2. INTRODUCTION
• Histamine is an organic nitrogenous compound involved in local
immune responses, as well as regulating physiological function in
the gut and acting as a neurotransmitter for the brain, spinal cord,
and uterus.
• Histamine is involved in the inflammatory response and has a central
role as a mediator of itching.
• Histamine is produced by basophils and by mast cells found in
nearby connective tissues.
3. HISTAMINE
• Histamine is present in practically all tissues, with significant amounts in
the lungs, skin, blood vessels, and GI tract
• Found at high concentration in mast cells and basophils
• A neurotransmitter in the brain
• Also occurs as a component of venoms and in secretions from insect
stings
• Histamine is an autacoid, which means it acts similarly to a local hormone,
near its site of synthesis. It is produced as part of the local immune
response to invading bodies and triggers inflammation.
4. HISTAMINE
• Functions: -It stimulates gastric secretion, -causes dilation of
capillaries, -constriction of bronchial smooth muscle, and -decreased
blood pressure.
• Synthesis of Histamine: Formed from the amino acid, Histadine in
a decarboxylation reaction with the enzyme histadine decarboxylase,
Occurs primarily in mast cells and basophils.
5. Release of histamine
• Most often, histamine is just one of several chemical mediators
released in response to stimuli
• The stimuli for release of histamine from tissues may include
destruction of cells as a result of cold, toxins from organisms,
venoms from insects and spiders, and trauma
• Allergies and anaphylaxis can also trigger significant release of
histamine.
6. HISTAMINE RECEPTORS
• There are four types of histamine receptor: H1, H2, H3 and H4.
• The binding of histamine to these receptors stimulates them to produce
functional responses.
• Released in response to certain stimuli and binds to various types of
histamine receptors (H1, H2, H3, and H4)
• H1 and H2 receptors are widely expressed and are the targets of clinically
useful drugs
7.
8. Type Location Function
H1 Found on smooth muscles,
endothelium, and central nervous
system tissue
Causes vasodilation, bronchoconstriction
bronchial smooth muscle contraction,
separation of endothelial cells, and pain and
itching due to insect stings; the primary
receptors involved in allergic rhinitis
symptoms and motion sickness; sleep
regulation.
H2 Located on parietal cells Primarily stimulate gastric acid secretion And
we use antiacidic drugs for this receptor
H3 Found on central nervous system and
to a lesser extent peripheral nervous
system tissue
Decreased neurotransmitter release:
histamine, acetylcholine, norepinephrine,
serotonin
H4 Found primarily in the basophils and
in the bone marrow. It is also found
onthymus, small intestine, spleen,
andcolon.
Plays a role in chemotaxis.
9. ANTIHISTAMINE
• Anithistamines are drugs used to block the activity of histamines, by
preventing the ability of histamine to bind to histamine receptors.
• The traditional antihistamines that are used to treat allergy block H1
receptors, while H2 antagonists inhibit gastric acid secretion to help treat
peptic ulcers.
• The H4 receptor is a potential target for treating allergic and inflammatory
conditions such as asthma and allergic rhinitis.
• The ability of the H3 receptor to modulate various neurotransmitters makes
this receptor a novel therapeutic target in the relief of symptoms caused by
several conditions including movement disorders, obesity, schizophrenia,
abnormal sleep/wake patterns and ADHD.
10. H1-ANTIHISTAMINES
• H1-antihistamines refer to compounds that inhibit the activity of the
H1 receptor.
• H1-antihistamines can be either neutral receptor antagonists or
inverse agonists.
• Normally, histamine binds to the H1 receptor and heightens the
receptor's activity; the receptor antagonists work by binding to the
receptor and blocking the activation of the receptor by histamine.
11. CLASSIFICATION
CLASSIFICATION EXAMPLE
I. HIGHLY SEDATIVE Diphenhydramine, Dimenhydrinate,
Promethazine, Hydroxyzine
II. MODERATELY SEDATIVE Pheniramine, Cyproheptadine,
Meclozine (Meclizine), Cinnarizine.
III. MILD SEDATIVE Chlorpheniramine,
Dexchlorpheniramine, Triprolidine,
Clemastine.
IV. SECOND GENERATION Fexofenadine, Desloratadine,
Cetirizine, Levocetirizine, Azelastine,
Mizolastine, Rupatadine.
12. I. HIGHLY SEDATIVE
DRUG DOSE ROUTE AVAILABLE
Diphenhydramine
Dimenhydrinate,
Promethazine,
Hydroxyzine
25–50 mg
25–50 mg
25–50 mg(1 mg/kg)
25–50 mg
Oral
Oral
Oral/I.M.
Oral
Capsule, 12.5 mg/5ml syr.
16 mg/5 ml syrup
5 mg/ml, 25 mg/ml inj.
10 mg/5 ml syr, 6 mg/ml
i.m. drops, 25 mg/ml inj.
13.
14. MECHANISM OF
ACTION
INDICATION CONTRAINDICATION INTERACTIONS
• Diphenhydramine
competitively inhibits the
histamine-1 (H1) receptor,
thereby alleviating the
symptoms caused by
endogenous histamine on
bronchial, capillary and
gastrointestinal smooth
muscles.
• This prevents histamine-
induced
bronchoconstriction,
vasodilation, increased
capillary permeability, and
GI smooth muscle
spasms.
• Temporary symptomatic relief
of various allergic conditions
and to treat or prevent motion
sickness, vertigo, and
reactions to blood or plasma
in susceptible patients.
• Also used in anaphylaxis as
adjunct to epinephrine and
other standard measures after
acute symptoms have been
controlled; in treatment of
parkinsonism and drug-
induced extrapyramidal
reactions; as a nonnarcotic
cough suppressant; as a
sedative-hypnotic; and for
treatment of intractable
insomnia.
• Hypersensitivity to
antihistamines of similar
structure; lower respiratory
tract symptoms (including
acute asthma); narrow-
angle glaucoma; prostatic
hypertrophy, bladder neck
obstruction;
• GI obstruction or stenosis;
lactation, premature
neonates, and neonates;
use as nighttime sleep aid
in children <12 y.
• Drug: Alcohol and
other CNS
Depressants,
mao inhibitors
compound CNS
depression.
• Pregnancy
(category C)
15. PHARMACOKINETICS ADVERSE EFFECTS NURSES RESPONSIBILITY
Absorption: Readily
absorbed from GI tract but
only 40–60% reaches
systemic circulation. Onset:
15–30 min. Peak: 1–4 h.
Duration: 4–7 h.
Distribution: Crosses
placenta; distributed into
breast milk. Metabolism:
Metabolized in liver; some
degradation in lung and
kidney.
Elimination: Mostly excreted
in urine within 24 h.
CNS: Drowsiness, dizziness,
headache, fatigue,
CV: Palpitation, tachycardia, mild
hypotension or hypertension.
Special Senses: Tinnitus, vertigo, dry
nose, blurred vision, diplopia, dry
eyes.
GI: Dry mouth, nausea, epigastric
distress, vomiting, constipation, or
diarrhea.
Urogenital: Urinary frequency or
retention, dysuria. Body as a Whole:
Hypersensitivity (skin rash, urticaria,
photosensitivity, anaphylactic shock).
Respiratory: Thickened bronchial
secretions, wheezing, sensation of
chest tightness
•Monitor cardiovascular status especially
with pre-existing cardiovascular disease.
• Monitor for adverse effects especially in
children and the older adult.
• Supervise ambulation and use side-rails
as necessary.
Patient & Family Education:
• Do not use alcohol and other CNS
depressants because of the possible
additive CNS depressant effects with
concurrent use.
• Increase fluid intake, if not contraindicated;
drug has an atropine-like drying effect
(thickens bronchial secretions) that may
make expectoration difficult.
•Do not breast feed while taking this drug
16. II. MODERATELY SEDATIVE
DRUG DOSE ROUTE AVAILABLE
Pheniramine 20–50 mg
0.3mg/kg/dose 6-
8 hourly
Oral/IM 25mg, 50mg tablet (AVIL)
15mg/5ml syrup,
22.5mg/ml injection
17.
18. MECHANISM OF
ACTION
INDICATION CONTRAINDICATION INTERACTIONS
Antihistamine that competes
with histamine for H1-
receptor sites on effector
cells, thus it prevents
histamine action that
promotes capillary
permeability and edema
formation and constrictive
action on respiratory,
gastrointestinal, and vascular
smooth muscles.
It is used in treatment of hay
fever, rhinitis, allergic
dermatoses, and pruritus.
Hypersensitivity to
antihistamines of similar
structure; lower respiratory
tract symptoms, narrow-angle
glaucoma, obstructive
prostatic hypertrophy or other
bladder neck obstruction, GI
obstruction or stenosis;
lactation; premature and
newborn infants.
Drug: Alcohol and
other CNS
Depressants,
compound CNS
depression
Pregnancy (category
B in first and second
trimester and
category D in third
trimester)
19. PHARMACOKINETICS ADVERSE EFFECTS NURSES RESPONSIBILITY
Absorption: Well absorbed
from GI tract; about 45% of
dose reaches systemic
circulation intact. Onset:
Within 6 h. Peak: 2–6 h.
Distribution: Highest
concentrations in lung,
heart, kidney, brain, small
intestine, and spleen. Half-
Life: 12–43 h.
Body as a Whole: Sensation of
chest tightness. CV: Palpitation,
tachycardia, mild hypotension or
hypertension. GI: Epigastric
distress, anorexia, nausea,
vomiting, constipation, or diarrhea.
CNS: Drowsiness, sedation,
headache, dizziness, vertigo,
fatigue, disturbed coordination,
tremors, euphoria, nervousness,
restlessness, insomnia. Special
Senses: Dryness of mouth, nose,
and throat, tinnitus, vertigo, acute
labyrinthitis, thickened bronchial
secretions, blurred vision, diplopia.
Urogenital: Urinary frequency or
retention, dysuria
•Monitor for CNS depression and sedation,
especially when chlorpheniramine is given in
combination with other CNS depressants.
• Monitor BP in hypertensive patients it may
elevate BP.
Patient & Family Education:
• Avoid driving a car and other potentially
hazardous activities until drug response has
been determined.
•Avoid or minimize alcohol intake.
Antihistamines have additive effects with
alcohol.
•Report any of the following: tinnitus or
palpitations.
•Consult physician before taking additional
OTC drugs for allergy relief.
20. III. MILD SEDATIVE
DRUG DOSE ROUTE AVAILABLE
Chlorpheniramine 2–4 mg (0.1
mg/kg)
Oral, I.M. 0.5 mg/5 ml syrup/ Tablet
21.
22. MECHANISM OF
ACTION
INDICATION CONTRAINDICATION INTERACTIONS
An antihistamine (H1-
receptor antagonist) which
competes for H1 receptor
sites on effector cells, thus
blocking histamine release.
Has greater selectivity for
preripheral H1 receptors and,
consequently, it produces
little sedation. Has prominent
antipruritic activity and low
incidence of unpleasant
adverse effects.
Effective in controlling various
allergic reactions, e.g. nasal
congestion, sneezing, itching.
Symptomatic relief of allergic
rhinitis (sneezing, rhinorrhea,
pruritus) and mild uncomplicated
allergic skin manifestations such
as urticaria and angioedema.
Hypersensitivity to clemastine
or to other antihistamines of
similar chemical structure;
lower respiratory tract
symptoms, including acute
asthma; concomitant MAO
INHIBITOR therapy;
Fexofenadine
amoxicillin
Aspirin Low Strength
(aspirin)
Benadryl
(diphenhydramine)
Cetirizine
Ibuprofen
pregnancy (category
B), lactation.
23. PHARMACOKINETICS ADVERSE EFFECTS NURSES RESPONSIBILITY
Absorption: Readily
absorbed from GI tract.
Peak: 5–7 h. Duration: 10–
12 h. Distribution:
Distributed into breast milk.
Metabolism: Metabolized in
liver. Elimination: Excreted
chiefly in urine.
Body as a Whole: Anaphylaxis,
excess perspiration, chills.
CV: Hypotension, palpitation,
tachycardia, extrasystoles.
GI: Dry mouth, epigastric distress,
anorexia, nausea, vomiting,
diarrhea, constipation.
Hematologic: Hemolytic anemia
thrombocytopenia, agranulocytosis.
CNS: headache, dizziness,
weakness, fatigue, convulsions,
tremors, irritability,insomnia,
Respiratory:tightness of chest,
wheezing. Skin: Urticaria, rash,
photosensitivity. Special Senses:
Vertigo, tinnitus, blurred vision,
diplopia.
Urogenital: urinary retention,
•Monitor for drowsiness, poor coordination, or
dizziness, especially in the older adult or
debilitated. Supervision of ambulation may be
warranted.
•Assess for symptomatic relief with use of the
medication.
•Lab tests: Periodic hematological studies with
long-term use.
Patient & Family Education
•Check with physician before taking alcohol or
other CNS depressants, since effects may be
additive.
•Avoid driving and other potentially hazardous
activities until response to the drug has been
established.
•Frequent sips of water or sugarless hard
candy to relieve dry mouth.
24. IV. SECOND GENERATION
DRUG DOSE ROUTE AVAILABLE
Fexofenadine,
Cetirizine,
Levocetirizine,
Loratadine.
120–180 mg
5 mg, 10 mg
5 mg/5 ml,5–10 mg
10 mg
Oral
Oral
Oral
Oral
Tablet (ALLEGRA)
Tablet/syrup (CETIZINE)
Tablet/syrup(LEVOSIZ)
Tablet, 5mg/ml suspension
25.
26. MECHANISM OF
ACTION
INDICATION CONTRAINDICATION INTERACTIONS
Inhibits antigen-induced
bronchospasm and histamine
release from mast cells.
It competes with endogenous
histamine for binding at
peripheral H1-receptor sites
on the effector cell surface.
This prevents the negative
symptoms associated with
histamine release and an
allergic reaction.
Efficacy is indicated by reduction
of the following: nasal congestion
and sneezing; watery or red
eyes; itching nose, palate, or
eyes.
Effectively treats allergic rhinitis,
and chronic urticaria by
eliminating or reducing the local
and systemic effects of histamine
release.
Hypersensitivity to H1-
receptor antihistamines;
lactation, children <2 y.
Theophylline may
decrease cetirizine
clearance leading to
toxicity.
27. PHARMACOKINETICS ADVERSE EFFECTS NURSES RESPONSIBILITY
Absorption: Readily
absorbed from GI tract.
Peak: 1 h. Distribution: 93%
protein bound; minimal
CNS concentrations.
Metabolism: minimal.
Elimination: 60% excreted
unchanged in urine within
24 h, 5% excreted in feces.
Half-Life: 7.4 h.
GI: Constipation, diarrhea, dry
mouth.
CNS: Drowsiness, sedation,
headache, depression.
Monitor for drug interactions. As the drug is
highly protein bound, the potential for
interactions with other protein-bound drugs
exists.
Monitor for sedation, especially the older adult.
Patient & Family Education
Do not use in combination with OTC
antihistamines.
Do not engage in driving or other hazardous
activities, before experiencing your responses
to the drug.
Do not breast feed while taking this drug
without consulting physician.
28. H2-ANTIHISTAMINES
• H2-antihistamines, like H1-antihistamines, occur as inverse agonists and neutral
antagonists.
• They act on H2 histamine receptors found mainly in the parietal cells of the
gastricmucosa, which are part of the endogenous signaling pathway for gastric
acid secretion. Normally, histamine acts on H2 to stimulate acid secretion; drugs
that inhibit H2 signaling thus reduce the secretion of gastric acid.
• H2-antihistamines are among first-line therapy to treat gastrointestinal conditions
including peptic ulcers and gastroesophageal reflux disease.
• Examples include: Cimetidine, Famotidine, Lafutidine, Nizatidine, Ranitidine,
Roxatidine, Tiotidine.
29. H3-ANTIHISTAMINES
• H3 receptor antagonist is a classification of drugs used to block the action
of histamine at the H3 receptor.
• H3R regulates the release of neurotransmitters by influencing the amount
of intracellular calcium. When activated, it blocks the influx of calcium
which leads to inhibition of the release of neurotransmitters.
• Regulating the release of histamine and also as a heteroreceptor,
regulating neurotransmitters such as acetylcholine, dopamine, serotonin,
norepinephrine and GABA
30. Cont…
• Examples of H3 Antihistamine: Burimamide, Thioperamide, Pitolisant
• Uses: To treat Neurodegenrative conditions like Narcolepsy,
Alzheimer's disease (AD), Attention deficit hyperactivity disorder
(ADHD), Schizophrenia (SCH).
31. • Examples of H3 Antihistamine: JNJ-7777120-JNJ-7777120 is a drug
being developed by Johnson & Johnson Pharmaceutical Research &
Development which acts as a potent and selective antagonist at the
histamine H4 receptor.
• It has anti-inflammatory effects and has been demonstrated to be
superior to traditional antihistamines in the treatment of pruritus
(itching) (Jiang, Lim & Zhang, et al. July 2008).
32. Histamine H4 receptor
• Function: The Histamine H4 receptor has been shown to be involved
in mediating eosinophil shape change and mast cell chemotaxis.
33. H4-ANTIHISTAMINES
• Thioperamide- Thioperamide is a potent HRH4 antagonist and
selective HRH3 antagonist capable of crossing the blood–brain
barrier.
• VUF-6002 (JNJ-10191584) is a drug which acts as a potent and
selective antagonist at the histamine H4 receptor.
• It has antiinflammatory and analgesic effects in animal studies of
acute inflammation
35. Cont..
Background
• Second generation H1 antihistamines (H1A) are currently recommended
as first choice medications for allergic rhinitis and rhino conjunctivitis.
However, little is known about what influences the choice of prescription of
one second generation (H1A) as opposed to another in real-life conditions.
Objective
• The aim of the study was to identify the main criteria determining the
choice of a second generation H1A by allergy specialists in mainland
France.
36. Cont..
Methods
• Consecutive patients suffering from allergic rhinitis or rhinoconjunctivitis
were included and followed prospectively for 30 days from the prescription
of a second generation H1A in monotherapy. Patients were asked to fill in
auto-questionnaires at baseline, daily during the first 10 days of the new
treatment, and at the end of follow-up. Data on efficacy, tolerance, safety,
rate and type of response to treatment, as well as patient satisfaction were
recorded and analyzed.
37. Cont..
Results
• 1,080 patients were included between March 2011 and October
2012, mostly suffering from moderate to severe rhinitis (82.0%). The
most frequently cited reason for choosing a specific H1A was the
expected efficacy (85.3%). The mean time to nasal and ocular
recovery was 6 days and 78.2% of patients responded to treatment
within this interval. The presence of conjunctivitis was significantly
associated with a more rapid response.
38. Cont..
• At the end of follow-up, the satisfaction rate was higher for patients who
were switched from a previous treatment (87.5%), compared to those
receiving their first treatment (78.8%).
Conclusion and clinical relevance
• The main reason for choosing a specific second generation H1A was its
expected efficacy. Concomitant conjunctivitis is associated with a more
rapid response to treatment. Symptom recovery necessitates a mean of 6
days.
39. REFERENCES
• Tripathy, K. D. (2013). Essentials of Medical Pharmacology 7th Edition,
Jaypee Brothers Medical Publishers (P) Ltd, New Delhi. Page- 158-167.
• Barbara G. Wells, Joseph T. DiPiro (2009). Pharmacotherapy, Handbook,
The McGraw-Hill Companies, Seventh Edition, New Delhi, page- 193-205
• Jiang W, Lim HD, Zhang M, et al. (July 2008). "Cloning and
pharmacological characterization of the dog histamine H(4) receptor". Eur.
J. Pharmacol. 592 (1–3): 26–32. doi:10.1016/j.ejphar.2008.06.095. PMID
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