Antihistamines and Antimuscarinics Flashcards
The histaminergic system and antihistamines. (41 cards)
What are autacoids?
- local hormones
- short acting endogenous mediators
- act as part of an inflammatory response
define pleitropic?
having more than one effect
what cells synthesise, store and release histamine?
- mast cells (in skin, GI, respiratory tract
- Basophils (in blood)
- Some neurons (in CNS and peripheral NS)
What is the effect of histamine secretion?
- acid secretion
- mucosal protection
- Fluid transport
- Neurotransmission
- Visceral sensitivity
- Motility
- Inflammation
- Allergy
- Tumour growth
How is histamine synthesised?
by decarboxylation from an amino acid precursor, histadine. Uses histidine decarboxylase
Where is histamine stored?
in granules in mast cells, basophils and enterocytes
Why is histamine released?
in response to a stimuli which is a Ca dependent exocytosis
how is histamine eliminated?
by oxidative deamination and/or transmethylation
what is produced when histamine undergoes deamination?
a ribose conjugate
what is produced when histamine undergoes transmethylation?
monoamine oxidase
Where are H1 receptors found and what do they control?
- found in smooth muscle, in endothelium cells and the CNS.
- control bronchoconstriction, vasodilation, pain itching, motion sickness, rhinitis, separation of epithelial cells
Where are H2 receptors found and what do they control?
- in gastric parietal cells, vascular smooth muscle cells, basophils
- regulate GA secretion, vasodilation, inhibition of IgE-dependent degranulation
Where are H3 receptors found and what do they control?
- in CNS cells and peripheral NS
- control release of DA, GABA, ACh, 5-HT and NE. Also controls presynaptic feedback, inhibiting histamine synthesis and release
Where are H4 receptors found and what do they control?
- in bone marrow and white blood cells
- mediate mast cell chemotaxis
What are H1 receptors coupled to?
Gq proteins which are coupled to phospholipase C (PLC)
What are H2 receptors coupled to?
Gs proteins which are coupled to adenylyl cyclase (AC) increasing cAMP.
What are H3 receptors coupled to?
Gi/o proteins which are coupled to AC as well as K-channels
What is the effect of H3 receptors on calcium influx and presynaptic neurotransmitter release?
reduces Ca influx and inhibits the neurotransmitter release.
What are H4 receptors coupled to?
Gi/o in mast cells and eosinophils
What is the effect of H4 receptors, coupled to eosinophils, on calcium?
it triggers calcium mobilisation causing mast cell chemotaxis.
What is the ‘triple response of Lewis’?
a cutaneous reponse that occurs from firm stroking of the skin producing:
- an initial red line
- a flare around the line
- a wheal
What happens when histamine is injected transdermally?
- a red spot appears
- flare
- wheal (oedema)
what is the effect of histamine on the heart?
- forces contraction of atrial and ventricular muscles by promoting Ca2+ influx.
- speeds heart rate by hastening diastolic depolarisation in SAN
- slows AV conduction to increase automaticity and elicit arrhythmias
Which receptor controls the majority of the effect of histamine on the heart?
H2 receptors and cAMP accumulation.
H1 only controls the slowing down of AV conduction
