Week 15: Pharmacology of Smooth Muscle in Relation to Cardiovascular Function

Question 1

What is angina?

Answer 1

-Pain that occurs when the oxygen supply to the myocardium is insufficient to meet its metabolic demands

Question 2

What are the 3 types of angina?

Answer 2

stable angina
unstable angina
varient angina

Question 3

What is hypertension?

Answer 3

-Abnormally high blood pressure (systolic and diastolic, or systolic only) that is sustained over time

Question 4

What classes of drug are used clinically to relax smooth. muscle?

Answer 4

Organic nitrates

Calcium channel blockers

Question 5

What do organic nitrate blockers treat?

Answer 5

• 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

Question 6

What are calcium channel blockers used for?

Answer 6

• 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)

Question 7

What is the alternative blocker in treatment of stable angina?

Answer 7

beta-blockers instead of calcium channel blockers

Question 8

What activates myosin-LC-phosphatase?

Answer 8

cGMP to PKG

Question 9

What does myosin-LC-phosphatase act on?

Answer 9

myosin-LC P to myosin-LC= relaxation

Question 10

What are the opposing enzymes in contraction and relaxation of cardiac smooth muscle?

Answer 10

MLCK (active)

Myosin-LC-phosphatase (relaxation)

Question 11

What does PKG act upon to cause relaxation?

Answer 11

MP

myosin phosphatase

Question 12

What type of smooth muscle do organic nitrates relax?

Answer 12

all types of smooth muscle

Question 13

What can clinical doses of NO cause? (3)

Answer 13

• Venorelaxation (small dose)-> preload

- Arteriolar dilation (decrease arterial pressure) ->afterload

Question 14

What is the effect of NO dosage on normal vs angina patients?

Answer 14

• Increased coronary blood flow (in normal subjects)

- In angina, there is no overall increase, but blood is redirected towards the ischaemic zone

Question 15

What zone is blood redirected to when a patient with angina takes NO?

Answer 15

Ischaemic zone

Question 16

What are the benefits to NO for people with angina?

Answer 16

1) decreased preload;
2) decreased afterload;
3) improved perfusion of the ischamic zone

Question 17

Where do the benefits derive from in angina?

Answer 17

Decreased myocardial oxygen requirement

Question 18

What are examples of organic nitrates that treat angina?

Answer 18

glyceryltrinitrate (GTN)
isosorbide mononitrate (ISMN)
both metabolise to NO

Question 19

What are the key features of glyceryltrinitrate (GTN)?

Answer 19

• 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

Question 20

What are adverse effects of organic nitrates?

Answer 20

headaches
hypotension and fainting
relex tachycardia
formation of methaemoglobin (haemoglobin that cannot carry oxygen)

Question 21

What do Ca2+ blockers physically block?

Answer 21

prevent L-type channels in excitable tissues in response to depolarisation and hence limit Ca2+ conc

Question 22

Where are the L-type calcium channels found that CCBs act upon?

Answer 22

heart, smooth muscle and other locations

Question 23

What are the 3 types of CCBs?

Answer 23

• 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)

Question 24

What are some clinical uses of CCBs?

Answer 24

• Hypertension and angina as it causes vasodilation by reducing conc of Ca2+ in smooth muscle
• Dysrhythmias

Question 25

What CCBs is used for dysrhythmias?

Answer 25

Verapamil

Suppresses conduction through the AV node