The document discusses the cardiovascular system and treatments for conditions like angina. It defines angina and describes different types. It then discusses various drug classes used to treat angina, including organic nitrates, calcium channel blockers, beta blockers, and dipyridamole. For each drug class, it explains the mechanism of action, effects, uses, and potential side effects. It also provides guidance on treating acute myocardial infarction and lists several reference pharmacology textbooks.

1. Cardiovascular System Module
By
Dr. Mohamed Farouk Ahmed, PhD
Assistant Professor of Clinical Pharmacology - Faculty of Medicine - University of Jeddah

2. Definition:
• Angina: is severe chest pain due to ischemia of the cardiac
muscle, generally due to obstruction or spasm of the
coronary arteries.

3. A- EXERTIONAL ANGINA
B- VARIANT ANGINA
C- UNSTABLE ANGINA

5. 1- Organic
Nitrates
2- Ca+ channel
blockers
4- Dipyridamole
3- Beta
blockers

6. Kinetics:
• Absorbed from buccal and intestinal mucosa.
• Extensive hepatic first pass metabolism.
• Excretion after conjugation with glucuronic acid.
Mode of Action:
• Organic nitrates are inactive in vitro.
• Nitrates and nitrites in the body form nitric oxide which
activate guanylate cyclase leading to increase cGMP,
• Inhibit platelet aggregation & spasmolytic effect.

7. 1-Blood vessels: V.D of normal vessels, (big veins).
• Powerful veinodilator: marked decrease VR and pre-load.
• Mild arterial V.D: mild decrease PR and after-load.
• Coronary V.D: of normal but not atherosclerosed ones
leading to redistribution.
• Meningeal V.D: Headache it disappears on tolerance.
• Cutaneous V.D: flush of face & chest (nitroid reaction).
• Retinal V.D: rarely increase intraocular pressure.
• Pulmonary V.D: decrease pulmonary pressure.

8. 2- Heart: ↓ cardiac work & oxygen requirements.
• Potent veinodilator: ↓ venous return causing
- ↓ pre-load on heart and ↓ end diastolic volume → to ↓
contractility
• Weak arteriodilator: weak reduction of PR and after-load.
But, with large dose hypotension → reflex sympathetic
stimulation, ↑ contractility & tachycardia
3- Blood pressure: hypotension
4- Spasmolytic effect: on bronchial , biliary, GIT & uterus.
5- Reflex stimulation of respiratory center

9. 1- All types of angina pectoris:
• Angina of effort: ↓ cardiac work (mainly preload) & O2-
consumption.
• Variant angina: coronary V.D.
• Mixed & unstable angina: ↓cardiac work and coronary V.D.
2- Acute myocardial infarction & acute pulmonary edema
3- Biliary colic & Bronchial asthma.
6- Cyanide poisoning: Na nitrite IV and amyl nitrate inhalation.

10.  Headache, flush & increase intraocular pressure.
 Postural hypotension (syncope).
 Hypotension leading to reflex sympathetic tachycardia.
 Tolerance & cross tolerance between nitrites & nitrates.
 Coronary dependence after prolonged exposure to nitrates.
 Hypersensitivity reaction especially with tetranitrate.
 Met-hemoglobinemia especially with nitrites.

11. Block voltage dependent L type Ca channels leading to:-
cardiac inhibition (specially verapamil) and arteriolar VD
(specially nifedipine) with smooth muscles relaxation.
1-Verapamil
- powerful cardiac depressant & coronary VD.
- weak peripheral VD.
2-Nifedipine
- powerful VD & coronary VD.
- very weak myocardial depressant.

12. 1-Exaggeration of VD: specially with nifedipine
• Tachycardia which may aggravate myocardial ischemia.
• Flushing, headache, ankle edema, dizziness.
• Hypotension.
2-Cardiac depressant effect: specially with verapamil
• Bradycardia & Heart block.
3-Other adverse effects
• Verapamil : Galactorrhea, hepatotoxicity.
• Nifedipine : Nasal congestion, tinnitus.
• Diltiazem : Blurred vision, gum hyperplasia.

13. 1- As antiarrhythmic (class IV)
• Verapamil is used in supra-ventricular tachycardia and in atrial
fibrillation.
2- As antianginal
• Used in all types of angina by decrease cardiac work
(verapamil, diltiazem) and coronary VD (nifedipine).
3- As antihypertensive
• Nifedipine is a potent arteriodilator used as monotherapy in
mild-moderate hypertension or as sublingual capsules in crisis.
4- Other therapeutic uses
• Nimodipine in cerebral vasospasm.
• Flunarizine in prophylaxis of migraine, PVD.

14. Used in prophylaxis of angina pectoris:
• Stable angina. Use either selective or non-selective B-blockers.
• Unstable angina. Use only selective B1-blockers.
N.B.
• Non selective B-blockers are contraindicated in variant
angina?
• B-Blockers are not used with verapamil.
• B-blockers are added to nitrates & nifedipine.

15. 1- Inhibit phosphodiesterase enzyme → activation of cAMP →
(Inhibit platelet aggregation + inotropic,V.D.)
2- Inhibit uptake & degradation of adenosine → increase
adenosine (V.D).
3- V.D of small coronaries and encourage → collateral
circulation.
4- Dipyridamol does not correct cardiac ischemia.
5- Used in prophylaxis of stable and unstable angina.

16. 1. Control of pain: Morphine IV 2-5 mg and repeated as needed
but more than 60 mg should be given during that first 12 hours.
2. Rest is absolutely essential until the infarct heals.
3. Mental rest can be achieved by Diazepam 5-10 mg to relieve
anxiety.
4. Oxygen should be given especially if shock, left ventricular
failure or persistent chest pain is present.

17. 5. Smoking must be completely forbidden.
6. Thrombolytics and anticoagulants: Streptokinase (SK) and
tissue plasminogen activators are given within 4-6 hours, (SK)
dose is (1500000 IU over one hour by IV infusion).
7. Measures used to limit the size of infarction: B-blockers,
calcium channel blockers, or nitroglycerin.
8. Treatment of complications : as HF or arrhythmias.

19.  Lippincott illustrated reviews pharmacology 5th Edition.
 Basic and clinical pharmacology 12th edition.
 Rang & Dale's Pharmacology. 9th Edition.
 Goodman and Gilman's the pharmacological basis of
therapeutics 13th edition.
 Katzung basic and clinical pharmacology 12th edition.