toxicokinetics and biotransformation

Question 1

difference between toxicokinetics and pharmacokinetics

Answer 1

pharmacodynamic effect is toxic
dosing info lacking or inaccurate
doses in excess of those ever studied
PK and PD often not know
drugs may be illegal unlicensed or untested
may be used in never studied before ocmbinations

Question 2

xenobiotic characteristics affecting GI absorption

Answer 2

physiological properties
dosage forms
dissolution profiles
presystemic elimination

Question 3

patient characteristics affecting gi absorption

Answer 3

GI motility
GI disease - ulcer, chrons
malnutrition
pregnancy -altered flora

Question 4

diffference between gastric emptying time and GI transit time

Answer 4

gastric emptying is time stomach takes to empty since absorption takes place in SI the longer the agent is in the stomach the less absorption
transit time is the time to go through the GI tract so if increased the drug is eliminated more quickly

Question 5

how cna pregnancy effect absorption

Answer 5

increased gastric emptying time
decreased intestinal motility
increased intestinal blood flow
increased hgastric ph and buffer capacity

Question 6

tendency towards ___ absorption in pregnant women

Answer 6

increased absorption so increased risk for toxicity but increased cardiac output and renal perfusion can increase clearance of some xenobiotics

Question 7

how can we alter gi absorption

Answer 7

gastric emptying - emesis, gastric lavage, increase in intestinal motility
administer activated charcoal

Question 8

large Vd drug will be

Answer 8

xenobiotic residues outside the plasma compartment ( in the tissues)

Question 9

____ binds acidic compounds

Answer 9

albumin

Question 10

____ binds basic compounds

Answer 10

alpha 1 acid glycoprotein

Question 11

factors affecting distribution

Answer 11

membrane diffusion principles 
affinit for plasma and tissue proteins
acid base status
physiological barriers
patient characteristics

Question 12

lipophilic xenobiotics effect on vd and serum concentration

Answer 12

higher affinity for fat gives a higher vd so lower serum levels and a decrease in toxicity

Question 13

hydrophilic xenobiotics effect on vd and serum levels

Answer 13

decreased vd increases level in serum and may increase toxicity

Question 14

increase in body fat will increase vd for

Answer 14

lipophilic xenobiotics

Question 15

decrease in total body water will decrease vd for

Answer 15

hydrophilic

Question 16

decrease in plasma albumin will cause

Answer 16

increased free fraction and increased toxicity

Question 17

pregnancy causes hypoalbuminemia so _____ binding of acidic drugs

Answer 17

decreases

Question 18

pregnancy increases plasma volume so ____ vd

Answer 18

increases

Question 19

pregnancy has no effect on

Answer 19

hepatic blood flow

Question 20

renal disease can cause hypoalbumiemia and accumulation of endogenous substances that may compete for binding sites will decrease binding of acidic drugs, examples of drugs afected

Answer 20

naproxen vd and half life increased

phenytoin fraction unbound increases

Question 21

3 ways to alter distribution

Answer 21

mainpulation of pH - salicylates
chelators - deferoxamine, have a higher affinity for the drug than tissues so can trap it
antibody fragments ex. digoxin fragments have higher affinity and take dig away from myocardium

Question 22

factors affecting elimination

Answer 22

environmental/social - drinking, smoking
age
gender
disease
pregnancy
genetics

Question 23

how does smoking affect elimination

Answer 23

induction of cytochrome P450 enzymes, even second hand smoke

Question 24

smokings affect on theophyllin

Answer 24

increases clearance causing serum levels to fall = therapeutic failure

Question 25

amoking affect on acetaminophen

Answer 25

NAPQI formed from acetaminophen due to the increased P450 enzyme activity may exceed glutathione stores

Question 26

acute effects of alcohol on elimination of acetaminophen

Answer 26

inhibition of oxidative metabolism immediately after ingestion

Question 27

chronic effects of alcohol on elimination

Answer 27

enzyme induction - metabolic tolerance

clearance of some drugs increases

Question 28

what is shunting

Answer 28

hepatic damageleading to obstruction of normal blood flow… another way alohol can affect elimination

Question 29

how can cirrhosis affect elimination

Answer 29

may decrease clearance but bc enzyme induction no changes may be seen until shunting occurs

Question 30

how does increasing age affect elimination

Answer 30

hepatic blood flow decreases so metabolism of high extraction drugs has decreased so increased risk of poisoning
renal function decreases therfore creatinine clearance so renally cleared drugs need to be adjusted

Question 31

pregnancy hormone changes affecting elimination

Answer 31

estrogen: inhibits oxidative metabolism, impaired hepatic elimination of biliary excreted drugs
progesterone induces enzymes thus may increase clearnace of some drugs

Question 32

example of inhibition of metabolism

Answer 32

acetaminophin od
give SH groups with N acetyl cystein
**slow the rate of NABQI formation with a P450 inhibitor

Question 33

types of renal excretion

Answer 33

glomerular filtration - non saturable
tubular secretion - saturable
passive tubular reabsorption - non charged, lipid soluble

Question 34

normal crcl

Answer 34

> 90ml/min

Question 35

how can we alter excretion

Answer 35

manipulate pH
chelators
multiple dose activated charcoal
extracorporeal devices (kind of like dialysis)

Question 36

how are drugs excreted in breast milk

Answer 36

simple diffusion into breast milk

pH 6.5 more acidic than plasma making an ion trap for basic compounds

Question 37

things affecting excretion into breast milk

Answer 37

basicity of compound
differences in affinity to serum proteins vs milk proteins
drugs with longer half life greater opportunity to be excreted