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Pharmacology I > 3. Drug toxicity, factors influencing drug toxicity > Flashcards

3. Drug toxicity, factors influencing drug toxicity Flashcards

1
Q

Give the effects given by drugs in general

A
  • Primary intended effects
  • Secondary unintended effects (side effects/adverse effects)
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2
Q

“On target” adverse effects

A
  • Intended receptor & intended tissue
  • Intended receptor but unintended tissue
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3
Q

“Off-target” adverse effects

A

Unintended receptor, intended tissue

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4
Q

Production of toxic metabolites

A

Relative metabolites of drugs can be involved in several related, potentially cytotoxic, non-covalent interactions

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5
Q

List the types of toxic metabolite formation from drugs

A
  • Lipid peroxidation
  • Reactive oxygen species
  • Depletion of glutathione
  • Modification of sulfhydryl groups
  • Acetaminophen = Paracetamol (overdose)
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6
Q

Lipid peroxidation

A

Peroxidation of unsaturated lipids

Initiated by:

  • Reactive metabolites
  • Reactive oxygen chain reaction
  • Peroxidative cascade
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7
Q

Reactive oxygen species

A

Reduction of molecular oxygen

  • ROS are cytotoxic
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8
Q

Depletion of glutathione

A

Glutathione redox cycle protects cells from oxidative stress

Depleted by:

  • Accumulation of normal products of cell metabolism
  • The action of toxic chemicals

Cell death/cellular defence against toxic compounds is impaired when glutathione falls below 20-30% of normal

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9
Q

Modification of sulfhydryl groups

A

Free sulfhydryl groups role: Catalytic activity of many enzymes

  • Acute Ca2+ overload → Activation of degradative enzymes
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10
Q

Acetaminophen (Paracetamol) overdose

A

Metabolised predominantly by glucuronidation & sulfonation

  • If glucuronidation & sulfonation pathways get saturated + glutathione in liver becomes depleted:
    • N-acetyl-benzoquinone imine accumulation
    • This reacts with nucleophilic groups on proteins
    • Covalent protein derivate produced
    • Highly toxic in the liver
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11
Q

Acetaminophen (Paracetamol) - antidote

A

N-acetylcysteine

  • Delivered within 8-16 hours after overdose
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12
Q

Harmful immune responses

A

Drugs are xenobiotics that can be recognised by the immune system

  • Caused by haptens
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13
Q

What are haptens?

A

Small molecules that when combined witha larger carrier such as a protein can elicit an immune response

Can be:

  • Type I
  • Type II
  • Type III
  • Type IV
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14
Q

Hapten type I

A

Immediate hypersensitivity

  • Production of IgE in response to antigen
  • E.g Penicillin
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15
Q

Hapten type II

A

Antibody-dependent cytotoxic hypersensitivity

  • IgG recognise drug bound to cell as antigen
  • E.g Sulphonamides
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16
Q

Hapten type III

A

Immune complex-mediated hypersensitivity

  • IgG or IgM
  • Antigen-antibody complexes are deposited in tissues
  • Kidney, joints, lung vascular endothelium
  • Complexes initiate inflammatory response (serum sickness)
    • Causing damage
17
Q

Hapten type IV

A

Delayed type hypersensitivity

  • Activation of TH1 & cytotoxic T-cells
  • First exposure wont produce a response
18
Q

Autoimmunity

A

Results when organisms immune system attacks its own cells

19
Q

Idiosyncratic toxicity

A

Toxicity for no obvious reason

20
Q

Give the types of drug interaction

A
  • Synergism
  • Addition
  • Potentiation
  • Antagonism
21
Q

Synergism

A

Two drugs elicit same type of response

22
Q

Addition

A

Summation of effected responses

23
Q

Potentiation

A

Response > Addition

24
Q

Antagonism

A

Response < sum of responses

25
Q

Which other factors can affect the toxicity of a drug?

A
  • Preexisting conditions
  • Dosage & route of administration
  • Age
  • Feeding
  • Gender
  • Tolerance
  • Dependence
26
Q

Preixsting conditions affecting drug toxicity

A
  • Liver/kidney dysfunction
  • Pregnancy
  • Depressed immune function
27
Q

Gender affecting drug toxicity

A

Metabolism can be faster in male because testosterone is a CPY3A inductor

28
Q

Tolerance affecting drug toxicity

A

Body builds up a resistance by receptor regulation & altered metabolism

29
Q

Dependency affecting drug toxicity

A
  • Habitation - Force of habit, mental
  • Addiction - Mental & physiological

Pharmacology I (19 decks)

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