Histamine & Anti-Histamines
Dr. Rawan Ghazwi
[email protected] Faculty of Medicine / Department of pharmacology
Office: M6L0
Histamine
Histamine is an Autacoids (Local Hormone)
Histamine a chemical messenger that mediates a wide range of cellular
responses, including:
Allergic and inflammatory reactions
Gastric acid secretion, &
Neurotransmission in parts of the brain
Histamine has no clinical applications, but agents that interfere with the action of
histamine (antihistamines) have important therapeutic applications
Local application of Histamine causes redness, swelling, & edema mimicking a mild
inflammatory reaction
Large systemic doses of Histamine leads to profound vascular changes similar to those
seen after shock or anaphylaxis
Mechanism of Action H1 Receptors
Distribution & their
pharmacological action
Histamine produces
effects by acting on
1. H1 Receptors (the most
important in our lecture)
2. H2 Receptors
3. H3 Receptors
4. H4 Receptors.
The Pharmacological action of H1 receptor
H1 receptor location
(Stimulation of H1 receptor by endogenous histamine)
1. Maintenance of Wakefulness state and prevent sleep
CNS 2. Decrease appetite.
3. Enhance emesis (vomiting)
Heart Increase heart rate
Peripheral Nerve
Stimulate sensory nerve ending Cause irritation of the sensory nerve ends Itching , local pain.
Endings
1. vasodilation of small blood vessels (vascular smooth muscle relaxation) and increased blood flow,
Blood which causes : Decrease in systemic blood pressure & Flushing.
vessels 2. Increased capillary permeability Edema
Nasal mucosa
(Blood vessel Gland & 1. Runny nose ( سيالن باالنفnasal discharge)
2. Sneezing العطس
peripheral nerve 3. Nasal Congestion احتقان باالنف
ending)
Eye 1. Lacrimation (watery eyes)
2. Eye Congestion (Red eye)
(Blood vessel & Gland)
Airways in lungs are smooth muscles
Smooth Muscles 1- Bronchoconstriction
Bronchi 2- Increasing the mucus secretion from the mucus glands in the air ways
& bronchial gland 3- Reflex Cough: Histamine has no role in cough center stimulation
Skin
the responses FROM Insect
Blood Vessels & Sensory Nerve Endings bite…..
Then, Triple response of
lewis
First response is itching;
there will not be too
1. Red Reaction
much pain.
2. Wheal or swelling
3. Flare or red flush
In allergic inflammation Effects of Histamine
Ranges from mild allergic symptoms
to anaphylactic shock
Histamine shock
Too much exposure to allergies, or to certain
stimuli Management
This will lead to too much production of Histamine
????????
( locally or systemically)
The degradation enzymes system will be unable to
deal will this too much amount of Histamine
Histamine will be speared systemically, and this
will cause hypotension & systemic vasodilatation.
Histamine is Antagonized by
Histamine has no therapeutic use.
It is used in diagnostic tests.
Histamine-1 Receptor antagonists by
H1-receptor blockers
The term antihistamine only refers to H1 receptor antagonists
Mechanism of action
H1 receptor blockers are competitive antagonist with histamine at the H1
receptor.
H1 - Receptor Blockers
(Anti-Histamines)
First generation H1 - Receptor Second generation H1 - Receptor
Wildly available over the counter Blockers
Blockers medication
(sedating antihistamine) (non-sedating antihistamine)
Anti- Histamine Dosage Forms
1. Chlorpheniramine 1. Oral 1. Loratadine
2. Diphenhydramine 2. Parental 2. Cetirizine
3. Topical creams, lotions,
3. Cyproheptadine sprays……..etc 3. Fexofenadine
4. Nasal spray common for relief of
allergic rhinitis
5. Eye drops common for itching &
watery, eyes
First generation H1 - Receptor Blockers Second generation H1 - Receptor Blockers
(sedating antihistamine) (non-sedating antihistamine)
Crossing No or little crossing BBB (but Some drugs may produce little
Cross the blood brain barrier (BBB) sedation)
BBB
1. They are short duration (4-6 hrs) 1. They are long duration (12-24 hrs)
Some Notes
2. They are inexpensive (ingeneral) 2. More expensive (ingeneral)
Non selective drugs
Receptor
Block H1 receptor & other receptors such as More Selective and specific to block H1 receptor
Selectivity
(Muscarinic, alpha 1 & serotonin)
Both generation are indicated for treatment of various immediate hypersensitivity reactions.
Allergic Diseases
Clinical uses 1. Allergic Conjunctivitis
both of
2. Allergic rhinitis (hay fever( by Reduction of sneezing, Runny nose inhibition & Decrease coughing (reflex)
first &
second 3. Allergic Dermatitis (reaction in the skin) :
1. Urticaria (hives) or itching (pruritus),
generation 2. In atopic dermatitis (Eczema) ex: diphenhydramine has local anesthetics effect
of H1- 3. Due Insect stings
blockers 4. Symptomatic relieve of common cold and Seasonal allergies.
5. In Nasal Congestion: 1st generations also have Antimuscarnic effect that give more benefit in this case (atropine like
effect)?????
6. Supportive in systemic anaphylactic shock
Clinical uses of First generation H1 - Receptor Blockers
(sedating antihistamine)
Due to CNS effect block both H1 & Muscarinic receptors: Due to block H1 & serotonin receptor centrally
1. Anti emetic effect to manage or control nausea & vomiting
in
Commonly prescribed to stimulate appetite in
people with anorexia
1. Motion sickness (nausea caused by motion, especially by Ex: Cyproheptadine
travelling in a vehicle)
2. Vertigo (a sensation of feeling off balance)
3. Morning sickness (vomiting of early pregnancy)
4. Treating the nausea and vomiting subsequent to chemotherapy
or radiation therapy for malignancies
First generation H1 - Receptor Blockers Second generation H1 - Receptor Blockers
(sedating antihistamine) (non-sedating antihistamine)
1. CNS effect : indue sleep, drowsiness, fatigue
Adverse 2. Anti-muscarnic effect (atropine like effect) o Second-generation H1 antihistamines are
effects leading not only to a drying of the nasal passage relatively free of adverse effects.
but also to a tendency to dry the oral cavity,
and……….
3. α- blocking effect ?????
Drug-drug Avoid the use of 1st generation with other sedatives
interaction medications that cause drowsiness and CNS
depressants drugs
1. Contraindicated in individuals working in jobs
where wakefulness is critical & in case required second-generation antihistamines are preferred for
to maintain alertness or drivers elderly patients (>65 years of age), and approved by
Notes the FDA for use in children
2. Are not recommended for use in children
Antihistamines in Bronchial Asthma?
The H1-receptor blockers are not indicated in treating bronchial
asthma, because histamine is only one of several mediators that are
responsible for causing bronchial reactions.
