Biopharmaceutics

Question 1

Biopharmaceutics definition

Answer 1

What happens to the drug until is is absorbed into systemic circulation
API administer > API release and dissolution > API absorption
- Determines amount of API reaching systemic reaching systemic circulation (bioavailibility)

Question 2

Pharmacokinetics definition

Answer 2

API can transfer from tissues to system circulation and vice versa
In tissue = pharmacological/clinical effect
In systemic circulation = metabolised/eliminated

Question 3

Bioavailibility (F)

Answer 3

F=AUC oral dose/AUC i.v. dose

• Take blood samples at various time points and extrapolate back to 0
• Integrate AUC, which tells you how much drug relates to 1 bioavailibility

Question 4

Graph regions

Answer 4

Cmax=Peak conc
Tmax=Time of peak conc.
MEC(minimum effective conc)=When the drug begins to exert therapeutic effect
MSC(maximum safe conc)=the conc below which side effects are reached
Ka= drug administered begins to disintegrate, dissolve and rate of absorption
Kel=rate of metabolism and elimination
AUC=amount of drug absorbed systematically
- Cmax and Tmax determine whether one dosage form is equivalent to another dosage form

Question 5

GIT

Answer 5

• Oesophagus to rectum/anus
• Circular muscles and longtitudinal muscles surround tube
• Muscles squeeze producing peristalsis moving materials down
• Epithelial cells on surface produce mucus protecting from physical damage and providing a barrier for diffusion as well as regulating water movement

Question 6

Unstirred water layer

Answer 6

• 30-100mcm
• Layer constantly eroding > constantly repaired and replaced > Produced by rapid overturning epithelial cells
• Binds bacteria
• Holds antibodies which act on pathogens

Question 7

Mucus components

Answer 7

• Mostly water
• 0.5-1% mineral salt
• 1% free proteins
• 0.5-5% glycoproteins (sugar moieties crosslinked) and lipids (proteins (cysteine)) - has mucoadhesive properties

Question 8

Taking tablets without water

Answer 8

• Risk of being lodged in the oesophagus i.e. alendronate sodium
• Leads to oesophageal ulceration

Question 9

Oesophagus

Answer 9

25-30cm long, 20mm diameter
pH 5-6
Transit time 10-14s

Question 10

Stomach

Answer 10

• Little absorption
• Reduces solid into uniform consistency (chyme)
• Chyme improves contact between contents of GIT and the mucus membrane
• Capacity = 1.5L

Question 11

Small intestine

Answer 11

• Absorption major site espc. jejunum
• 200m2 surface area
• Folds of kerckring’s, villi and microvilli
• Duodenum is where the bile from the liver comes and enzymes from the pancreas = neutralises the gastric fluids
• SI is 4-6m in length

Question 12

Colon/Large intestine

Answer 12

• 1.5m in length
• Some absorption of water, Na+, Cl- and some drug substances
• Contains microflora
• Microflora may be a drug target i.e. sulfasalazine

Question 13

Partition theory

Answer 13

GI epithelia is a lipid barrier so only lipid soluble drugs can pass through

• Most drugs are weak electrolytes so only the unionised form of weak acidic or basic drugs will pass through
• GI epithelia is impermeable to ionised forms of drugs
• Absorption of weak electrolyte largely depends on to which extent the drug exists in its unionised form at site of absorption

Question 14

Limitations of pH partition theory

Answer 14

• Small intestine has a large surface area for absorption
• Has a long residence time
  Weak acids are highly absorbed

Question 15

Partition coefficient

Answer 15

p = Conc of drug in lipid phase/ Conc of drug in aqueous phase
Higher p = greater absorption

Question 16

Aspirin interaction

Answer 16

• Metaclopromide + aspirin = increased gastric emptying and increased absorption
• Propanthaline + aspirin = decreased gastric emptying and decreased absorption

Question 17

Factors effecting gastric emptying

Answer 17

• Increased viscosity reduces emptying
• Emotional situations cause increased contractions and emptying rates
• Depression caused reduced contractions and emptying
• Diabetes and hypothyroidism = reduced emptying
• hyperthyroidism = increased emptying
• Exercise = Decreases emptying

Question 18

Complexation of food and drugs

Answer 18

• Tetracyclines form non-absorble complexes with calcium and iron so it is suggested not to have milk or iron remedies/indigestion tablets beforehand

Question 19

Food and pH

Answer 19

• Food acts as a buffer and increases pH of the stomach

- Decreases dissolution and absorption of weakly basic drugs + increases absorption of weakly acidic drugs

Question 20

Stimulation of GI secretions

Answer 20

• Some foods stimulate secrections i.e. pepsin = degradation of drug and reduced bioavailibility
• Fats stimulate secretion of bile = increase dissolution of poorly soluble drugs (griseofulvin) and may form insoluble non-absorbale complexes with some drugs (neomycin)

Question 21

Competition between food and drug

Answer 21

• Drug and nutrients may have similar structures resulting in competitive inhibition of drug absorption

Question 22

Food increases viscosity

Answer 22

• Reduction in rate of dissolution

- Reduction in rate of diffusion from lumen to membrane

Question 23

Food and metabolism

Answer 23

• Certain foods may interact with hepatic microsomal enzymes increasing/reducing their bioavailability

Question 24

Food and blood flow

Answer 24

• After a meal, bloodflow to GIT and liver increases, the faster the rate of drug in liver, the larger the fraction that overcomes first pass metabolism and increases bioavailibility