Antihistamines Flashcards
what is an allergy
a reaction to a previous sensitization to a particular chemical. It is mediated by the immune system
what does histamine cause, particularly H1
causes an allergic reaction and inflammation
where are H1 receptors mainly located - 4
- vascular endothelial cells = cause blood vessels to vasodilate due to endothelial dysfucntion and incr permeability leading to edema and redness
- smooth muscle cells = bronchocontriction
- brain = wakefullness and apettite suppression
- peripheral nerve endings = pain and itching sensation
compounds that release histamine without prior sensitization
- tubocuranine
- sch
- morphine
- radiocontrast media
- carbphydrate plasma exapanders
- venoms
antihistamines MOA
they bind to h1 receptors as inverse agonists/competitive agonists on target tissues and stabilize its inactive conformational state
symptoms of allergy - 4
- itching
- inflammation
- sneezing
- bleeding nose
why cant we use antihistamines for asthma
- Antihistamines are ineffective in asthma because they target histamine, not leukotrienes, which are the key drivers of inflammation and bronchoconstriction in asthma(montelukast)
- the concentration of histamine is not sufficient to block histamine in the bronchi
Anti histamines administration
TOI
1st gen antihistamine - older
- Doxylamine, Diphenydramine, Promethazine, Hydroxyzine
- sedation and significant autonomic receptor blocking effects
1st gen antihistamines - newer
- chlorpheniramine
- cyclizine - antiemetic and no any other activity
- cyproheptadine- anti serotonin = increased apettite
2nd gen - CLERM
Cetirizine
Loratadine
Ebastine
Rupatadine
Mizolastine
3rd gen
Desloratatine, Levocetirizine, Fexofenadine
first gen crossing the BBB causes
cognitive imparments and sedation
half life between first and second gen
second generation have a longer half life of 12-24h while first gen is only 4-12h
receptor specificity
- cholinergic blockade = DUB
- a adrenergic blockade = hypotension and reflex tachycardia
- serotonin - incr apetite and weight gain
other 1st gen drugs - 3
- brompheniramine
- meclizine
-clemastine
2nd gen characteristic
- bulkier and less lipo[hilic structure
- selctive for H1
- same allergy response with no sedation
- ALSO INHIBIT LATE PHASE ALLERGY BY ACTION ON LEUKOTRINES AND ANTI PAF
other 2nd gen drugs -3
- olopatadine
- ketotifen
- azelastine
clinical uses of antihistamines - 10
Allergies (hayfever and urticaria)
Urticaria (sedating)
Antimotion sickness
Morning sickness
Menieres disease and vertigo
Chemotherapy induced vomitting
OTC
Local anaesthetic
Peri operative pre medication
Cough syrups, combination of flu/cold preps - often contain 1st or 2nd gen
allergies
fexofenadine, loratadine, cetirizine
antimotion sickness
- due to anticholinergic/antimuscarinis effects on the vomitting centre in the brain
- cyclizine, cinnarizine, meclizine, diphenydramine, promethazine
urticaria
hydroxyzine, promethazine, chlorphenira,ine
morning sickness
doxylamine
menieres disease and vertigo
cinnarizine
chemotherapy induced vomiting
diphenydramine
OTC
DP
Local anaesthesia
DP
Perioperative premedication
PH
Drug interactions
- CNS depressants
- Alcohol
(especially DP)
Drug with more anticholinergic effects
Promethazine, a phenothiazine
effects of sodium channel blockade
conduction delays and dysrrythmias
rupatadine toxic effects
prolongs the QT
diphenydramine toxic effects
widens the QRS complex and prolongs the QT
hydroxyzine toxic effects
prolongs the QT
ebastine and mizolastine toxic effects
interfere with K channels and prolong the QT
less common A/E
- excitation and convulsions
- postural hypotention
- allergic reactions
cetirizine relation
LONG-ACTING metabolite of hydroxyzine
desloratidine relation
active metabolite of loratidine
levocetirizine relation
active enantiomer of certirizine
