Acute coronary syndrome 2 Fibronolytic drugs and Nitrates

Question 1

Explain the MoA of fibrinolytic drugs

Answer 1

fibrinolytic drugs act as thrombolytics by activating plasminogen to form plasmin, which degrades fibrin and so breaks up thrombi

Question 2

list 3 fibrinolytic drugs

Answer 2

1) Alteplase
2) Streptokinase
3) Tenecteplase

Question 3

who are fibrinolytic drugs indicated for and which patients have been shown to benefit from treatment the most?

Answer 3

1) Indicated for any patient with acute MI for whom the benefit is likely to outweigh the risk.
↳ patients should not be denied treatment due to age alone as mortality in elderly is high
2) benefit is greatest in those with ST segment elevation and in those with bundle branch block

Question 4

in order to reduce mortality, how soon after symptom onset should the following fibrinolytic drugs be administered :

1) Alteplase
2) Reteplase and streptokinase
3) Renecteplase

Answer 4

1) Alteplase- within 6-12h of symptom onset
2) Reteplase and streptokinase- within 12h of onset
↳ ideally (Above 1,2) should be given within 1 hour, use after 12 hours requires specialist advice
3) Renecteplase-as early as possible and within 6h of onset
↳ (dose in all varies with indication, time from onset and weight)

Question 5

Apart from MI, alteplase, streptokinase and urokinase fan be used for other thrombotic disorders. list these disorders (3)

Answer 5

1) DVT
2) PE
3) Alteplase is also used for acute ischemic stroke- Needs to be given within 4.5h of symptoms onset

Question 6

list the common adverse side effects of fibrinolytic drugs and identify the ones that would require treatment to be stopped.

Answer 6

1) nausea and vomiting, bruising around injection site, hypotension
2) stop if: serious bleeding, allergic reaction, cardiogenic shock and cardiac arrest
3) reperfusion of infarcted brain or heart may lead to cerebral odema and arrhythmias

Question 7

1) How should serious bleeding as a result of fibrinolytic drug therapy be managed?
2) Why is management rarely required?

Answer 7

1) Serious bleeding may require treatment with coagulant factors and antifibronylitic drugs e.g. Tranexamic acid
2) Fibronylitic drugs have a very short half life

Question 8

In which individuals should fibronylitic drugs be used in caution or are C/I in?

Answer 8

1) factors that predispose to bleeding: recent hemorrhage, trauma or surgery, bleeding disorders, severe hypertension and peptic ulcers
2) In acute stroke, intracranial hemorrhage must be excluded with CT scan
3) previous streptokinase treatment is a C/I to repeat dosing as development of antistreptokinase antibodies can block its effect.

Question 9

outline the important interactions with regards to fibronylitic drugs

Answer 9

1) Anticoagulants and Antiplatelets- increased risk of haemorrhage so caution
2) ACEi increases risk of anaphylactoid reactions

Question 10

what effect can the use of thrombolytic drugs have in pregnancy?

Answer 10

1) could possibly lead to premature separation of placenta in first 18 weeks of pregnancy
2) also risk of maternal haemorrhage throughout pregnancy and post-partum. Also theoretical risk of fetal haemorrhage

Question 11

should thrombolytic drugs be avoided in hepatic impairment?

Answer 11

yes- avoid in severe impairment as there is increased risk of bleeding

Question 12

outline the MoA of nitrates

Answer 12

nitrates reduce Ca2+ in vascular smooth muscle cells causing them to relax. Their principle benefit follows from a reduction in venous return which reduces left ventricular work thus reducing oxygen demand, relieving angina and cardiac failure

Question 13

list the common unwanted side effects of nitrates

Answer 13

1) Flushing
2) Headaches
3) Postural hypotension
4) Light-headedness

Question 14

sublingual GTN is one of the most effective drugs for providing symptomatic relief of angina. How long does its effects last for?

Answer 14

20 to 30 minutes

Question 15

what is the duration of action of M/R Isosorbide dinitrate?

Answer 15

1) M/R preps last 12h and are useful for prophylaxis of angina
↳ activity may depend on production of active metabolites- especially isosorbide mononitrate.
(Active sublingually and orally. Although its effects are slower when taken orally but last longer)

Question 16

which patients are nitrates are contraindicated in? (2)

Answer 16

1) Severe aortic stenosis - could lead to cardiovascular collapse of valve due to decreased pressure
2) Haemodynamic instability especially hypotension

Question 17

outline the important interactions with regards to nitrates

Answer 17

1) must not be used with PDE inhibitors (e.g. sildenifil) because they prolong the hypotensive effects of nitrates.
2) used with caution in those taking antihypertensive medicaton as they may precipitate hypotension

Question 18

when nitrates are regularly taken there is a risk of developing tolerance, this is especially a problem with those on long-acting or transdermal nitrates . Explain what should be done if this is suspected in transdermal patches and M/R tablets

Answer 18

Reduction of blood-nitrate conentrationc to low levels for 4-12 hours each day usually maintains effectiveness
1) patches: should be left off for 8-12h (usually overnight) in each 24 hour period
2) M/R tablets isosorbide dinitrate: The second of the two daily doses should be given after 8 hours rather than 12h
↳ conventional formulations of isosorbide mononitrate should not usually be given more than BD and M/R formulations should only be given once daily.

Question 19

why might a GTN spray be a better choice for patients with symptomatic angina, instead of sublingual tablets?

Answer 19

1) spray better for those who find it difficult to dissolve sublingual tablets
2) GTN tablets must be discarded after 8 weeks so spray might be better choice