pharmacology

Question 1

define volume of distribution

Answer 1

(Vd) the ratio of the total amount of drug in the body (D) to the plasma concentration of the drug (C): Vd = D/C

Question 2

significance of large Vd

Answer 2

-most of drug is distrubuted in some body compartment/ a smaller fraction of the drug is in plasma

Question 3

significance of small Vd

Answer 3

the drug is highly bound to plasma proteins; the drug does not distribute widely into other compartments

Question 4

effect of protein binding

Answer 4

drugs bound to a plasma rotein (i.e. albumin) stay inside the capillaries b/s the protein molecules are too lg to squeeze through the fenestrations

Question 5

displacement of a protein drug

Answer 5

depends on the volume of distribution; only unbound (free) drug has pharmacological role; as one free drug molecule is eliminated from the body, more drug dissociates from plasma proteins to replace it

Question 6

drugs highly bound to albumin - acidic drugs

Answer 6

aspirin, Furosemide, Ibuprofen, Penicillin, Phenytoin, Warfarin

Question 7

drugs highly bound to Alpha-1-acidic glycoprotein (AAG) - alkaline drugs

Answer 7

diazepam, Lidocaine, Nifedipine, Propranolol, Quinidine

Question 8

conditions that decrease palsma albumin and increase free drug levels, risking toxic levels

Answer 8

Malnutrition; liver disease, kidney disease, aging, trama (i.e. burns)

Question 9

Condi9tions that increase liver synthesis/release of AAG and decrease free drug levels (initial doeses of drugs that bind to AAG may need to be increased)

Answer 9

Aging, trauma, acute liver inflammation

Question 10

Why is it significant to know that digoxin is distrubuted in muscle?

Answer 10

Because the drug will have a low Vd as people age or weaken; if the pt. loses muscle mass quickly, dogoxin is iredistributed to plasma and plasma levels can rise to dangerous levels.

Question 11

Biotransformation

Answer 11

-the acto of non-polar, lipophilic molecules undergoing structural changes by enzymes in the body

Question 12

Name the sites where biotransformation takes place

Answer 12

Stomach (alcohol dehydrogenase); intestine (CYP3A4 and bacteria metabolize drugs befrore absorption; liver (12+ enzyme families in the smooth endoplasmic reticulum and cytosol; kidney (only a few drugs are metabolized here)

Question 13

The route through which drugs go through the liver

Answer 13

• the portal vein

Question 14

High-extraction-ratio drugs

Answer 14

-have low oral bioavailability; PO doeses of high ER drugs must be higher than IV doeses to compensate for the extensivve first-pass metabolism; small changes in hepatic enzyme activity prroduce lg. changes in bioavailability

Question 15

Low-extraction-ratio drugs

Answer 15

• have high oral bioabailability (< 20% of PO doese undergoes 1st-pass metabolism; PO doeses are similar to IV doeses; small changes in hepatic enzyme activity have little effect on bioabailability

Question 16

Phase I of biotransformation (transformation)

Answer 16

occurs in SER; adds polar groups such as -OH and thus increases polarity of drug; can increase, decrease or not alter drug’s pharm activiity; increase elimination of drug by kidney

Question 17

Phase II of biotransformation (conjugation)

Answer 17

-occurs in liver cytoplasm; attaches lg molecules thus increases ploarity of drugs; decreases drug or metabolite pharm activity; increase excretion by kidney