Drug Treatment of Angina

Question 1

what is angina?

Answer 1

check pain due to myocardial ischaemia
build up of metabolites [(eg adenosine, CO2 which dissolves in fluids) and lowers pH, lactate, K+ ions] activates sensory nerves
not a disease itself, it is symptoms

Question 2

How does ischaemia (aninadequateblood supply to an organ or part of the body, especially the heart muscles.) develop?

Answer 2

An increase in myocardial oxygen demand which is not met

Question 3

what are the 3 types of angina?

Answer 3

stable angina
unstable angina
variant angina

Question 4

what is stable angina?

Answer 4

most common
attacks are predictable, eg exercise, stress
myocardial O2 demand not met
involvement of chronic occlusive coronary artery disease, i.e. atherosclerosis (use of cholesterol lowering drugs-statins)

Question 5

what is unstable angina?

Answer 5

-attacks are unpredictable
-coronory artery occlusion due to platelet adhesion to ruptured atherosclerotic plaque (use of anti-platelet drugs)

Question 6

what is variant angina?

Answer 6

least common
-attacks unpredictable
-coronory artery occlusion by vasospasm

Question 7

What is the effect of dilation of coronary arteries in treating angina? What are the benefits and negatives?

Answer 7

• May be valuable in variant angina
• Dangerous in stable and unstable angina - may cause coronary steal (where dilatation can occur, this sends more blood to already well perfused areas, but where dilatation cannot occur, less blood is delivered because of the fall in input pressure)\The arteries distal to the occlusion are maximally dilated, which means these vessels can’t dilate any more, but the normal coronary vessels elsewhere will dilate and “steal” blood away from where it is needed

Question 8

how do beta-1 blockers work?

Answer 8

• β1-adrenoceptor blockers – competitive reversible antagonists of adrenaline and noradrenaline at cardiac β1-adrenoceptor
• reduced heart rate and force leading to reduced myocardial work
• reduced myocardial O2 demand
  -used in all forms of angina

Question 9

what are some examples of B-1 blockers?

Answer 9

propranolol (B1 and B2)
atenolol (B1 selective)

Question 10

what are some adverse effects of beta -1 blockers?

Answer 10

• Exacerbate asthma (block of β2-adrenoceptors in bronchi - avoid by use of alternative drug class)
• Intolerance to exercise
• Hypoglycaemia = deficiency of glucose in the bloodstream
• Blockade of β-adrenoceptors may uncover α1-mediated constriction in coronaries

Question 11

how do funny channel blockers work?

Answer 11

• Not first line intervention
• Recently introduced to treat angina (all forms)
• Blocks If (Na+) current that contributes to SA node depolarisation towards threshold
• Decreases heart rate but not force by slowing the signals of the sinus node
• This is beneficial if there are other conditions/drugs that the patient is on that reduce inotropy
• Leading to reduced myocardial O2 demand

Question 12

what is an example of a funny channel blocker?

Answer 12

ivabradine

Question 13

what is pre load?

Answer 13

amount of blood that comes back to the heart

Question 14

what is after load?

Answer 14

the force the heart has to contract against to open the aortic and pulmonary valves

Question 15

how is the dilation of arteries changed by vasodilator drugs?

Answer 15

-decreased after load
-decreased myocardial work
-myocardial O2 demand

Question 16

how is the dilation of veins changed by vasodilator drugs?

Answer 16

-decreased pre load

Question 17

how is the dilation of venous changed by vasodilator drugs?

Answer 17

-decreased venous return
-decreased pre load
-decreased stretch of ventricle + atria
-decreased strength of contraction
-decreased myocardial work
-decreased myocardial O2 demand

Question 18

what is the Bainbridge reflex?

Answer 18

If pre-load increases, you will get both the Starling and the Bainbridge reflex

Question 19

what are nitrovasodilators?

Answer 19

• Particularly used for prophylaxis and immediate relief
• Most commonly used anti-anginal
• The primary therapeutic effect of nitrates is on the veins. At high doses you see arterial dilatation, which can lead to side effects like throbbing headache. You also get tolerance.

Question 20

what is GTN?

Answer 20

GTN (nitroglycerine, 10% in inert lactose base)

• taken as sub-lingual tablet or spray
• not orally active (destroyed by first-pass metabolism)
• rapidly absorbed → rich blood supply

Question 21

what is amyl nitrate?

Answer 21

Amyl nitrite (volatile liquid)

• vials opened and inhaled
• not now used clinically but has become drug of abuse (poppers)

Both drugs rapid in onset, but action short-lived

Question 22

what are Isosorbide dinitrate/mononitrate?

Answer 22

• taken orally
• slower in onset and more prolonged in duration than GTN
• used for sustained prophylaxis in all forms of angina

Question 23

what are the uses of nitrates?

Answer 23

• prophylaxis in stable angina (i.e. taken immediately before exercise)
• rapid relief of ongoing anginal attack (all forms)

Question 24

what are the mechanisms of action of nitrates?

Answer 24

All nitrovasodilators are pro-drugs

• lipophilic - readily enter smooth muscle cells and are reduced to nitric oxide (NO)
• they are termed “NO donors”
• mimic action of endothelium-derived NO

Question 25

how do nitric oxides activate soluble granulate cyclase (sGC)?

Answer 25

- cytoplasmic (soluble) enzyme - receptor on soluble guanylate cyclase contains a ferrous (Fe2+) haem moiety (like O2 binding site of haemoglobin) - NO binds to haem receptor leading to enzyme activation which converts GTP to cGMP - This results in an increase of cGMP, therefore vasodilatation

Question 26

what are the side effects of nitrovasodilators?

Answer 26

- headache (dilatation of cerebral arteries) - particularly if you are naive to nitrates - tolerance on prolonged use – need drug free   “washout” period to restore efficacy

Question 27

what are the classes of voltage gated Ca2+ channels and their location?

Answer 27

L (long lasting current - smooth muscles, cardiac muscles and pacemakers T (transient current) - cardiac pacemakers and smooth muscle N - neurones (Ca2+ for exocytosis) P/Q (positive potentials) -neurones

Question 28

what does reduced Ca2+ entry result in?

Answer 28

coronory and peripheral arterial vasodilation

Question 29

what are some examples of L type calcium channel blockers?

Answer 29

-open channel block -cork in bottle -phenylalkylelamines (verapamil -benzothiazepines (diltiazem)

Question 30

What is the mechanism of action of the different L-type channel blockers?

Answer 30

-allosteric modulators bind at allosteric site and reduce probability of channel opening at a given voltage

Question 31

what is an example of a dihydropyridine antagonist?

Answer 31

nifedipine increase probability of channel opening at a given voltage

Question 32

What are the different tissue selectivities of L-type Ca++ channel blockers?

Answer 32

smooth muscle - nifedipine>diltiazem>verapamil cardiac muscle - verapamil- diltiazem > nifedipine also have N-, L- and T-type VOCs in the ZG of the adrenal cortex- blocking may reduce biosynthesis of aldosterone

Question 33

What are the vascular actions of L-type Ca++ channel blockers?

Answer 33

Dilate arteries (little effect on veins) →↓Total peripheral resistance (TPR)

Question 34

what are the uses of L-type blockers?

Answer 34

- anti-hypertensives (dihydropyridines preferred due to rebound tachycardia) - ↓ TPR plus ↓ C.O. due to ↓HR and ↓ SV - anti-anginals (drugs with more “cardiac” effects preferred due to less reflex tachycardia) - ↓ TPR → ↓ after-load and ↓ C.O → ↓myocardial Odemand - anti-dysrhythmic agents (Class IV) - verapamil > diltiazem > nifedipine

Question 35

what are the anti-anginal effects of Ca+ channel blockers?

Answer 35

- dilate arteries (little effect on veins) therefore reduced after-load - Reduced myocardial O2 demand - Reduced heart rate and reduced force  therefore reduced myocardial O2 demand - useful in all forms of angina - dilatation of coronary arteries valuable in variant angina   (vasospasm) but may cause coronary steal in stable and   unstable angina - nifedipine leads to coronary steal in 10% of patients - Other uses of L-type blockers: - anti-hypertensive agents (reduced TPR; reduced HR and reduced SV leading to reduced C.O.) - anti-dysrhythmic agents (Class IV)

Question 36

what are the limitations of beta-blockers, CCBs and nitrates?

Answer 36

-beta blockers-absolute or relative contradcation in asthma, COPD and peripheral vascular disease -CCBs, heart failure in patients with poor LVEF, ineffective in preventing no reflow phenomenon, ADRs (flushing & peripheral oedema) -nitrates, long term use associated with tolerance

Question 37

what is nicroandil?

Answer 37

K+ channel activation -> relaxation -cardioprotective action is good -key advantages- no tolerance, comparable efficiency and tolerability to existing agents, potent cardio protective action

Question 38

what is a hybrid compound?

Answer 38

-comprised of nicotinamide vitamin group and an organic nitrate -mechanism of action like action increased level of cyclic guanosine monophosphate, decrease in cytosolic calcium, vascular smooth muscle relaxation dilation of coronory epicardial arteries