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Toxicology > Toxicokinetics > Flashcards

Toxicokinetics Flashcards

1
Q

What effect does pregnancy have on absorption?

A
  • increased gastric emptying time (30-50%)
  • decreased intestinal motility
  • increased intestinal blood flow
  • increased gastric pH and buffer capacity
    (tendency towards increased absorption)
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2
Q

What things can decrease the bioavailability of a drug?

A
  • gastric emptying (emesis, gastric lavage and increase in intestinal motility)
  • administration of activated charcoal (direct intervention on absorption process)
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3
Q

Free drug is important for what?

A

the therapeutic (or toxic) effects of the drug

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4
Q

Albumin primarily binds what?

A

acidic compounds

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5
Q

alpha1-acid-glycoprotein primarily binds what?

A

basic compounds

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6
Q

What are some factors that affect distribution of a drug?

A
  • membrane diffusion principles
  • affinity for plasma and tissue proteins
  • acid-base status of the patient
  • physiological barriers
  • patient characteristics (obesity, age, pregnancy, disease)
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7
Q

What effect does lipophilic xenobiotics have on the Vd?

A
  • increases the Vd
  • decreases serum levels
  • decrease toxicity
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8
Q

What effect does hydrophilic xenobiotics have on the Vd?

A
  • decreases the Vd
  • serum levels increased
  • increased toxicity
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9
Q

What are age related changes that affect the Vd?

A
  • increase in body fat
  • decrease in total body water
  • decrease in plasma albumin
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10
Q

What are the pregnancy related changes that affect the Vd?

A
  • hypoalbuminemia (decreases binding of acidic drugs- salicylic acid, sulfonamides, phenytoin)
  • increases plasma volume (increase doses of aminoglycosides)
  • increased cardiac output (increased clearance)
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11
Q

What affect does renal disease have on distribution?

A
  • hypoalbuminemia with accumulation of endogenous substances that may compete for binding sites
  • decreased binding of acid drugs (phenytoin and naproxen is affected)
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12
Q

How can we effectively alter distribution?

A
  • manipulation of pH (salicylate)
  • chelators (deferoxamine)
  • use of antibody fragments (digoxin)
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13
Q

What 2 things are involved in elimination?

A
  • biotransformation AND excretion
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14
Q

What are the main clearance organs?

A
  • liver, kidney and lungs
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15
Q

What factors affect elimination?

A
  • environmental/social (smoking, alcohol, diet)
  • age
  • gender
  • disease
  • pregnancy
  • genetics
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16
Q

What affect does smoking have on elimination?

A
  • induction of cytochrome P450 isoenzymes
  • – theophylline: Cl increased, decreased t1/2, serum levels fall leading to therapeutic failure
  • – NABQI formed from acetaminophen may exceed glutathione stores
17
Q

What affect does alcohol have on elimination?

A
  • acute effects: inhibition of oxidative metabolism immediately after ingestion
  • chronic effects: enzyme induction - metabolic tolerance (clearance of drugs like warfarin/phenytoin increases)
  • cirrhosis: decreases clearance
  • shunting: hepatic damage leads to obstruction of normal blood flow
18
Q

What affect does age have on elimination?

A
  • influences hepatic function - hepatic blood flow decreases – increased risk for poisoning
  • renal function also decreases with age - as does CrCl, and dose or dosing internal of renally cleared drugs
19
Q

What effect does pregnancy have on elimination?

A
  • estrogen: inhibits oxidative metabolism
  • estrogen: cholestatic effects- impaired hepatic elimination
  • progesterone induces microsomal enzymes, and thus may increase clearance of some drugs
  • renal blood flow increased, thus increases renal clearance
  • caffeine metabolism decreased
  • diazepam met. decreased
  • metoprolol metabolism decreased
20
Q

What are some drugs that are metabolized by CYP2D6?

A
  • codeine

- antiarrythmics

21
Q

What drugs are metabolized by CYP2C9?

A
  • warfarin
  • phenytoin
  • NSAIDs
22
Q

What drugs are metabolized by CYP2C19?

A
  • antidepressants
  • clopridogrel
  • diazepam
23
Q

What drugs are metabolized by CYP2B6?

A
  • cyclophosphamide

- effavirenz

24
Q

What increases the metabolic elimination of a poison?

A
  • rifampin- is an inducer of p450
25
Q

What inhibitors the metabolism of a toxic metabolite?

A
  • cimetidine - inhibitor of P450
26
Q

What are ways to treat acetaminophen OD?

A
  • give SH group (N-acetyl-cysteine)

- slow the rate of NABQI formation (eg. cimetidine)

27
Q

At what pH are you ion trapping basic compounds?

A

6.5

Toxicology (4 decks)

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