2013-09-19 Drug Tx of CHF

Question 1

Define shock

Answer 1

– An acute and dynamic clinicalsyndrome, usually lasting only hours,
characterized by poor perfusion of vital organs and tissues(always),
and low blood pressure (usually)
– Variety of possible causes(hemorrhage,sepsis, burn, acute MI,
anaphylaxis)

Question 2

Define heart failure

Answer 2

(CHF)
– An acute or chronic clinicalsyndrome in which heart disease (ofmany
types,most often ischemic) produceslow cardiac output(forward
failure), high filling pressure (backward failure), or both
– Can involve either or both ventricles
– Variety of causes
– Helpfulto consider Rx of acute crisis, and Rx of chronic phase

Question 3

Positive inotropic agent

Answer 3

agents that increase the strength of cardiac contractions

Question 4

Positive chronotropic agent

Answer 4

drugs that increase HR by increasing rate of AV conduction

Question 5

Positive dromotropic agent

Answer 5

A dromotropic agent is one which affects the conduction speed in the AV node, and subsequently the rate of electrical impulses in the heart.

Agents that are dromotropic are often (but not always) inotropic and chronotropic.
[source = Wikipedia]

Question 6

ACUTE Neurohumoral response to low
perfusion, low cardiac output, or CHF
[– Role ofNE,renin, aldosterone]

Answer 6

• Salt and thus waterretention
– Mediated by aldosterone (and ADH)
• Activation of SNS
– Mediated byNE stimulating beta‐1 receptors
• Increase in renin production in kidney (JGA)
– Mediated by angiotensin II
– AT II produces vasoconstriction and stimulates
aldosterone release

Question 7

CHRONIC Remodeling response to low output

states

Answer 7

– Also called a proliferative response
– Leadsto premature death ofmyocardial cells
– Then progressive deterioration and death

Question 8

ATROPINE Pharm Card

[review Rang 1.02]

Answer 8

• Intrinsic actions vs blocking effects of Ach
• Effects on hearts/p heart transplant???
• Effects on SAN, AVN, ventricles
• Should all bradycardia be treated??
– Cf Bjorn Borg
• Systemic effects of atropine?
– Dry,mad, blind, hot
• Other drugs with atropine‐like effects?
– Scopolamine patches, diphenhydramine

Question 9

EPINEPHRINE Pharm Card

[review Rang 2.03]

Answer 9

• Review structures on board
• Mixed: Alpha‐1,(Alpha‐2),Beta‐1, Beta‐2 agonist
• When would you wantsuch amixture???
• Best drug for anapylactic shock
• Also cardiac arrest with asystole orfine VF
• Also after open heartsurgery as patientis
“warming up”

Question 10

DOPAMINE Pharm Card

[see also Rang 2.05]

—Clalss
—PD
—PK
—Toxicity
—Special issues
—Indications
—Similar drug in class?

Answer 10

• Class: adrenergic and dopaminergic receptor agonist; inotropic agent; vasopressor(Note: not useful in treatment of Parkinson’s Disease, why not???)
• PD:stimulatesDA (renal blood flow), beta‐1, and alpha‐1 receptors
at different concentrations(low,med, high infusion rates)
• PK: can only be infused IV; acts quickly withinminutes; half‐life
brief(minutes), hence continuousinfusion
• Toxicity: ectopy,tachycardia, angina, nausea
• Special issues: correct hypovolemia first; administerthrough large
vein; prevent extravasation;monitor patient closely
• Indications, dose:shock, CHF; 1mcg/kg/min up to 30mcg/kg/min (
low 1‐3,moderate 3‐10, high 10‐30mcg/kg/min)
• Dobutamine:similar actions, butless ability to cause vasoconstriction via alpha‐1 receptors;more specific for beta‐1

Question 11

Which vasodilators make sense in CHF tx?

Answer 11

• Lisinopril useful in reducing excessive SVR,
increasing CO
– Beststudies done with ramipril
• Hydralazine not useful by itself
– Reflex fluid retention and tachycardia
• Bidil™ (hydralazine plusisosorbide dinitrate)
– Tested and approved for AA patients only
– 43% reduction in death, 33% reduction in first
hospitalization compared to placebo
• Nitroprusside is very useful
– But only briefly IV

Question 12

Agents to reduce preload in CHF?

Answer 12

• Loop diuretics(e.g.furosemide, bumetanide)
– Most powerful diuretics
– Act on loop ofHenle
– Available po oriv with prompt action
• Thiazide diuretics(e.g.HCTZ)
– Available po only
– Lowermaximumefficacy
• Aldosterone antagonist diuretics(e.g.spironolactone)
– Not very strong diuretic
– POonly
– Can cause K retention (lesssecretion)

Question 13

Drugs to prevent chronic toxic remodeling

Answer 13

Block the effects of aldosterone on cardiac tissue
– Spironolactone

Block the stimulation ofmyocardial beta‐1 receptors
– Carvediolol (Coreg™) hasmost data, also slow‐release metoprolol (Toprol XL™)
– Must be titrated carefully to avoid worsening of CHF

Block the production of AT II
– Variety of ACE inhibitors

Outcomes that have been proven:
– Fewer hospitalizations
– Fewer cardiac deaths
– Longersurvival in disease with poor prognosis

Question 14

Define dromotropic vs. ionotropic vs. chronotropic vs. lustrophy

Answer 14

dromotropic - changes conduction velocity (symp stim —> faster; parasymp —> slower; acts on K+ channels in the AV node)

chronotropic - changes HR (symp stim —> faster; parasymp —> slower; act on Na+ channels in SA node)

ionotropic* - changes force of contraction (acts on ventricles; symp stim —> harder contraction by incr amount of Ca2+ let into the cytosol)

lusitrophy* - having to do with relaxation of the heart (acts on ventricles; symp stim —>relax faster; incr Ca2+ reuptake in SR)

*parasympathetic system has little effect