Block 3 - Ischemic Heart Disease Med Chem Flashcards
What are the symptoms of Ischemic Heart disease?
- Angina pectoris
- Silent myocardial ischemia
- Acute coronary insufficiency
- Myocardial infarction
What is angina pectoris?
Imbalance between oxygen requirement of heart and oxygen supplied to it via coronary vessels
Primary symptom of ischemic heart disease
What is the most common cause of angina pectoris?
Atheromatous obstruction of large coronary vessels (coronary artery disease, CAD)
What is classic angina? Cause?
inadequate blood flow in the presence of CAD caused when myocardial oxygen requirement increases but coronary blood flow does not i.e. exercise
- Ischemia with acidic metabolites → pain
- May not have pain = silent or ambulatory ischemia
What is coronary miscovascular dysfunction?
typical symptoms but normal epicardial coronary vessels
What is vasospastic (variant Prinmzmetals) angina?
transient spasm of localized portions of vessels→ myocardial ischemia and pain
O2 delivery decreases
What is unstable angina? Cause?
episodes occur at rest; increase in severity, frequency and duration of chest pain
Caused by episodes of increased epicardial coronary artery resistance or small platelet clots in area of an atherosclerotic plaque
Nitatrates are _____ absorbed due to ____ nature therefore it is highly effective in _____ situations
Rapidly; lipophilic; emergency
Describe structure of nitrates?
esters of simple organic alcohols or polyols with nitric acid
What are the function of nitrates?
- Vasodilation of veins → pooling of blood in veins and decreased return to heart (decrease preload)
- Vasodilation of coronary arterioles → decrease resistance of peripheral tissues (decreased after load)
Decrease in myocardial workload → reduced O2 demand by heart
What cells produce NO?
produced by vascular endothelial cells, causes relaxation of vascular smooth muscle (VSM)
Describe the nitrates MOA?
- Organic nitrates mimic the actions of endogenous NO by releasing NO radicals
- Prodrug
- Increases in cGMP
Why are nitrates hard to formulate?
- Small esters → very volatile
- Moisture can easily hydrolyze the ester bond
- Explosive when pure → must dilute
Does increase nitrogen groups mean increased activity of NO?
No, activity will be the same
What are nitrate formulations used for? What properties are important its use?
- Treatment of acute anginal attacks (Fast onset)
- Prevention of anginal attacks (Longer DOA)
What is acute NO for? Dosage forms?
rapid onset, can have short duration of action
SL/Inhalation
What is something to be aware of we use SL Nitrates?
- SL can avoid some hepatic metabolism (buccal and transdermal)
- Onset is 2 min, DOA: 30 min
What is something to be aware of we use inhalation Nitrates?
Inhalable amyl nitrate onset = 15 – 30 sec, duration 1 min
What is prevention NO for? Dosage forms?
Longer DOA, Longer onset
Active metabolites help isosorbide denigrate
Oral/ointment/transdermal patch
Common ADRs of nitrates?
HA, Tachycardia, and postural hypotension
Tolerance can develop → Shortened DOA
DDIS for nitrates?
Agents that cause hypotension (vasodilators, alcohol, tricyclic antidepressants)
MOA of ranolazine?
- Lowers intracellular Ca2+ → Reduces Na+ current (Ina) allowing Ca2+ entry through sodium-calcium exchanger
- Reduces diastolic tension, cardiac contractility and work
- Doesn’t change BP and HR
ADRs of ranolazine? Indication?
Prolongs QT intervals in patients with CAD
No torsades de pointes
Ind: PO prophylactic
DDI of ranolazine?
Metabolized by CYP3A4 – affected by inhibitors
Inhibits P-gp
What is MOA of pentoxifylline?
Reduces viscosity of blood and increases deformability of red blood cells → Blood flows more easily through partially obstructed areas
What is MOA of pentoxifylline?
Reduces viscosity of blood and increases deformability of red blood cells → Blood flows more easily through partially obstructed areas
