IHD Drugs Flashcards
Nitrates MOA?
Nitrates further activate the guanylyl cyclase enzyme (converts GTP to cGMP, which causes the myosin light chain to enter a relaxed state) thereby causing vasodilation. This does 2 things:
- Decreased venous tone, thereby reducing the venous return to the heart => Preload reduction!
- Arteriolar vasodilation that reduces arterial resistance => Afterload reduction
Reducing both preload and afterload of the heart reduces the oxygen consumption of the heart and reduces A.
Nitrates PK?
Nitroglycerin (Glyceryl trinitrate) has significant vasodilation activity -> Broken down into NO and Glyceryl Dinitrate by GSH S-Transferase
G dinitrate also has significant vasodilation activity
Then, NO kicked out again to make G dinitrate into G mononitrate. This has less vasodilation activity (because it is less wiling to donate it’s only NO group).
Sublingual -> 1-5min onset with 10-30min DOA
Transdermal -> 30-60min onset, 7-10H DOA!
Isosorbide dinitrate (ISDN) / ISMN vs. glyceryl nitrates?
ISDN / ISMN is better for prophylaxis -> See that it lasts much longer than glyceryl nitrates! Also note that the duration of action is dependant on the kind of drug - There are immediate release (IR) and sustained // extended release (SR) formulations.
Both PO.
ISDN: 60min onset, 8h IR and 12h SR formulations /
ISMN: 30-45min onset, 6h IR and >24H!!! SR formulations
ADR of nitrates
ADR of nitrates-
- Reflex tachycardia (baroreflex from the sudden drop in BP)
- Hypotension because of venous vasodilation
- Headache because of meningeal artery vasodilation!
Dihydropyridines MOA and two main effects?
Reduce contractility of the heart. Also reduce the vascular smooth muscle tone.
Nifedipine, amlodipine
This has two effects:
- Decreased BP because of reduced contractility and decreased vascular smooth muscle tone. Anti-hypertensive!
- Decreased oxygen requirement because of directly reduced contractility. Indirectly, the oxygen requirement drops because of reduced BP hence reduced afterload. Anti-angina!
Non-DHP calcium blockers MOA? Are they used in IHD?
Reduce SAN and AVN activity, thereby reducing supraventricular reentry tachycardia. This is called reentry tachycardia because the electrical signal loops in a circuit that exists above the ventricles, and so the same electrical signal causes multiple contractions, leading to tachycardia.
By reducing SAN and AVN activity, this kind of tachycardia is reduced. This is hence an Anti-arrhythmic!
Usage of DHP vs non-DHP?
It doesn’t matter if the drug is DHP or non-DHP. What matters is the aim of treatment.
Lower BP -> Verapamil / Diltiazem / Nifepidine
Vasodilator -> Nifedipine > Diltizaem > Verapamil
Cardiac depressant -> Verapamil > Diltizaem > Nifepidine
Calcium blocker MOA and indications?
These drugs of course work by blocking the Ca channels that allow Ca entry into the myocyte (these then form the Ca-Calmodulin complex, allowing MLCK to become activated and contract the muscle)
DHP are indicated in Htn, Stable angina (amlodipine). Amlodipine is also known to reduce risk of MI and stroke + known to reduce mortality
ADR of non-DHP?
ADR includes cardiac depression in the form of bradycardia / AV blockage / HF
If you have no arrhythmia and Ca blockers you may get a heart block / bradycardia!
ADR of DHP?
ADR include hypotension, HF, and MI
Ivabradine?
Its action is that it directly lowers the heart rate.
Good IHD medication indicated in stable AP, chronic HF with systolic dysfunction, pts with HR>75 (MUST have SINUS RHYTHM though)
Lowers HR by direct inhibition of the I(f) current. This is the current generated by “funny channels” in the heart, which controls the rate of spontaneous DIASTOLIC depolarisation in the SAN.
This reduces the cardiac workload and myocardial oxygen consumption
ADR are unique!
Luminous phenomena -> Transient enhanced brightness in a limited field, maybe even halos!
Other symptoms come from bradycardia, just as dizziness, hypotension, fatigue, malaise
Beta blockers C/I in _?
DM
