Antihistamines are divided into two major types. The first type is called H-1 receptor antagonists or H-1 blockers. This type of antihistamines is used to treat allergy symptoms. The second type is called H-2 receptor antagonists or H-2 blockers. They are used to treat gastrointestinal conditions, including gastroesophageal reflux disease [GERD] (also called acid reflux), peptic ulcers, gastritis, motion sickness, nausea and vomiting.

The H-1 blocker type is further broken down into two groups: first-generation antihistamines and second-generation antihistamines.

- First generation antihistamines  : 

They work on histamine receptor in the brain and spinal cord along with other types of receptors. Most notable about this generation of antihistamines is that they cross the blood-brain barrier, which results in drowsiness.

- Second-generation antihistamines:

They  do not cross the blood-brain barrier to the extent that first-generation do and therefore do not cause drowsiness at standard dosage levels. Second-generation antihistamines are considered to be safer than first generation antihistamines because they don’t cause drowsiness and interact with fewer drugs.

Histamine (an endogenous chemical messenger) induces an increased level of vascular permeability, which leads to fluid moving from capillaries into the surrounding tissues. The overall outcome of this is increased swelling and dilation of vessels. Antihistamines stop this effect by acting as antagonists at the H-1 receptors. The clinical benefit is a reduction in allergy symptoms and any related symptoms.

First-generation antihistamines easily cross the blood-brain barrier into the central nervous system and antagonize H-1 receptors, leading to a different therapeutic and adverse effect profile in contrast to second-generation antihistamines selectively bind to peripheral histamine receptors. 

The duration of the pharmacological action of first-generation antihistamines is about 4 to 6 hours. In contrast, second-generation antihistamines work for 12 to 24 hours. They are both metabolized by the liver using the P450 cytochrome system. 

Parietal cells in the gastrointestinal tract secrete hydrochloric acid. They undergo regulation by acetylcholine, gastrin, and also histamine. Histamine is released from enterochromaffin-like (ECL) cells. When histamine binds to the H-2 receptors on parietal cells, cyclic adenosine monophosphate (cAMP) increases, inducing protein kinase A. This action then leads to phosphorylation of the proteins that take part in the transport of hydrogen ions. Thus increased histamine leads to increased stomach acid, e.g., HCl secretion.

The use of antihistamines specific to the H-2 receptor blocks the entire process and reduces stomach acid secretion.

Some products that may interact with this drug are: antihistamines applied to the skin (such as diphenhydramine cream, ointment, spray).

Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction, avoid taking  isocarboxazid, linezolid, metaxalone, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine. during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before treatment with this medication. Ask your doctor when to start or stop taking this medication.

•Common side effects of first-generation antihistamines :

Drowsiness.

Dry mouth, dry eyes.

Blurred or double vision.

Dizziness and headache.

Low blood pressure.

Mucous thickening in the airways.

Rapid heart rate.

Difficulty urinating and constipation.

•Common side effects of second-generation antihistamines :

Headache.

Cough.

Tiredness.

Sore throat.

Abdominal pain or discomfort.

Nausea or vomiting.

Antihistamines are commonly used to relieve the symptoms associated with hay fever. These can include:

Inflammation of the nose and eyes (allergic rhinitis and allergic conjunctivitis).

Sneezing.

Itching of the eyes, nose and throat.

Runny nose (rhinorrhoea).

To reduce the severity of the rash and itching associated with nettle-type rashes such as hives (urticaria) and generalised itching (pruritus).

To help with the rash and itching following insect stings or bites.

To prevent motion sickness and other causes of feeling sick (nausea).

Occasionally to treat severe morning sickness in pregnancy.

In the care of the terminally ill, for their sedating and antisickness effects.

In the emergency treatment of severe allergic reactions

It’s safest to talk to your healthcare provider if you are pregnant, planning to become pregnant or are breastfeeding. Animal studies have shown that some antihistamines can cause birth defects. Small amounts of antihistamines pass on to your baby if you breastfeed. For these reasons your healthcare provider will want to talk with you and make careful choices (or different choices) if there is any concern for your or your child’s safety.