Histamine, Serotonin Flashcards
Test 3
Describe autocoid transmission
local release and action of mediators like histamine, serotonin, prostaglandins, and leukotrienes
Describe Neuropathic vs psychogenic pruitis
Neuropathic: autacoid group binding to receptor
Psychogenic: thinking about itching makes you itch
Histamine is ________ stored & inactivated
rapidly
What do histamine receptors in the stomach produce?
Hydrochloric acid
What drugs induce histamine release?
Morphine
Tubocurarine
_____ can induce histamine release
trauma
Where are H1, H2, H3 receptors
H1 - blood vessels
H2 - stomach
H3 - brain
List the major organ system effects of histamine and serotonin.
Histamine: CVS: vasodilation & increased permeability
Respiratory: bronchoconstriction
GI: stimulating gastric acid secretion
Serotonin: CNS: regulating mood, sleep, and appetite
CVS: vasoconstriction/dilation
GI: promoting peristalsis
List the effects seen in the Triple Response of allergy testing and mediators.
** injecting small amounts of allergens to see what has a positive reaction**
Redness (due to capillary dilation)
Flare (a wider area of redness due to arteriolar dilation)
Wheal (a raised area due to increased vascular permeability) Mediators involved include histamine and other inflammatory substances
Itch
These are mediated by the release of histamine and other inflammatory mediators from mast cells.
List H1 antagonist
1st generation: Benadryl, phenergan, dramamine (crosses BBB - sedative effects - can be used for nausea)
2nd: Claritin, allegra, zyrtec (no CNS effects)
What drug counters histamine but not on the H-Receptors?
Epi
List H2 antagonists
OTC antacids
-dine
Children may have _______ effects with H1 antagonist
reverse
T/F: Platelet degranulation releases serotonin
T
Where is most of our serotonin stored?
90% stored in enterochromaffin cells in the gut
Describe the pharmacology of the 2 groups of H1 antihistamines and list prototypical agents for each group
a. First generation (sedating): Cross blood-brain barrier, have anticholinergic effects.
i. Prototypes include diphenhydramine (Benadryl) and chlorpheniramine.
b. Second generation (non-sedating): Do not cross blood-brain barrier as readily, fewer anticholinergic effects.
i. Prototypes include cetirizine (Zyrtec) and loratadine (Claritin).
Where is serotonin produced in the brain?
raphe nuclei
Serotonin is a derative of _________. and _____________ is a derative of serotonin
tryptophan
melatonin
What does increase in 5-HIAA in stool indicate?
tumor that is overproducing 5-HT vs infection causing diarrhea
List the uses of the H2 antihistamines, contrast PPIs, and name 2 members of this group.
H2 antihistamines reduce gastric acid secretion in conditions like peptic ulcers and gastroesophageal reflux disease (GERD).
PPIs: Proton pump inhibitors (PPIs), (e.g. omeprazole) are more effective at reducing gastric acid secretion and have a longer duration of action compared to H2 antihistamines.
Describe serotonin effects in neural and non-neural tissues.
a. Neural: In the brain, serotonin regulates mood, anxiety, and sleep
i. Appetite, pain, itch can also be affected
b. Non-neural: Platelet aggregation, vasoconstriction, gastrointestinal motility
i. Remember, SERO (Serum) TONIN (tone) so vessel tone is how it received its name originally
Describe the serotonin receptors
5-HT 1-7
All are GPCRs except 5-HT3 which is an ion channel
What Serotonin receptor is associated with nausea? where is it located?
5-HT3
postrema in the brain
List the source of serotonin in the brain, three main 5-HT agonist targets, two main 5-HT antagonist targets, and drugs in each category.
a. Serotonin in the brain is primarily produced in the raphe nuclei.
b. Main 5-HT agonist targets:
i. 5-HT1A e.g. buspirone (anxiety)
ii. 5-HT1B/1D e.g. sumatriptan (migraine)
iii. 5-HT2 e.g. Phenoxybenzamine (platelet aggregation, smooth muscle)
c. Main 5-HT antagonist targets:
i. 5-HT3 e.g. ondansetron (nausea/vomiting)
Compare and contrast preventatives and treatments for migraine headache
Preventatives: beta blockers, CCB, antidepressants, anti-seizure medications, and CGRP monoclonal antibodies, glucocorticoids (prednisone), botox
Tx: Triptans (sumatriptan), NSAIDs (ibuprofen), ergots (ergotamine and dihydroergotamine), and antiemetics (metoclopramide)
Describe the action and indication for the use of sumatriptan.
5-HT1B/1D agonist used migraines
vasoconstriction of cranial blood vessels and block pain signaling to treat the headache and associated symptoms.
what neurotransmitters are associated with migraines?
CGRP
Substance P
Trigeminal nerves
What effect does St. John warts have on serotonin levels?
increases them
List the three categories of hyperthermia disorders, contributing factors, and treatments.
Serotonin Syndrome: triggered by serotonergic medications = SSRIs, MAOIs, and certain recreational drugs; serotonin excess
-Tx: Benzodiazepine, paralyze, intubate
Neuroleptic Malignant Syndrome: associated with antipsychotic medications, particularly those that block dopamine receptors.
Tx: Diphenhydramine IV, cooling
Malignant Hyperthermia: triggered by certain anesthetic agents, such as succinylcholine and volatile anesthetics
Tx: Dantrolene, cooling
dopamine is a derivative of ________
tyrosine
Describe the Dopamine receptors
D1-5
Located all over body
All metabotropic
D1 is postsynaptic
D2-5 are autoreceptors and postsynaptic
Recall the dopamine mesolimbic pathway for reinforcement of behaviors.
Vs Nigrostriatal and Mesocortical
pathway associated with reinforcement and reward in the brain
Plays a role in addiction/negative and positive reinforcement of behaviors
Nigrostriatal- movement
Mesocortical- memory/planning
Depression is ______ energy; anxiety is ________
lack of energy
excess of energy/worrying
Differentiate between anxiety and depression, and list major types of each.
Depression: dysthmia, psychosis, postpartum, seasonal, bipolar
Anxiety: generalized, obsessive- compulsive, PTSD, Social phobia
List the four categories of antidepressant medications in order of treatment severity.
Selective serotonin reuptake inhibitors (SSRIs)
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Tricyclic antidepressants (TCAs)
Monoamine oxidase inhibitors (MAOIs)
List SSRI
Inhibit SERT (Serotonin transporter)
Fluoxetine (Prozac)
Sertraline (Zoloft)
List SNRI
Inhibit SERT and NET (Serotonin&NE transporter)
Cymbalta
Pristique
List Tricyclic Antidepressants
inhibit SERT, NET, and anticholinergic effects
Elavil
List Monoamine oxidase inhibitors
MAOIs
inhibit all transporters; rarely used
LETHAL DRUG INTERACTIONS
Nardil - irreversible
Selegiline
List alternative therapies for depression.
-psychotherapy
-lifestyle changes
-electroconvulsive therapy
-light therapy for seasonal affective disorder
-herbal supplements: St. John’s Wort.
What is the major black box warning on all antidepressant?
Can cause suicidal ideation within the first 1-2 months of taking, especially in adolescence
