Serotonin Agonist & Antagonists Flashcards
Serotonin has biologic effects on which systems
CV & Platelets
GI tract
CNS
Disorders of the CNS, GI tract CV and others that affect the serotonin 5-HT receptor include:
CNS: migraines, depression, OCD, anxiety, schizophrenia, insomnia
GI tract: N/V, GERD
Obesity: Eating disorders
CV: smooth muscle contraction, stroke, coronary vasodilation, Bezold-Jarisch reflex (brady, hypotension, hypopnea, apnea)
Shivering
Premature ejaculation
Serotonin is synthesized from
L-tryptophan
L-tryptophan is obtained
in our diet
L-tryptophan is produced in what cells
enterochromaffin cells (intestines) serotonergic neurons
True or False
L-tryptophan is NOT synthesized
True
L-tryptophan is stored
Enterochromaffin cells
Platelets
CNS
Does L-tryptophan cross the BBB
No; must be synthesized in CNS
How is L-tryptophan biosynthesized
Hydoxylase»>decarboxylase»>serotonin (5-HT)
What are the modulators of 5-HT brain levels
Dietary intake (tryptophan)
consumption of competive aa
activity of alternate pathway of tryptophan degradation
** activity of degradation enzymes
activity of the 5-HT membrane transporter
Serotonin is metabolised by what intracellular enzyme and what gland
**MOA, type A»» 5-HIAA (measured in blood)
Pineal gland (forms melatonin via N-acetylation)
Reuptake occurs
serotonin trasporters
in the liver, lung endothelial cells
platelet accumulation
Serotonin effects on the CNS
enchances release of CRH via hypothalamus
Regulates temperature
What 5-HT receptor antagonist improves memory
5-HT6 receptor
The 5-HT1 receptors are primarily located
Hippocampus, basal gangllia, raphe nuclei
Decreases anxiety
5-HT2A receptors cause
CNS hallucinations
platelet aggregation
peripheral smooth muscle contraction
5-HT2B receptors cause
endothelium smooth muscle relaxation
Gastric fundus smooth muscle contraction
5-HT2C receptors cause
decreased appetite
** 5-HT3 receptors cause
Nausea NOT vomiting (area post rema)
Gastric empyting
***5-HT3 receptors are uniquely different than the other 5-HT receptors, how
5-HT 3 receptors are ligand-gated (Fast depolorizing channels)
All other 5-HT receptors are G-protein coupled receptors
Ecstasy works by
blocking serotonin transporters thereby significantly raising serotonin levels
What is serotonin’s effect on sleep, anxiety, aggressiveness, and depression
cause sleep induction, decreases anxiety, decreases aggressiveness, and depression
Serotonin’s effect on bronchiolar smooth muscle
contraction
** Serotonin CV effect on 5-HT1 receptor stimulation
Vasodilation
inhibits NE release
**Serotonin CV effects of 5-HT2 receptor stimulation
Contraction of most smooth muscle (bronchi, bladder) but
vasodiation of heart & skeletal muscle
**Serotonin CV effects on 5TH3 receptor stimulation
Immediate Bradycardia
Immediate Vomiting
*** Effect of serotonin on CV summary
Vasoconstriction/ Vasodilation Inc. contractility & heart rate Incr. GI motility Incr. blood viscosity Incr. SV/ CO Incr. PA pressure.
Membrane bound 5-HT transporter does what
removes serotonin from plasma»stores in dense granules cells (protects from MOA degradation)
Once secreted, induces vasoconstriction
5-HT2 receptors on platelets
enhances aggregation during bleeding
5-HT4 receptors on GI tract
ACH release
Prokinetic effect
anti-emetic effects
Too much serotonin causes
Anxiety, insomnia, Sexual dysfunction, GI disturbances, Seronoin syndrome»>death
Too little serotonin causes
Bulimia, panic, OCD, and depression
** Suicide receptor
5-HT2A
Pharm management of depression
TCA
SSRI
MOA inhibitors
SNRIs
Noradrenergic & Specific Serotonergic Antidepressants (NaSSAs)
Norepinephrine Reuptake inhibitors (NRIs)
Norepinephrine Dopamine Reuptake Inhibitors (NDRIs)
Selective Serotonin Reuptake Enhancers (SSREs)
Melatonergic Agonists
*TCAs- Reuptake inhibitors
" ptyline, and pramine" Amitriptyline Doxepin Imipramine Clomipramine Timipramine
- SSRIs- Reuptake inhibitors
Prozac luvox Paxil Zoloft Celexa Lexapro
- sertraline (zoloft), and warfarin
- inhibition of P450 system
- beware of patients on 2 or more SSRIs
- anticoagulants»incr. PT
- other antidepressants
- Lithium»CNS toxicity
- Antivirals»increased SSRI levels
- **Foods include: Banannas, kiwi, pineapple, plums, tomatoes incr. serotonin levels.
*MAO inhibitors-Degradation inhibitors
Marplan
Nardil
Parnate
Selegiline
Augmenter Drugs
Buspar-agonist Ariza-agonist Sediel- agonist Serzone-antagonist Desyrel-antagonis
*SNRIs- Reuptake inhibitors
Pristiq
Cymbalta
Effexor
Ixel
NaSSAs
Tolvon
Remeron
NRIs
Strattera
Mazanor
Edronax
Vivalan
SSREs
Stablon
Coaxil
Tatinol
Melatonergic Agonists
Valdoxan
Melitor
thymanax
5-HT3 antagonists
“setron”
Block receptor and cause immediate relief from nausea
5-HT1b & 5-HT 1d agonists
” Triptans”
Migrane regraine relief
*Contraindicated in CAD- Vasospasm
5-HT 2b agonists
“fen”
Anti-obesity
List the emetic centers in the brain that when ANTAGONIZED, decrease NAUSEA.
NTS- histamine, enkephalin, muscarinic
Area postrema (AP)- DA2, 5-HT3, opioid
CTZ- enkephalin, opioid, and DA2
NK 1- NK1 antagonist (Aprepitant) blocks substance P
Apfel score establishes risk for
PONV
What are the risk factors for PONV
PONV hx
female
nonsmoker
postop opioids
5-HT3 antagonists & Dexamethasone
Most effective against PONV
- Dose: zofran 4-8 mg: Dexam 8-10 mg adults
Serotonin syndrome
Serotonin syndrome is a potentially life threatening drug reaction that causes the body to have too much serotonin
Serotonin syndrome most often occurs when two drugs that affect the body’s level of serotonin are taken together at the same time
Signs & Symptoms of SS and Treatment
Symptoms are progressive and include: Agitation or restlessness Diarrhea Fast heart beat and high blood pressure Hallucinations Increased body temperature Loss of coordination Nausea Overactive reflexes Rapid changes in blood pressure Vomiting Muscle rigidity Tremor Nystagmus Myoclonus
TX: DC all Serotonergic drugs, Supportive
