Kaur: IE 2

Warfarin has the most drug-drug interactions with what enzyme?

CYP2C9

Warfarin has an [] hydroxy group which helps with [] formation.

Acidic

Salt formation

T/F: Warfarin is a water-soluble lactone

F → Water-insoluble

Warfarin is weakly acidic because of [] group

4-hydroxy

T/F: Warfarin is rapidly and completely absorbed (~100% bioavailability) after administration.

T

T/F: Heparin is a basic molecule.

F → Acidic

Route of administration for Heparin

IV/SQ

Structure of Heparin vs. Enoxaparin

Heparin: HMW (5-30 kDa) polysaccharide

Enoxaparin: LMW (4-6 kDa) polysaccharide

Describe structure of the first-selective factor Xa inhibitor

Fondaparinux is a synthetic, highly sulfonated pentasaccharide

Fondaparinux dosage and why?

Single daily dose d/t long elimination half-life

What drugs have the structure of 65 amino acids? What type of protein?

Hirudin: Small protein (65 amino acids)

Lepirudin → Recombinant protein (65 amino acids)

Desirudin → Recombinant protein (65 amino acids)

What drug has the structure of peptide (20 amino acids)?

Bivalirudin → Peptide (20 AAs)

Which drug is a peptide-mimetic?

Argatroban

What drugs have the structure of non-peptide mimetic prodrug?

Dabigatran etexilate

Which DTI has less risk of bleeding?

Bivalirudin

Dabigatran etexilate is orally [], has [] bioavailabiity, [] onset, and [] duration of action

Dabigatran etexilate is orally active, has low bioavailabiity, rapid onset, and short duration of action

What is a major advantage that Dabigatran has over other anticoagulant therapies?

• Rapid onset and rapid offset, so it does not require coagulation monitoring

T/F: Streptokinase is longer than alteplase.

F → Shorter

Streptokinase, Alteplase, and Tenecteplase

Descrobe fibrin speficity.

Streptokinase: Non-fibrin specific

Alteplase: Fibrin-specific

Tenecteplase: Fibrin specific

T/F: Alteplase has high affinity for free plasminogen and low affinity for plasminogen bound to fibrin

F → Alteplase has low affinity for free plasminogen and high affinity for plasminogen bound to fibrin

Compare half lives of Tenecteplase vs. Alteplase. Describe what the implications are for dosing.

Tenecteplase: Prolonged half-life → allows for single bolus application

Alteplase: Short half-life

What are the thrombolytic drugs made up of?

Serine protease

Route of Administration:

Hirudin

Lepirudin

Desirudin

Bivalirudin

Argatroban

Dabigatran etexilate

Hirudin: IV

Lepirudin: IV

Desirudin: SC

Bivalirudin: IV

Argatroban: IV/SC

Dabigatran etexilate: Oral

T/F: A basic drug (such as w/ secondary or teriary amines) will be charged and therefore freely soluble in basic solution (pH 9)

F → will be unionized and therefore less water soluble

T/F: Heparin based anticoagulants are negatively charged

T

T/F: Bile acid sequestrants are negatively charged resins

F → positively

What FGs does bile acid sequestrants have?

Quaternary ammonium groups

Secondary/tertiary amines

T/F: All of the groups in bile acid sequestrants shuold be primarily unionized at intestinal pH

F → primarily ionized

What type of interactions are there with bile acids?

Electrostatic interactions

Where are BAS excreted?

Feces

T/F: BAS has a delayed onset of action.

F → short onset of action

Statin pharmacophore

3,5-dihydroxyheptanoic acid; decalin (1st gen)/aromatic ring

T/F: Statins have active lactone prodrugs.

F → Statins have inactive lactone prodrugs

Name three 1st gen statins

Simvastatin

Lovastatin

Pravastatin

What structure is significant in 1st generation statins?

Decalin ring

Name three 2nd gen statins

Rosuvastatin

Atorvastatin

Fluvastatin

Statin stereochemistry

3R, 5R, stereochemistry at 3- and 5- positions is very important

In their active forms, all HMGRIs contain a [ ].

Carboxylic acid

What is the exception to peak reduction of plasma cholesterol after 4-6 weeks of therapy?

Atorvastatin → only 2 weeks

Which statin is the exception to low oral bioavailability?

• Pitavastatin

Which statins are prodrugs?

• Lovastatin

• Simvastatin

Which drug has aqueous instability?

Ezetimibe

T/F: Exetimibe has slow metabolism that turns into an active metabolite

F → Exetimibe has rapid metabolism that turns into an active metabolite

T/F: Ezetimibe has a short half-life

F → Long half-life

Fibrates contain a [], [] group, and [] acid

Phenoxy

Spacer

Isobutyric

T/F: Esters are prodrugs

T

T/F: Fibrates have poor bioavailability.

F → excellent bioavailability W

Where is fibrates excreted?

Urine

In Fenofibrate, [] produces compounds with significantly longer half-lives

para-substitution

Nicotinic acid is freely soluble in [] solutions

Alkaline

Is nicotinic acid carboxylic acid predominately unionized or ionized at physiologic pH?

Ionized

Describe half-life of Niacin and implications for dosing and formulation

Half-life: 1h

Needs frequent dosing or an ER formulation

T/F: colestipol is not absorbed after oral administration vecause it is highly positively charged at physiological ph

T → remember those positively charged resins!

T/F: Lovastatin and simvastatin are racemic prodrugs.

F → chiral prodrugs

T/F: The structure of fibrates must contain phenoxyisopentanoic acid

F → Phenoxy, spacer group, isobutyric acid