Pharmacokinetics

Question 1

What is pharmacokinetics?

Answer 1

• the studies of drug absorption, distribution, metabolism and excretion
• how to body acts on drugs

Question 2

What is drug absorption?

Answer 2

• passage of a drug from its site of administration into plasma from various sites in the body, e.g. orally via G.I. tract

Question 3

How does the drug get into plasma?

Answer 3

• drug must cross cell membranes

Question 4

How are drugs transported across membranes?

Answer 4

• membrane openings (filtration)
• passive diffusion
• active transport; against concentration gradient, requires energy
• carrier molecules, like little busses that move things between extracellular and intracellular areas

Question 5

What determines drug absorption?

Answer 5

• nature of absorbing surface (e.g. number of cell membrane layers, surface area, blood supply)
• chemical structure of the drug (e.g. lipid solubility, degree of ionisations - positive or negative charge, molecular weight, dissolution rate, pH of aqueous phase)

Question 6

What happens in the pH of aqueous phase?

Answer 6

• when you put a weakly acidic drug molecule in an acidic environment (e.g. asprin in stomach) , all of the charges cancel out and it becomes unionised

Question 7

What is drug distribution?

Answer 7

• the transfer of drug between locations via blood
• many drugs exist in circulatory system bound to plasma proteins
• once drug is in system, body is working hard to get rid of it
• only drugs ‘free’ from plasma proteins exert pharmacological effects and act on the body

Question 8

what are the determinants of drug distribution?

Answer 8

• concentration of free drug
• concentration of plasma proteins; how many are being made by the liver
• body fat and water effects the distribution of fat and water soluable drugs e.g. females have more body fat and therefore will have a greater VOD of fat soluable drugs
• barriers; blood-brain barrier and placenta

Question 9

What is drug metabolism?

Answer 9

• enzyme modification of drug molecules (lipid soluble)

- the start of the elimination process

Question 10

What is hepatic biotransformation?

Answer 10

• the liver metabolises lipid (fat) soluble drug molecules
• using enzymes, it turns the lipid soluble molecule into a water soluble (hydrophilic) molecule - no longer lipid soluble
• therefore it can no longer cross cell membrane, remains in the bloodstream and passes out via urine

Question 11

What is the hepatic first-pass effect?

Answer 11

• variable proportion of an orally administered drug that is metabolised by the liver before it exerts its effect
• all oral medication gets absorbed and goes to the liver before it has a chance to act on the body
• high = liver wipes out the drug
• low = not much is metabolised each time that drug circulates through the liver

Question 12

What is the hepatic portal system?

Answer 12

• blood system that drains the GI tract and takes this blood straight to the liver

Question 13

What is drug bioavailability?

Answer 13

• proportion of the administered dose that reaches systemic circulation in tact
• drug and person dependent

Question 14

What are pro drugs?

Answer 14

• drugs that go to the liver to get stronger; lipid soluble drug gets more lipid soluble due to enzymes

Question 15

What is drug excretion?

Answer 15

• irreversibe loss of drug from the body, e.g. urine

Question 16

What is the renal route of excretion?

Answer 16

1. glomerular filtration
   - only free, unbound drugs are filtered through the glomerulus
2. passive reabsorption
   - dependent on drug solubility and urinary pH
3. active tubular excretion
   - acidic and basic drugs secreted into proximal tubule by specific pumps

Question 17

What is the buliary route of excretion?

Answer 17

• drug compunds excreted in faeces enterohepatic cycling

Question 18

What are some other routes of excretion?

Answer 18

• sweat
• salvia
• expired air
• breast milk