Antihistamines Flashcards
What do these two drugs do?
Cromolyn Sodium
Nedocromolin
Prevent histamine release.
What effect does ACh have on histamine?
Induces histamine release from mast cells
What effect do B-adrenergic agonists have on histamine?
Inhibit histamine release
What type of receptor class do Histamine receptors belong?
All 4 are G-coupled receptors
H1 Receptors are found…..?
CV, Resp. Sys., GI smooth mm.
What effect does histamine have on the IP3 pathway?
When linked to the phosphoinositol pathway, activation causes contraction of smooth muscle.
Outline the cellular signal pathway starting with H1 that causes smooth muscle contraction.
Histamine+H1==>Gq==> PLC==>IP3+DAG==>Increaseed Ca2+==> Increased Ca2+-Calmodulin==> Phosphorylation of Myocyte Light chains (MLC)
The H1 receptor causes__________Via_______release from the vascular smooth muscle===> Increase cGMP==> Decreased Ca++.
- Vasodilation
2. NO
What other reflexes does the H1 receptor enable?
Sneezing and itching (pruritis). (Sensation from sesory nerve endings
What role does the H2 receptor play?
Linked to relaxation of vascular smooth muscle and gastric secretions. also reduces histamine release from mast cells as a negative feedback loop.
Where is the H2 receptor distribited?
CV, GI smooth muscle, Stomach
Colocalization of H1 and H2 receptors causes?
H1 in vasc. endothelium==> Increased NO release and contraction of the endothelial cells.
H2 in vascular muscle===> causes relaxation (vasodilation)
Where are H3 receptors found?
In the CNS
What role does the H3 receptor play in the brain?
Linked to inhibition of NT release.
(Hist===>H3====> Decreased Ca++) Gi coupled!
Where the hell are H4 receptors located?
what’s their role?
- On mast cells, basophils and eosinophils.
2. Linked to hista,mine-induced chemotaxis
What do the H1 and H2 receptors do in the CV system?
H2: Moderate increase in rate and force of contraction.
Vasodilation (H1 in endothelium and H2 in smooth muscle.
What histamine receptor is in the resp. sys and how does it work?
H1 mediated bronchial constriction of smooth muscle.
What histamine receptor is in the stomach and how does it function?
H2 mediated acid release from parietal cells of stomach
What effect does histamine have on the heart?
Positive chronotropy and ionotropy.
Cardio crap: Define Chronotropy and Ionotropy.
Chronotropy affects the heart rate.
Ionotropy affects force of heart contraction.
Outline pathway of how H2 receptor modulates chronotropy?
Hist+H2R==>G-couple»» AC…..Increase cAMP which binds to and opens HCN channel allowing Na+ influx. cAMP+PKA bind L-type Ca++ channel allowing Ca++influx into cell.
In inotropy, Histamine binds….G-coupled signaling….L-type Ca++ channels open=Contraction (No HCN)
What does histamine do do veins?
Constricts them
What effect does histamine have on capillaries?
Increases permeability. H1=Endothelial contraction, H2=Vascular smooth muscle relaxation.
List pathologies caused by histamine
Urticara-Hives, rash, edematous welts
Dermatographia- Redness on mechanical stimulation.
Flushing- Due to vasodilation or seeing bae.
Histamine causes_______ in the respiratory system via_______. This receptor uses________as second messengers.
- Broncocontriction
- H1
- Gq, IP3, DAG.
Anaphylaxis is treated with?
Epinephrin (Epi-Pen)
Differentiate H1 and H2 receptor antagonists
H1 antagonists are reffered to as antihistamines (Don’t bind H2)
H2 antagonists are referred to as acid blockers (don’t bind H1 receptors)
What is an inverse agonist?
This is basically a clown agent that binds a selected receptor like an agonist would but instead of causing an agonist effect, it does the exact opposite. (SO structurally these guys have to retain a structure very close to histamine)
Name the 1st gen antihistamine classes.
Alkymines Ethanolamines Ethylenediamines Phenothiazides Piperadines Piperazines
Give examples of 1st gen antihistamines
Bromopheniramine Cyproheptadine Diphenhydramine Promethazine Hydroxyzine Pyrilamine
What effct do H1 antagonists have in the CNS?
They have sedative effects as the block H1/H2 receptors in the brian which are important in wakefulness.
Which H1 class of drugs are the most sedative?
Ethanolamines and phenothiazines (ie diphenhydramine, promethazine)-Older H1 antagonists are sedating (someday we won’t have to give a shit about old drugs)
What other effect do H1 antagonists have?
Anticholinergic effects (atropine-like effects) only in 1st gen drugs.
Anti-motion sickness and antiemetic effects likely derived from anti cholinergic effect (Promethazine is potent ; Scopalamine-like)
Also cause typical anticholinergic effects: Dry mouth, decreased urination
Which 1st gen drugs are used as local anesthetics?
Pyrilamine, Promethazine
Which H1 antagonists have anti-serotonin activity? Used for?
Cyproheptadine, azatidine
Antipruritic
Which drugs H1 antagonists have Alpha adrinergic antagonism? Used for?
Phenothiazines, Used for hypertension
Which H1 antagonists have extrapyramidal activity? used for?
The Phenothiazine; promethazine
Dystonia, akathisia
Name the 2nd generation H1 antagonists!
Loratadine (Claitin) Desloratadine(Clarinex) Fexofenadine(Allegra) Cetirizine(Zyrtec) Terfidine (Seldane)
Difference between the 1st gen and second gen H1 antagonists
1st Gen H1 antagonists=Lipid soluble, CNS effects, not very selective
2nd gen= Low lipid solubility, little/no sedation, no antimuscarinic activity, no anti-emetic activity, no anti-motion sickness activity. Efflux from CNS via P-glycoprotein transporter
What other effects does Cetrizine (zyrtec) have?
Blocks: LTC4, Neutrophil migration, Eosinophil infiltration (H4 block maybe?)
What is Olopatadine? Whst is it used for?
2nd gen H1 antagonist eye drops
What are azelastine and Ketotifen?
Azelastine and Ketotifen are H1 antihistamines used as eye drops in the US to relieve eye irritation.
Name the 3 antihistamine drugs to treat motion sickness.
Dimenhydinate (Diphenydramine+Chlorotheophylline), Meclizine
Promethazine
Which antihistamines cause sadation?
Ethanolamines
Phenothiazines
These may interact with other sedatives (alcohol, anxilytics, antipsychotics
What are 1st gen antihistamines contraindicated in?
Urinary retension, narrow angle glaucoma
