[CA2 M4]: PCOL Anti-Angina

First-line drugs given to chest pain suggestive of ischemia

MONA

- Morphine (IV, not relieved by NTG)

- Oxygen (<94%)

- NTG (SL or IV)

- Aspirin (160-325 mg)

⭐️ DOA: amyl nitrite

Very short-acting

⭐️ DOA: NTG SL, ISDN SL

Short-acting

⭐️ DOA: NTG SR tab (PO)

Intermediate

⭐️ DOA: ISDN tab (PO)

Intermediate

⭐️ DOA: ISMN tab (PO)

Intermediate

⭐️ DOA: Transdermal NTG

Long-acting

⭐️ DOA: ISDN SR (PO), ISMN SR (PO)

Long-Acting

⭐️ MOA: stimulates NO release via NO synthase, leading to increased cGMP and vasodilation

Nitrates

⭐️ Effects: relaxes vascular smooth muscles (vasodilation), reduces cardiac preload and afterload

Nitrates (low dose, SL)

⭐️ Effects: causes arteriolar vasodilation leading to increased O2 supply

Nitrates (high dose, parenteral)

⭐️ Nitrates: tx for effort angina

Low dose nitrates (SL)

⭐️ Nitrates: tx for Prinzmetal angina

High dose nitrates (parenteral)

⭐️ Combine with nitrates to address reflex tachycardia

BB

⭐️ Clinical applications: angina pectoris, HTN emergency (alternative), acute pulmonary edema, cyanide poisoning (inhalational), ACS

Nitrates

⭐️ For CHF: Combined with hydralazine for African-American patient

ISDN

⭐️ Ax vs CN poisoning

Amyl nitrite

⭐️ S/E: reflex tachycardia, orthostatic hypotension, throbbing/vascular headache, methemoglobinemia, tolerance (Monday Disease)

Nitrates

Part of Lilly Cyanide Kit

Amyl nitrite

⭐️ Not combined with PDE5 inhibitors such as Sildenafil (causes dangerous hypotension)

Nitrates

Toxic agent causing blocked of ETC Complex IV

Cyanide

Content of Lilly Cyanide Kit (3)

- Inhaled amyl nitrite

- IV sodium nitrite

- IV sodium thiosulfate

Lilly Cyanide Kit: causes oxidation of hemoglobin iron from Fe+2 to Fe+3

Amyl nitrite, sodium nitrite

Lilly Cyanide Kit: reacts with cyanmethemoglobin and converts it into thiocyanate and methemoglobin (nontoxic)

Sodium thiosulfate

⭐️ Traditional drugs used in Angina (3)

Organic nitrates

CCBs

Beta blockers

⭐️ 1st line drug and used as maintenance VS effort angina

BB

⭐️ CCB used for the tx of effort angina (alternative)

Non-DHP CCB

⭐️ CCB used for the tx of Prinzmetal angina (alternative)

DHP CCB (Long-acting)

Newer drugs used in Angina

Rate inhibitors

Metabolism modifier

MOA: blocks late Na+ current in myocardium, which decreases intracellular Na+, causing Na+/Ca+2 exchanger stimulation, then decrease in intracellular Ca+2

Ranolazine

Drug class: Ranolazine

Rate modifier, metabolism modifier

Drug class: Ivabradine

Rate Modifier

MOA: block pacemaker Na+ current (If channel) in SA node

Ivabradine

MOA: decreases cardiac contractility, reduces HR and force of contraction

Ranolazine

MOA: decreases cardiac contractility, reduces HR

Ivabradine

Clinical applications: angina prophylaxis, HF

Rate modifiers (ranolazine, trimetazidine)

S/E: Bradycardia, QT prolongation, nausea, constipation, dizziness

Ranolazine

S/E: Bradycardia, atrial fibrillation

Ivabradine

Has dual mechanism of

action; both a rate modifier and

metabolism modifier

Ranolazine

Drug class: Trimetazidine

Metabolism modifier

MOA: Inhibits beta-oxidation of fatty acids (lipolysis) by inhibiting ketoacyl-CoA thiolase enzyme

Metabolism modifiers

MOA: Shifts the cardiac metabolism from being lipid-dependent to glucose-dependent

Metabolism modifiers

Enzyme inhibited by metabolism modifiers

Ketoacyl-CoA thiolase

Effects: Enhances glucose oxidation,

resulting in more efficient production of

ATP with less oxygen demand.

Metabolism modifiers

Clinical applications: angina, tinnitus, dizziness

Trimetazidine

S/E: EPS (involuntary movements, muscle stiffness, tremors, akathisia, dystonia), gait instability, restless leg syndrome

Trimetazidine

Interacts with MAO inhibitors wherein

they can induce hypertensive crisis

and serotonin syndrome.

Trimetazidine