Lecture 2

Question 1

List some reasons for adverse drug reations (side effects)

Answer 1

1. Overdosage
2. Increased sensitivity
3. Lack of selectivity
4. Drug allergy
5. Cutaneous reactions
6. Drug Toxicity in pregnancy and lactation

Question 2

Describe how an overdose can cause an adverse drug effect

Answer 2

• higher dose than is required for its principal therapeutic effect
• increased dose can affect other bodily functions either directly or indirectly.
• therapeutic index/margin of safety must be determined in a new drug; the level at which damage is likely to occur also needs to be assessed.

Question 3

Describe how Increased Sensitivity can cause an adverse drug effect

Answer 3

• when a patient say the elderly develop hypersensitivity as a result of varing pathologic changes/disease require a reduced doseage for the same drug effect.
• e.g. patients with chronic lung disease have ^ sensitivity in the respiratory centre to morphine - thus a smaller dose of the morphine is sufficient to paralyse control of breathing.

Question 4

Describe how Lack of Selectivity can cause adverse drug effects

Answer 4

• when a drug acts on more systems than desired because it can bind to many target receptors which are in many organs,
• e.g. atropine only acts at one type of receptors, the muscarinic acetylcholine receptor, although these are located throughout the body.
• e.g. promethazine works on a plethora of receptors and is deemed to be neither tissue or receptor specific.
• This can be overcome with local administration of the drug which avoids systemic effects of the drug. An example is atropine eye drops.

Question 5

Describe a drug allergy and some adverse effects

Answer 5

• The immune system functions by synthesising antibodies to destroy the antigen (drug) as it is foreign to the body
• The use of purified animal and microbial materials such as pig insulin or penicillin has resulted in a number of allergic reactions to these drugs.

4 types:

1. Acute anaphylactic reaction - Anaphylactic shock, Hypotension, Asthma, urticaria
2. Cytotoxic reaction - Haemolytic anaemia, Agranulocytosis, Thrombo-cytopaenia
3. Immune complex - Inflammation => fever, arthritis, neuropathy
4. Lymphocytic delayed reaction - Contact dermatitis

Question 6

Describe some Cutaneous Reactions that have arose as a result of a consumed drug

Answer 6

• it is an immunological reaction, generally caused by photosensitisation of the drug.
• range in severity from harmless to lethal mc antibiotics and NSAIDs.

1. Toxic erythema – rash similar to measles.
2. Urticaria – itchy swelling arising from from an anaphylactic shock
3. Fixed eruptions (drug exanthemas) – few, localised, painful lesions that will reoccur in the same spot with repeated drug exposure.
4. Toxic epidermal necrolysis (TEN) – death of skin keratinocytes and the detachment of the epidermis from the dermis. If over 30% of the body is affected, this condition is lethal.

Question 7

How can Drug Toxicity during Pregnancy and Lactation cause adverse effects

Answer 7

• Drugs can be passed on transplacentally or via breast milk and can adversely affect the unborn

Drug effects on the developing foetus fall into two basic categories.

1. effects based on pharmacological properties of the drug. e.g. masculinisation of F foetus by androgenic hormones and bradycardia due to b-blockers.
2. Drug effects that specifically affect foetus (teratogenicity) and can’t be predicted on the basis of its pharmacology.e.g. thalidomide = limb malformation in foetus.

Question 8

What factors should be considered when assessing the drug risk for a pregnant woman

Answer 8

1. Time of drug use: damage to the foetus by a drug may be dependent on its developmental stage. e.g. Tetracylines only produce effects on teeth and bones in the third month of gestation when mineralisation occurs
2. Ability to cross the placenta: most centrally acting drugs including anxiolytics and antidepressants are able to easily cross the placenta and affect the foetus.
3. Teratogenicity: