Anti-histamines Flashcards
What are autacoids?
biological factors which act like local hormones, have a brief duration, and act near the site of synthesis. The word autacoids comes from the Greek “Autos” (self) and “Acos” (relief, i.e. drug).
What is the triple response of Lewis?
- Red spot (capillary dilation)
- Flare (stimulate nerve to dilate)
- Wheal (increased capillary permeability)
What is histamine (what is it made from, and how is it different)?
Histidine without its carboxyl group
What is the enzyme that converts histidine to histamine?
Histidine decarboxylase
What is the use of histamine?
Plays a central role in immediate hypersensitivity reaction
What happens to histamine when it is released into tissues and blood?
Inactivated
What are the cells that contain histamine? (3)
- Mast cells
- Basophils
- Enterochromaffin-like cells
Where are mast cells found in high concentrations?
Bronchial and intestinal mucosa
Histamine release causes the release of what cytokines?
Leukotrienes
Cytokines
Enzymes
What are the two MOAs of histamine release?
Cytolytic
Noncytolytic
What is the cytolytic histamine release pathway?
Membrane damage leads to high levels of histamine release
What cause cytolytic release of histamine?
High levels of drugs such as phenothiazine, H1 receptor antagonists, opioids
Mechanical damage
What is the noncytolytic mechanism of histamine release?
Immune response that requires prior sensitization, leading to displacement of histamine
What is the MOA of allergic reaction and histamine release?
Antigen binds in Ig ab (FC-epsilon-R1) receptor on plasma cells, that then produces IgE that integrate into mast cells.
The next time they stimulate mast cells directly throught IgE
What are the three major chemicals that are released during anaphylaxis, besides histamine?
Leukotrienes
Prostaglandins
Cytokines
What is anaphylactoid?
Clinical syndrome indistinguishable from anaphylaxis, but not caused by an immune response
Where is H1 receptor highly expressed (3)? What G protein?
Smooth muscle
Vascular endothelial cells
CNS neurons
Gq
Where is H2 receptor highly expressed (3)? What G protein?
Gastric parietal cells
Cardiac muscle
CNS neurons
Gs
Where is H3 receptor highly expressed (2)? What G protein?
CNS neurons
Peripheral sensory nerves
Gi/o
Where is H4 receptor highly expressed (3)? What G protein?
PMNs
Eosinophils
Monocytes
Gi/o
Where in the brain is there a large amount of histamine receptors?
Hypothalamus
What is the cyclical pattern of histamine levels? What is the function of this?
High in the day
Low at night
Functions in sleep and appetite
What is the transmitter that mediates itch? Where does this act?
H1 receptors in the periphery
Centrally and peripherally
What happens when H1 is activated in vessels?
NO released from PKC activation, causing vasodilation
What happens when H2 is activated in vessels?
PKA causes vasodilation
What is the main receptor that mediates increased permeability of endothelial cells?
H1
H1 activation in the epidermis causes what? Dermis?
Epidermis = itch Dermis = pain
What histamine receptor increases airway fluid secretion?
H1
What type of histamine receptor is on the heart? Effect?
H2 Increased Ca (force and nodal speed)
Which response is greater: H1 vasodilation reflex tachycardia, or H2 receptor activation increase in HR?
H1
How does histamine help with immune system function?
Facilitate the accumulation of immune cells at the site of damage (p-selectins, integrins, and adhesions)
What WBC finding is found in CML? What is the significance of this?
Basophilia–can cause itching from histamine release
Gastric carcinoid tumors that secrete histamine cause what?
Episodes of vasodilation
What is mast cell leukemia? Ssx?
Mast cell proliferation causing Pruritus and flushing, diarrhea, and GERD
What is the drug that reverses the physiological effects of histamine?
Epinephrine
What are the three antihistamines that are release inhibitors of histamine?
Cromolyn
Nedocromil
Omalizumab
H1 receptor antagonism is used for what? H2?
H1 =Allergies
H2 = Gastric acid secretion
What are the H2 receptor antagonists?
Cimetidine and other-tidines
What are the side effects of the 1st generation of antihistamines?
Ach inhibition
Alpha 1 inhibition
5HT Inhibition
What are the three major symptoms that are treated with 1st gen antihistamines?
Rhinitis
Conjunctivitis
Urticaria
What is the role of antihistamines in motion sickness?
Inhibit H1 receptors in the emetic center in the medulla
What are the receptors in the emetic enter of the medulla?
H1
M
5HT3
What does it mean when H1 antihistamines are inverse agonists?
bind and stabilize the inactive form of the histamine receptors
What are the adverse effects of H1 antihistamines on the CNS?
Decreased alertness/sedation
What are the adverse effects of H1 antihistamines in terms of the antimuscarinic effects?
Dry mouth
Urinary retention
Sinus tach
What are the adverse effects of H1 antihistamines in the terms of the serotonin receptor agonization?
Increased appetite and weight gain
What are the adverse effects of H1 antihistamines in terms of alpha adrenergic antagonism?
Dizziness
Postural hypotension
What is the MOA of Chlorpheniramine? What is this used to treat?
1st gen antihistamine
Not an antiemetic, but allergies good
What is the major 1st generation ethanolamines? What is this used to treat? Side effects
Diphenhydramine (benadryl)
Motion sickness and allergies, but causes sedation
How does diphenhydramine work as a local anesthetic?
Blocks Na channels in excitable membranes
What are the uses of Pyrilamine? MOA? Side effects?
Allergies
1st gen antihistamine
Low sedation, no antimuscarinic or motion sickness
What is hydroxyzine used for? MOA? Side effects?
Antiemetic and anxiolytic
1st gen antihistamine
has a lot of antimuscarinic effects
What is meclizine used for? MOA?
Motion sickness and vertigo
1st gen antihistamine
What is the use of promethazine? MOA? Side effects?
Antiemetic and local anesthetic
1st gen antihistamine
Significant inhibition of alpha 1 adrenergic receptors and antimuscarinic effects
Promethazine is similar in structure to what drug? What does this mean?
Chlorpromazine
Similar D2 antagonism, but lower potency
What is Cyproheptadine? MOA? What is it used for?
- Significant antiserotonin activity
- 1st gen antihistamine
-Anti-5HT to treat serotonin syndrome and causes weight gain
What are the four strongest antiemetic antihistamines?
Diphenhydramine
Promethazine
Hydroxyzine
Meclizine
What are the three antihistamines that have the highest sedative effects?
Diphenhydramine
Hydroxyzine
Promethazine
What antihistamine has a very strong anti adrenergic action? What are the side effects of this?
Promethazine-
Hypotension
Dizziness
Which antihistamines have a strong anticholinergic effects? What are the side effects of this?
Diphenhydramine
Promethazine
Dry mouth
Urinary retention
Sinus tach
Which antihistamine has a strong anti serotonin effect?
Cyproheptadine
What class of drugs can intensify the anticholinergic effects of antihistamines?
MAOIs
What drugs have an additive effect on antihistamine sedative effect?
EtOH
opioids
Sedatives
True or false: most of the antihistamines are well absorbed in the GI tract
True
What are the enzymes that metabolize first gen antihistamines?
CYP2D6 and CYP3A4
What are the drugs that interact with p450s that antihistamines are metabolized by?
Imidazoles
Macrolides
What are the second generation of antihistamines (6)?
Azelastine Cetirizine Levocetirizine Desloratadine Loratadine Fexofenadine
What are the advantages of second generation antihistamines?
reduced lipophilicity
Higher selectivity
What is Azelastine? Use?
2nd gen antihistamine that also Inhibits histamine release from mast cells
intranasal and ophthalmic
What are the two second generation antihistamines that have high sedative effects?
Cetirizine
Levocetirizine
Which 2nd gen antihistamine is minimally metabolized by the liver? Which is extensively metabolized by CYP3A4?
Fexofenadine
Loratadine
True or false: 2nd gen antihistamine are generally greatly affected by liver or renal dysfunction.
Which one falls outside this commonality
False
Fexofenadine metabolism is affected by renal dysfunction
Fexofenadine should be avoided while taking what drug? Why?
Antacids d/t reduced absorption
Grapefruit juice causes what interaction with 2nd gen antihistamines? How?
Reduce bioavailability d/t inhibiting p-glycoproteins
What is the MOA of Omalizumab? Use?
Recombinant humanized anti IgE
Treats chronic urticaria and asthma
Which TCA inhibits H1 and H2 receptors? What is this used for?
Doxepin
Chronic urticaria
What is the MOA and use of ketotifen?
H1 antihistamine with additional mast cell and basophils stabilizing properties
Allergic conjunctivitis
What is the MOA of Cromolyn?
Prevents the release of histamine from mast cells through inhibition of Cl channels
What is the MOA of nedocromil?
Prevents the release of histamine from mast cells through inhibition of Cl channels
What are the two major differences between the first generation H1 antagonists and second generation?
1st generation his a lot of other receptors, and does not cross the blood brain barrier
