Distribution

Question 1

Which types of barriers affect drug distribution and selectivity of drug accumulation?

Answer 1

1) GI mucosa
2) BBB
3) placenta
4) Renal tubules

Question 2

Generally describe the therapeutic consequences of the barriers

Answer 2

• They have tight junctions —> require drugs pass through lipid membranes into/out of blood

Question 3

Which factors make a drug unable to pass through a lipid membrane?

Answer 3

1) large size
2) protein bound
3) highly charged
4) high water solubility

Question 4

Describe distribution of drugs via the GI mucosa

Answer 4

Negligible absorption of drug into blood if taken orally

Question 5

Describe distribution of drugs via BBB

Answer 5

Limited distribution of drug from blood into brain

B/c of structural differences of brain and non-brain capillaries

Question 6

Describe distribution of drugs via placenta

Answer 6

Limited distribution of drug from blood into fetal circulation

Question 7

Describe distribution of drugs via renal tubules

Answer 7

After glomerulus filtration, reduced drug reabsorption back into blood —> enhances excretion

Note: large and protein bound drugs are NOT filtered

Question 8

Where can selective accumulation of certain drugs occur?

Answer 8

Specific tissues:

• kidney
• eye
• lung
• bone
• ear

Can be harmful or beneficial

Question 9

With regards to protein binding, to what do acidic drugs bind?

Answer 9

Albumin

Question 10

With regards to protein binding, to what do basic drugs bind?

Answer 10

Alpha-1 acid glycoprotein

Question 11

As drug binding to protein increases….

Answer 11

• [free drug] decreases
• metabolic degradation/excretion rate decreases (increases half-life)
• Vd decreases
• Ability to enter CNS across BBB decreases

Question 12

Describe volume of distribution (Vd)

Answer 12

• Size of compartment necessary to account for total amount of drug in body
• gives an indication of extent to which a drug passes from plasma to extravascular tissues

Question 13

What do high values of Vd indicate?

Answer 13

Drug located mostly outside plasma

• increased tissue binding
• high lipid solubility

Question 14

What do low values of Vd indicate?

Answer 14

Drug located mostly inside plasma

• extensive binding to plasma proteins
• larger in size

Question 15

What pt characteristics affect Vd?

Answer 15

1) Body weight
2) Fat vs lean
3) Changes in protein binding

Question 16

How is Vd used to inform prescriber decisions?

Answer 16

• Determines necessary single dose of drug (loading dose)
• Allows prescriber to determine dose effect on plasma concentration

Think –> Dose = Vd x Cp