DRUGS Flashcards
Describe the synthesis, metabolism, storage and release of histamine
Synthesis: biosynthesized from histidine via Histidine Decarboxylase
Metabolism:
• Via Diamine oxidase (DAO) → Imidazole acetaldehyde
• Via Histamine N-Methyltransferase (HNMT) → N- methylhistamine
Storage: • Mast cells (tissues, especially skin, lung mucosa, intestinal mucosa) • Basophils (blood) • Enterochromaffin-like cells in stomach • Neurons
Release in Immune Response:
• Mast cells and Basophils sensitized by IgE antibodies degranulate → release histamine when exposed to antigen
• IgG or IgM-mediated reactions that activate complement cascade also release histimine
• Histamine attracts neutrophils, Eosinophils, basophils, and other inflammatory cells
Types of histamine receptors
Receptors: 4 G protein-coupled subtypes
• H1: peripheral nerve endings, CNS, smooth muscle in blood vessels, bronchi, & intestine; Gq-coupled
• H2: gastric mucosa, heart, mast cells, CNS; Gs-coupled
• H3: autoreceptors (feedback loop regulators) on histaminergic neurons in CNS and PNS: Gi-coupled
• H4: Eosinophils, neutrophils, CD4 T-cells; Gi-coupled
Describe the synthesis, metabolism, storage and release of serotonin (5-HT)
Synthesis: biosynthesized from tryptophan via Tryptophan hydroxylase and Aromatic amino acid decarboxylase
Metabolism:
• Via SNAT and HIOMT → melatonin
• Via Monoamine oxidase (MAO) and Aldehyde dehydrogenase (ADH) → 5-HIA (biomarker for serotonin in urine)
Storage:
• Most in enterochromaffin cells in GI epithelium
• In blood: stored in platelet vesicles
• In brain: in synaptic vesicles
o Receptors: at least 14 subtypes
• Most are G-protein couples
• 5-HT3 receptor is ligand-gated ion channels
Serotonins effects
- CNS NT: affect mood, appetite, sexual activity, thermoregulation, sensory perception, sleep, memory, cognition
- Mediates vomiting in chemoreceptor trigger zone (5-HT3 receptor) in BBB
- GI Tract: 5-HT3 activation suppresses GI motility vs 5-HT4 activation promotes motility
- CV system: released from platelets to initiate blood clotting
- Vasoconstriction (5-HT1, 5-HT2, 5-HT7), involved in BP and migraine
H1 receptor effects
o Vasodilation of small vessels → flushing, decreased TPR, decreased BP
o Increases capillary permeability → edema, urticaria
o Bronchoconstriction and bronchospasm (decreased airwary)
o Nerve endings: pain and itch
o Contraction of intestinal smooth muscle
H2 receptor effects
o Vasodilation of small blood vessels
o Increased HR → reflex tachycardia and direct stimulation
o Gastric acid secretion
Describe serotonin syndrome and its clinical presentation
• Caused by excessive serotonin concentrations at its receptors
• Can be precipitated by concomitant use of drugs that enhance synaptic serotonin concentrations (usually developing <12 hrs)
• Symptoms: agitation, hyperthermia, flushing, GI disturbances, myoclonus (twitching), rhabdomyolysis, tremor and seizures, psychological changes
• Treat:
o Remove precipitating drugs, supportive care (monitor vitals, IV fluids), control agitation (benzodiazepines), give 5-HT2A antagonists (cyproheptadine), control HT and tachycardia (sodium nitroprusside, esmolol), control hyperthermia (vecuronium = NMJ blocker to relax muscle) but no role for antipyretic drugs
Name antihistamine drugs
H1: Diphenhydramine (Benadryl, Sominex) Cetirizine (Zyrtec) Fexofenadine (Allegra) Loratadine (Claritin, Tavist ND)
H2:
Cimetidine (Tagamet)
Name drugs affecting serotonin
Ergotamine (Ergomar)
Sumatriptan (Imitrex)
Name steroid drugs
Betamethasone Dexamethasone Hydrocortisone Prednisone Fluticasone
Name Prostanoid drugs
Alporstadil
Latanoprost
Misoprostol
Leukotriene Agents
Montelukast
Zafirlukast
Zileuton
NSAID drugs
Aspirin Celecoxib Diclofenac Ketorolac Ibuprofen Indomethacin Meloxicam Naproxen
Thromboxane A2 effects
TP receptor
vasoconstriction platelet aggregation
Prostaglandin E2 Effects
EP1-4 receptors
vasodilation hyperalgesia fever diuresis immunosuppression
