Test 3 - Histamine, Serotonin and Depression Flashcards
What is the autocoid group for puritis? examples (4)
Released locally and act locally. biological substances that are released from the cell in response to variety of stimuli.
-histamine
-serotonin
-prostaglandins
-leukotrienes
(non neural)
The autacoid group can be _____ in neural tissues
neurotransmitters
In pruritis what induces the itch response?
the autacoid group
Pruritis can be _____ or _____
neuropathic or psychogenic
Histamine
mediator of allergic and inflammatory response
what are the effects of histamine on the nervous system?
Stimulates pain and itching via H1 and H3
Histamine release can be from a chemical response or a mechanical response. Give an example of each.
Chemical: morphine or tubocurarine causing itching
mechanical: damage to mast cells
What kind of receptors are Histamine receptors?
GCPR
H1 receptor subtype is located where?
smooth muscle, endothelium, brain. Gq
H2 receptor subtype is located where?
Gastric mucosa, cardiac muscle, mast cells, brain. Gs
H3 receptor subtype is located where?
presynaptic: brain, myenteric plexus, and other neurons. Gi
H4 receptor subtype is located where?
Esoinophils, neutrophils, CD4 T cells. Gi
Cardiovascular effects of histamine
decrease in BP - vasodilation
increase HR - reflex tachycardia (indirect response)
What are the effects seen with the Wheal and Flare - “Triple Response”
-injecting allergens that people might be allergic to
-the wheal is a positive test
-flare is the redness from capillary endothelium
What affect does histamine have in the stomach?
Secretory, stimulates release of hydrochloric acid
What effects does histamine have in the lungs?
Bronchoconstriction
Effects of histamine in the GI smooth muscle
contraction (peristalsis)
What are the two groups of H1 antihistamines?
- first generation
- second generation
First generation H1 antagonists effects
-sedative effects (crosses BBB)
-ANS blocking
Second generation H1 antagonists effects
more of a systemic reaction..less sedation (decreased CNS distribution)
Benadryl, dramamine and phenergan are examples of what?
First generation H1 antihistamines
Allegra, claritin and Zyrtec are all examples of what?
Second-generation H1 antihistamines
Biggest difference between first and second generation H1 antagonists
1st - sleepy
2nd - no sleepy
What are the effects of dramamine. what receptor?
H1 antagonist. first generation.
-sedation (resembles antimuscarinic drugs)
-antinausea/antiemetic
first generation H1 receptor antagonist toxicities
Sedation.
Anti-muscarinic effects (urinary retention, blurred vision)
Do we have the anti-muscarinic effects from H1 receptor or H2 receptor?
H1 receptor antagonist
Uses for H2 receptor antagonists
will shut down the production of hydrochloric acid in the stomach
Zantac, pepcid and tagamet are examples of what?
H2 receptor antagonists
H2 receptor antagonists have what effect?
shut down production of hydrochloric acid
H2 receptor antagonists, like zantac, have largely been replaced by what?
PPI’s
Histamine causes a _____ response while serotonin causes a ______ response
vasodilation
vasoconstriction
Serotonin causes what in the gut. how much is there?
peristalsis. 90%
Why is serotonin released?
Mast cell degranulation
describe serotonin and platelet clotting process
Vasoconstriction.
Serotonin is released via platelet degranulation. causing transient vasoconstriction due to the release of serotonin and that will give us time to form a clot so we don’t bleed out.
True/false: serotonin has a role in migraine headaches
True
Serotonin is stored or ______
rapidly inactivated
serotonin effects in the brain? (10)
- mood
- sleep
- appetite
- temp regulation
- pain perception
- blood pressure
- vomiting
- depression
- anxiety
- migraines
Primary place of serotonin production in the brain?
Raphe nuclei
What is the parent compound for serotonin?
L-Tryptophan
Serotonin is the parent compound for ______
melatonin
If were not getting enough sunlight, we wont produce enough _____ and this can cause depression (think seasonal depression)
melatonin
How many different 5-HT receptors are there
seven
how many of the 7 are GPCR and how many are ion channel?
6 GPCR
1 Ion (5-HT 3)
What is special about 5-HT3?
it is the only ion channel and it acts in an area in the brain to prevent nausea (ondansetron)
Serotonin effects in the nervous system
-melatonin precursor
-vomiting reflex
-pain and itch response
-chemoreceptor reflex (bradycardia and hypotension)
Serotonin effects in the respiratory system (2)
-Facilitate ACh release - constriction
-hyperventilation
CV affects of serotonin
-contraction of vascular SM (not skeletal or heart)
-platelet aggregation
Serotonin affects in the GI system
-increase tone
-facilitates peristalsis
-overproduction (diarrhea)
-Enteric nervous system (gut feeling)
Two main 5-HT agonists targets
- 5-HT 1A (anxiety)
- 5-HT 1B/D (migraine)
Two main 5-HT antagonists targets
- 5-HT2A
- 5-HT3 (antiemetic)
Buspirone acts on which 5-HT receptor. what is it used for?
1A.
anxiety or OCD.
It is a non-benzodiazapine anxiolytic (wont make us sleepy)
Sumatriptan works on which 5HT receptor? what is it used for?
5-HT 1D/1B agonist
migraine HA
What can we use as pain relief for migraine (4)
ASA, NSAIDS, ASA+Caffeine, opiods
Triptans are used to treat migraines. Which 5HT receptor does this act on? What does it do?
5-HT 1B/1D. Treats the aura as well as prevent dilation and stretching of pain endings
What can be given as a preventative for migraines (6)
- glucocorticoids - prednisone
- beta blockers
- antidepressants
- anti-seizure
- botox
- MAbs
Triptans for migraines are not _____
Prophylactic
Triptans for migraines can cause what toxicity
Serotonin syndrome which is a hyperthermic reaction with excess amounts of serotonin.
What are the three categories of hyperthermia disorders
- serotonin syndrom
- Neuroleptic malignant syndrome
- malignant hyperthermia
Treatment for serotonin syndrome
sedation (benzo), paralysis, intubation, ventilation
treatment for neuroleptic malignant syndrome
dihenhydramine
treatment for malignant hyperthermia
dantrolene
What are some drugs that can induce serotonin syndrome?
Anything that increases serotonin
- SSRI
- MAOI
- sumatriptan
- MDMA (molly)
- St Johns wort
What can cause neuroleptic malignant syndrome
D2 blocking antipsychotics
what can cause malignant hyperthermia?
ryanodine receptor stays open for longer. volatile anesthetics, succinylcholine
Serotonin and weight loss
used to be used for weight loss but no longer used
Phenoxybenzamine and cyproheptadine work on which 5-HT receptor?
5-HT2 antagonist
Ondansetron works on what 5-HT
5-HT3 antagonists. ion channel. prevent N/V
dopamine mesolimbic pathway
reinforcement and addiction.
What is DAT?
dopamine reuptake transporter
women in regards to depression and anxiety
women are affected twice as often as men by both
Depression is ____ energy. Anxiety is _____ energy
lack of
abundance of
major types of depression (5)
- dysthymia (overall depression)
- psychosis
- postpartum
- seasonal
- bipolar
major types of anxiety (4)
- generalized
- OCD
- PTSD
- social phobia
Four categories of antidepressant medications
- SSRI (selective serotonin reuptake inhibitor)
- SNRI (selective serotonin-NE reuptake inhibitor
- TCA (Tricyclic antidepressants)
- MAOI (monoamine oxidase inhibitors) (WE WANT TO AVOID THESE - severe side effects)
The pharmacology for all antidepressant medications is that they all …
increase monoamine neurotransmitter levels within the synapse
Prozac, celexa, paxil, zoloft and lexapro are examples of what?
SSRI
How do SSRI work?
inhibit SERT. allow serotonin to be in the synapse for longer.
Cymbalta and Pristique are what class of drugs? how do they work?
SNRI. Inhibit SERT and NET useful for more severe depression
Amitriptyline is an example of what? how does it work
TCA. Inhibit SERT, NET and some anticholinergic effects
uses and adverse effects of MAOI’s
refractory depression.
lethal drug interactions (CNS and PNS)
What bad side effect do all antidepression meds have in common?
suicidal ideation (first 1-2 months)
SERT
reuptake system for serotonin
MOA for MAOI’s
work on the enzyme in the presynaptic cell to inhibit the breakdown of serotonin, dopa and norepi
Other meds for depression
- NDRI (keep us awake)
- benzo (very sleepy)
- antipsychotics
True/false: All of the antidepressants mentioned have a black box warning
true
Alternative treatments for depression
- psychotherapy - “talk therapy”
- electroconvulsive therapy
- St Johns wort
What are the enterochromaffin cells? how do they relate to serotonin?
They are the cells that line the GI tract. 90% of serotonin is stored there
Adverse effects for antidepressants
-black box warning
1. drug interactions
2. N/V/D
3. sexual disfunction
pharmacokinetics for antidepressants
good bioav
plasma protein binding
liver M
renal CL
