21. Antihistamines, leukotriene receptor antagonists

Question 1

What are antihistamines?

Answer 1

They are drugs that block the histamine receptors, typically the H1 receptors, to reduce the allergic symptoms.

They are classified into two main generations based on their ability to cross the BBB (Blood-brain-barrier) = 1st and 2nd generation

Question 2

1st generation antihistamines, active substances

Answer 2

1. Ethanolamines:
- Dipehnydramine
- Dimenhydrainate

2. Piperazines
- Hydroxzine

3. Cyproheptadin

Question 3

2nd generation antihistamines, active substances

Answer 3

Cetirizine

Question 4

Mechanism of action of antihistamines

Answer 4

Antihistamines are inverse agonists, they are a type of receptor ligand that not only prevents receptor activation but also causes the receptor to become inactive. So in this case, antihistamines not only prevent histamine from binding to the receptors, but also force the receptor into an inactive state.

We shut down the histamine-driven process, and we see reduced swelling, itching, and other signs of allergic reactions.

Question 5

Indications of antihistamines

Answer 5

1. Allergic diseases, such as atpic dermatits, flea allergy dermatitis
2. Asthma and RAO
3. Anaphylatic reactions
4. Allergic problems during surgery

Question 6

Pharmacokinetics of antihistamines

Answer 6

1. Absorption
Good oral absorption.
2. Distribution
There is a distinction between the 1st and 2nd generation.
2nd generation: They are ionized and heavily bound to albumin, which is a protein in the blood. This binding can affect how much of the substance is free to move into the tissues
3. Metabolism
Liver ⭢ CYP450 inducers!!

CYP450 makes the metabolism quicker

Question 7

Side effects of antihistamines

Answer 7

1. CNS depression ⭢ Associated with 1st generation antihistamines, causing drowsiness, sedation or reduced mental alertness
2. Cardiac toxicity
3. Prolonged QT interval: Can increase the heart rhythm abnormalities as they increase thr QT interval on ECG
4. Anticholinergic effect ⭢ Associated with 1st generation antihistamines
5. Appetite depression ⭢ Especially associated with cyproheptadine

Question 8

Leukotriene receptor antagonists, active substances

Question 9

Leukotriene receptor antagonists, mechanism of action

Answer 9

Leukotriene receptor antagonists work by blocking the CysLT1 (Cysteinyl-leukotriene type 1) receptors, which is a receptor for cysteinyl leukotrienes. Cysteinyl leukotrienes are inflammatory mediators that play a role in conditions like asthma and allergic rhinitis. By blocking these receptors the antagonists can reduce inflammation, bronchoconstriction and mucus production.

Question 10

Leukotriene receptor antagonists, Indications

Answer 10

• Feline asthma
• Allergic bronchitis
• RAO (Recurrent airway obstruction

Question 11

Leukotriene receptor antagonists, pharmacokinetics

Answer 11

1. Absorption
Good oral absorption
2. Distribution
High plasma binding
3. Metabolism
Liver ⭢ CYP450 enzyme !!
4. Elimination
Most of the drug in faeces, the rest in urine.