Drug Toxicology I Flashcards
1
Q
Define: Pharmacology
A
The study of the effect of drugs on the function of living systems
2
Q
Define: Toxicology
A
The study of the effect of poisons on the function of living systems
3
Q
Name 3 chemical agents that cause toxicity
A
- Drugs
- Insecticides/herbicides
- Plant toxins
4
Q
Define: Adverse drug reaction
A
Noxious or unintended responses occurring at therapeutic doses
5
Q
Explain Type A (augmented) ADRs
A
- Related to known pharmacology but undesirable
- Common, dose-related
- Predictable
6
Q
Give an example of a Type A (augmented) ADR
A
Haemorrhage with anticoagulants (e.g. warfarin)
7
Q
Explain Type B (bizarre) ADRs
A
- Unrelated to known pharmacology
- Rare
- Unpredictable
- Often idiosyncratic (= peculiar, individual)
8
Q
Give an example of a Type B (bizarre) ADR
A
Anaphylaxis with penicillin
9
Q
Define: Toxicokinetics
A
The effects of the body on the poison
Relates to ADME
10
Q
What information does toxicokinetics provide?
A
Makes it possible to predict concentration of toxin that has reached the site of injury and the resulting injury
11
Q
Define: Detoxification
A
Compound rendered less toxic
Occurs during metabolism
12
Q
Define: Toxification
A
Relatively inert compound converted into toxin
Occurs during metabolism
13
Q
Name 2 ways that toxins are ‘absorbed’
A
Ingestion (salmonella) or inhalation (asbestos)
14
Q
How many phases of metabolism of toxins are there?
A
2: Phase I and Phase II
15
Q
What occurs during Phase I of metabolism of toxins?
A
- Oxidation
- Reduction
- Hydrolysis by cytochrome P450
16
Q
What occurs during Phase II of metabolism of toxins?
A
Conjugation to allow excretion in urine and bile
17
Q
Where may toxins be stored if they aren’t excreted?
A
- Bone (e.g. lead)
- Fat (e.g. DDE, a metabolite of the pesticide DDT)
- The toxin may be slowly released into the body
18
Q
Name a common form of ADR
A
Allergic reaction
19
Q
How many clinical syndromes of allergic reaction are there?
A
4: Type I, II, III & IV
20
Q
What is a Type I allergic reaction?
A
- A hypersensitivity reaction
- Mediated by IgE = an antibody
- IgE causes degranulation of mast cells = release of histamine
21
Q
What is a Type II allergic reaction
A
- Antibody-mediated cytotoxic hypersensitivity
- Involve haematological reactions = those pertaining to the blood cells and blood-forming organs
22
Q
What is a Type III allergic reaction?
A
Immune complex-mediated hypersensitivity
23
Q
What is a Type IV allergic reaction?
A
Delayed-type hypersensitivity
24
Q
What can Type I hypersensitivity reactions trigger?
A
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 **RBC**s
* 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. **NSAID**s (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
