Medchem

Nonglycosidic Positive Ionotropic Agents

• Milirone

  • Structure: Byridines 

  • Mechanism: Selective PDE3 inhibitors 

  • PK: 

    • Short elimination half life (2-3h)

    • Parental only 

  • Metabolism: Unchanged 83%

• Dobutamine

  • Structure: dopamine analogue 

  • Mechanism: B1 adrenergic agonist 

  • PK: IV only b/c of catechol structure 

  • Metabolism: rapid first pass metabolism by COMT 

  • Fewer SE

Nitrovasodilators

• Made of organic nitrates 

• Glyceryl Trinitrate (Nitroglycerin)

  • Structure: organic nitrate (ester of glycerol and nitric acid)

  • PK: Rapid onset of action (2 mins) b/c it’s highly lipophilic so it can rapidly be absorbed thru membranes 

• Isosorbide Dinitrate

  • PK

    • Last for 4-6 hrs 

    • Long-acting agent that can be used to treat acute angina 

  • Metabolism 

    • Reduced to 2 metabolites; 2- and 5- isosorbide mononitrate 

      • 5 - is active form

• Sodium Nitroprusside 

  • Structure/Physiological Properties

    • Complex of iron, cyanide groups, and nitroso moiety 

    • Reddish brown solution

    • Must be protected from light and heat

    • Solution of green or blue color → INACTIVE 

  • PK/Metabolism

    • Release nitric oxide and cyanide

    • Cyanide → less toxic thiocyanate → eliminated by kidney 

  • Prodrug, given IV 

Vasopressin Nonpeptide Antagonists

• Tolvaptan

  • Selective V₂ antagonist 

  • Administer PO 

  • Half life = 6-8hrs

• Conivaptan

  • Nonselective V_1A / V₂ receptor antagonist

  • Administered IV infusion 

  • Half life = 12 hrs 

Antiplatelets

	MOA	Info
Aspirin	COX - 1 Inhibitor	→ Irreversible acetylation of serine → Antithrombotic effect of aspirin remains for the life span of the platelet (7-10 days)  → QD dose 50-100mg can inactivate platelet COX-1 irreversibly  → Higher doses ↑ SE
Cilostazol	Phosphodiesterase Inhibitor	→ Quinolinone derivative  → Rapidly absorbed w/ PO esp. w/ high fat meal which ↑ bioavailability to ~90% which could ↑ toxic effects  Therefore, take on empty stomach
Ticlopidine	Irreversible P2Y12  Purinergic Receptor	→ Structure: thienopyridines → prodrugs  → Irreversible b/c there is antiplatelet activity for 7-10 days after D/C of medication
S - Clopidogrel	Irreversible P2Y12  Purinergic Receptor	→ Structure: thienopyridines → prodrugs  → Irreversible b/c there is antiplatelet activity for 7-10 days after D/C of medication → CHIRAL Thiol metabolite binds irreversibly to P2Y12 by forming a disulfide bond
Prasugrel	Irreversible P2Y12  Purinergic Receptor	→ Structure: thienopyridines → prodrugs  → Irreversible b/c there is antiplatelet activity for 7-10 days after D/C of medication → RACEMIC
Ticagrelor	Reversible Antagonist P2Y12  Purinergic Receptor	→ Heterocyclic compound  → PO  → W/ improved PK and PD profiles

Glycoprotein IIb/IIIa Receptor Antagonists

• Eptifibatide 

  • Cyclic heptapeptide → 7 AA’s

  • Parentarelly administered 

  • Short half life b/c of amide bonds → gets attacked by proteases → can’t be taken PO 

  • Has basic (guanidine)  and acidic (COOH) properties

• Tirofiban

  • Peptidomimetic 

  • Parenterally administered 

  • Short Half life