Lecture 15: Intro to cardiovascular pharmacology

Question 1

When does heart failure occur?

Answer 1

Occurs when the heart’s ability to pump blood has been compromised, resulting in a low cardiac output.

This results in congestion and accumulation of fluid in the lungs and/or periphery.

Endpoint for many diseases

Question 2

What does HF result in?

Answer 2

Myocyte loss

Fibrous accumulation

Question 3

Which ventricle fails during HF?

Answer 3

Can involve the left ventricle or the right ventricle.

However, once one ventricle fails, the other will ultimately fail as well.

Question 4

Modern theories of HF

Answer 4

Focused on the heart’s maladaptive response to cytokine and hormone stimulated growth (eg. AngII, aldosterone, adrenergic).

Helps explain why hypertrophy can sometimes occur in the absence of overload.

Question 5

What does pathological hypertrophy involve?

Answer 5

progressive myocyte loss and replacement by fibrous tissue

ultimately results in pump failure.

Question 6

Two categories of drug therapy for congestive heart failure

Answer 6

1) Drugs that reduce mortality: Beta-blockers, ACE inhibitors/ARBs, aldosterone antagonists
2) Drugs that reduce symptoms: digitalis, diuretics

Question 7

What is the mechanism of CHF drugs that reduce mortality?

Answer 7

block the maladaptive response that overworks the heart.

Question 8

Symptoms in CHF

Answer 8

Coughing

Tiredness

Shortness of breath

Pulmonary edema (excess fluid in lungs)

Pumping action of heart is weaker

Pleural effusion (excess fluid around lungs)

Swelling in abdomen

Swelling in ankles

See figure

Question 9

Where were cardiac glycosides first obtained?

Answer 9

From digitalis plant, foxglove

Question 10

When are cardiac glycosides used?

Answer 10

No longer used as a first line therapy

UNLESS, person has symptomatic heart failure and atrial fibrillation

Question 11

Four phases of action potential of SA node and purkinje fibres

Answer 11

SA node: slow upstroke, drive by calcium, not sodium

Purkinje fibers: Fast upstroke due to sodium

See figure

Question 12

What is the Vaughan Williams classification? What is it based on?

Answer 12

System commonly used to classify antidysrhythmic drugs

Based on the electrophysiologic effect of particular drugs on the action potential

Question 13

Mechanism of Class I of VW

Answer 13

Membrane stabilizing drugs

Fast sodium channel blockers (reduce excitability of heart cells)

Divided into Ia, Ib and Ic drugs according to effects

Question 14

What is the safest anti-arhythmic med?

Answer 14

Beta blockers

Question 15

What are the different types of angina?

Answer 15

Chronic stable angina (classic or effort angina)

Unstable angina (preinfarction or crescendo angina)

Vasospastic angina (Prinzmetal’s or variant angina)

Question 16

Supply and demand of heart in angina

Answer 16

Supply: coronary artery supply

Demand: Workload placed on heart

See figure

Question 17

Therapeutic objectives of drugs for angina

Answer 17

Increase blood flow to ischemic heart muscle

Decrease myocardial oxygen demand

Minimize frequency of attacks and decrease duration and intensity of anginal pain

Improve patient’s functional capacity with as few adverse effects as possible

Prevent or delay the worst possible outcome: MI or life threatening arrhythmia

Question 18

Uses of nitrates/nitrites

Answer 18

Prevention and treatment of angina

Alleviates coronary artery spasms

Question 19

Rapid acting vs long acting nitrates

Answer 19

Rapid acting (sublingual, IV): used to treat acute anginal attacks

Long acting: prevention of anginal episodes

Question 20

When does tolerance occur in patients taking nitrates?

Answer 20

When they are taking nitrates around the clock or with long acting forms

Question 21

How to prevent tolerance in patients taking nitrates

Answer 21

Allow a regular, nitrate-free period to allow enzyme pathways to replenish

Transdermal forms: remove patch at bedtime for 8 hours, apply new patch in morning

Question 22

What are diuretic drugs?

Answer 22

Drugs that accelerate the rate of urine formation

Results in the removal of sodium and water

Question 23

How do diuretics work?

Answer 23

All diuretics directly or indirectly inhibit sodium reabsorption in the kidney

Most will also result in the loss of potassium in the kidney as well

Question 24

Reabsorption of sodium in kidney

Answer 24

In the nephron, where sodium goes, water will follow

If water is not absorbed, it is excreted in urine

High Na reabsorption (20-25%): ascending loop of henle

Medium Na reabsorption (5-10%): distal convoluted tubule

Low Na reabsorption (3%): collecting ducts

Question 25

5 classes of diuretics and where they act in nephron

Answer 25

Carbonic anhydrase inhibitors

Loop diuretics

Osmotic diuretics

Potassium-sparing diuretics

Thiazide and thiazide-like diuretics

See figure