PHARM - Drugs for the Treatment of Ischaemic Heart Disease - Week 5 Flashcards
What are ischaemic heart diseases typically a result of?
Plaque buildup in the coronary arteries, narrowing them and preventing adequate blood flow to the heart, resulting in ischaemia.
What is the principal artery supplying blood to the heart?
Coronary arteries.
In what two ways can blood flow to the heart be increased, and why do they increase flow?
Dilating coronary arteries - self explanatory
Decreasing heart rate - arteries are less compressed
What does the O2 demand of the heart depend on?
The cardiac workload
Give the formula for cardiac output.
Stroke volume x heart rate
Define preload.
Degree of stretch pre-contraction
Define afterload.
Resistance the heart pumps against
Define angina.
Chest pain
Does ischaemic heart disease cause angina?
Yes
Name three possible causes of angina.
Imbalance between O2 supply and needs
Insufficient O2 to meet cardiac demand
Reduced perfusion rather than inadequate blood O2
Define stable angina, the pain it causes, two means by which it can be induced, and what it is associated with.
Chest pain that occurs with exertion or stress. It is associated with coronary artery disease.
Define variant angina, when it occurs, and its mediator.
Coronary vasospasm at rest, mediator unknown.
Define unstable angina, when it occurs (2), and what secondary complication it has the potential to cause.
Angina at rest and with effort.
Potential for thrombi formation.
Do arterioles typically get plaque buildup?
No
Consider stable angina treatment. What three things should treatment accomplish and what 2 effects should drugs have?
Treat to:
-prevent attacks
-relieve symptoms
-prevent progression to heart attack
Use drugs to:
-increase O2 supply
-reduce O2 demand
In what two ways can O2 supply be increased?
Dilating coronary arteries
Reducing heart rate
Is it relatively easy or difficult to dilate atheromatous arteries?
Difficult
Can coronary arteries always be dilated?
Not neccessarily, they may already be maximally dilated.
Explain why reducing heart rate increases O2 supply t othe heart.
Heart spends longer in relaxation phase
Coronary arteries have longer to fill
In what three ways can O2 demand be decreased?
Decrease cardiac output
Reduce preload
Reduce afterload
In what two ways can cardiac output be decreased?
Reduce heart rate
Reduce stroke volume
In what two ways can preload be decreased? Give an example of a drug class for this.
Dilate veins
Reduce venous return
Nitrates
In what two ways can afterload be decreased? Give an example of a drug class for this.
Dilate arterioles
Decrease resistance
Ca2+ channel blockers
How do nitrates work to treat angina?
They are biotransformed to NO, which dilates all vessels.
Describe the effect of NO on the following vessels (other than it dilates them) and whether it is major or minor:
Veins
Large arteries
Coronary arteries
Veins
-decreases preload (major)
Large arteries
-decreases afterload (minor)
Coronary arteries
-no effect
Consider nitrates for treating angina. Name two additional effects it has on other smooth muscle, and whether they are clinically significant.
Other smooth muscle - brief relaxation of the gut and airways.
Not clinically significant.
Name an effect nitrates can have on blood pressure, and why this occurs.
Postural hypotension due to venous pooling
Name 5 side effects of using nitrates for angina.
Headache
Flushing
-due to cerebral, head, and neck arterial dilation
Reflex tachycardia
What are nitrates typically used in combination with and to minimise what side effect?
B-blockers or cardiac-selective calcium channel blockers to minimise tachycardia.
Describe four ways in which tolerance to nitrates can occur with continuous use. Name which of the four is the classic mechanism.
-The classic mechanism involves depletion of tissue thoils needed for NO production
-Increased release/sensitivity to constrictors like AII
-Increased endothelial free radical production scavenging NO, reducing bioavailability
-Reduced/abnormal activity of muscle mitochondria, reducing NO production, increasing free radicals
How can the classic mechanism of nitrate tolerance be treated? What is required for nitrate tolerance in general?
Treatment with N-acetyl cysteine restores GTN (glycerine) effect.
A drug-free period is required to minimise tolerance - removing the patch overnight.
Name 2 main ways B-blockers can be used to treat angina.
They reduce heart contractility and decrease heart rate.
What is the first-line therapy for angina prophylaxis
Selective or non-selective B-blockers
Name 6 adverse effects and contraindications for B-blockers.
Cold extremities
Fatigue
Cardiac depression
Bradycardia
Broncoconstriction
Decreased symptoms of hypoglycaemia
What kind of calcium channel blockers can be used for angina treatment?
L-type
What four effects do calcium channel blockers have on the heart with angina treatment?
Decreased heart rate, stroke volume, cardiac output, and decreased O2 demand.
What two vascular effects do calcium channel blockers have with angina treatment?
Arterial dilation, reducing afterload and demand
What two drugs must calcium channel blockers never be taken with?
A B-blocker or digoxin
What is the effect of ivabradine, and how does it work?
Pure heart rate reduction
Specific and selective inhibition of inward sodium/potassium current in the sinus node
When is ivabradine given for angina treatment?
Only if heart rate is >70 beats per minute
Name 3 adverse effects of ivabradine.
Brightness in visual field due to retinal effects (same target, different site)
Bradycardia
Conduction abnormalities
Name two factors that require precaution when giving ivabradine.
Heart rate <70 bpm
Levels are increased by some antibiotics and antifungals
Consider angina therapy. Are the drugs used for treatment disease-modifying? Do they lower the risk of infarction or cardiac arrest?
They are not disease-modifying, so there is an unchanged risk to heart disease.
Are single drugs given for angina treatment is it a combination therapy?
Combination therapy
Summarise angina therapy by lising the following drugs by whether or not they effect the following factors:
Drugs
-ivabradine
-B-blockers
-Ca2+ channel blockers
-nitrates
Factors
-heart rate
-stroke volume
-afterload
-preload
Ivabradine
-lower heart rate
B-blocker
-lower heart rate
-lower stroke volume
Ca2+ channel blocker
-lower heart rate
-lower stroke volume
-lower afterload
Nitrates
-lower preload
What effect do the following factors (if decreased) have on O2 supply and demand (2):
Heart rate
Stroke volume
Afterload
Preload
They all decrease O2 demand
Decreasing heart rate increases O2 supply
How can a coronary spasm be treated?
Short-acting nitrate
Aside from nitrates, list another drug that can be used to treat variant angina.
Ca2+ channel blocker
Can B-blockers be used for treating variant angina?
No, they are contraindicated
How can unstable angina be treated? What additional drug is required and why?
Same as for classic angina, with the addition of aspirin to prevent thrombosis.
Name 6 ways the risk factor for angina can be reduced.
Stop smoking
Increase physical activity
Lose weight
Treat hypertension, dyslipidaemia, and diabetes
Name two revascularisation techniques for angina.
Percutaneous coronary intervention
Coronary artery bypass graft
