Week 15: Pharmacology of Smooth Muscle in Relation to Cardiovascular Function Flashcards
What is angina?
-Pain that occurs when the oxygen supply to the myocardium is insufficient to meet its metabolic demands
What are the 3 types of angina?
stable angina
unstable angina
varient angina
What is hypertension?
-Abnormally high blood pressure (systolic and diastolic, or systolic only) that is sustained over time
What classes of drug are used clinically to relax smooth. muscle?
Organic nitrates
Calcium channel blockers
What do organic nitrate blockers treat?
- Acute angina and chest pain associated with acute coronary syndrome (e.g. a ‘heart attack’) – short acting agents
- As prophylaxsis (prevention) of angina – long acting agents
- treatment of pulmonary oedema (‘water on the lungs’) – given intravenously with other agents
What are calcium channel blockers used for?
- Treat hypertension, reducing the risk of stroke, myocardial infarction (‘heart attack’) and death from cardiovascular disease
- Prophylaxis (prevention) of angina
- To control heart rate in patients with supraventricular arrhythmias (e.g. supraventricular tachycardia, atrial flutter and atrial fibrillation)
What is the alternative blocker in treatment of stable angina?
beta-blockers instead of calcium channel blockers
What activates myosin-LC-phosphatase?
cGMP to PKG
What does myosin-LC-phosphatase act on?
myosin-LC P to myosin-LC= relaxation
What are the opposing enzymes in contraction and relaxation of cardiac smooth muscle?
MLCK (active)
Myosin-LC-phosphatase (relaxation)
What does PKG act upon to cause relaxation?
MP
myosin phosphatase
What type of smooth muscle do organic nitrates relax?
all types of smooth muscle
What can clinical doses of NO cause? (3)
- Venorelaxation (small dose)-> preload
- Arteriolar dilation (decrease arterial pressure) ->afterload
What is the effect of NO dosage on normal vs angina patients?
- Increased coronary blood flow (in normal subjects)
- In angina, there is no overall increase, but blood is redirected towards the ischaemic zone
What zone is blood redirected to when a patient with angina takes NO?
Ischaemic zone
What are the benefits to NO for people with angina?
1) decreased preload;
2) decreased afterload;
3) improved perfusion of the ischamic zone
Where do the benefits derive from in angina?
Decreased myocardial oxygen requirement
What are examples of organic nitrates that treat angina?
glyceryltrinitrate (GTN)
isosorbide mononitrate (ISMN)
both metabolise to NO
What are the key features of glyceryltrinitrate (GTN)?
- Short-acting (30 min) – undergoes extensive first-pass metabolism
- Administered sublingually (as a tablet), or as a spray, for rapid effect before exertion (stable angina) or IV (in conjunction with aspirin) in unstable angina
- More sustained effect if delivered by transdermal patch
What are adverse effects of organic nitrates?
headaches
hypotension and fainting
relex tachycardia
formation of methaemoglobin (haemoglobin that cannot carry oxygen)
What do Ca2+ blockers physically block?
prevent L-type channels in excitable tissues in response to depolarisation and hence limit Ca2+ conc
Where are the L-type calcium channels found that CCBs act upon?
heart, smooth muscle and other locations
What are the 3 types of CCBs?
- Verapamil (relatively selective for cardiac L-type channels) – block the pore
- Amlodipine (dihydropyridine compound – relatively selective for smooth muscle L-type channels) – act allosterically to prevent channel opening
- Diltiazem (intermediate selectivity)
What are some clinical uses of CCBs?
- Hypertension and angina as it causes vasodilation by reducing conc of Ca2+ in smooth muscle
- Dysrhythmias
What CCBs is used for dysrhythmias?
Verapamil
Suppresses conduction through the AV node
