Administration, distribution, metabolism and elimination of drugs

Question 1

what routes of drug administration are enteral via the gut?

5

Answer 1

oral
rectal
nasogastric
nasointestinal
PEG - percutaneous endoscopic gastronomy

Question 2

what route of drug administration are parenteral via not the gut?

6

Answer 2

transdermal
transmucosal
intravenous IV
intramuscular IM
subcutaneous SC
inhalation

Question 3

what are the advantages of oral drug administration?

4

Answer 3

convenient, portable, painless
non-invasive
cost effective
patient can self administer

Question 4

what are the disadvantages of oral drug administration?

4

Answer 4

slow onset
may be inefficient
variable absorption - food interactions, GI disease
first-pass metabolism

Question 5

what is first-pass metabolism?

Answer 5

blood from GI tract drains to hepatic portal vein which drains to liver
liver metabolises drug which passes through liver once then enters systematic circulation and target tissues

Question 6

what 2 things can the liver do to a drug?

Answer 6

inactivate proportion of drug - more needed to get desired clinical effect
activate proportion of drug - makes an active form from an inactive drug - less needed by oral route

Question 7

what are the advantages of intravenous and intramuscular drug administration?

3

Answer 7

very rapid onset
predictable plasma levels
no first pass metabolism

Question 8

what are the disadvantages of intravenous and intramuscular drug administration?

5

Answer 8

allergic reactions more severe
short duration of action
requires trained staff to administer
higher drug cost
painful

Question 9

what are the advantages of transdermal and subcutaneous drug administration?

4

Answer 9

no first pass metabolism
allergic reactions often very localised
prolonged action
can be self-administered

Question 10

what are the disadvantages of transdermal and subcutaneous drug administration?

3

Answer 10

very slow onset
drug cost higher
effect will vary from person to person and site to site

Question 11

what is bioavailability?

Answer 11

proportion of an ingested drug that is available for clinical effect

Question 12

what is bioavailability modified by and affected by?

2 (3,3)

Answer 12

modified by pharmaceutical factors
* dosage
* formulation
* route of administration
affected by physiological factors
* destruction in the gut
* poor absorption
* first pass metabolism

Question 13

what is drug distribution and how does it occur?

Answer 13

the movement of a drug to and from the blood and various tissues
drug is dissolved in the blood and transported bound to plasma proteins

Question 14

what does the speed of diffusion into tissues depend on?

4

Answer 14

blood flow in the area
membrane characteristics
pH
active secretion of the drug into the tissues

Question 15

what is the single and two compartment model?

2

Answer 15

single compartment model - drug behaves as if it is evenly distributed around body
two compartment model - drug behaves as it is in equilibrium with different tissues in the body

Question 16

what is metabolism, what does it do and where can it occur?

Answer 16

• metabolism is the process of chemically changing the drug
• metabolism prepares the drug for elimination from the body
• occurs in the liver but some processes occur in the gut wall, kidneys, lungs, blood plasma

Question 17

where are drugs excreted from?

6

Answer 17

renal excretion of water soluble metabolites - urine
liver metabolism and excretion - bile
lungs - inhaled gases and volatile fractions of other drugs
small proportions as sweat, saliva, tears

Question 18

what are the three stages of renal excretion?

Answer 18

glomerular filtration
reabsorption
secretion

Question 19

what problems can cause excretion problems? what should be adjusted?

2(2,2)

Answer 19

renal disease
* chronic renal failure
* drug doses must be reduced
liver disease
* liver failure
* drug doses must be reduced

Question 20

what is plasma half life?

Answer 20

time taken to eliminate half the drug

Question 21

what are the first order kinetics in relation to drug clearing?

2

Answer 21

• drug elimination increases as drug concentration increases
• excretion is by passive diffusion only

Question 22

what are the zero order kinetics in relation to drug clearing?

3

Answer 22

drug elimination is at a fixed rate and irrespective of drug concentration
excretion is by active processes
can lead to drug accumulation if saturation exceeded

Question 23

what happens systemically if drugs are dosed too frequently or infrequently?

2

Answer 23

too frequent - results in plasma levels that may be toxic
too infrequent - results in sub-therapeutic plasma levels and no clinical effect

Question 24

what is the dosage for paracetamol overdose and where does metabolism occur? what can overdose cause?

Answer 24

safe dosage of 4g over 24 hours
metabolism occurs in the liver
can cause liver damage, failure, acute hepatoxicity