Antihistamines are drugs that reduce or eliminate the effects of the chemical histamine. They are used to treat allergic conditions like rhinitis, conjunctivitis, hives, and anaphylaxis. First generation antihistamines can cause sedation and other side effects due to crossing the blood brain barrier, while second generation antihistamines are more selective and have fewer side effects. Common structural features of antihistamines include two aromatic rings connected by a central atom, with small alkyl groups substituted on the amine. Newer second generation antihistamines are effective at relieving allergies with fewer adverse side effects.

1. Antihistamine
A drug that reduces or eliminates the effects
mediated by the chemical histamine.
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• Allergic rhinitis (common cold)
• Allergic conjunctivitis (pink eye)
• Allergic dermatological conditions
• Urticaria (hives)
• Angioedema (swelling of the skin)
• Puritus (atopic dermatitis, insect bites)
• Anaphylactic reactions (severe allergies)
• Nausea and vomiting (first generation H1antihistamines)
• Sedation (first generation H1-antihistamines)
Clinical Uses of Antihistamines :
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• Associated with the first generation H1-antihistamines and due to their lack of selectivity for the H1
receptor and anti-cholinergic activity. Side effects are due to CNS depression(by crossing BBB):
• Sedation
• Dizziness
• Tinnitus (ringing in the ear)
• Blurred vision
• Euphoria
• Uncoordination
• Anxiety
• Insomnia
• Tremor
• Nausea/vomitting
• Dry mouth/dry cough
• Newer second generation H1-antihistamines are more selective for the peripheral histamine
receptors and have far less side effects(doesn’t cross BBB) (drowsiness, fatigue, headache, nausea
and dry mouth)
Adverse side effects:
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• Piperoxan
• Discovered in 1933 by Jeff Forneau and Daniel Bovent while
developing a guinea pig animal model of anaphylaxis
• They received the Nobel Prize in 1957
First Antihistamine
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• Ethylenediamines
• Ethanolamines
• Alkylamines
• Piperazines
• Tricyclics
Classes of first generation H1 receptor antagonist antihistamines
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• 2 aromatic rings ESSENTIAL, connected to a central carbon, nitrogen, or oxygen amine gp
ESSENTAIL
• Spacer between central atom and the amine, usually 2-3 carbons in length. (Can be linear,
ring, branched, saturated or unsaturated)
• The amine is substituted with small alkyl groups
• Chirality at X and having the rings in different planes increases potency of the drug
Common Structural Features of classical first generation antihistamines
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• called "non- sedating" because they cause less sedation than their predecessors
• These are the newer drugs and they are much more selective for the peripheral H1-
receptors involved in allergies as opposed to the H1-receptors in the CNS
• Therefore, these drugs provide the same relief with many fewer adverse side effects
• The structure of these drugs varies and there are no common structural features
associated with them
• They are however bulkier and less lipophilic than the first generation drugs, therefore they
do not cross the BBB (reason of non –sedating name) as readily
• Recent studies have also showed that these drugs also have antiinflammatory activity and
therefore, would be helpful in the management of inflammation in allergic airways
disease (Devalia and Davies).
Second generation H1-receptor antagonists
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• Isomerism is an important factor in this class of drugs, which is due to the
positioning and fit of the molecules in the H1-receptor binding site
• These drugs have fewer sedative and GI adverse effects, but a greater incidence
of CNS stimulation
• These drugs lack the “spacer molecule” (which is usually a nitrogen or oxygen)
between the two aromatic rings and at least one of the rings has nitrogen
included in the aromatic system
Alkylamines
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9. Akylamines
Chlorphenamine
•Halogen at p-position of phenyl
ring,increases the activity 20 times
•Originally used to prevent allergic
conditions
•Shown to have antidepressant
properties and inhibit the reuptake of
serotonin
Pheniramine (Avil)
•Used most often to treat hay fever or
urticaria (hives)
•Antihistamine component of Visine-A
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10. Second generation H1-receptor antagonists
Loratadine (Claritin)
•It is the only drug of its class available
over the counter
•It has long lasting effects and does not
cause drowsiness because it does not
cross the BBB
•Used for watery eyes, runny nose
(rhinitis), itching eyes, and sneezing
Terfenadine (Seldane)
•It was formerly used to treat allergic
conditions
•In the 1990’s it was removed from the
market due to the increased risk of
cardiac arrythmias
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11. Second generation H1-receptor antagonists
Fexofenadine (Allegra)
•It was developed as an alternative to
Terfenadine
•Fexofenadine was proven to be more
effective and safe
•Used for chronic urticaria (hives)
Citrizine (Zyrtec)
• cetirizine is more sedating than the
other non-sedating antihistamines.
• Available over-the-counter Used for
sneezing, itchy nose (allergic rhinitis)
and itchy eyes
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12. Drug Interactions
• Increased effect of CNS depressants
• MAO inhibitors increase anticholinergic effect of antihistaminics
• First generation antihistaminics can decrease effectiveness of
cholinesterase inhibitors used in Alzheimer’s disease like donepezil
and rivastigmine
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13. Advantages of second generation antihistaminics
• They have no anticholinergic side effects
• Do not cross blood brain barrier (BBB), hence cause minimal
or no drowsiness and sedation
• Do not impair Psychomotor performance
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14. Therapeutic Uses
• Allergic rhinitis & common cold
• Allergic dermatitis, itching, urticaria
• Wasp stings/ bite: pain and itching decreases
• Mild blood transfusion reactions
• Allergic conjunctivitis
• Motion sickness: dimenhydrinate, promethazine
• Morning sickness: promethazine
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15. Pharmacological Actions
• CNS depression: (More with first generation)
• — Sedation and drowsiness
• — Some have antiemetic and antiparkinsonian effects
• Antiallergic action
• Anticholinergic actions (More with first generation)
• — Dryness of mouth , Blurring of vision
• — Constipation
• — Urinary retention
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16. Pharmacological Actions
• Antimotion sickness effect: Dimenhydrinate,
• Promethazine
• Antiemetic: Promethazine
• Antiparkinsonism: Diphenhydramine, orphenadrine,
promethazine(lV)
• Antivertigo: cinnarizine
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17. Pharmacological Actions (Contd)
• Visceral smooth muscles:
• Bronchospasm, abdominal cramps
• Secretions:
• Increased gastric secretion (H2)
• Increased nasal secretions (HI)
• Sensory Nerve Endings: Itching
• CNS:
• Wakefulness on intra Cerebroventricular Injection
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18. Therapeutic Uses
• Betahistine
• To control vertigo in Meniere's disease 8 mg
tab 1/2 tablet QID
• Histamine releasers
• stings and venom
• Ag-Ab reaction
• Drugs
• d-tubocurarine
• Morphine
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19. ThankYou!
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Mudassir Husain
Email: mudassirprnc@gmail.com
Website: www.yoututor.in