Second-generation antihistamines and mast cell stabilizers

What quality makes a drug a substrate for P-Glycoprotein?

Polar

What 3 things make it harder for a drug to cross the BBB?

Big / Bulky

Polar groups

Lack of monoamine

How does P-glycoprotein work?

Take the molecule and with the help of ATP pushes it back into the blood.

What is the benefit of lower BBB penetration in the second-generation antihistamines?

Don’t cause sedation or any other CNS effects (some may still cause little)

Can be used chronically

What is the half-life of this drug?

6-10 hours

What side effects can be expected when taking this drug?

Mild sedation

What does this drug treat?

Allergies

What type of drug is this? (Softdrug, prodrug, etc.)

Active metabolite of an active drug

What type of drug is this? (Softdrug, prodrug, etc.)

Prodrug

How is this drug activated?

CYP3A4 hydroxylation

Alcohol dehydroxynase oxidation

What does this drug treat?

Allergy

Is this molecule going to cross the BBB?

Not really

What is an important thing to avoid when taking this drug and why?

Fruit juice because they also bind to OATP

Where is this drug absorbed and by what?

Intestine

OATP

Where is this drug metabolized?

Liver

What type of drug is this? (Softdrug, prodrug, etc.)

Prodrug

What is the active metabolite of this drug (Where is it activated)?

The N is hydronated

Will this drug and/or its metabolite cross the BBB?

Not really.

What is this drug used to treat?

Allergies without the risk of cardiotoxicity

What does this drug treat?

Allergic rhinitis

Itching

Hives

Will this drug cross the BBB?

Yes

Acts on 5-HT receptors too

What are the side effects of this drug?

Appetite stimulation (5-HT receptor)

Why is this drug susceptible metabolization?

The double bond on the 7 ring

What are Mast cells’ role in allergic responses?

Once they interact with allergen they degranulate and release histamine

What is the down side to pure Mast cell stabilizers (No antihistamine action)

Immune response won’t stop at once

Histamine will still be released and there is nothing to stop it.

What is the body’s response to an increase of histamine?

Vasodilation

Increased vascular permeability

nociception (Pain)

How do mast cell stabilizers work?

Prevent the flow of calcium into the cell.

What type of drug is this?

Pure mast cell stabilizer

What does this drug treat?

Chronic treatment for asthma and allergies

What type of drug is this?

Pure mast cell stabilizer

What does this drug treat?

Chronic treatment of allergies

What is the dosage form of this drug?

Ophthalmic solution

What is the structural backbone of second generation antihistamines with mast cell stabilization?

6-7-6 ring

What addition to a 6-7-6 second generation antihistamine would make it have a shorter half life?

acid or O group.

What is the dosage form of all 6-7-6 second-generation antihistamines?

Ophthalmic solution

What is the dosage form of this drug?

Ophthalmic solution and nasal spray

Why can a drug have a long duration of action with a short half-life?

High Koff value. They attach to the receptor and take a long time to unattach

What is the activity of this drug?

Second-generation antihistamine with mast cell stabilization

What is this drug used to treat?

Allergic rhinitis and conjunctivitis

What is the downside of this drug?

High BBB permeability → more side effects

Tastes bad

What is the activity of this drug?

Second-generation antihistamine with mast cell stabilization

What does this drug treat?

Ocular allergic conjunctivitis and itching

What is the dosage form of this drug?

Ophthalmic drops