Drugs for Ischaemic heart disease Flashcards
explain the IHD
A consequence of inadequate coronary perfusion relative to
myocardial demand.
IHD is due to what?
3 marks
- 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
explain angina pectoris
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.
List the stepwise treatment for angina pectoris (stable)
- Beta-blocker:
Atenolol - Add 2nd agent:
Long-acting
calcium channel
blocker:
amlodipine - Add 3rd agent:
Isosorbide
mononitrate /
dinitrate
List agents for long term prophylaxis for thrombosis/cardiovascular events:
Low-dose Aspirin, isosorbide dinitrate SL, statin
List the agents for prophylaxis to relief of angina
Nitrates, short acting e.g.:
Isosorbide dinitrate, sublingual, 5 mg.
List the agents for long-term prophylaxis for thrombosis
Long-term prophylaxis for thrombosis:
Aspirin, oral, 150 mg daily.
HMGCoA reductase inhibitor (statin)
Simvastatin / Rosuvastatin
Atorvastatin
Instructions to give the patients when taking prophylaxis for thrombosis and relief of angina
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.
List the organic nitrates
- Glyceryl trinitrate
- Isosorbide mononitrate
- Isosorbide dinitrate
explain the action of organic nitrates at Smooth muscle
Relax smooth muscle, especially
vascular smooth muscle (also
oesophageal and biliary)
Explain the action for organic nitrates at veins
Relax veins, reduction in central venous
pressure (reduced preload)
explain the action of organic nitrates at stroke volume
Reduced stroke volume = venous
pooling on standing, postural
hypotension and dizziness
Explain the effect of therapeutic dose in different sites
Therapeutic doses has less effect on
small resistance arteries than on veins
but marked effect on larger muscular
arteries.
explain the action of organic nitrates in pulse
Reduce pulse wave reflection from
arterial branches and reduce central
(aortic) pressure and cardiac afterload.
explain the action for organic nitrates in heart
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
explain the anastomic channels
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.
explin the organic nitrates: anti-anginal actions
- Reduced cardiac work – reduced pre- & after load = reduced oxygen
demand - Redistribution of coronary flow to ischaemic areas via collaterals
- Relief of coronary spasm
MoA of organic nitrates
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.
TOLERANCE OF ORGANIC NITRATES
Tolerance – diminished effect of nitrates upon repeated
administration
explain the adverse effects for organic nitrates
Main adverse effects are direct consequence of pharmacological action
(type A)
* Postural hypotension and headache – tolerance to these effects
develops quickly
explain the half life of aspirin and binding of it
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).
explain about the dosing of aspirin
- 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.
Contraindication to aspirin
Contraindications to aspirin include hypersensitivity to aspirin and
major GI intolerance.
ASPIRIN is typicaly combined with what in ACS patients
- 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).
Explain the bond of P2Y12
P2Y12 receptor irreversible bond and prevents the receptor’s ability
to be activated by adenosine diphosphate and subsequent platelet
activation and aggregation.
Explain the use of clopidogrel
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.
Patients reciveing Dual Antiplatelet treatment demostrates what?
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.
Current anticougulant do what?
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.
when is anticoagulat is used
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).
Anticoagulant fort STEMI treatment
STEMI:
* Adjunctive treatment with thrombolytic therapy : alteplase,
streptokinase (do not use heparins after streptokinase)
* Enoxaparin
Anticougulant treatment for NSTEMI/Unstable angina
NSTEMI / unstable angina:
* Enoxaparin, sc, 1mg/kg, 12 hourly for minimum 2 days
OR
* Unfractionated heparin for minimum 2 days
Chronic management of STEMI / NSTEMI UNSTABLE ANGINA
- 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
