PK in Special Conditions

Question 1

When are maternal physiological changes most pronounced?

Answer 1

3rd trimester

Question 2

The effect of inc in plasma volume

Answer 2

1. Conc of plasma protein will dec.
2. Amount of total plasma protein will still remain the same
3. more free drug

Question 3

What plasma protein binds to basic drugs?

To acidic drugs?

Answer 3

Alpha Glycoprotein

Albumin and lipoprotein

Question 4

Maternal PK Changes in Pregnancy:
In Absorption (3)

Answer 4

1. Progesterone causes inc in GET
2. Hormonal Changes causes vomiting
3. Dec in Acid Secretion @ 1st and 2nd trimester, Inc in acid secretion @ 3rd

Question 5

Maternal PK Changes in Pregnancy:
In Distribution (1)

Answer 5

Hemodilution causing less concentration of Plasma Protein

Question 6

Maternal PK Changes in Pregnancy:
In Elimination (2)

Answer 6

1. Changes in Liver enzyme –> Drug adjustment (ex. CYP1A1 and smoking)
2. Inc in RBF and GFR

Question 7

“All or Nothing effect”

Answer 7

before 20th day

fetus can survive, can die or can have congenital defects

Question 8

Drug effect during Organogenesis

Answer 8

3rd-8th week
survival, abortion, with sub lethal anatomic defect (TRUE TERATOGENIC EFFECT), with subtle metabolic of fxnal defect (COVERT EMBRYOPATHY)

Question 9

2 organs that continue to grow after birth

Answer 9

Brain and reproductive organs

Question 10

Effects of:
Paxil and Thalidomide drug?
Anti-neoplastic agents?

Answer 10

Paxil - congenital malformation
Thalidomide - Phocomelia
Fetal death

Question 11

Closest animal model?

Answer 11

Sheep placenta

Question 12

2 metabolic processes that occur in liver but not in placenta?

Answer 12

Oxidation (Phase I) and Conjugation (Phase II)

Question 13

Passive diffusion to placenta:

MW? Lipid Solubility? Protein binding? pKa

Answer 13

Lower MW crosses placenta; lipophilic opiods and antibiotics easily cross; protein bound cant cross; lower pH more difficult to cross

Question 14

Factors that promote placental crossing

Answer 14

1. Higher concentration of drug

2. Inflammatory reaction

Question 15

famous placental transporter that pumps substrates out of the placenta

Answer 15

P-glycoprotein

Question 16

2 reasons for reduce drug metabolism in liver damage

Answer 16

1. Dec in enzyme metabolizing capacity

2. Dec liver blood perfusion

Question 17

3 Mechanisms involved in converting hepatotoxic drugs

Answer 17

Alkylating, Acylating, Arylating

Question 18

2 drugs that promote K+ loss and metabolic alkalosis resulting in Hepatic encephalopathy

Answer 18

Furosemide and thiazide diuretics

Question 19

Morphine, analgesics, sedatives and tranquilizers can precipitate hepatic encephalopathy thru

Answer 19

increasing brain sensitivity to centrally acting drugs

Question 20

What clotting factors need Vitamin K?

What condition decreases the absorption of fat soluble vitamins including Vit. K?

Answer 20

Factor 2,7,9,10.

Cholestasis