Anti-histamines

Question 1

Histamine

Answer 1

1. inflammatory mediator (acute phase)
2. gastric acid secretion
3. neurotransmitter

Question 2

Rapid and slow metabolism

Answer 2

Rapid - brain and other tissues

Slow - in mast cells and basophils

Question 3

Two state model H1 Anti-histamines

Answer 3

Histamine - agonist - bind to active
Anti- histamine drugs - inverse agonist - inactive
- inactive state of H1-receptor is in equilibrium with the active state

1. an agonist, which has preferential affinity for the active state stabilized the receptor causing a shit in the equilibrium toward the active state
2. an inverse agonist, which has a preferential affinity for the inactive state stabilizes the receptor and causes a shift in the equilibrium towards the inactive state

Question 4

All known H1- anti-histamines function as?

Answer 4

inverse agonists

Question 5

Two types of histamine receptor, 1 and 2

Answer 5

1 - inflammation, allergy

2 - gastric

Question 6

Anti- histamine drugs

-names

Answer 6

Clemastine, 
Meclizine, 
Cetirizine, 
Ebastine, 
Loratadine

Question 7

Classification of H1 antagonists

Answer 7

First generation

• Meclizine
• Clemastine

Second generation

• Cetirizine
• Loratadine
• Ebastine

Question 8

Benefits of H1 anti-histamines

Answer 8

decrease allergic inflammation
decrease rhinorrhea 
decrease itching 
decrease sneezing 
decrease antigen presentation
decrease chemotaxis 
decrease pro-inflammatory cyotkines 
decrease expression of adhesion molecules

Question 9

Potential adverse effect of H1 anti-histamines

Answer 9

decrease neurotransmission in CNS
increase sedation 
increase appetite 
increase dry mouth 
urinary retention
hypotension
sinus tachycardia

Question 10

Pharmacokinetics of H1 anti-histamines (2)

Answer 10

• first generation are not only substrate of CYP2D6 but also inhibit it
• must take into account when drugs are co-administered with substances that likewise require metabolization via CYP450

Question 11

Indications of H1 anti-histamines (5)

Answer 11

treat symptoms of allergies
adjunctive treatment of anaphylatic reactions
sedatives (first generation)
motion sickness
secondary parkinsonism (first generation)

Question 12

First generation drugs

Answer 12

• Meclizine - used to treat motion sickness,
• Clemastine - marked potential for producing sedation
• easily cross blood-brain barrier
• drug-drug interactions are possible - should be used carefully when combined with other drugs that are also metabolized in the liver

Question 13

Second generation drugs

Answer 13

• Cetirizine - weak potential for producing sedation,
• Loratadine - non-sedating
• low permeability to blood-brain barrier
• no drug-drug interaction
• much safer
• majority are eliminated via kidney
• very well tolerated