Ischaemic heart disease Drugs

Acute Coronary Syndrome (ACS)

A condition occurring because of a sudden blockage in the artery limiting blood supply to the heart, caused by the rupture of an atherosclerotic plaque leading to vasoconstriction, platelet aggregation, or thrombus formation.

Chronic Artery Disease (CAD)

A classification of Ischaemic Heart Disease that includes Stable angina and Variant Angina.

Non-ST elevated ACS

A category of Acute Coronary Syndrome that includes Unstable angina and Non-ST elevated myocardial infarction (NSTEMI).

ST-elevated myocardial infarction (STEMI)

A condition involving full thickness damage to the ventricular myocytes that requires immediate treatment.

Troponin and keratin kinase

Markers that are elevated in cases of sudden artery blockage, though their elevation is not always an emergency.

Levine signs

Signs shown by patients at presentation of a myocardial infarction.

Morphine or ketamine

Opioids administered to provide immediate pain relief and reduce anxiety in patients showing Levine signs.

Percutaneous coronary intervention (PCI)

The primary method used to revascularize patients; fibrinolytics are used if this is not available.

Rivaroxaban

A specific anticoagulant used in the management of Acute Coronary Syndrome.

Fibrinolytics

Agents used to dissolve clots in the artery that can only be administered within $3$ hours from the start of an episode before losing efficacy.

Arrhythmia and heart failure

Complications that myocardial infarction patients are at risk of developing, which treatment aims to prevent.

Stable Angina

A condition occurring due to the buildup of atherosclerotic plaque which narrows the artery and impacts blood flow, resulting in insufficient oxygen supply to the heart.

Atherosclerotic Plaque

A buildup along the walls of the arteries caused by an increase in cholesterol, which narrows the vessel and impacts oxygen delivery.

Lipid Regulating Drugs

Medications such as statins, fibrates, or ezetimibe used to remove or limit the buildup of plaques by reducing LDL and triglyceride levels and increasing HDL levels.

Antiplatelet Drugs

Medications used to increase oxygen supply by inhibiting platelet aggregation, preventing platelet activation, or both within a platelet-rich thrombus.

Aspirin and Clopidogrel

Specific antiplatelet medications that work by inhibiting both platelet aggregation and activation.

Percutaneous Coronary Intervention (PCI)

A method of physically opening a coronary artery, which includes inserting a stent or performing angioplasty.

Angioplasty

A procedure where a balloon is inflated at the site of the occlusion; notable because plaques are not physically removed and can build up again.

Restenosis

A condition where platelets stick to a stent or plaques build over the stent following a PCI procedure.

Drug Eluting Stent

A stent covered with drugs designed to prevent platelets from sticking or plaques from building over the device.

Coronary Artery Bypass Graft (CABG) surgery

An abrasive surgical procedure used for completely blocked arteries where a healthy artery is taken from another part of the body to replace the blocked one; usually takes $4-6$ months post-surgery to show improvements.

Nicorandil (Arterial Mechanism)

Opens potassium channels in the arteries leading to an efflux of $K^{+}$ ions, which promotes hyperpolarization and inhibits arterial contraction.

Hyperpolarization

A state where the inside of the cell becomes much more negative than usual, preventing the cell from undergoing depolarization and arterial contraction.

Afterload reduction

The result of arterial dilation, which decreases the resistance the heart must pump against; promoted by Nicorandil's action on potassium channels.

Nicorandil (Venous Mechanism)

The donation of a nitrogen group from the nitrogen part of the drug structure which promotes venous dilation and reduces preload.

Preload reduction

The result of venous dilation, which reduces the volume of blood returning to the heart.

Nicorandil Side Effects

Includes dizziness, headaches, facial flushes, orthostatic hypertension, reflex tachycardia, and fistula formation.

Fistula formation

The creation of new channels in areas where they should not exist, resulting in inflammation and putting the patient at risk of infection.

Sildenafil Interaction

A drug interaction occurring with Nicorandil through the same mechanism as nitrates.

Ivabradine

A sodium channel blocker that inhibits the sodium node at the myocytes to reduce Heart Rate ($HR$) and myocardial oxygen demand.

Ivabradine Visual Side Effects

Non-predictable but reversible symptoms including fuzzy vision and the appearance of a halo ring.

Cardiac Metabolism (Fatty Acids)

The process where free fatty acids, released by lipoprotein lipase, are taken up by cardiac myocytes; this process requires a significant amount of oxygen.

Perhexiline

Inhibits the enzyme involved in the metabolism of fatty acids at the heart, causing the heart to switch to glucose metabolism.

Glucose Cardiac Metabolism

A metabolic state that requires less oxygen than fatty acid metabolism, thereby reducing the amount of oxygen required by the myocardium.

CYP2D6 Genetic Polymorphism

Genetic variability that affects drug metabolism, creating a risk where small changes in dose can significantly change plasma concentrations.

Perhexiline Toxicity

A risk associated with the drug that makes it prone to damaging liver cells as well as neurons.

Organic Nitrates

A class of drugs used for the acute treatment and prevention of ischemic heart disease by reducing myocardial oxygen demand.

Nitric Oxide ($NO$)

An endogenous vasodilator produced by the endothelium; its release is triggered by the metabolic activation of nitrates.

Aldehyde Dehydrogenase 2 (ALDH2)

An enzyme found predominantly in the veins that breaks down nitrates to facilitate the spontaneous release of nitric oxide.

Cyclic GMP ($cGMP$)

A secondary messenger that increases within the vasculature in response to $NO$, leading to the relaxation of vascular smooth muscles.

Preload Reduction

The primary hemodynamic effect of nitrates at standard doses, achieved through venodilation which reduces the volume of blood returning to the heart.

Afterload Reduction

A hemodynamic effect achieved at higher nitrate doses through arteriolar dilation, reducing the resistance the heart must pump against.

Glycerol Trinitrate (GTN)

Also known as Nitroglycerin, this nitrate has a rapid onset of action but very low oral bioavailability due to extensive first-pass metabolism in the liver.

Sublingual GTN Tablets

A formulation for acute relief that bypasses the liver but is highly volatile with a limited shelf life of approximately $3$ months.

Sublingual GTN Spray

A stable formulation for immediate relief with a shelf life of up to $2$ years after opening, though the device requires priming before use.

Nitrate Tolerance

The loss of drug efficacy resulting from continuous exposure to nitrates, requiring a regular interval without the drug to restore effectiveness.

Nitrate-free Period

A mandatory interval of at least $8$ hours every $24$ hours where systemic nitrate levels return to zero to prevent or reverse tolerance.

Isosorbide Dinitrate (ISDN)

A nitrate with poor oral bioavailability that is metabolized by hepatic reductase into active mononitrate forms.

Isosorbide Mononitrate (ISMN)

The active metabolite of ISDN that is $100\%$ bioavailable when administered orally and features a significantly long half-life of $4$ hours.

Orthostatic Hypotension

A common side effect where blood pressure drops upon standing because nitrates reduce preload and interrupt the natural baroreceptor reflex.

Reflex Tachycardia

A compensatory increase in heart rate and contractility that occurs as the vasculature dilates and blood pressure drops, typically at higher nitrate doses.

Sildenafil (Viagra)

A $PDE5$ inhibitor that, when combined with nitrates, causes a massive buildup of $cGMP$, leading to life-threatening hypotension or priapism.

Phosphodiesterase 5 (PDE5)

The enzyme responsible for breaking down $cGMP$; its inhibition by drugs like Sildenafil prevents the degradation of $cGMP$.

Priapism

A medical emergency characterized by a painful erection lasting more than $2$ hours, which can cause permanent damage if not resolved within $4$ hours.

Pseudoephedrine

A vasoconstrictor that binds to alpha receptors in the periphery, used as an emergency treatment to reverse severe vasodilation or priapism.

Glucuronidation

The metabolic process by which all nitrates eventually undergo transformation before being excreted via the kidneys.

Beta 1 adrenoseptors

The primary therapeutic target in the heart for beta blockers (referred to as ‘blood blockers’ or ‘build blockers’) to reduce myocardial oxygen demand.

Selective Beta Blockers

The preferred class for angina treatment that mainly targets the heart, with examples including metoprolol, ethanol, atenolol, bisoprolol, and nebivolol.

Non-Selective Beta Blockers

Agents that target $BLUE2 receptors$ more than beta 1 receptors, cause peripheral vein constriction, and include pindolol, propranolol, and timolol.

BLUE2 receptors

Receptors that normally mediate vasodilation at the peripheral veins but are targeted by non-selective beta blockers, leading to an opposing mechanism of constriction.

Variant Angina

A condition involving vasoconstriction and spasm of the arteries where non slacktipid blockers are strictly contraindicated.

Non slacktipid blockers

A term used for non-selective beta blockers which are contraindicated in patients with ‘ovarian angina’ (variant angina) because they exacerbate vasoconstriction.

Metoprolol CNS effects

Due to being a ‘more lipophilic blood blocker’, it carries a significantly higher risk of causing nightmares and ‘daily dreams’.

L-type calcium channels

Channels found within ‘cardiac mass sites’ and vascular smooth muscle that are inhibited by CCBs to reduce inward calcium current.

Dihydropyridine calcium channel blockers

A class of CCBs including amlodipine, lercanidipine, felodipine, and nifedipine that have a higher affinity for arteriolar smooth muscles and primarily reduce afterload.

Non dihydropyridine calcium channel blockers

A more ‘cardio selective’ class of CCBs, such as verapamil and diltiazem, that primarily reduce heart rate and cardiac contractility.

Verapamil and Beta Blocker Combination

A lethal risk combination that can result in heart block, ventricular failure, and increased risk of patient death.

Reflex tachycardia

A compensatory heart rate effect more likely to be caused by the dihydropyridine class of calcium channel blockers.

Vasodilatory Side Effects

Symptoms more pronounced in dihydropyridines including headache, facial flushing, dizziness, and peripheral oedema.

Gastrointestinal adverse effects of CCBs

Verapamil is associated with causing constipation, while diltiazem can increase the risk of ‘diarrhoea’.

Cardioselectivity of Selective $\beta$-blockers

Characterized by an affinity for $\beta_1 > \beta_2$; examples include bisoprolol, metoprolol, atenolol, and nebivolol.

\beta + ̑_1 receptor blockers

A category of adrenergic antagonists represented by carvedilol and labetalol.

Sotalol

A medication classified as a $\beta$-blocker combined with a $K^+$ blocker.

Afterload

The resistance to outflow from the left ventricle, which is reduced by the arteriolar dilation promoted by calcium channel blockers.

Preload

Pressure related to venous inflow and filling of the right heart.

Bradycardia and Hypotension

Common physiological effects likely to be experienced by patients taking beta blockers.