Lecture 5- Autocids: Histamine + Antihistamine Drugs Flashcards
Autocoid
-common feature of being formed by the tissues on which they act
^as a result= function as local hormones
-differ from circulating hormones which are produced by many tissues rather than in specific endocrine organs
Examples; prostaglandins, histamine, serotonin and bradykinin
Histamine
-found in most tissues but is present in high concentrations in the lungs, skin and the GIT
-cellular level= found in mast cells and basophils
-non-mast cell histamine= occurs in ‘histaminocytes’ in the stomach and in the histaminergic neurones in the brain
Histamine synthesis and storage
-basic amine formed from histidine by the action of histidine decarboxylase
-mast cells + basophils= histamine is stored in intercellular granules in a complex with an acidic protein
Histamine release
-released in response to inflammatory and allergic stimuli
Conditions which release histamine
*tissue injury= physical/chemical agent which causes injury to the tissue/skin will trigger release of histamine from mast cells
*allergic reactions= exposure of an antigen to a previously sensitised individual can trigger allergic reactions through the actions of IgE antibodies
*drugs + other foreign compounds; such as morphine, dextran, anti malarial drugs, penicillins = can trigger histamine release
Histamine receptors
-histamine released in response to various stimuli exerts its effects by binding to either H1-H4 receptors
-H1 + H2 receptors = widely expressed are the targets of clinically useful drugs whilst H3 + H4 receptors are expressed in only a few cell types
-some pharmacological actions of histamine are mediated by both H1 + H2 receptors while others are mediated by 1 class
Histamine receptors
H1 receptors= mediate effects on smooth muscle leading to vasodilation + increased vascular permeability
H2 receptors mediate histamine stimulation of gastric acid secretion
H3 receptors occur at presynaptic sites + inhibit the release of a variety of neurotransmitters in the CNS, GIT, lung and heart
Pharmacological actions of histamine
*stimulating gastric acid secretion via H2 receptors-implicated in peptic ulcer
*contracts the smooth muscle of the ileum, bronchitis, bronchioles and uterus. Reduces airflow in the early phase of bronchial asthma
*promotes vasodilation by causing vascular endothelium to release nitric oxide
*intradermal injection of histamine causes H1-mediated reddening of the skin, accompanied by a wheal surrounding flare
Pharmacological actions of histamine
*IV injection of histamine produces symptoms similar to anaphylactic shock and allergic reactions;
- contraction of smooth muscle
- stimulation of secretions
- dilation and increased permeability of the capillaries
- stimulation of sensory nerve endings to produce itching
*produces many signs + symptoms of inflammation
Antihistamines
-refers to classic H1 receptor blockers
Drugs;
-block the receptor-mediated response of a target issue to histamine
-compete with histamine for binding
-displace histamine from receptor
H1 blockers;
1. First-gen antihistamines= older drugs which penetrate the CNS + cause sedation. Exert non-selective actions by blocking histamine H1 + cholinergic, a-adrenergic and serotonin receptors. Produce adverse effects
- Second-gen antihistamines= specific for H1 receptors since they do not penetrate the blood-brain barrier. Show less CNS effects than first-gen drugs
Antihistamines
First-gen (sedating) antihistamines;
*clemastine fumarate
*cyproheptadine hydrochloride
*chlorpheniramine maleate
*hydroxyzine hydrochloride
*promethazine hydrochloride
Second-gen (non-sedating) antihistamines;
*acrivastine
*cetirizine hydrochloride
*loratadine
*desloratadine
*fexofenadine
*mizolastine
Pharmacological actions of antihistamines
-actions of all histamine h1 blockers= similar
-effects reflect binding of these drugs to cholinergic (anti-nausea + anti-emetic effects), adrenergic or serotonergic receptors
Pharmacological actions of antihistamines
*h1 blockers inhibit most of the effects of histamine on smooth muscles; constriction of respiratory smooth muscle
*h1 blockers strongly block the increased in permeability + formation of oedema + wheal produced by histamine
*suppress the flare component of the triple response + itching caused by intradermal injection of histamine
*reduce allergy and anaphylaxis
Therapeutic uses of antihistamines
*allergic conditions- allergic rhinitis, sneezing + itching of eyes and nasal mucosa
*motion sickness-prevention and treatment of nausea and vomiting
Adverse effects of antihistamines
*sedation; first gen drugs
*appetite loss, nausea and vomiting, irritability, tachycardia, dry mouth, blurred vision, urinary retention and constipation
*CNS stimulation; hallucinations, motor disturbances and death
*drug interactions; first-gen antihistamines can potentiate CNS depressants
