Ischaemic Heart Disease pharm Flashcards
What is the main etiology of ischemic heart disease?
Atherosclerosis
What are some causes of IHD?
1) Atherosclerosis
2) Embolism
3) Dissecting aneurysm
4) Trauma
5) Arteritis
6) Hypoxemia
7) Ostial stenosis (syphilitic aortitis)
8) Anomalous origin of LCA
What are 4 complications of IHD?
1) Ventricles
- LV failure → CHF
- Ruptured myocardium → cardiac tamponade
- Fibrosis and aneurysm
- thrombus
2) Arrhythmias → sudden cardiac death
3) Pericarditis (post-MI: Dressler’s syndrome)
4) Valves (ruptured papillary muscle)
What are 3 factors that contribute to the pathogenesis of IHD?
1) ↓coronary flow (occlusion)
2) ↑ metabolic Dd (eg. exercise, pregnancy, infection, hyperthyroidism, myocardial hypertrophy)
3) ↓O2 availability in blood (eg. anemia, CO poisoning, pulmonary diseases, L→R shunt)
What is Prinzmetal angina?
A form of episodic myocardial ischemia
- secondary to coronary arterial spasm
- **unrelated to exertion HR, BP
- responds to vasodilators
How does chronic IHD lead to HF?
Chronic atherosclerotic narrowing of coronary arteries
→ loss of myocardial fibres → generalised myocardial fibrosis
→ insidious cardiac failure → death
What are 2 causes of sudden cardiac death?
1) Pronounced stenosis of 1 or more major arteries
2) Acute plaque change
For how long would a MI not be visible macro and micreoscopically?
12 hours
What are the 3 histological characteristics of an myocardial infarction and when would they occur?
12-24hrs
1) Coagulative necrosis (ghost outlines, no nuclei)
2) Intercellular oedema (spacing)
3) Bright eosinophilic infarcted myocytes
How would an MI appear macroscopically 12-24hrs after it occurs?
Pale with blotchy discolouration
When would neutrophil infiltration occur after an MI?
24-72 hrs
How would an MI appear macroscopically 24-72hrs after it occurs?
Soft pale and yellow
When would granulation tissue form after an MI?
3-10 days
How would an MI appear macroscopically 3-10 days after it occurs?
Hyperemic border surrounding yellow infarcted area
How would an MI appear macroscopically 6-8 weeks after it occurs?
Fibrous scar
What are the drugs used in angina?
1) Vasodilators (nitrates, Ca channel blockers)
2) Cardiac depressants (Ca channel blockers, ß-blockers)
3) Cardiac pacemaker retardant (Ivabradine)
What are the moa of nitrates used in angina treatment?
Nitrates release NO → (Guanylyl cyclase → cGMP )→ ↑myosin LC (inactive)
1) venodilation → blood pools in veins → ↓ preload
2) arteriolar dilation → ↓peripheral R → ↓ afterload
→ ↓ workload on myocardium → ↓ O2 consumption
Which nitrate is used for emergency angina therapy?
Sublingual nitroglycerin
What is the difference between sublingual and transdermal nitroglycerin?
Onset:
Sublingual: 1-5min
Transdermal: 30-60min
Duration:
Sublingual:10-30min
Transdermal: 7-10hrs
Nitroglycerin is metabolised to (active/inactive metabolite)?
Active but less active
What nitrate is used for angina pectoris prophylaxis and HF?
ISMN/ISDN
How is ISDN/ISMN adminstered?
Oral
ISDN has a (faster/slower) onset of action than ISMN?
Slower (mononitrate faster)
How does the PD of ISDN/ISMN differ at different plasma concentrations?
Low Pc: venous dilation → ↓preload
High Pc: also dilate arteries → ↓preload + ↓afterload
Which of the nitrates used in angina treatment have a direct dilatory effect on the coronary arteries, thereby lowering the intramural pressure and improving subendocardial blood flow?
ISMN/ISDN
What are 3 AEs of nitrates?
1) Reflex tachycardia (baroreflex engaged by vasorelaxation)
2) Hypotension
3) Headache (meningeal artery vasodilation)
How do the different types of calcium channel blockers differ in their ability to lower BP?
Verapimil=diltiazem=nifedipine
How do the different types of calcium channel blockers differ in their vasodilatory effects?
Verapimil < diltiazem < nifedipine
How do the different types of calcium channel blockers differ in their cardiac depressant effects?
Verapimil > diltiazem > nifedipine
What are 3 AEs of calcium channel blockers used in angina treatment?
Cardiac depression:
1) Bradycardia
2) AV blocker
3) HF
What are the clinical uses for DHP Ca channel blockers?
1) HTN
2) Stable angina (amlopidine)
3) ↓ risk of MI and stroke (amlopidine)
What are 3 AEs of DHP Ca channel blockers?
1) Hypotension
2) HF
3) MI
What is Ivabradine used for?
Stable angina pectoris and chronic HF with systolic dysfunction (sinus rhythm >75bpm)
What is the moa of Ivabradine?
“Pure” HR lowering agent:
inhibition cardiac pacemaker I(F) current that controls spontaneous diastolic depolarisation in the sinus node and thus regulates HR
→ ↓cardiac workload and O2 consumption
What are 3 AEs of Ivabradine?
1) Visual problems: luminous phenomena, transient enhanced brightness in a limited area of vision
2) Dizziness, fatigue, malaise
3) Hypotension
