Pharmacological Treatment of IHD Part 2

Question 1

Reducing Hypercholesterolaemia - secondary prevention

Answer 1

Drugs are designed to either inhibit uptake from GI tract or reduce production in liver
Statins (simvastin or atorvastin) are frontline treatments
They decrease production of chol in liver by inhibiting CoA enzyme
This stimulates liver cells to express LDL receptors and liver cells to scavenge LDL chol from plasma, lowering plasma LDL chol levels

Question 2

Further Secondary Prevention

Answer 2

Aspirin - antiplatelet agents (aspirin/clopidogrel)
ACE inhibitors (ramipril) and ARBs (losartan) - decrease heart work load

Question 3

Mechanism of action and key antiplatelet agents

Answer 3

Platelet activation occurs when the endothelial cells become damaged
This releases ADP which acts on P2Y12 receptors to stimulate the platelet to express GPIIb/IIIa receptors
Fibrinogen binds to these receptors to cross link different platelets
Activation of COX helps platelet activation through production of Thromboxane A2
Aspirin inhibits COX irreversibly
Clopidogrel & prasugrel are ADP antagonists and block P2Y12 receptors

Question 4

Mechanism of Action of Clopidogrel/Prasugrel/Ticagrelor

Answer 4

Clopidogrel requires CYP2C19 to become active and prevent platelet activation
Prasugrel does not require CYP2C19 - instead is hydrolysed by esterase to become active
Both are irreversible
Ticagrelor is orally active - absorbed form gut, gets metabolise and is absorbed as the active ingredient/metabolite, but is reversible

Question 5

Diagnosis of acute coronary syndromes

Answer 5

pain, sweating, tachycardia, cold clammy skin, markers of acitvation of SNS
Heart damaged -> impaired CO -> decreased BP -> activate SNS -> causes these symptoms

Question 6

Treatment

Answer 6

Pain relief: diamorphine u opioid receptors, decreases pain, anxiety, vasodilates
Oxygen, aspirin, clot busting drugs (tenecteplase)
Beta blockers: decrease cardiac workload, prevent arrythmias, e.g. metoprolol/bisoprolol
ACE inhibitors: decrease cardiac workload, prevents remodelling development of heart failure e.g. ramipril
Anti-coagulant: e.g. warfarin/apixaban, rivoxaban/dabigatran/LMWH (tinzaparin)

Question 7

Treatment of Heart Failure

Answer 7

Dixogin binds to the Na+/K+ ATPase and inhibits its action leading to an increase in levels of Na+ inside heart muscle cells
This increase will inhibit the Na+/Ca2+ exchanger, leading to a build up of Ca2+ inside the muscle cell and stronger contraction

Question 8

Treatment of Dysrhthmias

Answer 8

Amiodarone: K+ channel blocker, that increases the refractory period of ventricular myocytes that can terminate arrythmias