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BY-
MADHUMITA DIXIT
JR-3
PHARMACOLOGY DEPARTMENT
CLASSIFICATION OF H1 ANTIHISTAMINICS-
FIRST GENERATION ANTIHISTAMINICS-
1)HIGHLY SEDATIVE-DIPHENHYDRAMINE,DIMENHYDRINATE,
PROMETHAZINE,HYDROXYZINE
2)MODERATELY SEDATIVE-PHENARIMINE,CYPROHEPTADINE,
MECLIZINE,CINNARIZINE
3)MILD SEDATIVE-CHLORPHENIRAMINE,DEXCHLORPHENIRAMINE
TRIPROLIDINE,CLEMASTINE
SECOND GENERATION ANTIHISTAMINICS-FEXOFENADINE,
LORATADINE,DESLORATADINE,CETIRIZINE,LEVOCETIRIZINE,
AZELASTINE,MIZOLASTINE,EBASTINE,RUPATADINE
Mechanism of action of 2nd generation antihistaminics-
These drugs competitively antagonize actions of
histamine at the H1 receptors.
Pharmacological actions-
1) Antagonism of histamine-The H1 antagonists
effectively block histamine induced
bronchoconstriction, contraction of intestinal and
other smooth muscle and triple response especially
wheal, flare and itch. Constriction of larger blood
vessel by histamine is also antagonized.
2) Antiallergic actions-Many manifestations
of immediate hypersensitivity (type I reactions)
are suppressed. Urticaria, itching and angioedema
are well controlled.
3) CNS action-The older antihistamines produce
variable degree of CNS depression.But in case of 2nd
gen antihistaminics there is less CNS depressant
property as these cross BBB to significantly lesser
extent.
4) Anticholinergic action- many H1 blockers
in addition antagonize muscarinic actions of ACh.
BUT IN 2ND gen histaminics there is Higher H1
selectivitiy : no anticholinergic side effects
•Cetirizine, sold under the brand
name Zyrtec among others, is a second-
generation antihistamine
•It was patented in 1981and came into medical
use in 1987. It is available as a generic
medication.It is on the World Health
Organization's List of Essential Medicines.
USES-
1 . Allergic disorders –cetirizine do not suppress AG:
AB reaction, but block the Effects of released
histamine. Cetirizine's primary indication is
for allergic rhinitis(hay fever),dermatitis and other
allergies. Because the symptoms of itching and
redness in these conditions are caused by histamine
acting on the H1 receptor, blocking those receptors
temporarily relieves those symptoms.
Cetirizine is also commonly prescribed to treat acute
and chronic urticaria(hives)
Route of administration-Cetirizine comes as a tablet, a
chewable tablet, an extended release tablet, and a
syrup (liquid) to taken orally. It is taken once a day with
or without food usually before bedtime.
Pharmacokinetics-
Bioavailability-Well-absorbed (>70%)
Protein binding-88–96%
Metabolism Minimal (non-cytochrome P450 mediated)
Onset of action-20–42 minutes
Elimination half-life Mean: 8.3 hours Range: 6.5–10
hours
Duration of action≥24 hours
Excretion-
Urine: 70–85%
Feces: 10–13%
Dosing-The dosing of cetirizine depends on patient age. In
adults and children 12 years or older, the recommended dose is
5 or 10 mg per day orally, depending on symptom severity. It is
available in 5 mg and 10 mg tablets and 5 mg/ 5 ml oral
solution
•In children 6 to 11 years old, 5 or 10 mg (1 or 2 teaspoons)
once daily in syrup form is recommended depending on
symptom severity.
•In children 2 to 5 years old, the recommended dose is 2.5 mg
(half teaspoon) in syrup form once daily.
•In children six months to 23 months old, the recommended
dose is 2.5 mg (half teaspoon) in syrup form once daily.
•One drop (0.24% cetirizine hydrochloride ophthalmic solution) is
instilled in the affected eye twice daily for patients with allergic
conjunctivitis.
•Abuse potential-Antihistamines are easily accessible
medications, usually sold OTC to treat allergic
reactions, pruritus, or peripheral vertigo. Their
sedating effects have led to usage as a sleep aid or an
anxiolytic, often by child and adolescent mental health
practitioners, particularly in acute inpatient psychiatric
hospital settings.
• Although widely used and generally considered safe,
cases of antihistamine abuse and dependence,
especially of DPH, have been described in the medical
literatures.
2nd-generation Antihistaminic Part I.pptx
ADVERSE EFFECTS- Nervous system-common
adverse effect(more then 10%) in adults include
somnolence(upto 14.3%)
Headache( upto 14%), dizziness(upto 10%)
GIT-(1-10%):dry mouth ,nausea ,diarrhoea ,vomiting
abdominal pain.
Respiratory(1-10%)pharyngitis,rhinitis,cough,epistaxis
Psychiatric-insomnia(1-10%)
Others-fatigue(1-10%)
Musculoskeletal-less then0.01%-myelitis
Interactions-
Isocarboxazid -cetirizine interaction-
Using cetirizine together with isocarboxazid may increase side effects
such as dizziness, drowsiness, and difficulty concentrating. Some people,
especially the elderly, may also experience impairment in thinking,
judgment, and motor coordination.
Tranylcypromine -cetirizine interaction-
Using cetirizine together with tranylcypromine may increase side effects
such as dizziness, drowsiness, and difficulty concentrating.
cetirizine -alcohol interaction-
Alcohol can increase the nervous system side effects of cetirizine such as
dizziness, drowsiness, and difficulty concentrating. Some people may also
experience impairment in thinking and judgment. You should avoid or
limit the use of alcohol while being treated with cetirizine. Do not use
more than the recommended dose of cetirizine, and avoid activities
requiring mental alertness such as driving or operating hazardous
machinery.
Also avoid use of sedatives, and tranquilizers as cetirizine can
increase the risk of drowsiness. Cetirizine may cause central
nervous system depression; avoid activities requiring mental
alertness until accustomed to the medication.
First-generation antihistamines are considered safe to use during
pregnancy. There are relatively fewer data on the nonsedating
second-generation antihistamines; however, published studies are
reassuring. All antihistamines are considered safe to use during
breastfeeding, as minimal amounts are excreted in the breast milk
and would not cause any adverse effects on a breastfeeding infant.
Dose, preparations and pricing of second generation
antihistaminics-
1)Cetirizine 10mg (Rs 18-30)for 10 tablet strip-Okacet,
Cetcip ,alerid tablet (Cipla), Cetzine (Dr Reddy's)
CZ 3 tablet (Lupin ltd)
2)Levocetirizine 5mg –Rs(70-140) for 15 tablet strip-Xyzal
(Dr Reddy’s), Levorid (Cipla) ,Lecope (mankind pharma)
3)Fexofenadine 120 mg –Rs(180-230) for 10 tablet strip-
Allegra (Sanofi India), histafree 120 (mankind pharma),
Fexy 120 (lupin ltd),fexova 120 (Ipca laboratories)
Lorfast meltab (Cadila pharmaceuticals)
4)Loratadine 10 mg-Rs (105) for 10 tablet strip- Lorfast
meltab (adila pharmaceuticals)
THANKYOU

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2nd-generation Antihistaminic Part I.pptx

  • 2. CLASSIFICATION OF H1 ANTIHISTAMINICS- FIRST GENERATION ANTIHISTAMINICS- 1)HIGHLY SEDATIVE-DIPHENHYDRAMINE,DIMENHYDRINATE, PROMETHAZINE,HYDROXYZINE 2)MODERATELY SEDATIVE-PHENARIMINE,CYPROHEPTADINE, MECLIZINE,CINNARIZINE 3)MILD SEDATIVE-CHLORPHENIRAMINE,DEXCHLORPHENIRAMINE TRIPROLIDINE,CLEMASTINE SECOND GENERATION ANTIHISTAMINICS-FEXOFENADINE, LORATADINE,DESLORATADINE,CETIRIZINE,LEVOCETIRIZINE, AZELASTINE,MIZOLASTINE,EBASTINE,RUPATADINE
  • 3. Mechanism of action of 2nd generation antihistaminics- These drugs competitively antagonize actions of histamine at the H1 receptors. Pharmacological actions- 1) Antagonism of histamine-The H1 antagonists effectively block histamine induced bronchoconstriction, contraction of intestinal and other smooth muscle and triple response especially wheal, flare and itch. Constriction of larger blood vessel by histamine is also antagonized. 2) Antiallergic actions-Many manifestations of immediate hypersensitivity (type I reactions) are suppressed. Urticaria, itching and angioedema are well controlled.
  • 4. 3) CNS action-The older antihistamines produce variable degree of CNS depression.But in case of 2nd gen antihistaminics there is less CNS depressant property as these cross BBB to significantly lesser extent. 4) Anticholinergic action- many H1 blockers in addition antagonize muscarinic actions of ACh. BUT IN 2ND gen histaminics there is Higher H1 selectivitiy : no anticholinergic side effects
  • 5. •Cetirizine, sold under the brand name Zyrtec among others, is a second- generation antihistamine •It was patented in 1981and came into medical use in 1987. It is available as a generic medication.It is on the World Health Organization's List of Essential Medicines.
  • 6. USES- 1 . Allergic disorders –cetirizine do not suppress AG: AB reaction, but block the Effects of released histamine. Cetirizine's primary indication is for allergic rhinitis(hay fever),dermatitis and other allergies. Because the symptoms of itching and redness in these conditions are caused by histamine acting on the H1 receptor, blocking those receptors temporarily relieves those symptoms. Cetirizine is also commonly prescribed to treat acute and chronic urticaria(hives)
  • 7. Route of administration-Cetirizine comes as a tablet, a chewable tablet, an extended release tablet, and a syrup (liquid) to taken orally. It is taken once a day with or without food usually before bedtime. Pharmacokinetics- Bioavailability-Well-absorbed (>70%) Protein binding-88–96% Metabolism Minimal (non-cytochrome P450 mediated) Onset of action-20–42 minutes Elimination half-life Mean: 8.3 hours Range: 6.5–10 hours Duration of action≥24 hours Excretion- Urine: 70–85% Feces: 10–13%
  • 8. Dosing-The dosing of cetirizine depends on patient age. In adults and children 12 years or older, the recommended dose is 5 or 10 mg per day orally, depending on symptom severity. It is available in 5 mg and 10 mg tablets and 5 mg/ 5 ml oral solution •In children 6 to 11 years old, 5 or 10 mg (1 or 2 teaspoons) once daily in syrup form is recommended depending on symptom severity. •In children 2 to 5 years old, the recommended dose is 2.5 mg (half teaspoon) in syrup form once daily. •In children six months to 23 months old, the recommended dose is 2.5 mg (half teaspoon) in syrup form once daily. •One drop (0.24% cetirizine hydrochloride ophthalmic solution) is instilled in the affected eye twice daily for patients with allergic conjunctivitis.
  • 9. •Abuse potential-Antihistamines are easily accessible medications, usually sold OTC to treat allergic reactions, pruritus, or peripheral vertigo. Their sedating effects have led to usage as a sleep aid or an anxiolytic, often by child and adolescent mental health practitioners, particularly in acute inpatient psychiatric hospital settings. • Although widely used and generally considered safe, cases of antihistamine abuse and dependence, especially of DPH, have been described in the medical literatures.
  • 11. ADVERSE EFFECTS- Nervous system-common adverse effect(more then 10%) in adults include somnolence(upto 14.3%) Headache( upto 14%), dizziness(upto 10%) GIT-(1-10%):dry mouth ,nausea ,diarrhoea ,vomiting abdominal pain. Respiratory(1-10%)pharyngitis,rhinitis,cough,epistaxis Psychiatric-insomnia(1-10%) Others-fatigue(1-10%) Musculoskeletal-less then0.01%-myelitis
  • 12. Interactions- Isocarboxazid -cetirizine interaction- Using cetirizine together with isocarboxazid may increase side effects such as dizziness, drowsiness, and difficulty concentrating. Some people, especially the elderly, may also experience impairment in thinking, judgment, and motor coordination. Tranylcypromine -cetirizine interaction- Using cetirizine together with tranylcypromine may increase side effects such as dizziness, drowsiness, and difficulty concentrating. cetirizine -alcohol interaction- Alcohol can increase the nervous system side effects of cetirizine such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. You should avoid or limit the use of alcohol while being treated with cetirizine. Do not use more than the recommended dose of cetirizine, and avoid activities requiring mental alertness such as driving or operating hazardous machinery.
  • 13. Also avoid use of sedatives, and tranquilizers as cetirizine can increase the risk of drowsiness. Cetirizine may cause central nervous system depression; avoid activities requiring mental alertness until accustomed to the medication. First-generation antihistamines are considered safe to use during pregnancy. There are relatively fewer data on the nonsedating second-generation antihistamines; however, published studies are reassuring. All antihistamines are considered safe to use during breastfeeding, as minimal amounts are excreted in the breast milk and would not cause any adverse effects on a breastfeeding infant.
  • 14. Dose, preparations and pricing of second generation antihistaminics- 1)Cetirizine 10mg (Rs 18-30)for 10 tablet strip-Okacet, Cetcip ,alerid tablet (Cipla), Cetzine (Dr Reddy's) CZ 3 tablet (Lupin ltd) 2)Levocetirizine 5mg –Rs(70-140) for 15 tablet strip-Xyzal (Dr Reddy’s), Levorid (Cipla) ,Lecope (mankind pharma) 3)Fexofenadine 120 mg –Rs(180-230) for 10 tablet strip- Allegra (Sanofi India), histafree 120 (mankind pharma), Fexy 120 (lupin ltd),fexova 120 (Ipca laboratories) Lorfast meltab (Cadila pharmaceuticals) 4)Loratadine 10 mg-Rs (105) for 10 tablet strip- Lorfast meltab (adila pharmaceuticals)