Biotrans

Question 1

Liver function tests (LFTs), what are they? Name a couple of them

Answer 1

Alanin amino transferase
Asparate aminotransferase
Alkaline Phosphate
Bilirubin
Prothrombin Time

Question 2

Reference Interval (RI) concept and use

Answer 2

R

Question 3

Lipophilic to hydrophilic conversion

Answer 3

compound to disolve in fat, no polor (hexane)- need metaboism for elimation, widely distrubted in body
Lipo drug converts to water solube to be excreted by kidney in urine
Drugs needs to stay mild hydrophilic enough to remain in fluid that becomes urine

Question 4

Biotransformation (metabolism) definition

Answer 4

conversion of drug/xenobiotic into more polar (water soluble
Main is LIVER
use same pathways as mother nature

Question 5

How urine pH alters renal drug clearance (CL) (aspirin)

Answer 5

Ionization changes rate of secretion
Ionized are water soluble
molecue acquires a - or +, by gain or lose of elcectron
Aspirin = weak acid
Acidic- ionized in basic
Basic- ionized in acidic
Amphetamine- weak base, administer Vitamin C- will then clear rapidly in acidic urine

Question 6

Phase I reactions oxidations, reductions and hydrolysis to name a few

Answer 6

Variable phase, not step wise Phases
Add or unmask : OH, NH2, SH makes more water soluble
Converts parent drug to a polar/water sol.
Metabolites inacvtive- may be secreted fast

Oxidation- N-dealkylation, aliphatih hydoxily, N, Deaminantin, Epox, Desulf

Reduction- Azo, Nitro, Carbonly

Hydolyses- ester, amides

Question 7

Phase I enzymes location in the liver
Phase I enzyme-alternative names
Phase I enzyme official nomenclature (CYP 450)

Answer 7

Endoplasmi Reticulum- smooth ER
Enzyme-MFOs, cytochrom pigment 450s, Monooxygenases
CYP
2-gene family
D-gen subfamily
6-specific gene

Question 8

Phase II enzymes, location,

Phase II reactions, give some examples

Answer 8

Cytoplasm
Conjugation
mostly transferases
glucur, sulf, acetyl, methylation, glutathione and amino acid add…

Question 9

Direction of biotransformation (isoniazid, ethylene glycol, acetaminophen)

Answer 9

Toxix metabolits are bad
Isoniazid- ethylene glycol-anitfreeze
Acetaminopine-safe, PHase 2 glucorindtion-water solubble. 5% is NABQ
But if you take alot, malunurish, alcohol, then body runs out of Glutotione, 5% toxic= LIVER failure

Question 10

Note that some drugs are biotransformed by different CYPs at the same time

Answer 10

Many reactions- 60 diff enzymes to take RX out of body

CYP 1A2, CYP 3A4

Question 11

Prodrug definition, name one

Answer 11

inactive or slight active compoutn converted by biotrnas into active drug
Codeine

Question 12

Reasons for making a prodrug, name one or two

Answer 12

Enteric coated to stop dissolution in stomach, non sedative, more potent
Phenacetin___Acetaminophen

Question 13

Phase I enzyme Induction explain the possible consequences , Induction by rifampin

Answer 13

2 medication can induce the amount of enzyme made
Problem- inc. enzyme inc. biotrans of the RX, thus one drug may be ineffective LEAVING BODY FAST
Birth contral and Cortisol

Question 14

Case study of CYP Inhibition by fluoxetine

Answer 14

2 drugs compete for the limited
supply of a CYP enzyme, which will reduce the biotransformation of drug A in the body.
Ireversible inhibits the metabolizing enzyme. Therefore, the drug STAYS IN THE BODY LONGER
74y/o many RX, depressed after death of husband
Givein fluoxetine-depression
Pt- S/s DUMBELSS- anticholinergic toxicity

Question 15

Name some factors that alter rates of biotransformation

Provide some reasons to account for variability in drug response among patients

Answer 15

Age
Sex
Nutrition and Enviroment - grapefruit juice
LFTs
Inducer/Inhibs 
depletion or stays in body
Genetics

RX effect in 25-60% (30%) of Pts
ADE 2mil
100K deaths ADE

Question 16

Original Case Study at the start of this lecture: acetaminophen and N-acetylcysteine

Answer 16

Depletion of GSH- acetaminophen
Combo drugs
Overdose of Acet
Malnurished
Hep C
TREAT w/ N-ACETYLCYCSTEINE (NAC), GSH will substitute for GSH
Glucose IV