Drugs (IL)- Anti-histamines (3)- Leah* Flashcards
How is histamine synthesized?
histidine –> histamine via histidine decarboxylase
WHERE is histamine synthesized and stored?
#1? In blood? Other (3)
- Mostly Masts
- Basos in the Blood
- Others: epidermal cells, ECL cells in the GI tract, and neurons
What are two urinary metabolites of histamine?
How are they synthesized?
Urinary metabolites:
- N methylhistamine (NMH)
- imidazole acetic acid
- histamine –>NMH (N meth. transferase–NMT)
- NMH –> imidazole acetic acid (Diamine oxidase)
What triggers mast cells/ basophils to release histamine/ other inflammatory mediators? (5)
- allergens
- morphine
- curare
- inflammatory mediators (*bradykinin, cytokines)
- venoms
“I.V. morphine Causes ALLERGies via histamine release”
What causes ECL cells to release histamine? (2)
gastrin; Ach
What are the 2 CNS effects of histamine?
What are the 2 Nerve Ending effects of Histamine?
- wakefulness 2.appetite suppression
1. Pain 2. Itching
How many histamine receptors are there?
Which are targeted by drugs?
- H1-4
- Only 1 +2 are currently drug targets.
- H1:H2 determine effects of drugs
Location(3) and response (mechanism) of the H1 receptor
smooth muscle, endothelium, brain
works via Gq/IP3/DAG
Location (4) and response (mechanism) of the H2 receptor
cardiac/ gastric tissue, mast cells, brain
works via Gs/ ^^cAMP
What are the mechanisms for H3-4
both work through Gi to DECREASE cAMP
Name one H1 and one H2 agonist
H1: 2 methyl histamine
H2: dimaprit
Name the only important effect that needs to be correlated with the H2 receptor
gastric secretions
Name 3 cardio related effects of H1 receptors
- Decreased TPR (via direct relaxation of sm muscle and short lived release NO / PG1)–>Flushing
- increased HR
- increased capillary permeability –>Swelling
Name 4 non-cardio effects of H1 receptors
- bronchoconstriction
- wheal and flare
- wakefulness and appetite
- pain/flushing/pruritis
How are “wheal and flare” responses mediated?
Both H1:
wheal- capillary permiability
flare- neuron reflex (vasodilation)
physiologic histamine antagonist?
mechanism?
use?
- epinephrine
- antagonizes histamine but works through NON HISTAMINE RECEPTORS!!!!
- Gold standard for anaphylaxis
Cromolyn and Nedocromil:
MOA?
Histamine RELEASE inhibitors (CROM drugs)
Block IgE/antigen interaction–> thus block Ag mediated histamine release
What type of antagonists are 1st and 2nd gen antihistamines?
both are H1 REVERSIBLE, COMPETITIVE antagonists
Where are H1 antihistamines metabolized?
Why does this matter?
HEPATIC METABOLISM:
- kids metabolize faster
- hepatic patients metabolize slower
When might H1 anti-histamines cause uncharacteristic sleep changes? (2)
CNS stimulation in kids and H1 antag toxicity
CNS depression esp. with other depressants like alcohol
What effects do anti-H1s fail to effectively block? (3)
- effects on HR and bronchoconstriction is poor.
- effects on pruritis are mild, corticosteroids more efficiently treat dermatitis
- DO NOT suppress gastric secretions!!
Typical H1 antihistamine uses (4)
Used in asthma, allergies, sedation and prophylaxis for motion sickness (promethazine)
Which generation of anti-histamines cause drowsiness and why?
- 1st gen because it readily enters the CNS
- 2nd gen doesn’t easily enter the CNS
How long do gen 1 antihistamines last? gen 2?
1st gen: 4-6 hours
2nd gen: 12-24 hours
