vilasinee hirunpanich b pharm m sc in pharm pharmacology n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Vilasinee Hirunpanich B.Pharm, M.Sc In Pharm (Pharmacology) PowerPoint Presentation
Download Presentation
Vilasinee Hirunpanich B.Pharm, M.Sc In Pharm (Pharmacology)

Loading in 2 Seconds...

play fullscreen
1 / 51

Vilasinee Hirunpanich B.Pharm, M.Sc In Pharm (Pharmacology) - PowerPoint PPT Presentation


  • 150 Views
  • Uploaded on

Drugs treatment in heart failure. Vilasinee Hirunpanich B.Pharm, M.Sc In Pharm (Pharmacology). Congestive heart failure. Definition. Systolic dysfunction ผลจากการที่กล้ามเนื้อหัวใจไม่สามารถสูบฉีดเลือดไปเลี้ยงเนื้อเยื่อต่างๆ ได้เพียงพอกับความต้องการของร่างกาย

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Vilasinee Hirunpanich B.Pharm, M.Sc In Pharm (Pharmacology)' - calvine


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
vilasinee hirunpanich b pharm m sc in pharm pharmacology

Drugs treatment in heart failure

Vilasinee Hirunpanich

B.Pharm, M.Sc In Pharm (Pharmacology)

congestive heart failure
Congestive heart failure
  • Definition
  • Systolic dysfunction ผลจากการที่กล้ามเนื้อหัวใจไม่สามารถสูบฉีดเลือดไปเลี้ยงเนื้อเยื่อต่างๆ ได้เพียงพอกับความต้องการของร่างกาย
  • Diastolic dysfunction กล้ามเนื้อหัวใจไม่สามารถคลายตัวรองรับเลือดเข้าสู่หัวใจได้ดีพอ
slide3
อาการแสดง

Dypnea

Fatigue

Fluid retention

Shortness of breath

compensatory mechanisms
Compensatory mechanisms

1. Extrinsic compensatory

2. Intrinsic compensatory

extrinsic compensatory
Extrinsic compensatory
  • Increase the sympathetic system

HR, contraction

  • Stimulate renin-angiotensin system

aldosterone

  • Sodium and Water retention
intrinsic compensatory
Intrinsic compensatory
  • Frank-Starling mechanism
  • Myocardial hypertrophy
  • remodeling
slide8

Left Ventricular cannot pump blood

ลด Cardiac output

Intrinsic compensatory

Extrinsic compensatory

เพิ่มsympathetic discharge

ลดrenal perfusion

เพิ่มcontractility

vasoconstriction

HR

เพิ่มการหลั่ง renin

AT II

aldosterone

เพิ่ม afterload

Fluid retention

Ventricular hypertrophy

เพิ่ม preload

failure compensatory mechanism
Failure compensatory mechanism

Congestive heart faliure

management of heart failure
Management of heart failure
  • Prevention of initial causative
  • Pharmacological treatment
slide12
increase contractility

Treatment

Conventional drugs

Diuretic

Digitalis

vasodilators

Progressive remodeling with impaired myocardial performance

Treatment

Conventional drugs

Decreasing the process of cardiac remodeling

(ACEI, -blocker, nitrate)

Neurohormone blockers

ACEI (RAAS)

Spironolactone (aldosterone)

-blocker (renin)

Digoxin (renin)

  • Neurohormone model (1980-2000)
  • Hemodynamic model
  • (1950-1980)
treatment of chf
Treatment of CHF
  • Goal: to relief symptom

1. Control salt and water retention (diuretic)

2. Increase myocardial contractility

(inotropic drugs)

3. Reduce work load of heart by

Preload: Diuretic, Nitrate, ACEI

Afterload: Direct vasodilator

Decrease activation of neurohormone: ACEI, -blocker, spironolactone

slide14

Heart failure

Positive inotropic

vasodilator

Decreased cardiac output

Increased venous volume and pressure

Decreased tissue perfusion

Neuroendocrine system activation

Congestion and edema

Dysnea and orthopnea

Sympathetic activation

RAS

Na retention

vasoconstriction

Increased afterload

positive inotropic drugs
Positive inotropic drugs
  • Cardiac glycoside

Digitalis, digoxin, quabain

  • Non-cardiac glycoside
    • Phosphodiesterase inhibitors (PDEI)
    • Catecholamine (Dopamine, Dobutamine)
cardiac glycoside
Cardiac glycoside
  • Digoxin is the prototype.
  • Digitalis lanata, Digitalis purpurea
  • Digoxin, digitoxin, quabain
slide18

structure

  • Lactone ring and steroid nucleus are essential for activity
  • sugar molecule influence pharmacokinetic
pharmacological effects
Pharmacological effects

1. Positive inotropic effect

Glycoside

Inh. Of Na+/K+ ATPase

Decrease Na+/Ca2+ exchange

Increase cardiac [Ca2+]

Increase contraction

positive inotropic effect cont
Positive inotropic effect (cont)
  • Binding with Na+/K+ ATPase thus inhibit Na+ pump
    • 20-40 % inhibition therapeutic
    • >50 % inhibition toxic

Increase the force of contraction of both normal and failure heart.

Improvement hemodynamic in failure heart.

2 sensitized baroreceptor reflex
2.Sensitized baroreceptor reflex
  • Parasympathetic activation

AV-node inhibition, increase refractory period

  • Sympathetic inhibition
    • Inhibit sympathetic discharge
    • Inhibit renin release
3 decrease electrical activity
3. Decrease electrical activity
  • Decrease action potential depolarization
  • Decrease conduction velocity
4 other effects
4. Other effects
  • Muscle
    • Slightly increase Ca2+ in muscle
  • GI
    • N/V, stimulate CTZ (vomiting center)
  • CNS
    • Disorientation, hallucination, convulsion
pharmacokinetics
Pharmacokinetics

Absorption

  • Variable oral bioavailability depend on dosage form
    • 70% tablet
    • 85% elixir
    • 95% capsule

10% of pts. metabolism by Eubacterium lentum

distribution
Distribution
  • Vd 7-8 L/kg
  • Little affinity for distribution into fat (dosing should base on ideal body weight)
  • Myocardial/serum digoxin concentration ratio are approximately 30:1.
  • Hypokalemia increase the binding of digoxin to heart.
metabolism
Metabolism
  • Enterohepatic recycling
  • Gut bacterial enzyme
  • conjugation
excretion
Excretion
  • Renal route
  • T1/21.6 day
  • Pts with renal disease increase T1/2 3.5-4.5 d.
therapeutic concentration
Therapeutic concentration
  • Drug has narrow therapeutic index.
  • Therapeutic range 0.5-2 ng/ml

(after 4-5 T1,/2)

  • Dose adjustment when drug reach to steady State. (equilibrium between heart and serum)
slide30
ADR

GI

  • N/V, vomiting, diarrhea, abdominal pain, constipation

Neurologic

  • Headache, fatigue, insomnia, vertigo

Visual

  • Color vision (green or yellow), colored halos around the subject

Miscellenoues

  • Allergic, thrombocytopenia, necrosis
adr cont
ADR (cont)

Heart

  • SA and AV node suppression
  • AV block
  • Atrial arrhythmia
  • Ventricular arrhythmia
risk of treatment
Risk of treatment
  • Serum digoxin level > 2 ng/ml
    • Cardiac arrhythmia
    • GI symptom
    • Neurogenic compliant
  • Lower digoxin level is toxic if hypokalemia, hypomagnesemia and hypercalcemia.
  • Comcomittent use of quinidine, verapamil, flecainide and amiodarone which increase digoxin level.
clinical use
Clinical Use
  • To improve clinical status of the patient
  • Combination with -blocker, diuretic, ACEI
slide34

Non cardiac glycoside

1.catecholamine

2. PDEI

catecholamine
Catecholamine
  • Dopamine

 1, 1 DA receptor

Increase NE… tachycardia

  • Dobutamine
  • synthetic analoge of dopamine
  • Stimulate 1> 2 receptor and >  receptor (not DA receptor)
  • positive inotropic
  • Use in refractory HF, sever acute MI, cardiotonic shock
pdei phosphodiesterase enzyme inhibitor
PDEI (phosphodiesterase enzyme inhibitor)
  • Bipyridine derivatives
    • Amrinone, milrinone, vesnarinone
pharmacological actions
Pharmacological actions
  • Positive inotropic effect
  • Peripheral vasodilation
  • Coronary vasodilation
mechanism of pde inhibitors
Mechanism of PDE inhibitors

Drug inhibit PDE enz.

Increase cAMP

Vascular smooth muscle

heart

เพิ่ม Ca2+ influx

ลด Ca2+ efflux

เพิ่ม Ca2+ efflux

ลด Ca2+ influx

HR

vasodilation

slide39
ADR
  • Cardiac arrhythmia
  • Hypotension
  • N/V
  • Amrinone………. Thrombocytopenia, liver enzyme
  • Milirinone…….. Bone marrow suppression, liver toxicity
vasodilators
Vasodilators
  • Reduce preload/afterload
  • Venodilator…Isosorbide, nitroglycerine
  • Vasodilator….hydralazine, minoxidil, Ca2+ channel blocker
  • Both Venodilator and Vasodilator……ACEI, prazosin
slide42
ACEI
  • ACEI in CHF
    • Report that reduce remodeling
    • Reduce aldosterone from the compensatory mechanism
    • Vasodilate (Preload/after load)
  • Improve symptoms and clinical status and decrease the risk of death and hospitalization in mild, moderate, severe heart failure.
  • Decrease risk of HF in pts with LV-dysfunction
acei in chf
ACEI in CHF

Contraindicated in

  • Angioedma
  • Anuric renal failure
  • Pregnancy

Use with caution in pts with

  • Serum K+> 5.5 mmole/L
slide45

Diuretic

Goal: decrease edema and pulmonary congestion

  • เพิ่มการขับน้ำออกจากร่างกาย, ลด blood volume
  • Thiazide diuretic, loop diuretic, K+ sparing diuretic
  • Loop diuretic ใช้ในกรณีที่มี CO ลดลงรุนแรงและใช้ thiazide ไม่ได้ผลแล้ว (GFR <30 ml/min)
  • Diuretic+ACEI/-blocker > monotherapy

(will stimulate RAAS)

diuretic chf
ข้อควรระวังในการใช้ diuretic ในการรักษา CHF

Electrolytes depletion

  • Serious cardiac arrhythmia
  • Add K+ sparing diuretic

Neurohormonal activation

  • increase activation of RAAS
  • Add ACEI

Hypotension

  • Excessive use
  • Worsening heart failure
beta blockers
beta-blockers
  • Effect in CHF
    • Block SNS effects
    • Block renin
  • Improve symptoms and clinical status
  • Combination with diuretic, ACEI, digoxin, vasodilators
  • Bisoprolol, metoprolol, Carvedilol
risk of treatment1
Risk of treatment
  • Hypotension
  • Fluid retention & worsening CHF
  • Bradycardia & heart block
  • Contraindication in pts with CHF exacerbation
aldosterone antagonist
Aldosterone antagonist
  • Spironolactone
  • Research study indicate that spironolactone reduce mortality and morbidity in CHF.
  • Monitor K+ level.