Pharm 9- Ca Channel Blockers Flashcards
4 Categories of Antianginal Drugs
- Organic Nitrates
- Sodium Channel Blockers
- Calcium Channel Blockers
- B Blockers
Types of Angina
- “Classic,” “Stable,” “Effort-induced”
- “Unstable”
- “Variant,” “Rest,” “Vasospastic,” “Prinzmetal”
- Acute Coronary Syndrome
- Mixed
Classic Angina
Most common form of angina
Caused by a fixed coronary artery obstruction (generally atheromatous)
Stable pain pattern
Relived by rest or Nitro
Relationship between % blockage and degree of debilitaiton
Not a great relationship; ex. sometimes even a 30% blockage can be very debilitating
How does classic angina present in women?
Does not always present as pain
Exhaustion, nausea, diaphoresis
Unstable Angina
Pain at rest or with increasing frequency, during, severity, or as the result of less exertion
Pain not relieved by NTG or prolonged rest (>20 minutes)
Prinzmetal Angina
Pain is episodic and unrelated to exertion
May have atherosclerosis, but angina is the result of arteriospasm and unrelated to exertion or rest
Tx: NTG; calcium channel blockers
Acute Coronary Syndrome
Atheromatous plaque ruptures
Inflammatory cells and mediators activated
“Lipid pool” forms
Thrombus forms and propagates
Vasoconstriction occurs
Vascular occlusion
Cardiac muscle sickens and dies; MI “biomarkers” are released
Mixed Angina
Patients have angina during exertion and at rest
Cause: Fixed obstruction combined w. vasospasm and or endothelial disruptions
Two Angina Rx Strategies
- Increase O2 Delivery
2. Decrease O2 Demand
What are the determinants of myocardial oxygen consumption?
- Wall stress (intraventricular pressure, ventricular radius/vol, wall thickness)
- Heart Rate
- Contractility
What percent O2 does the heart extract at rest?
75% of oxygen delivered to it; O2 “sucker”
What determines how much myocardial wall stress is necessary to overcome that resistance and pump blood?
Arterial blood pressure
What determines SVR?
Arterial (overwhelmingly arteriolar) tone determines SVR ~ systolic wall stress.
What determines how much blood can be “stored” in the venous blood delivery system before it’s returned to the heart?
Venous (capacitance) tone determines this.
What does venous tone determine?
Diastolic wall stress
What do organic nitrates and nitrites do?
Cause RAPID decrease in myocardial demand and prompt relief of stable, unstable, and variant angina.
% Obstructions vs. Angina
50% Obstruction: Potential angina
99% Obstruction: Resting angina
70% obstruction: Exercise induced angina
30% obstruction: no angina
What are the 4 organic nitrates and nitrites?
Nitroglycerine (Nitrobid)
Nitroprusside (Nipride)
Isosorbide mononitrate (Imdur)
Isosorbide dinitrate (Isordil)
How do nitrates result in vascular smooth muscle relaxation?
Increase nitrates
Increase nitric oxide
Increase cGMP
Increase dephosphorylation of myosin light chain
What is the most common nitrate/nitrite?
NTG
What are the side effects of organic nitrates and nitrites?
Cyanide toxicity and Nipride
Reflex tachycardia (increase myocardial demand and decrease coronary perfusion via diastolic filling)
Reflex positive inotropy (increase myocardial demand)
What can a high sustained dose of organic nitrates and nitrites cause?
Methemoglobinemia; particularly in peds +/- Tylenol exposure
Methemoglobinemia
Blood turns chocolate brown, blood disorder in which an abnormal amount of methemoglobin – a form of hemoglobin – is produced; blood with an oxidized heme group
What do you do if you have methemoglobinemia on bypass?
- Tell physician
- Prepare to give methylene blue at 1-2 mg/kg (up to 50 mg) IV over 3-5 minutes
- Absorbic acid
- Lots of pure o2