Drugs for Ischaemic heart disease

Question 1

explain the IHD

Answer 1

A consequence of inadequate coronary perfusion relative to
myocardial demand.

Question 2

IHD is due to what?
3 marks

Answer 2

• Pre-existing (“fixed”) atherosclerotic occlusion of the coronary
  arteries
• Acute plaque change with superimposed thrombosis and/or
  vasospasm
• In most patients, unstable angina, infarction, and sudden cardiac
  death occur because of abrupt plaque change followed by
  thrombosis—hence the term acute coronary syndrome

Question 3

explain angina pectoris

Answer 3

Characteristic chest pain (burning or heavy discomfort behind the sternum), of duration <
15 minutes, due to myocardial ischaemia, usually occurring on exercise and relieved by
rest.

Question 4

List the stepwise treatment for angina pectoris (stable)

Answer 4

1. Beta-blocker:
   Atenolol
2. Add 2nd agent:
   Long-acting
   calcium channel
   blocker:
   amlodipine
3. Add 3rd agent:
   Isosorbide
   mononitrate /
   dinitrate

Question 5

List agents for long term prophylaxis for thrombosis/cardiovascular events:

Answer 5

Low-dose Aspirin, isosorbide dinitrate SL, statin

Question 6

List the agents for prophylaxis to relief of angina

Answer 6

 Nitrates, short acting e.g.:
 Isosorbide dinitrate, sublingual, 5 mg.

Question 7

List the agents for long-term prophylaxis for thrombosis

Answer 7

Long-term prophylaxis for thrombosis:
 Aspirin, oral, 150 mg daily.
HMGCoA reductase inhibitor (statin)
Simvastatin / Rosuvastatin
Atorvastatin

Question 8

Instructions to give the patients when taking prophylaxis for thrombosis and relief of angina

Answer 8

May be repeated if required at 5‐minute intervals for 3 or 4 doses.
o Instruct patients to keep the tablets in the airtight and lightproof container in
which they are supplied.
o Instruct patients that nitrates are not addictive.
o Instruct patients to use prophylactically, before activities which may provoke
angina.

Question 9

List the organic nitrates

Answer 9

• Glyceryl trinitrate
• Isosorbide mononitrate
• Isosorbide dinitrate

Question 10

explain the action of organic nitrates at Smooth muscle

Answer 10

Relax smooth muscle, especially
vascular smooth muscle (also
oesophageal and biliary)

Question 11

Explain the action for organic nitrates at veins

Answer 11

Relax veins, reduction in central venous
pressure (reduced preload)

Question 12

explain the action of organic nitrates at stroke volume

Answer 12

Reduced stroke volume = venous
pooling on standing, postural
hypotension and dizziness

Question 13

Explain the effect of therapeutic dose in different sites

Answer 13

Therapeutic doses has less effect on
small resistance arteries than on veins
but marked effect on larger muscular
arteries.

Question 14

explain the action of organic nitrates in pulse

Answer 14

Reduce pulse wave reflection from
arterial branches and reduce central
(aortic) pressure and cardiac afterload.

Question 15

explain the action for organic nitrates in heart

Answer 15

Direct dilation of coronary
arteries – increased coronary flow
* Decreased myocardial oxygen
consumption (decreased pre- &
afterload)
* Increased in oxygen of coronary
sinus blood.
Also cause the dilation of collateral
vessels that bypass narrowed
coronary artery segments

Question 16

explain the anastomic channels

Answer 16

Anastomotic channels, known as
collateral vessels, connect a territory
supplied by one epicardial coronary
artery with that supplied by another.
Collateral arteries therefore provide
an alternative source of blood
supply to myocardium that has been
jeopardized by occlusive coronary
artery disease, and they can help to
preserve myocardial function in the
setting of coronary artery disease.

Question 17

explin the organic nitrates: anti-anginal actions

Answer 17

• Reduced cardiac work – reduced pre- & after load = reduced oxygen
  demand
• Redistribution of coronary flow to ischaemic areas via collaterals
• Relief of coronary spasm

Question 18

MoA of organic nitrates

Answer 18

Organic nitrates release nitric
oxide, which activates
guanylyl cyclase and
increases formation of cyclic
guanosine monophosphate
(cGMP). Investigators believe
that cGMP causes smooth
muscle relaxation by
activating kinases that
increase myosin phosphatase
activity and decrease myosin
phosphate levels –
responsible for contraction.

Question 19

TOLERANCE OF ORGANIC NITRATES

Answer 19

Tolerance – diminished effect of nitrates upon repeated
administration

Question 20

explain the adverse effects for organic nitrates

Answer 20

Main adverse effects are direct consequence of pharmacological action
(type A)
* Postural hypotension and headache – tolerance to these effects
develops quickly

Question 21

explain the half life of aspirin and binding of it

Answer 21

While unbound aspirin has a half-life of only about 15 to 20 minutes,
the irreversible binding of aspirin to the platelet COX1 enzyme
inhibits thromboxane A2–induced platelet activation for the life of
the platelet (7 - 10 days).

Question 22

explain about the dosing of aspirin

Answer 22

• After the initial dose of aspirin, daily doses of aspirin should be
  continued indefinitely.
• Higher daily maintenance doses of aspirin (300- 325 mg) do not
  reduce CV death, MI, or stroke compared to lower daily maintenance
  doses (75 – 100 mg), but significantly increase the incidence of
  gastrointestinal (GI) bleeding.

Question 23

Contraindication to aspirin

Answer 23

Contraindications to aspirin include hypersensitivity to aspirin and
major GI intolerance.

Question 24

ASPIRIN is typicaly combined with what in ACS patients

Answer 24

• Aspirin is rarely used as the sole antiplatelet agent in patients with
  ACS and is typically combined with an oral P2Y12 inhibitor as part of
  dual antiplatelet therapy (DAPT).

Question 25

Explain the bond of P2Y12

Answer 25

P2Y12 receptor irreversible bond and prevents the receptor’s ability to be activated by adenosine diphosphate and subsequent platelet activation and aggregation.

Question 26

Explain the use of clopidogrel

Answer 26

Clopidogrel has been extensively evaluated in patients with ACS. The CURE trial (Clopidogrel in Unstable Angina to Prevent Recurrent Events) compared aspirin alone to clopidogrel given as a 300 mg loading dose, followed by 75 mg daily for up to 12 months.

Question 27

Patients reciveing Dual Antiplatelet treatment demostrates what?

Answer 27

Patients receiving DAPT demonstrated a significant reduction in CV death, MI, and stroke compared to aspirin alone. This trial not only demonstrated the efficacy of clopidogrel but also established DAPT as the standard of care for patients presenting with ACS.

Question 28

Current anticougulant do what?

Answer 28

Currently available anticoagulants inhibit the production of thrombin by inhibiting factor Xa, inhibiting thrombin itself, or a combination of these. * While the use of oral anticoagulants may be common for other thromboembolic disease states, all the current evidence in the acute management of ACS is with injectable agents.

Question 29

when is anticoagulat is used

Answer 29

Although patients with ACS are typically treated with two antiplatelet agents for at least a year, usually a single anticoagulant is used in these patients and the duration is abbreviated (typically the initial few days of hospitalization).

Question 30

Anticoagulant fort STEMI treatment

Answer 30

STEMI: * Adjunctive treatment with thrombolytic therapy : alteplase, streptokinase (do not use heparins after streptokinase) * Enoxaparin

Question 31

Anticougulant treatment for NSTEMI/Unstable angina

Answer 31

NSTEMI / unstable angina: * Enoxaparin, sc, 1mg/kg, 12 hourly for minimum 2 days OR * Unfractionated heparin for minimum 2 days

Question 32

Chronic management of STEMI / NSTEMI UNSTABLE ANGINA

Answer 32

* Clopidogrel, oral 75mg daily for (12) months * Aspirin, oral, 150 mg daily (continued indefinitely in absence of contraindications). When clinically stable without signs of heart failure, hypotension, bradydysrhythmias or asthma(caution): * Cardio-selective beta-blocker: Atenolol * HMGCoA reductase inhibitors: Simvastatin 40mg * AND If there is cardiac failure or LV dysfunction * ACEI: enalapril / ARB: losartan