Pharmacokinetics Part 1: Absorption

Question 1

what do we need to keep the concentration of drugs between?

Answer 1

the therapeutic range

Question 2

what is passive diffusion of drugs and what factors contribute to this being able to happen

Answer 2

drugs move down their concentration gradient from one side of a membrane to another

factors:
- size
- solubility in the lipid bilayer

Question 3

what is facilitated/carrier mediated transport of drugs and waht is 1 feature of this

Answer 3

• a passive process relying on concentrion gradients that uses a carrier protein to transport the drug from one side of the membrane to another

1 feature: bidirectional

Question 4

what is active transport of drugs and what are they usually driven by and waht direction can the pumps work

Answer 4

when a drug that is a substrate for a transporter/carrier protein is pumped from one of an interface/membrane to another

• usually driven by ATP
• bidirectional

Question 5

At low and high pH, outline how absorption of drug differs when the drug is a weak acid in the stomach/intestines ( example, A- + H+ –> HA)

Answer 5

• at low pH ( like in stomach ), [H+] is high
• equilibrium goes towards HA (the drug)
  Very little HA is ionised, so lots of HA is absorbed as HA is uncharged
• At high pH ( like in intestines ) , [H+] is low
• so equilibrium shifts towards A- + H+
• so more HA is ionised and less is absorbed as charged drugs cannot cross membranes

Question 6

At low pH and high pH outline how absorption of drug differs when the drug is a weak base in the stomach/intestines ( example, B + H+ –> BH+)

Answer 6

at low pH ( like in stomach ), [H+] is high
- equilibrium goes towards BH+ (the drug)
- lots of this is ionised and little is absorbed as cannot pass the gut wall membrane

at high pH ( like in intestines ), [H+] is low, so equilibrium shifts towards B + H+ (drug constituents).
- this means less is ionised and more is absorbed as the B can cross the blood brain barrier because it is uncharged

Question 7

when weak base drugs get filtered into the urine, outline how absorption of drug differs at high and low urine pH (B + H+ –> BH+)

Answer 7

at lower urine pH, [H+] conc is high, so eqilibrium goes to BH+. lots is ionised and little absorption as BH+ cannot cross the epithelial cell membrane as it is charged

opposite for higher pH

Question 8

what 2 things can rate of absoption into systemic circulation by modified by

Answer 8

site of administration
drug formulation

Question 9

define absorption

Answer 9

transfer of drug from site of administration to systemic circulation

Question 10

define bioavailability (F)

Answer 10

F = quantity of drug reaching systemic circulation as intact drug / quantity of drug administered (dose)

Question 11

what 2 things need to be true for 2 drugs to be bioequivalent

Answer 11

2 drugs are bioquivalent if:

• they contain same active ingredient
  AND
• when the rate and extent of bioavailability of the active ingredient in the 2 products are NOT significantly different

Question 12

where does more absorption occur in the gastrointestinal tract

Answer 12

in the small intestine due to increases surface area due to villi

Question 13

outline how oral tablets is absorbed in the gastrointestinal tract

Answer 13

1. tablet dissolves
2. passes across intestinal wall
3. passes through portal vein
4. passes through the liver
5. enters systemic circulation

Question 14

what 5 things can affect absorption form the gut

Answer 14

1. gastric emptying
2. gastrointestinal motility
3. blood flow
4. particle size and formulation
5. physicochemical factors
6. metabolism

Question 15

how can particle size and formulation affect absorption from the gut

Answer 15

• extended release formulations
• enteric coatings

Question 16

what is first pass metabolism/effect

Answer 16

when drugs are metabolised by enzymes in liver or gut wall when they are first absorbed

Question 17

what 2 things can first pass metabolism lead to and overview each

Answer 17

• activation: pro drugs are drugs that are converted to an active form by enzymes in the liver
• inactivation: a drug is converted to inactive metabolites

Question 18

what are the 2 types of mouth drug administration (NOT oral) and why can they avoid first pass metabolism

Answer 18

• sub-lingual (under tongue)
• buccal (in the cheek)

avoid first pass metabolism because the blood from their avoids the liver

Question 19

what 2 reasons is the rectal route of administration good

Answer 19

• avoids First pass metabolism
• useful for vomitting

Question 20

why is glyceryl trinitrate given sublingually? (for angina)

Answer 20

• undergoes first pass metabolism
• gives a quick response

Question 21

why is local anaesthetics given subcutaneously?

Answer 21

• only want it to act locally
• can be given with vasoconstrictor to delay systemic absorption

Question 23

lol

Answer 23

lol