Drug Toxicity: Molecular Mechanisms Flashcards Preview

PM2C: Therapeutics and Patient Care: Autumn > Drug Toxicity: Molecular Mechanisms > Flashcards

Flashcards in Drug Toxicity: Molecular Mechanisms Deck (31):
1

What is toxicology?

The study and effect of poisons on the living system

2

Give examples of chemical agents that can cause toxicity?

1. Drugs
2. Insecticides and herbicides
3. Plant toxins
4. Animal toxins
5. Chemical weapons
6. Radioactive substances

3

Define what an adverse drug reaction is?

Noxious or unintended responses occurring at therapeutic doses

4

What are type A adverse drug reactions and give an example of one?

1. Related to pharmacology but undesirable effects

2. Common, dose related

3. Predictable

4. Example: respiratory depression with opioids

5

What are type B adverse drug reactions and give an example of one?

1. Unrelated to known pharmacology

2. Rare, unpredictable

3. anaphylaxis (allergic reaction) with penicillin

4. Individual allergies/genetic basis

6

How are toxins absorbed by the body?

1. Ingestion

2. Inhalation

7

What are the two phases toxins metabolised in the body?

1. Phase I Cytochrome P450 goes through oxidation, reduction and hydrolysis

2. Phase II Conjugation to allow excretion in urine and bile

8

What is toxification and detoxification?

1. Detoxification: compound rendered less toxic

2. Toxification: relatively inert compound turned into a toxin

9

Where are toxins stored when they are not excreted?

Bone and fat

10

What is a type I hypersensitivity reaction?

IgE mast cell degranulation

11

What is a type II antibody mediated cytotoxic hypersensitivity reaction?

Haematological reactions i.e. pertaining to the blood cells and blood forming organs

12

Describe the process of how a type I hypersensitivity reaction can trigger anaphylactic shock?

1. Low molecular weight allergen: bee venom, peanut oil and drugs like penicillin

2. hapten attaches onto a protein to start off an immune response

3. Immunogenic conjugate is made which attaches onto Mast cells which gets degranulated

4. IgE recognition releases histamine which starts off bronchoconstriction, vasodilation and inflammation

13

How do you treat a type I hypersensitivity reaction? And what does it treat?

1. Adrenaline (EPI PEN)

2. Treats bronchoconstriction, vasodilation and inflammation

14

Describe the process of how a type II hypersensitivity reaction can deplete blood cell types?

1. Red blood cell has toxin antigen blinded to it

2. IgG attaches onto the antigens on the red blood cell

3. T cells binds to it which creates a cytotoxic T cell

4. Causes mediated cell lysis

5. Can deplete RBC, neutrophils and platelets

15

What are the four major superfamilies of receptors that molecular drugs and toxins target?

1. Nuclear Receptors (regulate gene transcription factors)

2. G coupled protein receptors (metabotropic receptors)

3. Ligand gated ion channels (ionotropic glutamate)

4. Enzyme coupled receptors (tyrosine kinase)

16

Give two sources of toxins that are derived from plants and their mechanisms of action?

1. Digoxin: Na+/K+ ATPase Inhibitor

2. Atropine: blocks muscarinic acetylcholine receptors

17

Give two sources of toxins that are derived from bacteria and their mechanisms of action?

1. Botulinium toxin: Inhibits synaptic protein (prevents acetylcholine from leaving via exocytosis)

2. Cholera toxin: activates G alpha S proteins

18

Give two sources of toxins that are derived from animals and their mechanisms of action?

1. Dendrotoxins (green mamba): blocks the K+ channels

2. Tetrodotoxin: blocks the Na+ channels

19

What are some irreversible anti-cholinesterases used?

Sarin and Parathion

20

What is the first line of defence against biological gases?

1. Atropine: mAChR blocker- central respiratory depression

2. Pralidoxime: Reactivation of acetylcholinesterase

21

What are the two biochemical examples and what do they do?

1. Cyanide: Inhibits mitochondrial cytochrome c oxidase which prevents cellular respiration

2. Carbon monoxide: Displaces oxygen from haemoglobin causing hypoxia

22

What is hepatic inflammation known as?

Hepatits (liver infection)

23

What is chronic liver disease known as?

Cirrhosis

24

Explain what happens to paracetamol in the body when you overdose?

1. Phase 1: 10% of it creates NAPQI which is hepatotoxic (binds to protein thiol group)

2. Phase 2: 90% is turned into glucuronide or sulphate conjugate

3. Phase I is excreted as a compound called glutathione conjugate which is less toxic

25

Explain why an overdose can cause problems in paracetamol?

1. The NAPQI cannot be broken into glutathione conjugate

2. NAPQI is toxic

26

What can nephrotoxicity do, and how do the problems happen in the first place?

1. Changes in glomerular filteration rate
- Largely due to drugs that alter blood flow
- NSAIDS (aspirin)
- ACE inhibitors (ramipril)

2. Allergic nephritis (inflammation of kidneys)
- Allergic reaction to NSAIDS and proteins

3. Chronic nephritis
- Long term NSAID and paracetamol use

27

What is a mutagen?

1. Changes to cell DNA that are passed on when cell divides

2. Produces a neoplastic cell the agent is termed carcinogen

28

What are photo-oncogenes?

Promote cell cycle progression

29

What are tumour suppressor genes?

Inhibit cell cycle progression

30

What is Teratogenesis?

The creation of birth defects during fetal development

31

What is Teratogens?

Substances that induce birth defects