HISTAMINE

Pharmacology Presentation
Presented by: Prachi Sharma
WHAT IS A HISTAMINE?
Histamine is a chemical messenger mostly generated in mast cell that mediates a
wide range of cellular responses, including allergic and inflammatory reactions,
gastric acid secretion and neurotransmission in parts of the brain.
Histamine is an amine, derived from the amino acid histidine by L-histidine
decarboxylase.
Tissues rich in histamine are skin, gastric and intestinal mucosa, lungs, liver and
placenta. Nonmast cell histamine occurs in brain, epidermis, gastric mucosa and
growing regions. Histamine is also present in blood, most body secretions,
venoms and pathological fluids.
Histamine has no clinical application but antihistamines have important
therapeutic applications
 SYNTHESIS, STORAGE AND DESTRUCTION

Synthesis Storage Destruction

Histamine is synthesized In mast cells, histamine Increase in intracellular cAMP

locally from the amino acid (positively charged) is held by (caused by β adrenergic
histidine and degraded rapidly an acidic protein and heparin agonists and methylxanthines)
by oxidation and methylation (negatively charged) within inhibits histamine release.
intracellular granules.
When the granules are
extruded by exocytosis, Na+
ions in e.c.f. exchange with
histamine to release it free
SYNTHESIS AND DEGRADATION OF HISTAMINE

Figure 1: Synthesis and degradation of histamine

HISTAMINE RECEPTORS
There are 4 types of histaminergic receptors: H1, H2, H3 and H4
Till now, only these two receptors are clinically relevant: H1 and H2
Though some selective H3 agonists and antagonists have been produced, none has found any
clinical application.
 PHARMACOLOGICAL ACTIONS
BLOOD VESSELS VISCERAL SMOOTH MUSCLE

Histamine causes marked dilatation of smaller blood Histamine causes bronchoconstriction, patients of
vessels, including arterioles, capillaries and venules. asthma are highly sensitive. Smooth muscle
Larger arteries and veins are constricted by contraction is a H1 response.
histamine. This is mediated by H1 receptor on
vascular smooth muscle
AUTONOMIC GANGLIA AND ADRENAL
MEDULLA
GLANDS These are stimulated by Histamine and release of
Adr occurs, which can cause a secondary rise in BP.
Histamine causes marked increase in gastric
secretion—primarily of acid but also of pepsin.
HEART
This is a direct action exerted on parietal cells
through H2 receptors, and is mediated by increased
cAMP generation, which in turn activates the Increased heart rate (H2) and positive inotropic
membrane proton pump (H+ K+ ATPase). effect (H1 & H2), at moderate-high dose
PATHOPHYSIOLOGICAL ROLES OF HISTAMINE
1 Gastric secretion - Histamine is released locally under the influence of all stimuli that evoke
gastric secretion (feeding, vagal stimulation, cholinergic drugs and gastrin) and activates the
proton pump (H+ K+ ATPase) through H2 receptors.

Allergic phenomena - Mediation of hypersensitivity reactions. Histamine is causative in urticaria,

2
angioedema, bronchoconstriction and anaphylactic shock.

As transmitter - Histamine is the afferent transmitter which initiates the sensation of itch and
3
pain at sensory nerve endings.

Inflammation - Histamine is a mediator of vasodilatation and other changes that occur during
4
inflammation. It promotes adhesion of leukocytes to vascular endothelium
 ANTIHISTAMINIC AGENTS
Antihistamines are a pharmaceutical class of drugs that act to treat histamine-mediated
conditions.
There are two main classes of histamine receptors:

H1 RECEPTOR BLOCKER H2 RECEPTOR BLOCKER

These drugs competitively antagonize actions of Drugs that bind to H-2 receptors treat upper
histamine at the H1 receptors gastrointestinal conditions that are caused by
excessive stomach acid.
Antihistamine drugs that bind to H-1 receptors are
generally used to treat allergies and allergic rhinitis. They are used to treat peptic ulcer, acid reflux,
gastritis
They are divided into 2 Generations: The older first
generation drugs and Second generation (Non- They block H2 receptors on gastric parietal cells
sedating) agents attenuating gastric acid secretion
H1 ANTIHISTAMINICS
H 1 antihistamines, formerly known as H 1 receptor antagonists or H 1 receptor
blockers, are among the most commonly used medications in the world not only
for prevention and treatment of symptoms in allergic rhinitis, allergic conjunctivitis,
and urticaria, in which there is good evidence for their efficacy.

H1 antihistamines act as inverse agonists that combine with and stabilize the
inactive conformation of the H1 receptor, shifting the equilibrium toward the
inactive state.
MECHANISM OF ACTION
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 SECOND GENERATION

1. Can cross BBB → High lipophilicity 1. Cannot cross BBB → Less lipophilicity
→ Low molecular weight → Bulkier molecule.

2. Low H1 receptor selectivity. 2. High H1 receptor selectivity

Hence, inhibit transmission at Here, have little or no affinity for other receptors.
→ Cholinergic receptors → Adrenergic receptors
→ Serotonin receptors 3. Weak potential to induce sedation.

3. Marked potential for inducing sedation 4. Therapeutic uses.

- Allergies, rhinitis and conjunctivitis
4. Therapeutic uses: - Reduce symptoms of itching, sneezing,
- Rhinitis, Urticaria rhinorrhea, common cold.
- Bronchial asthma
- Anaphylaxis 5.No anti-cholinergic side effects
- Motion sickness (antiemetic) - Minimal to no sedation or drowsiness.
- Insomnia

5. Side effects :
- Anticholinergic - Blured vision, dry month,
tachycardia, urinary retention, drowsiness, dizziness.
 FIRST GENERATION SECOND GENERATION

EXAMPLES: EXAMPLES:

1. HIGHLY SEDATIVE 1. Cetirizine

a. Diphenhydramine 2. Levocetirizine
b. Promethazine 3. Loratadine
c. Hydroxyzine 4. Mizolastine
2. MODERATELY SEDATIVE 5. Ebastine
a. Pheniramine 6. Rupatadine
b. Cyproheptadine 7. Fexofenadine
c. Meclozine
3. MILD SEDATIVE
a. Chlorpheniramine
b. Triprolidine
c. Clemastine
H2 ANTIHISTAMINICS
H2 receptor blockers, or histamine-2 receptor antagonists (H2RAs), are gastric
acid-suppressing agents frequently used to treat various gastric conditions.

H2 receptor antagonists may also be used off-label for stress ulcer prophylaxis,
esophagitis, gastritis, gastrointestinal bleeding, or urticaria.

These drugs are also sometimes included in a multidrug regimen for Helicobacter
pylori eradication.

Examples: Cimetidine, ranitidine, famotidine, roxatidine

MECHANISM OF ACTION
H2RAs decrease gastric acid secretion by reversibly binding to
histamine H2 receptors located on gastric parietal cells

Inhibiting the binding and activity of the endogenous ligand

histamine

H2 blockers thus function as competitive antagonists

 PHARMACOLOGICAL ACTIONS OF ANTIHISTAMINICS
1 2 3

Antagonism of histamine Antiallergic action Anticholinergic action

Block histamine induced Manifestations of immediate H1 blockers in addition antagonize
bronchoconstriction, contraction hypersensitivity (type I reactions) muscarinic actions of ACh. which
of intestinal and other smooth are suppressed. Urticaria, itching are adverse effect-inducing; Dry
muscle and triple response— and angioedema are well mouth is a relatively common
especially wheal, flare and itch. controlled. adverse effect. Some users
experience dizziness and tinnitus.

4 5

Blood Pressure CNS

The older antihistamines produce variable degree
Most antihistaminics cause a fall in BP on i.v.
of CNS depression due to their ability to penetrate
injection (direct smooth muscle relaxation or α
the blood-brain barrier and its affinity for the
adrenergic blockade).
central (compared to peripheral) H1 receptors
 CLINICAL USES OF ANTIHISTAMINICS
1 2 3

Allergic disorders Common cold Motion sickness

They effectively control certain Antihistaminics do not affect the Promethazine, diphenhydramine,
immediate type of allergies, such course of the illness but may dimenhydrinate and meclozine
as itching, urticaria, seasonal hay afford symptomatic relief by have prophylactic value in milder
fever, allergic conjunctivitis and anticholinergic (reduce types of motion sickness.
angioedema of lips, eyelids, etc. rhinorrhoea) and sedative
actions.

4 5

Parkinsonism As sedative, hypnotic, anxiolytic

Promethazine and some others afford mild Antihistamines with CNS depressant action have
symptomatic relief in early cases—based on been used as sedative and to induce sleep,
anticholinergic and sedative property. especially in children. Hydroxyzine has been used in
anxiety associated with autonomic manifestations.
 SIDE EFFECTS OF ANTIHISTAMINICS
Side effects antihistaminics are frequent, but generally mild.

Sedation, diminished alertness and concentration, light headedness, motor incoordination, fatigue
and tendency to fall asleep are the most common.

Objective testing shows impairment of psychomotor performance.

Dryness of mouth, alteration of bowel movement, urinary hesitancy and blurring of vision can be
ascribed to anticholinergic property of older antihistaminics.

Acute overdose produces central excitation, tremors, hallucinations, muscular incordination,

convulsions, flushing, hypotension, fever and some other features of belladonna poisoning.

Death can be caused due to respiratory and cardiovascular failure.

THANK YOU
 SOURCES
1. Tripathi, K. D. (2018). Essentials of medical pharmacology (8th ed.). Jaypee Brothers Medical.
2. Tiligada, E., & Ennis, M. (2018). Histamine pharmacology: from Sir Henry Dale to the 21st
century. British Journal of Pharmacology, 177(3), 469–489. https://doi.org/10.1111/bph.14524
(FIGURE 2)
3. Simon, F. E. R., & Simons, K. J. (2008). H1 antihistamines: current status and future directions.
World Allergy Organization Journal, 1(9), 145–155. https://doi.org/10.1186/1939-4551-1-9-145