Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

850 > Toxicokinetics > Flashcards

Toxicokinetics Flashcards

1
Q

Absorption Drug Variables (6)

A
  1. Dose: sheer bulk extends absorption with delayed/wide [peak]
  2. Formulation
  3. Water Solubility
  4. Slowed gut motility
  5. Increased gut motility
  6. First pass effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Formulation Effects

A
  • Liquids may have enhanced absorption due to volume stimulating gastric emptying
  • EC and SR are designed to prolong absorption
  • Excipients form concretions (phenytoin)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Water Solubility

A
  • Poor water solubility has prolonged absorption
  • Phenytoin Cmax increases significantly with dose increases
  • Carbamazepine has a wider plateau
  • Aspirin solubility increases in alkaline medium due to ionized form, net result is increased absorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Gut Motility

A
  • TCA, phenothiazines, antihistamines**, anticholinergics, CCB, opioids
  • Total drug absorbed increases due to prolonged contact
  • Increased gut motility: salicylates, theophylline
  • Emesis decreased total amount absorbed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

First Pass Effect

A
  • Saturable in overdose, resulting in less presystemic clearance and higher blood levels
  • Drugs: opioids, verapamil, lidocaine, propranolol, TCA
  • Removal of drug after ingestion: gut enzymes, liver uptake, vomiting, AC, WBI, etc.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Absorption Pathophysiology Effects

A
  • Hypothermia or hypotension decreases mesenteric perfusion and decreases/delays absorption
  • CCB, B-blockers, procainamide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

High First Pass Effect Drugs

A
  • Propranolol
  • Cyclosporine
  • Morphine
  • Desipramine and other TCAs
  • Implications: first pass effect can saturate in overdose, greater proportion of drug will reach systemic circulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Large Vd Drugs

A
  • Camphor
  • Antidepressants
  • Digoxin
  • Opioids
  • Phenothiazines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Small Vd Drugs

A
  • Alcohol
  • Lithium
  • Phenobarbital
  • Phenytoin
  • Salicylate
  • Valproic Acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Vd + [Peak]

A
  • Vd can use to predict max [peak] or body burden in overdose
  • Cp = Dose/Vd
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Compartments

A
  • Part of distribution
  • Shallow peripheral: highly perfused organs, brain, liver, kidneys
  • When rapidly equilibrated, one compartment model is evident
  • Deep peripheral: slow distribution to muscle, adipose tissue, bone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Protein Binding

A
  • Part of distribution
  • Poly-drug overdose: competes for binding sites
  • High dose: can saturate protein binding resulting in higher free levels
  • Drugs not normally considered dialyzable may be so in overdose (valproic acid, salicylates)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Increased Vd

A
  • Increased Vd in chronic vs acute overdose produce toxicity at levels considered mildly toxic or therapeutic in acute overdose
  • Ex: theophylline, salicylate, lithium
  • Cause a [gradient] created by chronically elevated serum levels, leading to increased tissue compartment stores
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Drug Metabolism + Overdose

A
  • Altered rate of biotransformation
  • Prominence of enterohepatic recirculation
  • Relative utilization of elimination routes
  • Relative utilization of elimination routes
  • Impact of toxic or active metabolites
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Phase I Metabolism

A
  • CYP P450s, hydroxylation, demethylation, epoxidation
  • Metabolites excreted into bile, transported from central compartment for renal elimination, or further metabolized
  • Drugs w/ active metabolites: TCA, diazepam, meperidine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Liver Toxic Metabolites

A
  • APAP: NAPQI
  • Valproic Acid: 4-ene, 2/4-dienes, inhibit fatty acid metabolism, alkylate 3-ketoacyl-CoA thiolase
  • Halothane: trifluoroacetyl chloride, hapten, immune hepatitis
17
Q

Skin Toxic Metabolites

A
  • Aromatic anticonvulsants: pheytoin, CBZ, PB, lamotrigine, epoxide metabolites, deficient in epoxide
  • Sulfonamides: hydroxylamine
  • Procainamide: defective N acetylation, oxidative metabolite, form DNA adducts, SLE syndrome
18
Q

Blood Toxic Metabolites

A
  • Aromatic anticonvulsants: aplastic anemia
  • Phenylbutazone: 4-hydroperoxyphenyl, butazone, aplastic anemia
  • Chloramphenicol: hydroxylamines
  • Zidovudine: 3’-amino-3’-deoxythymidine, bone marrow toxicity
  • Clozapine: oxidized by myeloperoxidase to free radical
19
Q

Methemoglobinemia Toxic Metabolites

A

-Dapsone: hydroxylamine, occurs in all, induced by cimetidine
-Sulfasalazine, hydroxylamine, not induced by cimetidine
Phenacetin: forms APAP by CYP2D6, alternate pathway forms phenetidine
-Naphthalene: epoxides, hemolysis

20
Q

Neurologically Toxic Metabolites

A
  • Meperidine: normeperidone, seizures

- Bromethalin: demethyl, inhibits oxidative phosphorylation

21
Q

Phase II Metabolism

A
  • Conjugation with water soluble moiety, sulfate, glutathione, glucuronide, enterohepatic circulation
  • Clinical course prolonged in overdose
  • Greater toxicity, linger half-life, conjugate depletion
  • Hypotension can decrease metabolism
22
Q

Enterohepatic Recirculated Toxins

A
  • Amatoxin (mushroom)
  • Carbamazepine
  • Dapsone
  • Meperidine
23
Q

First vs Zero Order Kinetics

A

First Order

  • Curve on linear paper, straight line on semi-log
  • t1/2 = Kel/.693 on linear paper, time elapsed at [1/2] on semi-log

Zero Order

  • Fixed elimination rate, common in overdose
  • Straight line on linear paper, curve on semi-log
24
Q

Zero Order Drugs

A
  • Theophylline
  • Salicylates
  • Phenytoin
  • Ethanol
  • Toxic alcohols (methanol, ethylene glycol)
25
Q

Interventions for Altered Absorption

A
  • Late gastric evacuation
  • Late gastrointestinal decontamination
  • Multiple dose activated charcoal: anticholinergics (concretions, slowly absorbed), salicylates, meprobamate, phenytoin
  • Whole bowel irrigation: delayed absorption, not bound to charcoal (lithium, iron)
26
Q

Interventions for Altered Distribution

A

-Digoxin immune fab
-Multiple dose activated charcoal
-Gut dialysis: these patients drink charcoal quickly
(+aspirin)
-All have Vd < 1L/kg and/or protein binding <60%

27
Q

Interventions for Altered Metabolism

A
  • Multiple dose activated charcoal

- Enterohepatic circulation, prevent reabsorption in distal ileum

28
Q

Interventions for Altered Elimination

A
  • Urinary alkalinization: for drugs with pKa in urine normal range (5-8), normal GFR, low hepatic metabolism
  • EX: salicylates, phenobarbital (not as effective) 2/4-D
  • Urinary acidification isn’t appropriate

850 (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions