Pharmacokinetics

Question 1

what is the henderson-hasselbalch equation for weak acid

Answer 1

pKA=pH+log(unionised/ionised)

Question 2

what is the henderson-hasselbalch equation for weak base

Answer 2

pKA=pH+log(ionised/unionised)

Question 3

Ionisation is the greatest at alkaline of acid pH for weak acid ?

Answer 3

alkaline

Question 4

Ionisation is the greatest at alkaline of acid pH for weak base ?

Answer 4

acid

Question 5

Which of the steps is most critical to achieve a therapeutic drug concentration in plasma ?

Answer 5

Absorption

Question 6

A 26-year-old man overdosed on methamphetamine (weak base;
pKa=10) and is treated in the local emergency room. Part of the
treatment involves the administration of ammonium chloride which
adjusts the urine pH to accelerate the excretion of
methamphetamine. After this treatment the ratio of excretable
(protonated) methamphetamine to the lipophilic (unprotonated) form
is 100 to 1.
What is the urine pH?

Answer 6

8

Question 7

Five minutes after administration of drug A, peak plasma levels of
the drug have been achieved. Which route of administration was
most likely utilised for this drug?

Answer 7

inhalational

Question 8

A lipid soluble drug with a molecular weight of 10kDa is excreted via
the kidney. Which excretory routes could the drug utilise?

Answer 8

Active tubular secretion, glomerular filtration and passive diffusion across the tubular epithelium

Question 9

The table below shows the pKa for five different opioid drugs. All
five drugs are weak bases. Which of the five drugs would be most
unionized at a tissue pH of 7.4?
pKa 
1. 8.0
2. 8.5
3. 8.4
4. 6.5
5. 7.1

Answer 9

4

Question 10

Which tissue do you think a water soluble drug could access most readily?

Answer 10

liver

Question 11

A therapeutic dose of a drug with a high oil/water partition
coefficient is administered to a patient.
Which of the following would largely explain the observed
distribution of this drug to brain tissue and adipose tissue?
1. Accumulate in adipose tissue faster than brain tissue
2. Require transport proteins to access brain tissue but not adipose
tissue
3. Retained longer in adipose tissue compared to brain tissue
4. Will only be distributed to the adipose tissue
5. Distribution to adipose tissue would increase the oil/water
partition coefficient of the drug more than in the brain

Answer 11

3

Question 12

The following table contains four different drugs and their
corresponding pKa values. Metoprolol is a weak base. The other
drugs are weak acids.
If the urine pH increases from 6.5
Levodopa - 2.3
warfarin - 5
ciprofloxacin-6.1
phenobarbital - 7.4
metoprolol - 9.8

Answer 12

phenobarbital

Question 13

name the 4 mechanisms that drug move across lipid membranes

Answer 13

pinocytosis, diffusion through lipid membranes, diffusion through aqueous pores, carrier proteins

Question 14

name all the first target for oral, inhalational and intranasal

Answer 14

small intestine microvilli, alveoli and mucous membranes of nasal sinus

Question 15

name the 4 factors of drug distribution

Answer 15

regional blood flow, plasma protein binding, capillary permeability and tissue localisation

Question 16

what properties do glomerulus of kidney have to allow small drugs to pass to kidney tubules for excretion ?

Answer 16

fenestrated

Question 17

what properties do liver have to allow drugs to easily diffuse out of bloodstream and access liver tissue?

Answer 17

discontinuous

Question 18

what does active tubular secretion depends on

Answer 18

available transporters

Question 19

what does passive diffusion across tubular epithelium depends on

Answer 19

uring pH (acidic drugs reabsorbed better at low pH) and extent of drug metabolism (phase 2 metabolites more water soluble-> less well reabsorbed)

Question 20

mechanism of enterohepatic recycling

Answer 20

1. A glucuronide metabolite is transported into the bile
2. The metabolite is excreted into the small intestine, where it is hydrolysed by gut bacteria releasing the glucuronide conjugate.
   3. Loss of the glucuronide conjugate increases the lipid solubility of the molecule
   4. Increased lipid solubility allows for greater reabsorption from small intestine back into the hepatic portal blood system for return to the liver.
   5. The molecule returns to the liver where a proportion will be re-metabolised, but a proportion may escape into the systemic circulation to continue to have effects on the body.