Drug Toxicology I Flashcards Preview

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Flashcards in Drug Toxicology I Deck (99):
1

Define: Pharmacology

The study of the effect of drugs on the function of living systems

2

Define: Toxicology

The study of the effect of poisons on the function of living systems

3

Name 3 chemical agents that cause toxicity

  1. Drugs
  2. Insecticides/herbicides
  3. Plant toxins

4

Define: Adverse drug reaction

Noxious or unintended responses occurring at therapeutic doses

5

Explain Type A (augmented) ADRs

  • Related to known pharmacology but undesirable
  • Common, dose-related
  • Predictable

6

Give an example of a Type A (augmented) ADR

Haemorrhage with anticoagulants (e.g. warfarin)

7

Explain Type B (bizarre) ADRs

  • Unrelated to known pharmacology
  • Rare
  • Unpredictable
  • Often idiosyncratic (= peculiar, individual)

8

Give an example of a Type B (bizarre) ADR

Anaphylaxis with penicillin

9

Define: Toxicokinetics

The effects of the body on the poison

Relates to ADME

10

What information does toxicokinetics provide?

Makes it possible to predict concentration of toxin that has reached the site of injury and the resulting injury

11

Define: Detoxification

Compound rendered less toxic

Occurs during metabolism

12

Define: Toxification

Relatively inert compound converted into toxin

Occurs during metabolism

13

Name 2 ways that toxins are 'absorbed'

Ingestion (salmonella) or inhalation (asbestos)

14

How many phases of metabolism of toxins are there?

2: Phase I and Phase II

15

What occurs during Phase I of metabolism of toxins?

  1. Oxidation
  2. Reduction
  3. Hydrolysis by cytochrome P450

16

What occurs during Phase II of metabolism of toxins?

Conjugation to allow excretion in urine and bile

17

Where may toxins be stored if they aren't excreted?

  • Bone (e.g. lead)
  • Fat (e.g. DDE, a metabolite of the pesticide DDT)
  • The toxin may be slowly released into the body

18

Name a common form of ADR

Allergic reaction

19

How many clinical syndromes of allergic reaction are there?

4: Type I, II, IIIIV

20

What is a Type I allergic reaction?

  • A hypersensitivity reaction
  • Mediated by IgE = an antibody
  • IgE causes degranulation of mast cells = release of histamine

21

What is a Type II allergic reaction

  • Antibody-mediated cytotoxic hypersensitivity
  • Involve haematological reactions = those pertaining to the blood cells and blood-forming organs

22

What is a Type III allergic reaction?

Immune complex-mediated hypersensitivity

23

What is a Type IV allergic reaction?

Delayed-type hypersensitivity

24

What can Type I hypersensitivity reactions trigger?

Anaphylaxis

25

What is a hapten?

A small molecule that binds to a bigger molecule which triggers an immune response

26

What is the molecular process of a Type I hypersensitivity reaction?

  1. Low MW allergen enters the body
  2. A hapten binds to the allergen to form an immunogenic conjugate
  3. IgE recognition of immunogenic complex causes degranulation of mast cells
  4. Massive histamine release

27

What does the release of histamine from the mast cells cause?

  • Bronchoconstriction
  • Vasodilation
  • Inflammation

28

What substance is used to treat allergic reactions?

Adrenaline (epipen)

29

What is the molecular process of a Type II hypersensitivity reaction? (Antibody-mediated cytotoxic hypersensitivity)

  • The toxin antigens bind to RBCs
  • Antibody IgE molecules trigger T cells
  • T cells begin lysis = cytotoxic T cell-mediated cell lysis

30

How can sulphonamides be toxic?

Can deplete red blood cells = haemolytic anaemia

Due to Type II hypersensitivity reaction

31

How can some NSAIDs be toxic?

They can deplete neutrophils = agranulocytosis

Due to Type II to hypersensitivity reaction

32

How can quinine an heparin be toxic?

They can deplete platelets = thrombocytopenia

Due to Type II hypersensitivity reaction

33

Define: Haemolytic anaemia

When the levels of RBCs are depleted (e.g. by sulphonamides)

34

Define: Agranulocytosis

When the levels of neutrophils are depleted (e.g. by some NSAIDs)

35

Define: Thrombocytopenia

When the levels of platelets are depleted (e.g. by quinine and heparin)

36

Name the 4 major superfamilies of receptor

  1. Ligand-gated ion channels (voltage-gated ion channels)
  2. GPCRs (metabotropic receptors)
  3. Enzyme-coupled receptors (tyrosine kinase activity)
  4. Nuclear receptors (regulate gene transcription)

37

Name 4 targets of toxins

  1. Receptors
  2. Enzymes (metabolic and catabolic pathways)
  3. Carriers (uptake/transport systems)
  4. Others e.g. proteins involved in vesicle release

38

What do animal toxins block?

Ion-conduction

39

What substance blocks voltage-gated K+ channels?

Dendrotoxins

40

What substance acts on Na+ channels?

Tetrodotoxin

41

What effect does blocking the Na+ channels have?

Block action potentials

42

What kind of toxin blocks ion conduction?

Animal toxins

43

What do dendrotoxins block?

Voltage-gated K+ channels

44

What does Tetrodotoxin act on?

Na+ channels

45

List 4 symptoms of high quantities of acetylcholine

  1. Convulsions
  2. Bradycardia (= abnormally slow heart action)
  3. Bronchodilation
  4. Increased secretion (eyes watering, nose running)

46

Name the enzyme that oximes reactivate

ACh-esterase

47

Name the strong nucleophile that reactivates ACh-esterase

Oximes

48

What does cyanide inhibit?

Cytochrome C oxidase

49

What effect does inhibiting cytochrome C oxidase have?

Prevents cellular respiration

50

Where is Cytochrome C oxidase found?

Mitochondria

51

What effect does carbon monoxide have on haemoglobin and what does this cause?

It displaces the oxygen causing hypoxia = COHb

52

Define: Hypoxia

Deficiency in the amount of oxygen reaching the tissues

53

Name the 2 organs that are particularly susceptible to toxin damage

Liver and kidney

54

Why are the liver and kidney more susceptible to toxin damage?

Their major role is excretion

55

What is toxin damage of the liver called?

Hepatotoxicity

56

What is hepatic necrosis caused by?

Paracetamol poisoning

57

Define: hepatic necrosis

Death of liver tissue

58

What is hepatitis?

Hepatic inflammation

59

What can cause hepatitis?

Halothane (anaesthetic) can covalently bind to liver proteins to trigger an autoimmune response

60

What is cirrhosis?

Chronic liver damage

61

What can cause cirrhosis?

Long term alcohol (ethanol) abuse causes:

  • Toxicity 
  • Inflammation 
  • Malnutrition (ethanol becomes a food source)

62

What effect can paracetamol poisoning have on the liver?

Hepatic necrosis = death of liver tissue

63

What effect can halothane (anaesthetic) have on the liver?

Hepatitis

64

What effect can long term alcohol abuse have on the liver?

Can cause cirrhosis = chronic liver damage

65

What occurs in Phase II conjugation (metabolism) with regards to paracetamol?

90% of the paracetamol is safely conjugated with conjugating agents (e.g. sulphate)

66

What occurs in Phase I metabolism of paracetamol?

  • 10% of the paracetamol undergoes Phase I reactions
  • This produces an intermediate species (NAPQI)
  • NAPQI = very toxic to the liver (binds to protein thiol groups)
  • = Hepatotoxicity

67

Why is NAPQI very toxic to the liver?

It binds to the protein thiol groups = hepatotoxicity

68

Name the process that NAPQI undergoes

Phase II conjugation with glutathione = makes NAPQI non-toxic and it is therefore safely excreted

69

Why is it more difficult to get rid of NAPQI after a paracetamol overdose?

  1. Large quantities of NAPQI produced
  2. Enzymes are saturated
  3. Levels of glutathione are quickly depleted

70

Name 2 treatments for paracetamol overdose

Acetylcysteine and Methionine

71

Why are acetylcysteine and methionine used to treat paracetamol overdose?

Both are glutathione precursors = more glutathione and excess NAPQI is excreted

72

Define: Nephrotoxicity

Poisonous effects of some substances on the kidney

73

What effect does altering the blood flow have on the kidney?

Causes changes in glomerular filtration rate (GFR)

74

Name 2 types of drug that can cause changes in the GFR due to altering blood flow

  • NSAIDs (e.g. aspirin) - reduce prostaglandins (prevent arachidonic acid binding to cyclooxygenases) which in turn reduces blood flow/GFR
  • ACE inhibitors (e.g. ramipril) - increase blood flow/GFR

75

How do NSAIDs affect the GFR?

NSAIDs reduce the GFR as they lower the number of prostaglandins which reduces blood flow

76

How do ACE inhibitors affect the GFR?

ACE inhibitors increase blood flow and so increase the GFR

77

Why can lowering the GFR have dangerous consequences?

Makes it more difficult to excrete toxic compounds

78

Define: Allergic nephritis

Inflammation of kidney due to allergic reaction

79

Give 2 examples of substances that can cause allergic nephritis

  1. NSAIDs (fenoprofen)
  2. Antibiotics (e.g. metacillin)

80

Name 2 drugs that can cause chronic nephritis

Long term NSAID and paracetamol use

81

Define: Mutagen

  • A physical or chemical agent
  • That causes changes to the DNA
  • Increasing the frequency of mutation above the natural background level
  • The mutations are passed on when the cell divides

82

Define: Carcinogen

A mutagen that capable of causing cancer

83

Name the 2 major classes of gene that are involved in carcinogenesis

  1. Proto-oncogenes
  2. Tumour-suppressor genes

84

What is the role of proto-oncogenes?

Promote cell progression

85

Define: neoplasm/neoplastic cell

  • An abnormal mass of tissue
  • Results when cells divide more than they should or do not die when they should (due to a mutation)
  • May be benign or malignant (cancerous)

86

What is the role of tumour-suppressor genes?

Inhibit cell cycle progression

87

Define: Teratogenicity

The property or capability of producing congenital malformations

88

Define: Teratogenesis

The creation of birth defects during foetal development

89

Define: Teratogens

Substances that induce birth defects

90

Name a teratogen

Thalidomide (S)

91

How was thalidomide able to cause birth defects?

The (R)-enantiomer was a sedative but the (S)-enantiomer was a teratogen

92

What was thalidomide marketed to treat?

Marketed as an anti-emetic to treat morning sickness in pregnant women

And as a sleeping pill (sedative)

93

Name the cellular process that occurs during blastocyst formation

Cell division

94

What substances affect blastocyst formation?

  1. Alcohol
  2. Cytotoxic drugs (toxic to cells)

95

What are the 3 stages of foetal development?

  1. Blastocyst formation
  2. Organogenesis
  3. Maturation

96

Name the cellular processes that occur during organogenesis

  1. Division
  2. Migration
  3. Differentiation
  4. Death

97

What substances affect organogenesis?

Teratogens = thalidomide, retinoids, antiepileptics, warfarin

98

Name the cellular processes that occur during maturation

  1. Division
  2. Migration
  3. Differentiation
  4. Death

99

What substances affect maturation?

  1. Alcohol
  2. Nicotine
  3. ACE inhibitors (e.g. Ramipril)
  4. Steroids