHALIDONE

HIGH CEILING:FUROSEMIDE

K- SPARING: SPIRONOLACTONE,AMILORIDE

A

B

C

D

2


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Other Anti-hypertensives

6. + BLOCKERS: LABETALOL, CARVEDILOL

7. ADRENERGIC BLOCKERS: PRAZOSIN,

TERAZOSIN

8. CENTRAL SYMPATHOLYTICS: CLONIDINE,

METHYL DOPA

9. VASODILATORS :

Arterioles- HYDRALAZINE, Minoxidil, Diazoxide

Venous + Arteriole- SOD. NITROPRUSSIDE, Nicorandil, -

blockers

10. Newer drugs-Natriuretic peptides, Fenoldopam

11. Obsolete agents- Reserpine, Guanethidine, Trimethaphan

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Antihypertensive drugs

BP = CO X PVR

CO = HR X SV

Anatomical sites for regulating BP

1. Arterioles

2. Heart3. Post-capillary venules

4. Kidney

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DIURETICS -THIAZIDES

MECHANISM OF ACTION:-

1.Diuresis reduces plasma and e.c.f vol by 5-15%

leads to decreased CO2. Despite compensatory mech. fall in BP is

maintained by a slowly developing reduction in

PVR.

3. Reduction in PVR is due to persisting sod and

vol. deficit

4. Fall in B.P develops over 2-4 weeks

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HIGH CEILING DIURETICS

PrototypeFUROSEMIDE.

Weaker than THIAZIDES.

Fall in b.p dependent on reduction in plasma vol

and CO

Indications -when HTN is complicated by1.CRFthiazides are ineffective.

2. Coexisting refractory CHF.

3.Resistance to combination regimes containing athiazide or marked fluid retention due to use of

potent vasodilators

4. Hypertensive emergencies.6


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Merits of DIURETICS as Anti HTN

1. Once a day dosing + flat DRC.

2. No fluid retention.

3. No tolerance.4. Low incidence of postural HTN.

5. Less CNS side effects.

6. Effective in isolated systolic HTN.

7. Decreased risk of hip fracture in elderly &

post menopausal pts.7


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Demerits of Diuretics as Anti-HTN

1.Hypokalemia.

2.Erectile dysfunction in males.

3.Carbohydrate intolerance(inhibition ofinsulin release).

4.Dyslipidemia.

5.Hyperuricemia(inhibit urate excretion).

6.Increased incidence of sudden cardiac

death- Tdp.

8


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POTASSIUM SPARING DIURETICS

Spironolactone or amiloridelower b.p

slightly.

Used in conjunction with a thiazide

(1) to prevent pot.loss.

(2) to augment Anti-HTN action.

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VasoconstrictionSympathetic system

Aldosterone releaseVent. hypertrophy(Remodelling)

AT1


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ACE INHIBITORS (ACEI)

Pharmacological actions:

vasodilatation sympathetic activation

Na+ & water retention Heart remodelling Bradykinin

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Drugs:

Captopril

Enalpril- 2.5- 10mg OD (prodrug)Ramipril

Perindopril

LisinoprilFosinopril

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ACE INHIBITORS (ACEI)-

Therapeutic Uses

1. Mild to Moderate CHF

2. HTN (+ DM) / 1st line

3. MI4. LVH

5. Diabetic Nephropathy

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ADR-

1. Hyperkalemia

2. Postural HTN

3. Cough

4. Laryngeal

angioedema

5. Dysgeusia6. Granulocytopenia

7. Fetotoxic

C/I-

Pregnancy

Bilateral renal arterystenosis

D.i-

Pot. Sparing diuretics Pot. Supplements

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1st

choice of drug in essential andrenovascular HTN.

Improve RBF.

Retard diabetic nephropathy.

Capacity to regress LVH.

Most appropriate A-HTN in patients with

diabetes, nephropathy,LVH,CHF,post MI

cases.

More effective in younger HTN.

Dose = 2.510 mg/day (Enalapril).

S/Edry persistent cough. 15


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AT1 Receptor BLOCKERS (ARB)

Drugs-

Losartan (50mg/day)

Irbesartan

Telmisartan

Valsartan

Therapy-

HTN- Early action and

progresses to peak at

2-4 wksCHF

D.i- K+

Merits: No cough / No

angiooedema

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CALCIUM CHANNEL BLOCKERS

Classification 1.dihydropyridinesamlodipine

2.phenylalkylamine- verapamil

3.benzothiazepine- diltiazem

They lower the B.P by decreasing peripheralresistance without compromising cardiac output.

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Advantages of CCBs

1.Quick onset of action.

2.Can be administered once a day.

3.No sedation or CNS effects.

4.Not contraindicated in asthma and angina5. Do not impair renal perfusion.

6. Do not effect male sexual function.

7. No effect on plasma lipid profile,uric acidlevel,electrolyte balance.

8. No adverse foetal effects.

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Disadvantages of CCBs

1. Negative inotropic/dromotropic action of

diltiazem may worsen CHF & cardiac

conduction defects.

2. By smooth muscle relaxant action- worsen

GERD.

3. May accentuate bladder voiding difficulty in

males.

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BLOCKERS

Response develops over 1-3 wks.

Cardioselective- Atenolol / Metoprolol

Non-cardioselective- Plol/ Pindolol Others- Carveidilol / Celiprolol

Drugs with ISAcause less reduction of

H.R and C.O ,but lower vascular resistanceby beta 2 agonism.

Non selective beta blockersdecrease RBF

and GFR. 20


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Demerits- BLOCKERS

C/I-Peripheral vascular disease / ----.

Unfavourable efffect on lipid profile.

Fared poorly on quality of life.

Rebound HTN occurs on sudden

discontinuation of beta blockers.

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ADVANTAGES- BLOCKERS

Absence of postural HTN.

No Bowel alteration.

No Salt and water retention.

Less S/E.

Low cost.

Once a day regimen.

Cardioprotective potential.

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VASODILATORS

Arteriolar vasodilators-

Hydralazine, Minoxidil, Diazoxide

Arteriolar & venous vasodilators-

Sodium nitroprusside

Adrenergic blockers- eg., Prazosin

Nicorandil

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ARTERIOLARVASODILATORS

Hydralazine-

MECHANISM OF ACTION:

Endothelium dependent may involve generation of NO

and stimulation of cGMP.

USES:

drug of choice in acute severe hypertension in pregnancy

CHF ( + ISDN)

Emergency HTN- IV Hydralazine

ADVERSE EFFECTS


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ADVERSE EFFECTS:

reflex sympathetic activation (reflex tachycardia, peripheral edema,

IHD)

extreme hypotension

Lupus erythematosus

CONTRAINDICATIONS:

CAD

multiple CVS risk factors

elderly patients

ARTERIOLAR


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Minoxidil (Prodrug)-

MECHANISM OF ACTION:K+ channel opener relax VSM PVRBP.

USES:

Adjuvant use in HTN

Male patterened Alopecia

ADR: reflex sympathetic activation

diffuse hirsutism (minoxidil)

hypertrichosis (minoxidil)

ARTERIOLAR


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Diazoxide-

MECHANISM OF ACTION:K+ channel opener relax VSM PVRBP.

USES: Emergency HTN

ADR:

reflex sympathetic activation

Hyperglycaemia

ARTERIOLAR AND VENOUS


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ARTERIOLAR AND VENOUS: eg. Sodium nitroprusside

MECHANISM OF ACTION :

NO released from endothelium

dilatation of arterioles and venules

cardiac output , t.p.r.

USES:

hypertensive emergencies

CHF with pulmonary edema

acute aortic dissection

controlled hypotension during anesthesia


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Sodium nitroprusside ADVERSE EFFECTS :

hypotension

palpitation

weakness

nervousness

vomiting

lactic acidosis

disorientation

thiocyanate toxicity


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ADRENERGIC BLOCKERS

eg. prazosin, doxazosin

MECHANISM OF ACTION:

block action of nor-epinephrine on vascular adrenergic

receptors

Dilates both resistance and capacitance vessels ((arteriolar

& venodilaor) BP

USES :

in conjugation with diuretics and blockers

drug of second line


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ADVERSE EFFECTS ( ADRENERGIC BLOCKERS):

postural hypotension ( first dose effect)

headache

drowsiness

dry mouthweakness

palpitation

fluid retention

nasal blockage

blurred vision


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CENTRAL SYMPATHOLYTICS

IMIDAZOLE DERIVATIVE- CLONIDINE

-METHYL DOPA

MOA:- Stimulation of pre-synaptic 2 receptors.

Decrease sympathetic outflow

Plasma NA declines

heart rate and cardiac output

t.p.r. and BP

USES :

add on therapy

non emergent HT in pregnancy(-METHYL DOPA)


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ADVERSE EFFECTS (Central Sympatholytics):

1. sedation

2. dry mouth

3. depression

4. autoimmune hemolytic anaemia

5. lupus erythrematosus

6. rebound hypertension

7. orthostatic hypotension


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Management of Hypertension

BP category SBP

(mm Hg)

DBP

(mm Hg)

Non-

Pharma T/t

Drug

therapy

Normal < 120 < 80 Encourge

life style

changes

No Anti-HT

drugs

Pre-

Hypertensive120-139 80-89 No Anti-HT

drugs except

compelling

indications

Stage-I HT 140-159 90-99 ABCD &

combinations

Stage-II HT > 160 > 100 ABCD &combinations


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Non-Pharmacological treatment in the

management of HT

Salt restriction

Diet- saturated fats / Fibre / calcium

Alcohol & abstain from smoking

Control DM Control Obesity

Exercises- brisk walk for 30mins x 5days/wk

Relaxation / meditation / Yoga


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SBP > 140 / DBP > 90

Pt. young (< 55yrs)

& not Black

Pt. Old (> 55yrs)

& Black

C or DA + C or D

Or

B + C or D

A or B

A or B + C + D + blocker or spironolactoneA or B + C + D

DRUG

THERAPY


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Individualization of anti-hypertensive

therapy

Diuretics- Elderly / Blacks/ post-menopausalosteoporosis(Thiazides)

ACEI- CHF/ LVH/ DM/ post MI

CCB- Angina/ PVD/ elderly/ isolated HT/ Blacks -blockers- Angina/ post MI/ tachyarrythmias/

anxiety/ migraine

-blockers- BPH/ poor lipid profile Pregnancy- -methylDOPA/ nifedipine/ vasodialtors


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Management of Hypertensive

Emergencies

Requires in BP within 1 hr. DBP > 130

High risk of end organ damage

Emergencies include-

- HT encephalopathy

- HT Nephropathy

- Intra-cranial hemorrhage

- Aortic dissection- Pre-eclampsia / Eclampsia

- Pulmonary edema

- Unstable angina / MI


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Management of HT Emergencies

Goal-

- to reduce BP by 25%(not more) within mins to 1 hr.- excessive reductions- IHD / Cererbral & Renal ischaemia

Parenteral drug therapy-

- Sod. Nitroprusside- IV NTG

- Furosemide

- Enalprilat

- Labetalol

- Fenoldapam

- Esmolol

- Phentolamine

+ -Blocker

(Atenolol-50mg oral)

Documents

HTN_JMI.ppt