Basic Pharm 4

Question 1

What is distribution?

Answer 1

The process of translocating drugs reversibly from the blood stream into the tissues/interstitium

Question 2

What is the volume of distribution (Vd) equation?

Answer 2

Vd = Dose (L) / Plasma Conc (mg)

Question 3

What property of a drug increases its volume of distribution?

Answer 3

The drug is more ionized inside cells than it is in the plasma

Question 4

A drug typically distributes into what 3 compartments?

Answer 4

Plasma = 4 L 
ECF = Plasma (4L) + Interstitial fluid (10 L) = 14 L 
TBW = Plasma (4L) + IF (10 L) + ICF (28L) = 42 L

Question 5

When does the drug distribute?

Answer 5

Once the drug reaches the max plasma concentration

Question 6

What happens after distribution?

Answer 6

It starts eliminating –> clearance

Question 7

How do you calculate plasma concentration?

Answer 7

Mg of drug / liters of plasma

Question 8

How do you calculate concentration in general?

Answer 8

Mass / volume

Question 9

What is a loading dose?

Answer 9

A priming dose that’s given to rapidly establish a therapeutic plasma drug concentration

Question 10

If Vd is high, then loading dose is also, which makes loading dose what to Vd?

Answer 10

High, so loading dose is directly proportional to Vd

Question 11

Loading Dose (LD) equation?

Answer 11

Plasma concentration (Cp) x Vd

Question 12

What are the 2 areas of safeguard in our body? And what what kind of drugs can easily cross?

Answer 12

BBB and Placenta

High lipid soluble drugs can easily pass

Question 13

What CYP enzyme metabolizes 60% of drugs?

Answer 13

CYP3A4

Question 14

What are drugs that induce CYP450?

Answer 14

Carbamezepine, phenobarbitone, phenytoin (anti-convuls)
Rifampin, chronic alcohol, glucocorticoids

Makes CYP450 active, and these drugs get meatbolized more, decreasing effectivness

Question 15

Drugs that INHIBIT CYP450?

Answer 15

Cimetidine, Erythromycin, Ketoconazole

Question 16

What juice inhibits metabolism of alprozolam, atorvastatin, and midazolam?

Answer 16

Grapefruit juice

Question 17

PPBinding: High affinity drugs will do what to low affinity drugs?

Answer 17

Displace them.

E.g. Sulphonylureas displace Warfarin (99% protein bind, 1% free)

Sulfonamides displace bilirubin in neonates (leading to kernicterus

Question 18

What is redistribution?

Answer 18

Drugs that first go to organs with high blood flow (i.e. brai, heart, liver, and kidney) - E.g. Thiopental (anesthetic)
Then redistribute to other tissues (e.g. muscle and fat)

When drug administration is stopped, redistribution causes brain levels to drop and patient comes out of anesthesia

Hangover effect due to drug slowly leaking out of tissue droplets

Question 19

Metabolism (Biotransformation)

Answer 19

Process to increase water solubility, inactivate drug, and convert to excretabe form

Question 20

What are prodrugs?

Answer 20

Inactive compounds that require biotransformation to become active

E.g. enalapril –> enalaphilat (Active form)

Morphine is active to active

Question 21

What is first pass metabolism in the liver?

Answer 21

Mostly oral route,

some loss of drug before reaching circulation

Question 22

What is Phase II Biotransformation?

Answer 22

Drugs undergo conjugation rxns to become water soluble for excretion

Question 23

Phase II Biotransformation: glucuronide Conjugation

Answer 23

UDP - glucuronyl transferase
e.g. Chloramphenicol - drug glucurinodes exrected in bile can be hydrolysed by bacteria in the gut –> the liberated drug is absorbed

E.g. OCP

Question 24

Phase II Biotransformation: Acetylation

Answer 24

E.g. Isoniazid: slow acetylators, risk for peripheral neuritis

Procainamid, hydralazine –> SLE

Question 25

Phase II Biotransformation: Glutathione Conjugation

Answer 25

Acetaminophen poisoning (glutathione supply falls short)