EXAM #5: ANTIHISTAMINES Flashcards
What is cytolytic histamine release?
Histamine release in response to damage of the mast cell membrane e.g.
- Skin damage
- High concentrations of certain drugs
What is noncytolytic histamine release?
- Immune mediated release of histamine
- Non-immunological response caused by some polypeptides
- Displacement of histamine from mast cells by certain drugs
Describe the mechanism of histamine release in an allergic response.
1) Initial contact with allergen leading to T-cell induced B-cell production of IgE
2) Plasma-cell released IgE antibodies that bind to mast cells
3) Subsequent exposure to allergen causes mast cell degranulation/ histamine release
Where are H1 receptors primarily located?
1) Smooth muscle cells i.e. respiratory and GI
2) Vascular endothelial cells
3) CNS neurons
4) Peripheral sensory nerves
Itching
Where are H2 receptors located?
1) Gastric parietal cells
2) Cardiac muscle
3) CNS neurons
What G-protein subunit is H1 associated with?
Gq
PLC, IP3, Ca++
What G-protein subunit is H2 associated with?
Gs
adenylyl cyclase, cAMP, PKA
What is the function of histamine in the CNS?
1) Controls release of pituitary hormones
2) Wakefulness
3) Appetite/ satiety
Also responsible for some itching
What is the effect of histamine in the vascular system?
1) Vasodilation
2) Increased vascular permeability–>edema
(hypotension and reflex tachycardia)
What histamine receptor is primarily responsible for increased vascular permeability?
H1
What histamine receptor is responsible for itching?
H1 in the epidermis
What are the H1 effects of histamine in the respiratory system?
1) Elevated secretion of airway fluid
2) Bronchoconstriction
What histamine receptor predominates in the heart itself?
H2
What are the H2 effects on the heart?
1) Positive ionotrope
2) Positive dromotrope
What are the actions of histamine in the immune system?
Facilitates the accumulation of immune cells at the site of infection or damage
What are the classes of antihistamines?
1) Physiologic antagonists– reverse physiologic EFFECTS of histamine
2) Release inhibitors–block degrandulation
3) Receptor antagonists
What is the difference between a 1st and 2nd generation antihistamines?
1) Specificity
- 2nd generation are more specific for H1 only
2) CNS penetration
- 2nd don’t penetrate the BBB as much as 1st
Generally, what conditions are treated with 1st generation antihistamines?
1) Allergic rhinitis
2) Allergic conjunctivitis
3) Urticaria
4) Motion sickness
5) Anti-emetic
Why can antihistamines be used as anti-emetics?
Vomiting center in the medulla contains H1 receptors
What is the MOA of the H1 antihistamines?
“Inverse agonist” which means that they:
- Binds receptor
- Stabilizes the receptor in the inactive confirmation
What are the major side effects of the 1st generation antihistamines?
1) CNS depression (H1)
2) Anticholinergic (M) effects
- Dry mouth
- Urinary retention
3) Increased appetite and weight gain (5-HT)
4) Dizziness and postural hypotension (Alpha-1)
Also can lead to paradoxical excitation and seizures in neonates and young children
List the first generation antihistamines.
Chlorpheniramine Diphenhydramine Pyrilamine Hydroxyzine Meclizine Promethazine Cyproheptadine
What is the unique indication for Diphenhydramine?
Extrapyramidal sx. of antipsychotics
What is the unique indication for Cyproheptadine?
Reversal of Serotonin Syndrome
List the H1 antihistamines with the strongest antiemetic effects.
Diphenhydramine
Promethazine
Hydroxyzine
Meclazine
List the H1 antihistamines with the highest sedative effects.
Diphenhydramine
Hydroxyzine
Promethazine
Which H1 antihistamines have the strongest anticholinergic effects?
Diphenhydramine
Promethazine
Which H1 antihistamine has the strongest alpha-1 antagonism?
Promethazine
Which H1 antihistamine has the strongest anti-5HT effects?
Cyproheptadine
How do the 2nd generation antihistamines differ from 1st generation?
1) Noncompetitive H1 inhibitors
2) Reduced lipophilicity i.e. less CNS penetration
3) Higher H1 selectivity
List the 2nd generation antihistamines.
Fexofenadine Loratadine Desloratadine Levocetirizine Cetirizine Azelastine
Which of the 2nd generation antihistamines have a higher sedative effect compared to the others?
1) Cetirizine
2) Levocetrizine
What do you need to remember about Fexofenadine clinically?
1) Decrease dose in renal dysfunction
2) Avoid taking with antacids
What is the MOA of Cromolyn and Nedocromil?
Stabilization of mast cells and inhibition of mast cell degranulation
What are the indications for Cromolyn and Nedocromil?
1) Allergic rhinitis
2) Allergic conjunctivitis
3) Exercise induced asthma
What is Omalizumab?
IgE monoclonal antibody
What are the indications for Omalizumab?
1) Chronic urticaria
2) Asthma
What is Doxepin?
TCA that is useful for treating chronic urticaria
What is Ketotifen?
H1 antihistamine that has additional mast cell and basophil stabilizing properties
Available as ophthalmic preparation
What is Ketotifen used to treat?
Allergic conjunctivitis
