Cardio Exam 2: Kaur

Warfarin:

• Structure:

  • _____, _____

  • _____ group → salt

  • (_)-warfarin more potent

• PK:

  • Rapidly + completely absorbed (_____)

Lactone, coumarin, acidic 4-hydroxy, S, 100% bioavailability

Heparin-Based Anticoags

• Heparin

  • High _____

  • _____ charged _____ molecule

  • Administered _____ (NOT _____)

MW polysaccharide, negatively, acidic, IV or SQ, orally

Heparin-Based Anticoags

• Fondaparinux

  • _____

  • _____ PK

  • _____ inhibitor

Synthetic pentasaccharide, improved, 1st selective Factor Xa

Heparin-Based Anticoags

• _____ + _____ (same as Heparin) but _____ selective

Enoxaparin, Dalteparin, more

DTIs

• Prosteases (degradation) → L-AA = natural proteins/peptides

• _____ → small proteins with short half-lives

• Bivalirudin → _____ + _____ (less risk of _____)

• Dabigatran Etexilate → _____-mimetic _____ + _____

  • _____: Major advantage over other anti-coag therapies (rapid onset/offset + doesn’t require coag monitoring)

Hirudin, Lepirudin, and Desirudin, peptide, reversible inhibitor, bleeding, Non-peptide, prodrug, orally active, Metabolism

Thrombolytic Drugs

• Streptokinase (_____)

  • _____ (_____)

1st Gen, Serine protease, enzymes

Thrombolytic Drugs

• Alteplase (_____)

  • _____ (_____)

  • _____ (_____ bound to _____)

2nd gen, Serine protease, enzymes, selective, plasminogen, fibrin

Thrombolytic Drugs

• Tenecteplase (_____)

  • _____ activity

  • _____

3rd gen, improved, prolonged half-life

BAS

• Structure: _____

• Freely soluble in _____ solutions

• DDI: potentially bind and sequester any _____, such as _____

positively charged resins, acidic, acidic drug, Warfarin

HMGRIs or Statins

• “_____”

• _____ + _____ = Prodrugs

• SAR:

  • Pharmacophore: _____ + _____ or other _____

    • Hepatanoic = carboxylic acid

  • ___, ___ stereochemistry

    • Active forms = contains a carboxylic acid

• PK: Peak _____ of plasma cholesterol EXCEPT _____ (2 weeks)

• Elimination half-life for Atorvastatin + Rosuvastatin ~_____, most others _____

chiral, Lovastatin, Simvastatin, 3,5-dihydroxyheptanoic acid, decalin, aromatic ring, 3R, 5R, reduction, Atorvastatin, 19 hours, 1-4 hours

Cholesterol Absorption Inhibitor: _____

• _____ molecule (LogP = 3.5 → very _____)

  • -1 to +1 = hydrophilic

  • > 2 = lipophilic

Ezetimibe, small, lipophilic

Fibrates

• SAR

  • Compounds containing an _____ = _____

  • _____ substitution produces compounds with _____ half-lives

• Contains a _____–_____–_____

ester, prodrugs, Para, longer, Phenoxy, Spacer Group, Isobutyric Acid

Nicotinic Acid (Niacin)

• Structure

  • _____ (pka = 4.76) → predominantly _____ at physiological pH

  • Nicotinic Acid is freely soluble in _____ solutions

• PK

  • Half-life is ~_____ → _____ or an _____ formulation

Carboxylic Acid, ionized, alkaline, 1 hour, frequent dosing, ER

KNOW IMAGE