Anti-histamines

What type of hypersensitivity reaction leads to the release of histamines?

Type 1

What cell or antibody is involved with Type I hypersensitivity reactions?

IgE

What leads to IgE antibody production?

Repeat exposure to allergens

What cells release histamine?

Mast cells.

Describe type 1 hypersensitivity reaction.

- Mast cells contain granules containing histamines in the cytoplasm as well IgE receptors on their surface.

- IgE antibodies bind to the IgE receptors however nothing will take place if the IgE antibodies are not exposed to allergens whilst attached to the mast cell.

- This activates of mast cells which leads to degranulation where histamine is released.

- The immediate hypersensitivity reaction/allergic reaction or a late phase reaction take place.

What are the types of histamine receptor antagonists/antihistamines?

First generation and second generation

What are 1st Gen histamine receptor antagonists/antishistamines?

- Can be used on allergic reactions and for motion sickness.

- Very lipophillic so can cross blood brain barrier.

- Short duration of action.

What are 2nd Gen histamine receptor antagonists/antishistamines?

- Can be used on allergic reactions.

- Not lipofillic so cannot cross blood brain barrier.

- Long duration of action.

What effects does being lipophillic have on 1st gen anti-histamines?

- They have lots of effects on the CNS such as causing a sedative effect.

- Also allows them to have an anticholinergic effect which has some side-effects.

- This allows them to effective motion-sickness drugs.

What effects do antihistamines have that are not related to H1 receptors?

- Anticholinergic effects

- Effect the CNS

Describe the anticholinergic effect of antihistamines.

- Many 1st gen antihistamines can inhibit responses to muscarinic receptors e.g., acetylcholine cannot work.

- Can lead to side effects of dry mouth, blurred vision and constipation.

Describe the effects of antihistamines on the CNS.

- Most 1st gen antihistamines have a sedative effect.

- They can have an excitatory effect rather than a sedative effect e.g., convulsions.

- Some 1st gen can prevent motion sickness.

What are the essential groups for 1st gen anti-histamines activity towards H1 receptors?

- Tertiary amine with 2 R groups.

- X group being a C, O or an N.

- 2 aromatic groups on X group.

- 2 or 3 carbons in between tertiary amine and X group.

What 2 R groups can be present on the tertiary amine of a 1st gen anti-histamine?

- Most common is 2 methyl groups.

- Can be 2 different groups.

- No more than 1 benzene group.

- Can be a closed ring around nitrogen.

What are the types of 1st gen anti-histamines?

- Ethylene diamines

- Ethanolamines

- Alkylamines

- Piperazines

- Tricyclics

Why do 2nd gen anti-histamines work in the periphery (not in the brain)? (relate to structure)

They have an additional negative polar group like a carboxylate that prevents it from passing through blood brain barrier.

What is an antihistamine for asthma and what is the dosage?

Fexofenadine, up to 240mg daily