Antihistamines Drugs Pharmacology 2024.ppt

Pharma drugs which are anihistamines

1. Antihistamines Antihistamines
Dr. Wardah Siddique
Assistant Prof. Pharmacology

2. HistamineHistamine
An important mediator of An important mediator of
1. allergic and inflammatory reaction 1. allergic and inflammatory reaction
2. it has an important role in gastric 2. it has an important role in gastric
acid secretion; and functions as a acid secretion; and functions as a
neurotransmitter and neuromodulator neurotransmitter and neuromodulator
3. 3. histamine also plays a role in histamine also plays a role in
chemotaxis of WBCs chemotaxis of WBCs

3. Histamine exerts its biological actions by Histamine exerts its biological actions by
combining with specific cellular receptors combining with specific cellular receptors
located on the surface membrane. located on the surface membrane.
present in lungs, skin, blood vessels,
and GI tract,
Found at high concentration in mast
cells and basophils, and as
neurotransmitter in brain
Also occurs as a component of venoms
and in secretions from insect stings
HH
11 , H , H
22 , H , H
3 3 , H, H
44

4. H
1
= Smooth
muscle,
endothelium, brain
H
2 = Gastric Mucosa,
Cardiac muscles, mast
cells
H
3 = Presynaptic: Brain,
myenteric plexus, other
neurons
H
4
Eosinophils,
Neutrophils,
CD4T cells

5. Synthesis: Histamine is 
formed by the decarboxylation of
histidine by histidine
decarboxylase In mast cells,
histamine is stored in granules
If histamine is not stored, it is
rapidly inactivated by the enzyme
amine oxidase

6. Upon release!Upon release!
It causes:

CVS:
Vasodilation ( H
1 & H
2)
H
1 Rapid
H
2
Slow – sustained
Increased capillary permeability (H
1) (H
2 uncertain)
Effects on small vessels passage of plasma
proteins and fluid in extracellular space, increased
flow of lymph & its protein content lead to edema
It causes SM contraction

7. Triple response
Localized red spot (direct effect)
Brighter red flush (Flare) *indirect , histamine
induced stimulation of axon reflexes cause
vasodilation.
Wheal formation (increase capillary
permeability)
Histamine Shock (large doses)
anaphylaxis
Marked fall in BP
diminished effective blood volume, reduced
venous return, decreased COP

8. Heart: (H
2 more) (H
1 less only on AV node)

Increase force of contraction

Increase heart rate

Positive inotropic and positive chronotropic
Constriction of larger vessels in some
species

9. Extra vascular smooth muscles

It stimulates more, rarely relaxes various
smooth muscles.
Contraction H
1
Relaxation H
2
Bronchospasm is observed with H
1
receptor
stimulation, especially in asthma or some
other pulmonary diseases. (less pronounced
in normal population)
Although the spasmogenic influence of H
1
receptors is dominant in Human Bronchial
Muscles, H
2
with dilator effect are also present, therefore histamine-induced response in
vitro is potentiated with H
2
blockade

10. In asthmatic patients histamine induced
response may involve additional reflex
component that arises from irritation of
afferent nerve endings.
Uterus : mild contraction ( in humans this
effect is negligible)

11. Exocrine Glands:

Histamine is an important physiological regulator of
gastric acid secretion (H
2
)

Nerve endings (pain, itch and indirect effect)

Stimulates various nerve endings

When released in epidermis causes itch

When released in dermis evokes pain with or without
itching

Indirect effect (explained earlier – bronchospasm, flare)

12. HH
11 Receptor antagonists Receptor antagonists
Classification:
They are classified in two generations.
The basis of this classification is the
sedative property and the ability to block
autonomic receptors.

13. ClassificationClassification

First Generation

Ethanolamines

Carbinoxamine

Dimenhydrinate
Diphenhydramine

Doxylamine

Ethylaminediamines

Pyrilamine

Tripelennamine

Piperazine derivatives

Hydroxyzine

Cyclizine

Meclizine

Alkylamines

Brompheniramine

Chlorpheniramine

Phenothiazine derivatives
Promethazine

Miscellaneous
cyproheptadine
Second generation

Piperidines
Fexofenadine

Miscellaneous
Loratadine
cetirizine
Desloratadine
Levocetirizine

14. First generation
drugs
Penetrate the
CNS and cause
sedation
Interact with
other receptors,
producing a
variety of
unwanted
adverse effects
Second-generation
agents
Do not penetrate the
BBB causing less
CNS depression
Desloratadine,
fexofenadine and
loratadine show the
least sedation
Cetirizine and
levocetirizine are
partially sedating

15. Pharmacological properties of AntihistaminesPharmacological properties of Antihistamines

Smooth muscles:
H
1
blockers --- inhibit most responses of smooth
muscles to histamine

Capillary permeability:
decrease the permeability – formation of edema
and wheal.

Exocrine glands:

Gastric secretions – not inhibited by H
1

Histamine-evoked salivary, lacrimal, and other
exocrine secretions – suppressed with variable
response

Non-histamine receptor mediated action – lessened
secretions in cholinergically innervated glands –
e.g., respiratory tree

16. Immediate Hypersensitivity Reactions: Anaphylaxis and Immediate Hypersensitivity Reactions: Anaphylaxis and
AllergyAllergy
Histamine is one of many potent autacoids released
(along with others e.g., prostaglandins D
2) -- the
protection afforded by antihistamines thus also varies
accordingly

Some phenomena – edema formation and
itch are effectively suppressed

Hypotension – less effected

Bronchoconstriction: reduced little if at all.

17. Central Nervous SystemCentral Nervous System
First Generation:

Both stimulate and depress the CNS
Stimulation occasionally after conventional doses–
restlessness, nervousness, unable to sleep.
Central excitation – striking feature of poisoning –
convulsions, particularly in infants.

Central depression
Usual accompaniment of therapeutic doses (esp.
older antihistamines)
Diminished alertness, slowed reaction times, and
somnolence (varied response)

18. CNSCNS
Second-Generation: (non-sedating)
In therapeutic doses do not cross BBB
appreciably
Can be safely used by many patients for
whom sedation is a problem
Capacity to counter Motion Sickness
Anticholinergic property of some
Antihistamines is responsible
Dimenhydrinate, diphenhydramine, various
piperazine derivatives, promethazine (strongest
antimuscarinic activity)

19. Anticholinergic effectsAnticholinergic effects
First generation H
1
antagonists – inhibit
acetylcholine response at muscarinic
receptors (atropine-like action)
Second generation – no effect on
muscarinic receptors

20. Local Anesthetic effectLocal Anesthetic effect
At higher doses some H
1
antagonist have
local anesthetic effect activity
(promethazine)

21. PharmacokineticsPharmacokinetics
1
st
generation:

Well absorbed from GIT, can be given
parenteral

Distributed widely including CNS (first
generation)

Excreted variably in urine, mostly appear in
metabolites

Eliminated more rapidly by children than by
adults, more slow in those with liver disorders

Induce hepatic microsomal enzyme – may
facilitate their own metabolism

22. PharmacokineticsPharmacokinetics
Second generation:

Rapidly absorbed from GIT

Metabolized in the liver

Excreted in the urine

Fexofenadine excreted in feces

23. Adverse effects of AntihistamineAdverse effects of Antihistamine

Sedation:

Highest incidence in 1
st
generation, not a feature of 2
nd

generation

Although it may be a desirable adjunct in treatment of some
patients, interferes with daytime activities

Dizziness

Tinnitus

Lassitude

In-coordination

Fatigue

Blurred vision

Diplopia

Euphoria

Nervousness

Insomnia

tremors

24. Loss of appetite
Nausea
Vomiting
Epigastric distress
Constipation OR diarrhea
these can be decreased by giving the drug with meals
Some antagonists increase appetite and may cause
weight gain
Gastrointestinal Tract

25. Side effects caused by anti-muscarinic
Action of H
1 antagonist
Dryness of mouth and respiratory
passage
Cough may be there
Urinary retention or frequency
Dysuria

26. 
Drug allergy may develop, more common
after topical application
Drug induced fever
Photosensitization

Hematological complications

Leukopenia

Agranulocytosis

Hemolytic anemia (rare)

Teratogenic effects seen with piperazine
compounds – others not noted

27. Acute poisoning with HAcute poisoning with H
11 antagonists antagonists
Central excitatory effects constitute the
greatest danger

Hallucinations

Excitement

Ataxia

Incoordination

Athetosis

convulsions

28. Therapeutic Uses:Therapeutic Uses:
Diseases of allergy

Most useful in acute type of allergies
Rhinitis
Urticaria
Conjunctivitis
Dermatitis medicamentosa
Allergic dermatitis
Motion sickness, vertigo, nausea &
vomiting
Anticholinergic property of some Antihistamines is responsible
In controlling motion sickness

29. Insomnia
Diphenhydramine ( 25mg / night)
Hydroxizine ( 25mg /night)
Advantage – no dependence, but anticholinergic
activity is unwanted
Limited use in asthma
In systemic anaphylaxis- where other
autacoids are also involved these are
used as adjuvant (mainstay therapy is
epinephrine)

30. H2 blockers H2 blockers
Cimetidine ◦ Ranitidine ◦ Famotidine ◦
Nizatidine
You will read in detail with peptic ulcer
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