CVD Drug development: an overview Flashcards
What is evidence based medicine?
‘integration of best research evidence w clinical expertise + patient values
What does evidence based medicine require?
Requires latest scientific evidence to be applied to clinical practice
Involves assessment of research in terms of category + level of evidence
Category + level is used to define strength of recommendation
How is EBM classified?
1a (best)
Systematic reviews of randomised clinical trials
1b
Individual randomised clinical trials
2a
Systemic reviews of cohort studies
2b
Individual cohort studies + low-quality RCTs
3a
Systematic reviews of case=controlled studies
3b
Individual case-controlled studies
4
Case series, poor quality cohort + case-control studies
5
Expert opinion based on clinical experience
What are the classes of drugs currently used to treat CVD?
Nitrates
Beta-blockers
Ca2+ channel blockers
Diuretics
ACE inhibitors
Angiotensin receptor blockers
Anti-arrhythmics
Example and effect of Nitrates:
Example:
Gylceryl trinitrate
Effect:
Stimulate NO release causing vasodilation
Example and effect of Beta-blockers:
Examples:
Carvedilol, bisoprolol, nebivolol, atenolol
Effects
Block B-adrenoreceptors, reducing effect of adrenalin
Example and effect of Ca2+ channel blockers:
ex:
Verapamil, diltiazam, amlodipine
eff:
Relaxes arterial SMCs, increases vasodilation
Example and effect of Diuretics:
Furosemide, bumetanide,
bendroflumethiazide
effects:
Act on kidney to increase salt + water loss
Example and effect of ACE inhibitors:
Captopril, ramipril, lisinopril
effects:
Inhibits ACE, salt, water loss + vasodilation
Example and effect of Angiotensin receptor blockers :
Valsartan, losartan, candesartan
Angiotensin receptor antagonists, increase vasodilation
Example and effect of Anti-arrythmics:
Amiodarone, digoxin, verapamil
Reduce electrical activity of the heart
Example and effect of Thrombolytics :
Alteplase, reteplase, tenecteplase
streptokinase
Activate plasmin system, fibrin
breakdown
Anti-platelet drugs
Example and effect of anti-platelet drugs :
Aspirin, clopidogrel
Inhibit platelet aggregation
Example and effect of anti-coagulants :
Wafarin, heparin, FIIa and FXa inhibitors
Inhibit clotting cascade
Example and effect of statins:
Simvastatin, pravastatin, atorvastatin,
lovastatin
Decrease cholesterol production,
increase LDL receptors
Example and effect of fibrates :
Bezafibrate, ciprofibrate
Shift from LDL to HDL profile
What are the 3 stages of a project?
Drug discovery- candidate molecules chosen on basis of pharmacological properties
Preclinical development- non-human studies, toxicity testing, pharmacokinetic analysis + formulation
Clinical development- volunteers + patients, efficacy testing, side-effects + potential dangers
Steps in DRUG DISCOVERY:
Target identification/selection
Lead finding + optimisation