Antihistamines for allergies

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Introduction0:00–0:29

Antihistamines for allergies, also known as H1 blockers, are medications that are primarily used to treat allergic reactions, such as urticaria, angioedema, and allergic rhinitis.
These conditions are related to an increased release of histamine. Now, H1 blockers work by blocking the effects of histamine in tissues that have H1 receptors, thereby alleviating symptoms of allergic reactions.

Pathophysiology0:29–2:14

In order to understand how antihistamines work, first we need to talk briefly about histamine and allergic reactions. Histamine is a small molecule that’s mainly produced by mast cells and basophils.
Once released, they cause local inflammation and vasodilation. However, they are also present in the brain as neurotransmitters, and they are produced by enterochromaffin cells in the stomach to increase gastric acid secretion.
Okay, so in order to develop an allergic reaction, an allergen, say pollen, needs to enter the body and cause the activation of B cells.
Activated B-cells produce IgE antibodies that get released into the bloodstream and bind to mast cells. The mast cells are now “primed,” meaning that if pollen enters the body again in the future, the mast cells degranulate and release their histamine into the local tissue.
Now, there are 4 types of histamine receptors: H1, H2, H3, and H4 receptors. Since we’re going to talk about antihistamines for allergies, we’re going to focus only on histamine H1 receptors.
These receptors are predominantly found on endothelial cells, smooth muscle cells, sensory nerve endings, and in the brain.
On endothelial cells, stimulation of H1 receptors, causes blood capillaries to dilate and become leaky, eventually leading to redness and edema.
On the flip side, on smooth muscle cells in the lungs, stimulation of H1 receptors results in bronchoconstriction, while on sensory nerve endings leads to pain and itching.
Finally, in the brain, H1 receptors promote wakefulness and appetite suppression. Now, switching gears and moving on to pharmacology.

Mechanism of Action2:14–2:52

Antihistamines are medications that work by blocking histamine receptors; and depending on the type of the receptor they affect, antihistamines are subdivided into two main groups: H1 blockers, which are used to treat allergies, and H2 blockers, which are primarily used to treat gastric problems like heartburn.
Now, let’s focus on H1 blockers. These medications work by reversibly inhibiting H1 receptors and they are subdivided into 2 main groups: first-generation H1 blockers and second-generation H1 blockers.

First-Generation H1 Blockers2:52–4:17

First-generation H1 blockers include medications that contain letters “-en” and end with the suffix “-ine” or "-ate" like diphenhydramine, chlorpheniramine, and dimenhydrinate.
These medications are primarily used to treat allergic reactions, such as urticaria, angioedema, and allergic rhinitis. But, since they have high lipid solubility, these medications can easily cross the blood-brain barrier and block H1 receptors in the brain.
This way, first-generation H1 antihistamines can cause cognitive side effects like sedation, therefore they can be also used as a short-term treatment for sleeping problems.
For medicine specific indications, diphenhydramine can be used to treat nausea and vomiting in motion sickness. Moreover, due to its anticholinergic properties, diphenhydramine can also be useful in the treatment of conditions with extrapyramidal symptoms, such as Parkinsonism.
Finally, common side effects of first-generation H1 blockers can be subdivided into antihistaminic effects, such as sedation, increased appetite, and weight gain; antimuscarinic effects, or atropine-like side effects, such as dilated pupils, blurry vision, and dry mouth; and anti-α-adrenergic effects, like orthostatic hypotension and dizziness.

Second-Generation H1 Blockers4:17–4:54

Second-generation H1 blockers include medications that end with the suffix “-adine”, like fexofenadine, desloratadine, and loratadine, with one exception - cetirizine.
Just like the first-generation, second-generation H1 blockers are primarily used to treat allergic reactions; but since they have far less lipid solubility than the first generation, they cause less cognitive side effects.
In addition, the antimuscarinic side effects also tend to be less severe, so the second generation is preferable to the first-generation H1 blockers.

Memory Palace4:54–7:02

Now, we want to make a simple and fun mnemonic that’ll help you efficiently memorize and retain all these pharm facts! So let’s set the scene in a flower garden during the spring since we’re talking about allergies.
There’s a giant coiled up snake here with a runny nose to remind you these drugs act on the Hiss-tamine 1 receptor. Now, the first generation drugs will go on the left side of the garden.
These drugs ends in “ine” and “ate,” so let’s put a table here with a large plate balanced on a wine glass. Now these drugs cross the blood brain barrier and cause sedation, which can be both an indication if you want to treat insomnia, or a side effect if you’re treating allergies.
So let’s have a man napping peacefully in a chair after his meal. One particular medication of this class, diphenhydramine, can be represented by a hydra with dolphin heads.
For its indications, let’s put this monstrosity in a parking lot for Parkinsonism. It just got out of a car and is vomiting, so it’s also used to treat motion sickness.
Okay for the side effects of the first generation H1 antihistamines we have the antihistamine side effects, like sedation and weight gain.
So let’s put a snake by the table who’s sleeping after eating a big meal. We also have Antimuscarinic side effects like dilated pupils, blurry vision and dry mouth, so we can use a Muskrat with big dilated pupils who can’t see well.
It mistook a big wad of cotton for cotton candy, giving itself dry mouth. Finally, we have anti-α-adrenergic side effects like hypotension, so let’s have an ant with the alpha symbol on it get dizzy and faint.
Okay, moving on to the right side of the garden where we have the second generation H1 antihistamines. These drugs end in “adine” so we can set up a diner here.
Since these drugs don’t cross the blood-brain barrier, we can have a “No brain” sign outside the diner. This means there’s less CNS side effects so these second generation drugs are very popular, as can be seen by the large line of people waiting to get in.
All right, as a quick recap. Antihistamines for allergies, also known as H1 blockers, are medications that work by reversibly inhibiting H1 receptors.

Review7:02–7:57

They are subdivided into 2 main groups: first-generation H1 blockers and second-generation H1 blockers. First-generation H1 blockers include diphenhydramine, chlorpheniramine, and dimenhydrinate; and they can be used to treat allergic reactions and sleep problems.
Diphenhydramine can also be used to treat motion sickness and conditions with extrapyramidal symptoms, such as Parkinsonism.
On the other hand, second-generation H1 blockers include fexofenadine, desloratadine, loratadine and cetirizine; and they're primarily used to treat allergies.
They do not cross the blood brain barrier and are better tolerated. But wait, there’s more: Here’s a mind map with all of the mnemonics.

Mind Map7:57–8:24

Go ahead and pause the video so you can test yourself to see what you remember. Stay tuned for the answers after the credits.