CHLORPHENIRAMINE

AND 2ND GENERATION

OF ANTI-HISTAMINES
PRESENTED BY
B-7
 GROUP MEMBERS

 Abbas Ahmad
 Kanwal
 Rayeesa Tanveer
 Sundus
 ALLERGY
• Unusual response to substance or condition that is harmless to
the other individuals is called as allergy.
• Type of hypersensitivity reactions of the immune system.
Allergy may involve more the one type of reaction.

HYPERSENSITIVITY
• Hypersensitivity (hypersensitivity reaction)
refers to undesirable immune reactions
produced by the normal immune system.
HYPERSENSITIVITY REACTIONS
Antihistamines

An antihistamine is a type of pharmaceutical drug that

opposes the activity of histamine receptors in the body.

• Antihistamines are subclassified according to the

histamine receptor that they act upon:
• the two largest classes of antihistamines are 
• H1-antihitamines 
• H2-antihistamines
 Histamine H1-receptor  Histamine H2-receptor 
• are used to treat allergic • are used to treat gastric
reactions by binding to acid conditions (e.g., peptic
histamine H1- ulcers and acid reflux) by
receptor in mast binding to histamine H2
cells, smooth muscules, receptors in the
and endothelium in the upper gastrointestinal tract,
body as well as in primarily in the stomach.
the tuberomammilary
nucleus in the brain.
Classification of Antihistamines

1ST Generation
.Sedating
H-1 Blockers
2nd Generation
Antihistamine .Non- Sedating
s
.
Cimetidine
Nizatidine
H-2 Blockers Famotidine
Ranitidine
CHLORPHENIRAMINE
Classification
Chlorpheniramine
• First-generation alkylamine ANTIHISTAMINE
• Chemical formula: C16H19ClN2
• IUPAC name :
3-(4-chlorophenyl)-N,N-dimethyl-3-pyridin-2-
ylpropan-1-amine
Chlorpheniramine

Brand names:
Chlorphen-12,
Chlor-Trimeton
Aller-chlor,
Cholrex,
Rhinogesic,
ChlorDex GP
Clorfeniramina
Haynon
 DOSAGE FORMS
• Chlorpheniramine Maleate
- Tablets 4 mg
- Syrup 2 mg per 5 mL
- Capsules, sustained-release 8 mg
- Capsules, sustained-release 12 mg
COMMON MEDICATION COMBINATION
• Nexium (esopemrazole)
• Vitamin b12 (cyanocobalamine)
• Lasix (furosemide)
• Zyrtec ( citrizine)
 Mechanism of Action

• Chlorpheniramine binds to the histamine H1

receptor.
• This blocks the action of endogenous histamine,
which subsequently leads to temporary relief of the
negative symptoms brought on by histamine.
Pharmacokinetics

• Readily absorbed.
• 72% protein bound.
• Metabolized predominantly in the liver,
• Primarily hepatic via Cytochrome P450 (CYP450) enzymes
but also in the lung and kidneys.
• Renally eliminated,
• mostly as metabolites within 24 h.
• Half life: 21 – 27 hours
Indications and Usage

• Temporary Relief Of Sneezing And Itching.

• Allergic Reactions
• Allergic Rhinitis
• Respiratory Allergies.
• Cold Symptoms
• Hay Fever, Urticaria, And Asthma.
• It Has Also Been Used In Veterinary Applications
Dosage and Administration

Immediate-release tablet or syrup Extended-release tablets

 Adults and children 12 yr of age

Adults and children 12 yr of age and
and older
older
 PO 8 mg every 8 to 12 h or 12 mg
 PO 4 mg every 4 to 6 h (max, 24
every 12 h (max, 24 mg/day).
mg/day).
 Children 6 to younger than 12 yr of
age Extended-release capsules
 PO 2 mg every 4 to 6 h (max, 12
mg/day).  Adults and children 12 yr of age
 Children younger than 5 yr of age and older
 PO As recommended by health care  PO 8 or 12 mg in the morning and
provider. evening (max, 24 mg/day).
Storage/Stability
• Store all dose forms at controlled room temperature (59°
to 86°F).
Contraindications

• Hypersensitivity To Antihistamines
• Narrow-angle Glaucoma
• Peptic Ulcer
• Symptomatic Prostatic Hypertrophy
• Asthmatic Attack
• Bladder Neck Obstruction
• Pyloroduodenal Obstruction
• Use In Newborn Or Premature Infants And In Breast-
feeding Mothers.
Drug Interactions

Alcohol, CNS depressants,and tricyclic antidepressants

 May cause additive CNS depressant effects.
MAOIs
 May increase anticholinergic effects of chlorpheniramine.
Ototoxic medications
 Concurrent use may mask the symptoms of ototoxicity.
Laboratory Test Interactions
Skin testing procedures
 Antihistamines may prevent or diminish otherwise positive
reaction to dermal reactivity indicators.
Adverse Reactions
Cardiovascular
• Bradycardia orthostatic hypotension; palpitations; reflex
tachycardia.
CNS
• Confusion; convulsions; disturbed coordination; dizziness;
drowsiness, fatigue; headache; insomnia, nervousness;
neuritis;; restlessness; sedation; tremor; vertigo.
ENT
• blurred vision, diplopia, dry nose and throat, sore throat,
tinnitus.
GI
• Anorexia, constipation, dry mouth, epigastric distress,
nausea, vomiting.
Cont…

Genitourinary
• Difficult urination; dysuria, urinary frequency or retention.
Hematologic
• hemolytic anemia, thrombocytopenia.
Metabolic
• Increased appetite, weight gain.
Respiratory
• Chest tightness, respiratory depression, thickening of bronchial
secretions, wheezing.
Miscellaneous
• Chills; excessive perspiration; hypersensitivity reactions;
photosensitivity.
Use with cautions in :
• allergy symptoms
• (eg, cough, rhinitis, nasal congestion, sneezing, watery eyes,
or itching nose, throat, or eyes)
• patient with dizziness and excessive drowsiness
• Pregnancy and lactation.
• In Children
• Overdosage may cause hallucinations, convulsions, and death,
diminish mental alertness.
• In Elderly starting at the low end of the dosage range because
of the greater frequency of decreased hepatic, renal, or cardiac
function.
• Use drug with caution in patients with cirrhosis or other hepatic
disease.
Overdosage

Symptoms
 CNS depression (including sedation, apnea, CV collapse)
 tinnitus
 blurred vision
 dizziness
 hypotension
 Stimulation and atropine-like signs and symptoms (including
dry mouth, fixed dilated pupils, flushing, hyperthermia, GI
symptoms) are more likely in children.
Patient Information

• Instruct patient to stop taking drug and immediately

report to health care provider if any of these symptoms
appear :
• persistent dizziness
• excessive drowsiness
• severe dry mouth, nose, or throat
• difficulty breathing
• weakness
• fever, fast or irregular heartbeat, confusion
• difficulty with urination.
Second Generation Antihistamines
Second-generation Antihistamines

• much more selective for peripheral H1 receptors as

opposed to the central nervous system H1
receptors and cholinergic receptors.
• This selectivity significantly reduces the occurrence
of adverse drug reactions, such as sedation.
• they are very polar
• do not cross the blood-brain barrier and act mainly
outside the central nervous system.
Examples

• Cimetidine • Loratadine
• Famotidine • Rupatadine
• Lafutidine • Acrivastine
• Nizatidine • Ebastine
• Ranitidine • Bilastine
• Roxatidine • Bepotastine
• Tiotidine Astemizole • Terfenadine
• Ketotifen • Quifenadine
• Cetirizine
H-1Receptor Blockers Classification :
2nd Generation:

Alkylamines

Piperazines

Piperadines
Classification of 2nd generation Anti-
Histamines :

• Acrivastine
Alkylamines

• Cetrizine HCL
Piperazines

• Loratadine
Piperadines •
Terfanadine
2nd Generation Anti-Histamines

ALKYLAMINE
S

ACRIVASTINE
ACRIVASTINE
ORIGIN :
• Acrivastine also known as Propionic acid .
:
• It is of Synthetic origin
• belongs to Alkyl amine antihistamine.

BRAND NAME :
Semprex-D
Benadryl Allergy Relief
• PHARMACOKINETIC :
o Metabolism is reported 1.1 hours.
o Renal Excretion accounts for 84% and
o plasma half life is 1.5 hrs.
• Route of administration : Oral

• DOSAGE :
Adult : 8 to 60 mg/day
Pederatic : 20 Kg
• DOSAGE FORM : Capsules
Common medication combinations:
Ventolin( albuterol)
Zovirax (acyclovir)
Marcain (bupivacaine)
STORAGE CONDITIONS :
Capsule…Store Between 15°C-25°C.
Protect from Moisture and Heat
INDICATIONS :
• Decongestant
• Hay fever
• Rhinitis
• Urticaria
CONTRAINDICATIONS :
• Renal impairment
• Porphyria.
• Closed Angle Glaucoma
• High Blood Pressure
SIDE EFFECTS ::
• Increased blood pressure
• Bleeding
• Fast or uneven Heartbeat.
• blurred vision;
• dry mouth;
• upset stomach, constipation;
• loss of appetite;
• dizziness, drowsiness;
• problems with memory or concentration;
• warmth, tingling, or redness under your skin;
• feeling restless or excited (especially in children);
INTERACTIONS
• Administered cautiously in patients with asthma or
COPD because of its anticholinergic effects, cause
thickening of bronchial secretions, resulting in
obstruction of respiratory tract.
• Not recommended in the presence of renal
impairment.
• May cause cardiovascular adverse effects related to
their anticholinergic activities. Tachycardia, palpitation,
ECG changes, arrhythmias. Although these effects are
uncommon and usually limited to overdosage
situations.
2nd Generation Anti-Histamines

PIPERAZIN
E

CETIRIZNE
S HCL
CETRIZNES HCL:

ORIGIN:
• Cetirizine also known as Cetirizine Dihydrochloride.
• Cetirizine (HCl) are the derivatives of Cetirizine.
• Synthetic origin and belongs to Diperazine

BRAND NAME : ZIXANT, TARCIT

• DOSAGE FORM :
Tablets, capsules, syrup
Common medication combinations:
Aspirin Calcuim 600D
Singulair Vitamin D3
• STORAGE CONDITIONS :
• TABLET….Store in a well closed container
• Below 40°C.
• PHARMACOKINETIC :
o Half life 8.3 hrs.
o Renal Excretion accounts for 70.9 % and 10 % feaces
o plasma half life is 6.7-10.9 hr.
• Route of administration : Oral
• DOSAGE :
Adult : 5 to 20 mg
Pederatic : 2.5 to 5 mg
INDICATIONS :
• Atopic dermatitis
• Chronic idiopathic urticarial
• Perennial rhinitis
• Seasonal allergic rhinitis
CONTRAINDICATIONS :
• Hypersensitivity
• Pregnancy
• Porphyria
• Breast feeding.
SIDE EFFECTS :
• Leukopenia
• Headache
• Drowsiness
• GI upset
• Somnolence
• Agitation
• GI discomfort
• Dry mouth.
INTERACTIONS

• Using cetirizine together with alcohol can

increase CNS side effects such as dizziness,
drowsiness, and difficulty in concentration.

• Patients with renal and/or liver disease may

be at greater risk for adverse effects from
cetirizine due to decreased drug clearance.
2nd Generation Anti-Histamines

PIPERADINE

LORATADINE

TERFANADINE

LEVOCABASTINE
LORATADINE
:
ORIGIN :
• It is of Synthetic origin
• Belongs to Piperidine carboxylate
• Chemical formula: C22H23ClN2O2

BRAND NAME :
Claritin
Allerget
Alertina
Alavert
• PHARMACOKINETIC :
o Half life 8 hrs.
o Renal Excretion accounts for 27%
o plasma half life is 3-20hrs.
• Route of administration : Oral
• DOSAGE :
Adult : 5 to 20 mg
Pederatic : 2.5 to 5 mg
DOSAGE FORM :
Tablets, oral suspension, syrup
Common medication combinations:
Tylenol (acetaminophen)
Crestor (lovastatin)
Fish Oil
STORAGE CONDITIONS :
• Syrup store between 15°C-30°C.
• Protect from Sunlight and Heat
INDICATIONS:
• Chronic urticaria
• Hay fever
• NSAID associated ulceration
• Perennial rhinitis
• Allergies
CONTRAINDICATIONS:
• Seasonal allergic rhinitis
• Hypersensitivity
• Liver disease
SIDE EFFECTS:
• Sinus tachycardia
• Hair loss
• Tinnitus
• Hypotension
• Insomnia
• Blood dyscrasias
• Tremors
INTERACTIONS:
Substances that act as inhibitors of the CYP3A4
enzyme such as ketoconazole, erythromycin,
cimetidine, and furanocoumarin derivatives (found in
grapefruit) lead to increased plasma levels of
loratadine.
Advice to Patients
 Importance of taking only as prescribed dosage.
 Importance of consulting a clinician if nervousness, dizziness, or
sleeplessness occurs with fixed-combination preparations
containing pseudoephedrine hydrochloride.
 Do not break, crush, or chew.
 Importance of informing clinicians of existing therapy, including
prescription and OTC drugs and dietary or herbal supplements, as
well as any concomitant illnesses
 Advise patients to avoid concomitant use of fixed-combination
preparations with other OTC antihistamines and/or
decongestants.
 Importance of informing clinicians of existing or contemplated
concomitant therapy, including prescription and OTC drugs and
dietary or herbal supplements, as well as any concomitant
illnesses.
 Importance of informing patients of other important precautionary
information.
GLOBAL VIEW
% PRESCRIBED
Statistical Analysis of Use of Anti-
Histamines :