Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pharm > Drug Translocation / Biotransformation > Flashcards

Drug Translocation / Biotransformation Flashcards

(54 cards)

Start Studying
1
Q

Absorption

A

Translocation of drug across lipid bilayers into vasculature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Distribution

A

Distribution of drug via vasculature and across lipid bilayers from vasculature to drug’s target

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Metabolism

A

Biotransformation of drug (primarily by liver)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Elimination

A

Removal of drug from a body (primarily by kidney) (most in urine/feces)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What happens to a drug as it enters the body?

A

Absorption —> distribution to tissue —> biotransformation —> redistribution —> elimination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Drugs that undergo passive diffusion

A

Small
Neutral/non polar
Lipophilic
Large Vd (i.e. in organs/fat, not water)
Not saturable

I.e. alcohol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Drugs that undergo active transport

A

Large
Charged/polar
Hydrophilic
Smaller Vd (distribution into blood)
Uses transporters (saturable)

I.e. NSAIDS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Transporter superfamilies

A

ABC family (P-glycoproteins)
SLC family (solute carriers - i.e. Organic Anion/Cation Trasnporters)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

ABC family

A

ATP-binding cassette

Transmembrane effluent pump, moves drugs/metabolites out of cell

REQUIRES ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

SLC family

A

Solute Carriers

(I.e. OAT, OCT)

Facilitated transporters; use ionic gradients/built in tranmembrane potentials

Does NOT require ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Organs with ABC/SLC transporters

A

Intestine
Liver
Kidney
Brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Function of ABC family transporter in brain

A

Important for pumping chemicals / substances OUT of brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Mutation of ABCB1 gene in collies

A

Causes ivermectin toxicity - MDR1 deficiency due to early stop codon

Neurotoxicity - inability to pump out of brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Biotransformation phases

A

Phase I - oxidation

Phase II - conjugation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Most common phase I rxn

A

Oxidation - Cyt P450

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Common phase II reactions

A

Glucuronidation / glucosidation
Acetylation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Most metabolic products are

A

Less pharmacologically active

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Prodrugs

A

Drugs where metabolite is more active than substance administered

E.g. cefpodoxime proxetil, erythromycin-ethylsuccinate, codeine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Types of oxidation reactions

A
  1. Oxygen incorporated (hydroxylation)
  2. Oxidation causes loss of part of drug (oxidative delaminating, dealkylation)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Oxidative enzymes

A

Mixed function oxidases / monooxgygenases (CYP450)

Flavoprotein (NADPH-CYP450 reductase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Oxidation by cytochrome P450

A
  1. Oxidized (Fe3+) CYP450 complexes with drug
  2. NADPH donates 2 electrons —> Fe2+ —> oxygen binds
  3. Second electron activates oxygen
  4. Activated oxygen transferred to drug
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Biotransformation by CYP450

Study These Flashcards
A

Aliphatic/aromatic hydroxylation
Dealkylation
N-oxidation, S-oxidation
Deamination
Dehalogenation

23
Q

Families of most drug metabolizing CYP450 families

Study These Flashcards
A

CYP 1, 2, 3

Humans - CYP3A4/5 and CYP2D6

24
Q

Significance of diversity of CYP enzymes

Study These Flashcards
A

Many drugs are metabolized by different family’s

Some drugs may be metabolized by multiple family’s —> redundancy

25
Phase II - Conjugation reactions
Glucuronidation Acetylation Sulfonation Amino acid conjugation Glutathione conjugation
26
Reactions catalyzed by UDP-glucuronosyltransferase
Glucuronic acid conjugation to… Phenols, tertiary amines, aromatic amines
27
Metabolism of ibuprofen
CYP2C9 and 2C19 hydroxylation at different positions ALDH1 / ALDH2 carboxylate the drug Glucuronyl transferase conjugates to glucuronic acid
28
Elimination of ibuprofen
15% as parent drug 9% oxidized 17% conjugated
29
Principal site of Phase I/II reactions
Liver
30
Supplemental sites of Phase I/II reactions
GI, lungs skin, kidneys, brain, heart
31
Enterohepatic recycling
Reabsorption of nutrients from liver Responsible for second peak of absorption
32
Modifications by microbiota
Microbiota can deconjugate drugs to facilitate reabsorption
33
Factors affecting drug translocation / biotransformation
Species/breed Within individual: Age, obesity, hydration status, diet, hepatic disease, renal disease, drug-drug interactions
34
CYP450 activity in greyhounds
Lower CYP2B11 activity in greyhounds Decreased activity + lean body mass (lower Vd for lipophilic drugs) —> slow recovery from anesthetics (because slow metabolism)
35
CYP450 activity in cats
Lack CYP2B6 in liver (Enzyme that metabolizes diazepam) Diazepam —> hepatic necrosis
36
CYP450 activity in horses
Low activity of CYP2D —> monensin toxicity (never given to horses, but possible contamination at feed plant - from ruminant feed)
37
CYP450 activity in micro/mini pigs
Increased CYP activity —> need higher doses in general
38
Effects of CYP2D6 polymorphisms
Studies in humans Inactive alleles —> low metabolism - homozygous carriers —> poor metabolizes (18% population) - homozygous or WT carriers —> 60-70% population - multiple copies of CYP2D6 —> ultra rapid metabolizers (10-22%)
39
Metabolized by CYP450 2D6
Codeine, beta-blockers, tricyclic antidepressants, estrogen receptor modulators, antihypertensive drugs, SSRI
40
Slow and fast metabolizers have been demonstrated in …
Humans and beagles
41
Phase II differences in cats
Lack glucoronidation - lack UGT1A6 —> slow clearances of aspirin; toxicity of acetaminophen (by alternate pathway of metabolism - toxic intermediates)
42
Phase II differences in dogs
N-acetyltransferase deficiency —> hypersensitivity of sulfonamides, longer HL of hydralazine, procainamide not metabolized to active metabolite (some activity as parent) Thiopurine methyltransferase (TMT) —> metabolizes azathioprine (immunosuppressant) + active metabolites into inactive metabolites —> activity varies across breeds
43
Phase II differences in pigs
Lack sulfate conjugation —> compensate with other Phase II pathways
44
Phase II differences in avian / reptiles
Unique amino acid conjugation, unknown clinical relevance
45
Ruminant sensitivity to Xylazine
Pharmacodynamic difference Terminal phase of elimination similar between cows and horses, but lower threshold for conc in cows Difference accounted for by the way in which the drug interacts with the G protein in cattle - direct results of active site interactions
46
Effect of age on Phase II
Vd of polar drugs highest in young animals —> decreases with age Vd of lipophilic drugs increases with age In geriatric patients —> decrease in metabolism of drugs —> decrease dose in geriatrics
47
Effect of obesity on Phase II
Higher percentage of body fat —> higher Vd for lipophilic drugs —> need higher doses Drugs that do not distribute to fat may need to be dosed based on optimal body weight!
48
Effect of diet on Phase II
Chloride - affects Br absorption (epileptic drugs) Grapefruit juice - CYP3A4 inhibitor St John’s wort - CYP3A4 + CYP2D6 inhibitors
49
Effect of dehydration on Phase II reaction
Decreases Vd for polar, hydrophilic substances
50
Diseases altering drug metabolism
Chronic liver disease Cardiac disease (reduced hepatic blood flow) Acute myocardial infarction Viral/bacterial infection Intestinal disorders (including cancer) Autoimmune disease Chronic kidney disease
51
Impact of CKD on drug metabolism/excretion
Dec globular filtration/tubular secretion Accumulation of uremic toxins —> to intestine —> increased drug bioavailability (down regulate CYPs, down regulate efflux transporters) Decreased hepatic uptake/metabolism Increased biliary excretion
52
Three categories of CYP450 inducers
Phenobarbital Polycyclic aromatic hydrocarbons Glucocorticoids
53
Inhibitors of CYP450
Azole family of antifungals (e.g. ketoconazole)
54
Coadministration of Ketoconazole and cyclosporin
Ketoconazole inhibits CYP450 + MDR1 (Decreases metabolism of cyclosporin) reduce amount of cyclosporin needed to administer (decrease expense)

Pharm (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions