Histamines

Question 1

Sources of histamine (Major histamine-producing cells)

Answer 1

Major histamine-producing cells (release histamine through type1 hypersensitivity)

1. Mast cells
2. Basophil
3. ECL cell
4. Histaminergic neuron (Activation of histaminergic neurons release of histamine )

Question 2

Basophil histamine release

Answer 2

• In response to allergies, in type I hypersensitivity mechanism
• Activated by IgE crosslinking, complement system, allergy-inducing drugs

Question 3

ECL cell histamine release

Answer 3

In GI tract, activated by gastrin; inhibited by somatostatin

Question 4

Histaminergic neuron (Activation of histaminergic neurons release of histamine) histamine release

Answer 4

Activated by opioid, dopamine, serotonin receptors

Question 5

CNS effects of H1 antihistamines

Answer 5

(histamine is a CNS neurotransmitter)

1. Antiemetic effects
2. Sedation
3. Impaired cognition, memory and psychomotor function

Question 6

antihistamines cell level effects

Answer 6

blocks G protein activity

• • decreased IP3 activation → decreased mediator release, increases mast cell stabilisation
• • decreased PKC β activation → decreased NF-KB protein which binds to transcription factors → decreased gene expression → decreased antigen presentation and expression of pro-inflammatory cytokines, cell adhesion molecules and chemotactic factors

Question 7

side effects of 1st gen H1 antihistamines - CNS H1 receptors

Answer 7

decrease in alertness, cognition, learning, memory ⇒ avoided for pilots, drivers and any machinery operations which require psychomotor skills

Question 8

side effects of 1st gen H1 antihistamines - muscarinic receptors

Answer 8

dry mouth, urinary retention, sinus tachycardia, blurred vision and constipation

Question 9

side effects of 1st gen H1 antihistamines - serotonin receptors

Answer 9

increase appetite, leading to weight gain (eg ketotifen, cyproheptadine)

Question 10

side effects of 1st gen H1 antihistamines - α-adrenergic receptors

Answer 10

increase dizziness and postural hypotension (eg promethazine)

Question 11

side effects of 1st gen H1 antihistamines — contraindication

Answer 11

• patients with glaucoma/prostatic hyperplasia

Question 12

side effects of 1st gen H1 antihistamines in drug abuse

Answer 12

the patient may have euphoria/hallucinations (eh cyclizine, diphenhydramine)

Question 13

1st generation vs 2nd generation H1 antihistamine examples - allergic conditions

Answer 13

1st gen is preferred choice for: Non-allergic conditions (Eg. motion sickness and vertigo, nausea and vomiting, insomnia and perioperation
- Mediated through some of the side effects of 1st generation drugs

2nd gen is - Preferred choice for: Mild-moderate allergies (Eg. allergic rhinitis, conjunctivitis, urticaria, food allergy, mastocytosis)
- Note: use epinephrine in anaphylaxis instead of antihistamines due to faster onset time

Question 14

1st generation properties

Answer 14

• Sedating antihistamine
• Low H1 receptor selectivity (it is anti-muscarinic cholinergic, anti-adrenergic and anti-5HT)
• More lipophilic
• Lower molecular weight
• Readily passes BBB
• Lacks interaction with P-glycoprotein efflux pump
  
  • ⇒ Accumulation in CNS → sedation is a major side effect
• Onset action is 2-3h, duration of action is ~12h

Question 15

2nd generation properties

Answer 15

• Non-sedating antihistamine
• High H1 receptor selectivity (less side effects)
• Less lipophilic
• Higher molecular weight
• Less ready to pass BBB
• High affinity with P-glycoprotein efflux pump
• Onset action is 1-2h, duration is 24h (once daily)