Histamine

Question 1

Name the first generation antihistamines

Answer 1

1. cyclizine
2. cyproheptadine
3. chlorpheniramine
4. hydroxzine
5. ketotifen
6. diphenhydramine
7. pyrilamine
8. promethazine

Question 2

Name the second generation antihistamines

Answer 2

1. acrivastatine
2. azelastine
3. cetirizine
4. levocetirizine
5. loratidin
6. fexofenadine
7. desloratidin

Question 3

Mast cell degranulation is mediated by 2 types of processes… and …

Answer 3

igE mediated & non-igE mediated

Question 4

Ig E mediated mast cell degr

Answer 4

igE binds to FcepislonRI of mast cell
antigen binds to igE
trigger degranulation

Question 5

Non-IgE mediated mast cell degr

Answer 5

1. IgG binding to FcgammaRI
2. drugs
   - vancomycin (red man syndrome)
   - opoids
   - tubocurarine
   - radiocontrast medium
3. substance P
4. anaphylatoxin C3a C5a
5. kit ligand: stem cell factor
6. bacterial products eg LPS

Question 6

Histamine pathophysiological actions

Answer 6

1. smooth muscle contraction
2. vasodilation
3. increased vascular permeability - edema & extravasation (contraction of epithelial barrier & increased gap junction)
4. sensory neuron itch & pain
5. wheal & flare in skin
6. increase histamine release from mast cell & other cells
7. immunomodulation
8. modulation of neurotransmission, sleep/wake, arousal, cognition, learning, memory
9. gastric acid secretion

Question 7

List the functions of each 4 types of histamine receptors

Answer 7

1. H1: acute allergic reaction
2. H2: gastric acid secretion
3. H3: neurotransmission, cognition
4. H4: immunomodulation

Question 8

MOA of antihistamine

Answer 8

1. histamine receptors constitutively active
   - active:inactive R in eqm
2. stabilised in active state by histamine
3. antihistamine inverse agonist: binding stabilises antihistamine receptor in inactive state

Question 9

Chemical & functional classification of antihistamines

Answer 9

1. alkylamines
2. piperazine
3. piperadine
4. ethanolamine
5. ethyleneeamine
6. phenothiazine
7. others

1st gen

1. chlorpheniramine
2. cyclizine, hydroxyzine
3. cyproheptadine, ketotifen
4. diphenhydramine
5. pyrilamine
6. promethazine

2nd gen

1. acrivastatine
2. cetirizine
3. loratidin, desloratidine, fexofenadine
4. azelastine

Question 10

Clinical use of antihistamines

Answer 10

2nd gen: mild to moderate allergy

• allergic rhinitis/conjuctivitis/urticaria
• food allergy
• mastocytosis

1st gen: non allergy

• N/V
• motion sickness/vertigo
• insomnia/perioperation

*note anaphylaxis use epinephrine
as onset 2nd gen AH 1-2 hr

Question 11

Differentiate first gen & second gen antihistamines

Answer 11

1. sedative vs non-sedating
2. low specificity vs high specificity for H1 receptr
3. anti M/A/HT vs nil
4. highly lipophilic vs low
5. low mlc weight vs high
6. gd BBB pentrance vs poor
7. lack interaction vs high affinity for P-glycoprotein efflux pump
8. high vs low CNS H1 receptor occupancy
9. onset: 2-3 vs 1-2
10. DOA: 12 vs 24

Question 12

Special clinical properties of antihistamines shld know

Answer 12

1. N/V: 1st gen inhibit histaminergic neurons (h1 r) in vestibular nucleus & vomiting centre in medulla
2. atopic dermatitis, insomnia, perioperation: 1st gen sedative effects
3. azelastine: rapid onset 15 mins: eye drop + nasal spray
4. nasal spray aslo ketotifen both have mast cell stab effect
5. wheal & flare: combo h1 + h2 R blockers synergistic effect for acute and chronic urticarial
   as h2 blocker blocks vasodilation

Question 13

Side effects of antihistamines

Answer 13

1. CNS H1 R: decrease alertn, cog, learn, mem, psyco
2. muscarinic R: urinary retention, blurred vision, dry mouth, constipation, sinus tachycardia
3. HT serotonin R: weight gain, increase appetite
4. alpha adrenergic R: dizziness, postural hypotension
5. CVS - increase QT interval + ventricular arrythmia

Question 14

Contraindications of first gen AH

Answer 14

1. glaucoma
2. BPH
3. pilots etc: avoid 1st gen, recommend fexofenadine 2nd gen