Lecture 15: Intro to cardiovascular pharmacology Flashcards
When does heart failure occur?
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
What does HF result in?
Myocyte loss
Fibrous accumulation
Which ventricle fails during HF?
Can involve the left ventricle or the right ventricle.
However, once one ventricle fails, the other will ultimately fail as well.
Modern theories of HF
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.
What does pathological hypertrophy involve?
progressive myocyte loss and replacement by fibrous tissue
ultimately results in pump failure.
Two categories of drug therapy for congestive heart failure
1) Drugs that reduce mortality: Beta-blockers, ACE inhibitors/ARBs, aldosterone antagonists
2) Drugs that reduce symptoms: digitalis, diuretics
What is the mechanism of CHF drugs that reduce mortality?
block the maladaptive response that overworks the heart.
Symptoms in CHF
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
Where were cardiac glycosides first obtained?
From digitalis plant, foxglove
When are cardiac glycosides used?
No longer used as a first line therapy
UNLESS, person has symptomatic heart failure and atrial fibrillation
Four phases of action potential of SA node and purkinje fibres
SA node: slow upstroke, drive by calcium, not sodium
Purkinje fibers: Fast upstroke due to sodium
See figure
What is the Vaughan Williams classification? What is it based on?
System commonly used to classify antidysrhythmic drugs
Based on the electrophysiologic effect of particular drugs on the action potential
Mechanism of Class I of VW
Membrane stabilizing drugs
Fast sodium channel blockers (reduce excitability of heart cells)
Divided into Ia, Ib and Ic drugs according to effects
What is the safest anti-arhythmic med?
Beta blockers
What are the different types of angina?
Chronic stable angina (classic or effort angina)
Unstable angina (preinfarction or crescendo angina)
Vasospastic angina (Prinzmetal’s or variant angina)
Supply and demand of heart in angina
Supply: coronary artery supply
Demand: Workload placed on heart
See figure
Therapeutic objectives of drugs for angina
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
Uses of nitrates/nitrites
Prevention and treatment of angina
Alleviates coronary artery spasms
Rapid acting vs long acting nitrates
Rapid acting (sublingual, IV): used to treat acute anginal attacks
Long acting: prevention of anginal episodes
When does tolerance occur in patients taking nitrates?
When they are taking nitrates around the clock or with long acting forms
How to prevent tolerance in patients taking nitrates
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
What are diuretic drugs?
Drugs that accelerate the rate of urine formation
Results in the removal of sodium and water
How do diuretics work?
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
Reabsorption of sodium in kidney
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
5 classes of diuretics and where they act in nephron
Carbonic anhydrase inhibitors
Loop diuretics
Osmotic diuretics
Potassium-sparing diuretics
Thiazide and thiazide-like diuretics
See figure
