Anti-Histamines Flashcards
What are some common 1st generation anti-histamines?
- Diphenhydramine (Bendryl)
- Dimenhydrinate (Dramamine)
all short acting (4-6 hrs)
What are some 2nd generation anti-histamines?
- Fexofenadine (Allegra)
- Loratadine (Claritin)
- Cetirizine (Zyrtec)
How is histmaine synthesized?
via L-histadine by giving off water
What cells make histamine?
- mast cells (less likely to circulate)
- basophils
- CNS neurons (its a neurotransmitter)
- epidermal cells and intestinal mucosa
Functions of histamine?
- stimulate production of hydrochloric acid in stomach
- vasodilation in allergies/etc.
- neurotransmitter: regulates sleep, brain arousal, memory
Histamine is mediated by 4 receptors and is only active when bound to an appropriate receptor
Histamine is mediated by 4 receptors and is only active when bound to an appropriate receptor
What are the effects of H1 binding?
-increased vascular permeability
-enhancement of histamine and arachidonic acid
derivatives release,
-NO formation,
-increased wakefulness
Clinical effects of H1 binding?
Sneezing, itching, rhinorrhea
and perhaps some degree of nasal congestion via increase vascular permeability with leakage of fluid into the tissues and vasodilation
What are the effects of H2 binding?
stimulate mucous glands
in airways, increases vascular permeability;
stimulate release of gastric acid (most important)
Clinical effects of H2 binding?
Potentially increase nasal
airway swelling, producing
nasal congestion and perhaps increased rhinorrhea
What are the effects of H3 binding?
stimulate nasal sub-mucosal gland secretion
Clinical effects of H3 binding?
can produce a runny nose
What are the effects of H4 binding?
Chemotaxis and chemokinesis of mast cells and eosinophils, enhancement of the activity of other chemoattractants (e.g. chemokines) on eosinophils, upregulation of adhesion molecules
Clinical effects of H4 binding?
Could enhance the
inflammatory response to nasal allergen exposure
What causes histamine release?
IgE binding and crosslinking to mast cells (takes several days to restore the reserves of histamine)
How does H1 binding affect arteries? arterioles?
capillaries?
venules? veins?
arteries- smooth muscle constriction and endothelium dilation
arterioles- rapid onset, short term dilation
capillaries-none
venules- rapid onset, short term dilation, capillary permeability
veins- smooth muscle constriction and endothelium dilation
How does H2 binding affect arteries? arterioles?
capillaries?
venules? veins?
H2 all dilation (slower onset, but more persistent)
capillaries still not effect (same as H1)
What is the net effect of histamine in the vasculature?
vasodilation via H1 receptors everywhere (H2 is minor everywhere outside the stomach)
What does H1 binding in the lungs cause?
broncho-constriction
Roles of H1 antagonists?
- attenuation of allergy and hay fever symptoms
- treatment of symptoms of insect bites, stings, and contact flora poisoning
What additional effect do 1st gen H1 antihistamines have?
attenuation of motion sickness and vertigo
Which generation of anti-histamines have anti-cholinergic effects?
1st generation only
Which generation of anti-histamines has a shorter duration of action?
1st-multiple doses required
Why do the 1st generation anti-histamines cause sedation?
H1 receptors in the hypothalamus binding to histamine promotes alertness (these can pass the BBB because they are mostly uncharged)
T or F. 1st generation anti-histamines have anti-asthmatic effects
FALSE. They increase the viscosity of bronchial secretions and decrease cilia motility via anti-cholinergic effect (do not take if asthmatics)
2nd gen are safer
T or F. 1st generation anti-histamines can prevent the release of histamine endogenously
F.
AEs of 1st generations?
the main AEs stem from the fact that H1 receptor antagonists can bind to other types of receptors
What other receptors can 1st gen H1 receptor antagonists bind to?
- muscarinic receptors
- a-adrenergic receptors
- serotonergic receptors
- Ikr and other cardiac channels
What are the (other) effects of H1 receptor binding of 1st gen H1 receptor antagonists?
- sedation
- increased appetite
What are the effects of muscarinic receptor binding of 1st gen H1 receptor antagonists?
- xerostomia (dryness)
- urinary retention
- sinusoidal tachycardia
- can bind CN XIII to block transmission to vomit center in the brain
beneficial in treatment of vertigo and motion sickness
What are the effects of a-adrenergic receptor binding of 1st gen H1 receptor antagonists?
- hypotension,
- dizziness, and
- reflex tachycardia
What are the effects of serotonergic receptor binding of 1st gen H1 receptor antagonists?
-increased appetite
What are the effects of Ikr and other cardiac channels receptor binding of 1st gen H1 receptor antagonists?
- QT prolongation
- ventricular arrhythmia
T or F. 2nd generation anti-histamines are far more specific for H1 receptors
T.
Properties of 2nd generation H1 antagonists?
- good H1 blockade and anti-asthmatic (safe) effect
- no sedation, GI effect, anticholinergic effect
- doesn’t inhibit histamine release
long acting
T or F. 2nd generation H1 blockers are good for the treatment of asthma
No, they are just safe if you need to take one and are asthmatic
What is the role of 3rd generation anti-histamines?
increase specificity and binding to H1 receptor and block histamine release
What is Desloratadine (Clarinex®)?
Exhibits 14- to 17-fold greater binding to H1 receptors than
loratadine.
• 15- to 50-fold lower affinity for muscarinic receptors
(M1,M2,M4,M5) compared with H1-receptors.
• Has a relatively long elimination half-life (27 hours).
What is Olopatadine (Patanol®)? Advantages?
• Its selectivity for the H1 receptor is greater than that of other ocular
antihistamines.
• Inhibits the release of histamine from mast cells.
Other advantages of Olopatadine?
• Olopatadine may block the activities of some additional mediators of
ophthalmic inflammation by inhibiting the release of tryptase and
prostaglandin D2 from inflammatory cells.
• The drug prevents or reduces ocular inflammation reactions induced
by a variety of common allergens.
How does Levocabastine (Livostin®) work?
• Rapid-acting agent for as needed-use against nasal and ocular effects of rhinitis.
• Piperidine derivative: 1250 times more potent than
chlorpheniramine. 40,000 times the effective dose exhibits no other pharmacological effects.
What does Azelastine (Astelin®, Astepro ®) do?
Inhibits both histamine and
leukotriene activity.
- Blocks calcium mobilization and the 5-lipoxygenase pathway.
- Inhibits PAF through receptor antagonism.
What is Emedastine (Emadine®) approved to treat?
allergic conjunctivitis.
How does Emedastine work?
Anti-allergic potency is comparable to other 2nd generation H1-antagonists.
- Also inhibits histamine and LTC4 release from leukocytes in asthmatic patients.
- Anti-asthmatic potency is comparable to ketotifen
What is Mizolastine (Mistamine®) approved to treat?
allergic rhinitis and chronic idiopathic
urticaria.
How does Mizolastine work?
- Antagonizes PAF- and LTD4-induced bronchoconstriction.
- Effective in relieving nasal and ocular symptoms of seasonal allergic rhinitis.
- Relatively non-sedative at antiallergic doses with no significant difference in efficacy over other non-sedating agents.
What is Ebastine?
Hybrid of 1st generation (diphenylpyraline) and 2nd generation (terfenadine) H1-
antagonists.
Effects of Ebastine?
Exhibits antileukotriene and antibradykinin activities 5-fold lower than anti-histaminic activity.
• Anti-histaminic potency is greater than that of loratadine with similar adverse effects
Which generations of anti-histamines would be good for allergic rhinitis?
both
Which generations of anti-histamines would be good for urticaria?
both
Which generations of anti-histamines would be good for atopic dermatitis?
both
Which generations of anti-histamines would be good for asthma?
neither, but 2nd is safe
Which generations of anti-histamines would be good for itching dermatosis?
both, 1st slightly better
Which generations of anti-histamines would be good for motion sickness, insomnia, appetite stimulation, and as an antiemetic?
1st only
