Drug Transport - Issar

Question 1

What are the molecular/structural factors that influence membrane drug transport?

Answer 1

1. Molecular weight
2. Log P
3. Hydrogen-bond donor/acceptor
4. Chirality
5. Number of routable bonds

Question 2

What are the physiochemical factors that influence membrane drug transport?

Answer 2

1. pKa of drug and solvent pH
2. Drug solubility
3. Drug dissolution

Question 3

pH-partition Theory

Answer 3

The extent of ionization of a weak electrolyte depends on:
• pKa of the drug
• pH of the solvent

Question 4

Ion-trapping

Answer 4

• Weak base or weak acid will ionize to different degrees on the respective sides
• Unequal drug conc. on either side of membrane
• Compartment containing greater proportion of ionized drug will contain greater total drug concentration

Question 5

Clinical applications of ion-trapping on weakly acidic drugs

Answer 5

o Largely non-ionized in stomach
o 40-50% non-ionized in plasma
o Forced alkaline diuresis traps drug in urine
• By administering sodium bicarbonate

Question 6

Passive transport

Answer 6

• Aka simple diffusion
• Fick’s law of diffusion allows you to determine the rate of diffusion of a rug across a biological membrane (therefore drug absorption) by passive diffusion
• First order diffusion
o The rate of diffusion is proportional to the conc of drug at the site of absorption

Question 7

Facilitated diffusion

Answer 7

• No energy consumption
• Limited role in drug absorption
• Low drug concentrations: Cabs (conc at absorption site) << Km (affinity of drug to carrier)
    o First order diffusion
• High drug concentrations Cabs >> Km
    o Zero order diffusion

Question 8

Active transport

Answer 8

• Energy consumption (uses ATP)
• Ex: Na+, K+ ions via Na+/K+ ATPase pump
• Can be competitive
• Goes against concentration gradient
• Is saturable

Question 9

What types of drugs get trapped in breast milk?

Answer 9

Weak bases because breast milk is a weak acid

Question 10

Clinical applications of ion-trapping on weakly basic drugs

Answer 10

o Mainly ionized in stomach
o Relatively non-ionized in plasma
o Acidification of urine can trap drug
• By administering ammonium chloride