Term 1 Pharm - CHF

Question 1

Shock

Answer 1

An acute and dynamic clinical syndrome, 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)

Worst = shock (it is dynamic, rapidly changes)

Question 2

Heart failure (CHF)

Answer 2

An acute or chronic clinical syndrome in which heart disease (of many types, most often ischemic) produces low cardiac output (forward failure), high filling pressure (backward failure), or both
Can involve either or both ventricles
Variety of causes
Helpful to consider Rx of acute crisis, and Rx of chronic phase
May progress to shock, but often not

Question 3

Inotropic agent

Answer 3

Contraction

An inotrope is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular (usually of LV) contractions. Positively inotropic agents increase the strength of muscular contraction.

Question 4

Chronotropic agent

Answer 4

SA Node

Change the heart rate by affecting the nerves controlling the heart, or by changing the rhythm produced by the sinoatrial node. Positive chronotropes increase heart rate; negative chronotropes decrease heart rate.

Question 5

Dromotropic agent

Answer 5

AV Node

Affects the conduction speed in the AV node, and subsequently the rate of electrical impulses in the heart.

Question 6

Remodeling response to low output states

Answer 6

Also called a proliferative response
Leads to premature death of myocardial cells
Then progressive deterioration and death

Question 7

Atropine sulfate

Answer 7

Class: Pharmacologic class—muscarinic receptor antagonist, belladonna alkaloid; therapeutic class—antiarrhythmic, vagolytic, mydriatic
(Doesn’t do anything to SA node receptor itself, just BLOCKS that of Ach)

PD: blocks the effects of ACh on the SA and AV nodes, thereby increasing conduction and HR; also decreases secretions in various glands (e.g. salivary, bronchial, sweat)

PK: given IV, endotracheally, and topically (in the eye)

Toxicity: avoid in patients with glaucoma. Obstructive uropathy, GI obstruction, ileus, toxic megacolon;

Special issues: can cause agitation, confusion (especially in the elderly), delirium, disorientation; blurred vision; constipation; urine retention; watch out especially in older men with BPH

Question 8

Best drug for anaphylactic shock

Answer 8

Epinephrine

Question 9

Dopamine (Intropin™)

Answer 9

Class: adrenergic and dopaminergic receptor agonist; therapeutic class: inotropic agent; vasopressor (Note: not useful in treatment of Parkinson’s Disease)

PD: stimulates DA receptors (renal blood flow), beta-1, and alpha-1 receptors at different infusion rates (low, med, high infusion rates)

PK: can only be infused IV; acts quickly within minutes; half-life brief (minutes), hence continuous infusion

Toxicity: ectopy, tachycardia, angina, nausea, peripheral gangrene (excess vasoconstriction); extravasation

Special issues: correct hypovolemia first; administer through large vein; prevent extravasation; monitor patient closely

Question 10

Dobutamine (Dobutrex™)

Answer 10

Class: adrenergic receptor agonist; positive inotropic agent;

PD: selectively stimulates beta-1 adrenergic receptors to increase contractility and SV resulting in  cardiac output; intrestingly, HR usually remains unchanged

PK: can only be infused IV; acts quickly within minutes; half-life brief (minutes), hence continuous infusion

Toxicity: ectopy, PVC’s, tachycardia, hypertension, hypotension

Special issues: correct hypovolemia first; monitor patient closely

Question 11

Vasodilators used for CHF

Answer 11

Lisinopril useful in reducing excessive SVR, increasing CO
- Best studies done with ramipril in CHF patients

Hydralazine not useful by itself
- Reflex fluid retention and tachycardia

Bidil™ (hydralazine plus isosorbide dinitrate)

• Tested and approved for AA patients only
• 43% reduction in death, 33% reduction in first hospitalization compared to placebo

Nitroprusside is very useful to reduce after load
- But only when given briefly IV

Question 12

Agents to Reduce Preload in CHF

Answer 12

Loop diuretics (e.g. furosemide, bumetanide)

• Most powerful diuretics
• Act on loop of Henle
• Available po or iv with prompt action

Thiazide diuretics (e.g. HCTZ)

• Available po only
• Lower maximum efficacy

Aldosterone antagonist diuretics (e.g. spironolactone)
- Not very strong diuretic
- PO only
Can cause K retention (less secretion)

Question 13

Short-term Neurohumoral Response to Low Cardiac Output (or CHF)

Answer 13

Salt and thus water retention
- Mediated by aldosterone (and ADH)

Activation of SNS (increased contractility/conduction/HR)
- Mediated by NE stimulating beta-1 receptors

Increase in renin release in kidney (JGA)

• Mediated (eventually) by angiotensin II (Beta1 stimulator)
• AT II produces vasoconstriction and stimulates aldosterone release

Question 14

How Prevent of Chronic Toxic Remodeling

Answer 14

Block the effects of aldosterone on cardiac tissue
- Spironolactone

Block the stimulation of myocardial beta-1 receptors

• Carvediolol (Coreg™) has most data, also slow-release metoprolol (Toprol XL™)
• Must be titrated carefully to avoid worsening of CHF

Block the production or action of AT II

• Variety of ACE inhibitors
• Variety of AT II receptor blockers (ARBs)

Outcomes that have been proven:

• Fewer hospitalizations
• Fewer cardiac deaths
• Longer survival in disease with poor prognosis