Drug Distribution

Question 1

Influence of pH on the ionization of weak acid/base drugs: Most drugs are either ________, therefore they are present in biological fluids are ionized or non-ionized species _______.

Answer 1

• weak acids or weak bases

- present in biological fluids are ionized or non-ionized species

Question 2

Influence of pH on the ionization of weak acid/base drugs: _______ forms are more readily absorbed. _______ forms DO NOT cross lipid membranes

Answer 2

• non-ionized

- ionized

Question 3

Influence of pH on the ionization of weak acid/base drugs: R-COOH is the protonated/non-ionized form of the _______ and can _______. R-COO- is the _______ form of the acid and will be ________

Answer 3

• acid
• cross biological membranes (in acidic environment)
• un-protonated
• “ion-trapped”

Question 4

Influence of pH on the ionization of weak acid/base drugs: R-NH3+ is the protonated form of the _______ and will be _______. R-NH2 is the un-protonated/non-ionized form of the ________ and will _______

Answer 4

• base
• “ion-trapped”
• base
• cross biological membranes (in basic environment)

Question 5

Henderson-Hasselbach equation

Answer 5

pH-pKa= log (non-protonated: A- or B)/ (protonated: HA or BH+)

Question 6

If pH is lower than pKa (lots of protons): protonated form of _______ or ______ will predominate

Answer 6

weak acid (unionized-lipophilic) or weak base (ionized)

Question 7

If pH is higher than pKa (fewer protons): unprotonated form of _______ or _______

Answer 7

weak acid (ionized) or weak base (unionized) will predominate.

Question 8

“Ion Trapping”:.
i.
ii.

Answer 8

lipid barriers may separate two aqueous solutions with different pH’s. Only non-ionized drugs can diffuse through membrane and this form of the drug will equilibrate and be the same on both sides of the membrane. At equilibrium, un-ionized concentration of drug is the same on both sides of the membrane, but total concentration of drug is greater on the side where ionization is greater

Question 9

Acidic drugs will be trapped in _______ solutions. Basic drugs will be trapped in _______ solutions. They are trapped where they are predominantly _______

Answer 9

• BASIC
• ACIDIC
• ionized

Question 10

Clinical significance of ion trapping:

Answer 10

altering urinary pH to ion trap weak acids or bases and hasten renal excretion (in aspirin overdose situations), greater potential to concentrate basic drugs in more acidic breast milk

Question 11

Explain the therapeutic consequences of anatomic “barriers” to distribution and selective accumulation of drugs.

Answer 11

Tissues with tight junctions between cells (GI mucosa, BBB, placenta, renal tubules), require that drugs pass through lipid membranes to or from this compartment and into or out of the blood. Drugs that can’t pass through membranes (large size, protein bound, highly charged, high water solubility) will be UNABLE to move between these compartments and blood.

Question 12

Explain the therapeutic consequences of anatomic “barriers” to distribution and selective accumulation of drugs: GI mucosa

Answer 12

negligible absorption of drug into blood in administered orally

Question 13

Explain the therapeutic consequences of anatomic “barriers” to distribution and selective accumulation of drugs: Renal tubules

Answer 13

following filtration at glomerulus (note that large or protein bound drugs are NOT filtered), reduced reabsorption of drug back into blood, thus enhancing excretion via urine

Question 14

Explain the therapeutic consequences of anatomic “barriers” to distribution and selective accumulation of drugs: BBB/placenta

Answer 14

limited distribution of drug from blood into brain or into fetal circulation, due to structural differences between brain and non-brain capillaries