Antihistamines Flashcards
What is the triple response of Lewis?
Red Spot- Cap Dilation
Flare- Axon reflex and BV dialtion
Wheal- Inc. Capillary Permaiability
Where is histamine created and stored?
Mast cells
What is the Tx for anaphylaxis?
Epinephrine
What is Cytolytic Histamine Release? Caused by?
Membrane damage
High levels of drugs (phenothiazines, opioids and H1 receptor agonists)
Mechanical Damage
What is Noncytolytic Histamine Release?
Immune Response that requires prior sensitization
Non-immuneological responsefrom basic polypeptides
Susbtances such as morphine, codeine, abtx, etc can displace Histamine from granules!
What type of Ab receptor is on the surface of the Mast cell?
IgE receptor. FceRI
What are the symptoms of an anaphylactic reaction?
Hypotension, vasodilation, myocardial depression, dysrhythmias, uticaria, angioedema, bronchospasm
What is an anaphylactoid response?
Indistinguishable from anaphylaxis but not caused by an allergic response
Where are H1 receptors expressed?
SM cells
Vascular endothelial cells
CNS Neurons
Peripheral sensory nerves
Where are H2 receptors expressed?
Gastric Parietal Cells
Cardiac Muscle
CNS Neurons
What G protein does H1 signal with?
Gq
PLC-IP3-Ca2+
What g protein does H2 signal with
Gs
Inc Adenylyl cyclase
Inc Cyclic AMP-PKA
Whaere are H3 receptors seen?
CNS Neurons
Peripheral sensory nerves
Where are H4 receptors seen?
Inflammatory cells Neutrophils Eosinophils Monocytes Other immune Cells
Where are Histaminergic neuron cell bodies seen?
The small area of the hypothalamus
What is the end result of H1 and H2 receptor Activation
Vasodilation
Increase in vascular permiability
What is the mechanism for itch?
H1 in peripheral neurons
Activation in epiderm causes itch
Activation in dermis causes pain
What is the action of H1 activation in Smooth Muscle cells of the lung?
Elevation of airway fluid and electrolytes and bronchostriction
What is the Action of H2 activation on cardiac muscle?
Increased Ca2+ => INC FORCE OF CONTRACTION
Speeds up SA node Depolarization which INC HR
What is the action of Histamine in the immune response?
Accumulation of immune cells at the site of injury
What are diseases that increaseHistamine levels?
Myelogenous Leukemia - Basophils– Chronic itching
Gastric Carcinoid tumors secrete histamine- -Vasodilation
Systemic mast cell diseases
-Mast cell leukemia
What are the classes of antihistamines?
Physiological Antagonists
Release Inhibitors
Receptor antagonists
What is the MOA of the Physiological Antagonists?
Reverse The phys effects of histamine.
-Sympathomimetic: Epinephrine
Relaxes bronchial SM
What is the MOA of the Release inhibitors?
PRevents release of Histamine Prophylactic Tx of Allergy CROMOLYN, NEDOCROMIL OMALIZUMAB -monoclonal IgE Ab Epinephrine
What is the MOA of the Receptor Antagonists?
Compeditively Block receptors
H1-allergy
H2- Gastric acid secretion
What are the common conditions treated by 1st gen Antihistamines?
Allergic Rhinitis
Allervic Conjunctivitis
Uticaria
N/V
Motion sickness
sedatives
Sleep Aids
How is Emesis treated by antihistamines?
H1 receptors in the Vomiting center (tractus solitarus)
What are the Sa of the 1st gen AHM?
Dec alertness, learning, memory
Dry mouth, Urinary retention, Sinus tachy
Inc appetitie, Weight gain
Inc Dizziness, Inc Postural Hypotension
Paradoxical exitation and seizures in kids
What are the effects of Chlorpheniramine?
Mod sedationt
Tx: Allergic Rhinitis and other allergic conditions
No antiemetic action
What are the effects of Diphenhydramine(benadryl?
Sig. Sedative
Antimuscarinic Effects
Allergic rhinitis, conjunctivitis, uticaria
Local anesthetic effects Blk Na channels
Acute Dystonic Rxns
What is Pyrilamine used for?
Low sedation
Little Antimuscarinic therefore
No antimotion sickness
What is Hydroxyzine used for?
Sedation and Antimusc
Antiemetic, Sedative
anxiolytic
skin allergies
What is Meclizine used for?
Minimal Antimuscarinic Actions
Less sedating than hydroxyzine
What is Promethazine for?
Antiemetic, anti MS
Local anesthetic
Alpha Adr. receptor ant.
Antimuscarinic
Waht is the use of Cyproheptadine?
Sedative, antimuscarinic
ANTI-SEROTONIN.
Inc appetite/ wt gain
Tx Serotonin Synd
What are the drug interactions of H1 Antihistamines?
MAOI
ADDITIVE SEDATIVE EFFECTS
Dyphenhydaramine (benadril) overdose
Leads to extreme sedation
What is the metabolizer of Antihistamine? What can decrease their effects?
CYP2D6 and CYP3A4 ez in the liver Imidazole antifungals Cimetidine Macrolides H2 receptor antagonists
What is different about the 2nd Gen H1 Antihistamines?
More selective for H1 Lower lipophilicity(less CNS) Non-compeditive inhibitor
What are the applications of Azelastine?
Inhibits mast cell histamine release.
Intranasal and opthalmic
H1 receptor Antagonist
What are the adverse effects of 2nd Gen H1 inhibitors?
Generally less sedative than 1st gen
Which 2nd gen H1 receptors have a higher sedative effect?
Levocetirizine and Cetirizine
If a patient had renal disorder which 2nd gen H1 receptor would you want to avoid?
Fexofenadine
Drug interactions of fexofenadine?
Dont take with antacids or citrus juices
What meds stabilize mast cells and decrease degranlation?
Cromolyn and Nedocromil
What is the MOA of Omalizumab
Binds IgE and keeps it from activting MAst cells
Which Tricycliclic antidepressant acts as antihistamine?
Doxepin and Ketotifen
