HISTAMINE & ANTIHISTAMINES (Part #2):





Role in Allergy and Anaphylaxis:

The symptoms occur from IV injection of histamine are similar to anaphylactic shock and allergic reaction symptoms.

They result from the release of chemical like histamine, but there are some other chemical mediators like; serotonin, leukotrienes, eosinophil, chemotactic factor.

It is thought that the difference between these two situations (allergy and anaphylaxis) result from the difference in the sites from which mediators are released or may be in their release rate, that's why they are producing two different situations i.e allergy and anaphylaxis.

How the histamine is going to produce the specific situation either allergy or either anaphylactic shock?

If the release of histamine is slow enough to part permit its inactivation before it enters the bloodstream so a local allergic reaction occur.

If the release of histamine is fast enough to permit its inactivation so a full blown anaphylactic shock occurs.

H-1 Antihistamine:

- They are primarily refers to h1 receptor blockers. 

Type of generation of Drugs:

First generation drugs:

- They are still widely used because they are effective and inexpensive.

- Mostly drugs penetrate CNS and causes sedative effect.

- They also interact with other receptors produces many unwanted adverse effects.

Second generation drugs:

- They are specific for peripheral h1 receptors.

- They don't penetrate to BBB (Blood Brain Barrier) and they are modified in such a way that they are being added carboxyl group and make them polar

Example:

Cetrizine:

- Cetrizine is actually a carboxylated derivative of hydroxyzine.

- These agents don't penetrate to blood brain barrier because of the carboxylation and they causes less CNS depression as compared to the first generation drugs.

Examples of Second generation drugs:

- Ceterizine

- Levocetrizine

- Cesloratadine

- Fexofenadine

- Loratadine

NOTE:

First two drugs are partially sedative and the rest three drugs produces least sedative effect.

Effect of H-1 antihistamine on different receptors:

H-1 Antihistamine acting on cholinergic receptor:

- Increase drymouth

- Increase urinary retention

- Increase sinus tachycardia

Example:

- Diphenhydramine

- Promethazine

H-1 Antihistamine acting on alpha adrenergic receptor:

- Increase hypotension

- Increase dizziness

- Increase reflex tachycardia

Example:

- Promethazine

H-1 Antihistamine acting on serotonin receptor:

- Increase the appetite stimulation

Example:

- Cyproheptadine

H-1 Antihistamine acting on histamine receptor:

- Decrease allergic inflammation, itching, sneezing and rhinorrhea.

- Decrease neurotransmission

- Increase sedation

- Decrease cognitive and psychomotor performance

- Increase appetite

Example:

- All H1 antihistamine drugs

Multiple Effect of H-1 Antihistamine:

Lets consider the following example given below.

Cyproheptadine:

It is also act as serotonin antagonist (means that it is going to stimulate appetite)

Azelastine & Ketotifen:

It also produces mast cell stabilizing effect

Therapeutic uses:

1) Allergic and Inflammatory conditions:

Antihistamine are useful in treating allergic and inflammatory conditions which are caused by the antigen acting on the immunoglobulin e antibody

Example:

Oral Antihistamine:

It control allergic rhinitis, urticarial etc.

Ophthalmic Antihistamine:

- It control allergic conjunctivitis.

- Drug includes are Olopatadine, Ketotifen, Azelastine, Alkaftadine, Bepotastine, Emedastine.

Note:

H1 receptor blocker are not indicating are not indicated in treating bronchial asthma because histamine is the only one of mediators that are responsible for causing bronchial reactions.

Epinephrine has an action on smooth muscle that are exactly opposite to histamine . So it acts on beta-2 receptors on smooth muscle and causes cAMP mediated relaxation, therefore we can say that epinephrine is the drug of choice in creating systemic anaphylaxis and other conditions that involve massive release of histamine

Because of their lower potential to intrude you to induce drowsiness,  we can consider Loratadine and Fexofenadine may good for the people working in jobs where wakefulness is critical.

2) Motion sickness and nausea:

H1 antihistamine along with antimuscarinic agent (Scoploamine), so they are going to do prevention from motion sickness and they also prevent nausea and vomiting

The drug Meclizine are used to treat vertigo which are associated with vestibular disorders.

 Example:

- Diphenhydramine

- Dimenhydrinate

- Cyclizine

- Meclizine

- Promethazine

3) Insomnia:

- A condition that can make it hard to fall asleep.

- Many first generation drugs like diphenhydramine, doxylamine have strong sedative properties hence they are used to treat insomnia.