Term
| 5HT is synthesized from ___ by ___ and ___ |
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Definition
Dietary tryptophan
Tyrptophan hydroxylase and L-aromatic aa decarboxylase |
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Term
| Circulating 5HT is eliminated from the plasma by ___ and ___ |
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Definition
Pulmonary uptake
Hepatic metabolism |
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Term
| 5HT is metabolized by ___ to ___ which is excreted by ___. |
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Definition
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Term
| 5HT sites of synthesis (4) |
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Definition
Central neurons (raphe nuclei)
Myenteric and submucosal plexuses
Enterochromaffin cells
Plants, venoms
Not platelets or mast cells! |
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Term
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Definition
NT: CNS, GI tract
Precursor for melatonin
Autocoid: VC, increased plt aggregation
*Act on the CTZ and cerebral blood vessels* |
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Term
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Definition
Directly stimulate VSM
Stimulate endothelial cells to produce NO
Inhibit prejunctional NE release from sympathetic fibers |
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Term
| 5HT1BR stimulation: effects (2) |
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Definition
Constricts large extracerebral arteries, arteriovenous anastomoses, coronaries
Inhibits release of pro-inflamm peptides from trigeminal nerve endings into perivascular space (5HT1D-R too) |
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Term
| 5HT1R: behavior physiology |
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Definition
| 5HT1A stimulation opens CNS K channels => hyperpolarizes the cell => inhibits neuronal activity |
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Term
| 5HT2R stimulation: physiology |
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Definition
| Increase IP3 and intracellular Ca |
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Term
| Peripheral 5HT2R: effects (5) |
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Definition
VC
Stimulate endothelial cell PGI2 synthesis
Plt aggregation (amplifies aggregation caused by TXA2, EPI, thrombin)
*Bronchoconstriction*
*Increased intestinal motility and secretion* |
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Term
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Definition
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Term
| Central 5HT2R are the major 5HTR involved in ___ |
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Definition
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Term
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Definition
| Stimulation of prejunctional receptors increases ACh release from intramural neurons of GI tract |
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Term
| 5HT3R: sensory physiology (3) |
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Definition
Bezold Jarisch chemoR reflex
Stimulation of dermal afferent pain fibers
Stimulation of afferent vagal fibers to CTZ
Emesis by direct stimulation of CTZ |
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Term
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Definition
Dolasetron
Metoclopramide
Ondansetron |
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Term
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Definition
| Stimulation of prejunctional receptors increases ACh release from intramural cholinergic neurons of the GI tract |
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Term
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Definition
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Term
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Definition
CNS
CV
Hemostasis
Bronchoconstriction in asthmatics (5HT2)
Sensory (5HT3)
Contraction of uterus
GI tract |
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Term
| Serotonin: CNS effects (6) |
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Definition
| Regulation of sleep, affect, temperature, sexual behavior, perception of pain, BP |
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Term
| Serotonin: peripheral blood vessel effects (5) |
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Definition
5HT2: constricts all vessels except skeletal muscle and heart (5HT1 dilates)
But 5HT1B: constricts coronaries in CAD
Pulmonary blood vessel constriction lowers venous return and thus CO
Afferent arteriolar constriction lowers GFR and thus urine flow
Constricts venules > arterioles => blood pools in capillaries => flushing, bluish hue (no effect on capillary permeability |
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Term
| Serotonin: cerebral blood vessel and heart effects (2) |
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Definition
5HT1B: constricts large extracerebral arteries and arteriovenous anastomoses
CV reflexes cause secondary change in rate and dp/dt |
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Term
| Serotonin: BP effects (triphasic) |
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Definition
5HT3: Bezold Jarisch reflex = central inhibition of sympathetic tone => vagally-mediated bradycardia and VD
5HT2: direct constriction of resistance vessels
5HT1 in skeletal muscles: VD |
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Term
| Serotonin: hemostasis effect |
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Definition
Repair of damaged blood vessels: plt release 5HT => 5HT2: accelerates plt aggregation and local VC
Doesn't produce a plt release reaction! |
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Term
| Serotonin: sensory effects (3) |
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Definition
5HT3
-Decreased BP
-Pain, itching
-Vomiting |
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Term
| Serotonin: GI origins (2), effects (2) |
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Definition
5HT release stimulated by:
-Vagal release of ACh
-Rise in intraluminal pressure causing release from enterochromaffin cells
5HT2 and 5HT3: directly increase tone and motility, indirectly lower threshold of intraluminal pressure required to activate peristalsis
5HT3 and 5HT4: enhances release of ACh => increased GI motility, tone, secretion
Not important in the normal regulation of GI motility! |
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Term
| Serotonin: pathophysiological effects (5) |
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Definition
Depression
N/v
CV disease
Carcinoid syndrome
Post-gastrectomy dumping syndrome |
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Term
| Serotonin: carcinoid syndrome effects (5) |
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Definition
RARE!
Enterochromaffin cell tumors secrete serotonin autonomously or in response to stimuli like alcohol
Bronchospasm
Intestinal cramping and diarrhea
Steatorrhea
Unusual flushing of skin of trunk and neck |
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Term
| Carcinoid syndrome: S/E large tumors, treatment, other players |
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Definition
Large tumors may use so much tryptophan for 5HT synthesis that niacin synthesis suffers and the patient contracts pellagra
*Treat with cyproheptadine (block 5HT1 and 2) or octreotide (inhibits release of 5HT)*
Histamine and PG may play a role |
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Term
| Post-gastrectomy dumping syndrome: pathophysiology |
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Definition
Surgical tx of peptic ulcer => rapid dumping of hyperosmolar stuff into intestines
Rapid shift of water from vascular to gut => hypovolemia => baroreflexly-mediated increase in sympathetic activity
Stimulation of 5HT release into the lumen
Direct/indirect increase in tone, motility, peristalsis, stimulation of afferent vagal fibers |
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Term
| Post-gastrectomy dumping syndrome: symptoms (6) |
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Definition
Tachycardia
Dizziness
Postural hypotension
Sweating
Ab pain
v/d |
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Term
| Migraine and cluster headaches: drug |
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Definition
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Term
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Definition
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Term
| Sumatriptan: pharmacologic effects (2) |
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Definition
5HT1B/D: stim inhibits release of proinflamm peptides from trigeminal nerve endings into perivascular space => no stimulation of sensory pain receptors => no VD or neurogenic extravasation of plasma
5HT1B: stim constricts large extracerebral arteries and arteriovenous anastomoses |
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Term
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Definition
Slight VC in normal vessels but cause arterial spasm in CAD
Rebound headache
Atypical sensations
Dizziness/vertigo
Increased SBP/DBP
Don't use with ergot-type drugs or w/in 24 hrs of them |
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Term
| Sumatriptan: cluster headache effects (2) |
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Definition
Significantly decreases severity of pain
Decreases functional disability and ipsilateral conjunctival injection |
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Term
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Definition
Antagonist at 5HT3 (vagal afferents, CTZ), D2 (CTZ): antiemetic
Agonist at 5HT4: enhances ACh release from cholinergic neurons innervating LES and stomach |
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Term
| Metoclopramide: pharmacologic effects (4) |
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Definition
Enhances esophageal clearance of gastric acid
Elevates LES pressure
Accelerates gastric emptying
Decreases small bowel transit time |
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Term
| Metoclopramide: indications (6) |
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Definition
Increase LES pressure in GERB (including babies)
Empty stomach and increase LES pressure pre-op
Clear stomach/duodenum pre-endoscopy
Enhance gastric emptying in patients with diabetic gastroparesis
Prevent n/v in patients with peptic ulcer, UC, gastric cancer
Prevent n/v in chemo or XRT for cancer |
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Term
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Definition
Sedation, fatigue
Altered GI absorption of other drugs
Blockade of central D2R: dystonias, Parkinson's syndrome, tardive dyskinesia, akathisia, galactorrhea, amenorrhea, gynecomastia |
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Term
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Definition
Cyproheptadine
Dolasetron
Ondansetron |
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Term
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Definition
| Selective 5HT3 blocker = no effect at 5HT4 or DA-R |
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Term
| Ondansetron: pharmacologic effect |
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Definition
| Inhibits 5HT from binding at 5HT3R at vagal nerve endings or CTZ => no n/v (chemo, XRT) |
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Term
| Ondansetron: indications (3) |
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Definition
N/v due to:
-Chemo/XRT
-Post-op
Morning sickness (category B) |
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Term
| Ondansetron is preferred over metoclopramide because... (2) |
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Definition
Doesn't cause dystonia or akathisia
Can use in kids/younger adults (who are already most likely to get dystonia) |
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Term
| Ondansetron is equally as effective as ___ in treating n/v caused by chemo. Their combination is ___ than either agent given alone |
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Definition
Dexamethasone
Combination is more effective |
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Term
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Definition
| Blocks 5HT1/2, H1, muscarinic (adverse S/E) |
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Term
| Cyproheptadine: indications (6) |
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Definition
Allergic diseases (antihistamine effects)
Appetite stimulant
Migraines
Carcinoid syndrome
Post-gastrectomy dumping syndrome: partially relieves GI symptoms
PTSD (5HT2R): soporific to prevent nightmares |
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Term
| Cyproheptadine: allergic indications (4) |
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Definition
Allergic rhinitis
Conjunctivitis
Pruritic dermatoses
Prophylaxis of cold urticaria |
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Term
| Cyproheptadine: appetite stimulant effects (3) |
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Definition
Due to blockage of 5HT2R, but other than that MOA is unknown
Stimulates food intake in kids and adults
Produces variable weight gain/linear growth in babies/kids
Effective in some patients with anorexia |
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Term
| Cyproheptadine: migraine effect |
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Definition
| Prophylaxis reduces frequency/intensity of attacks |
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Term
| Cyproheptadine: carcinoid syndrome effects (3) |
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Definition
| Decreases GI hypermotility, hypersecretion, and diarrhea |
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Term
| Cyproheptadine: S/E (5, just like atropine) |
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Definition
Exacerbation of angle-closure glaucoma, BPH, GI/GU obstruction
CNS depression (additive with other drugs)
Drowsiness, sedation
Paradoxical restlessness/excitation in kids
Dry mouth, nose, throat |
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