Histamine & Serotonin (Exam IV) Flashcards
What two types of pruritis exist?
Differentiate the two.
- Neurogenic = Suppressed pain response or noxious stimuli.
- Psychogenic = Imagined. (think of your nose being itchy so it then becomes itchy)
What are mediators of pruritis called?
What are the main members of this “group”
Autacoid Groups.
1. Histamine
2. Serotonin
3. Leukotrienes
4. Prostaglandins
What are histamines derived from?
Histadine (amino acid)
Where are the three main places where histamine is found?
- Mast cells (Immune system “vesicles”)
- Brain (as a neurotransmitter)
- Stomach (to create acid)
What are the two ways that histamine is released?
- Chemical Response
- Morphine and Tubocurarine - Mechanical Response
- Mast Cell damage (particularly crush injuries)
Which two drugs cause an itchiness response by displacing histamine from mast cells?
Morphine and Tubocurarine
How many histamine receptor subtypes are there? (that we need to know about)
H1 - H4
Where are H1 receptors found?
Brain, smooth muscle, endothelium
Where are H2 receptors found?
Gastric Mucosa
Where are H3 receptors found?
Brain
Where are H4 receptors found?
WBC’s
What two ways exist to antagonize histamine?
- Physiologic reversal of effects with epinephrine.
- Histamine receptor antagonists.
Do 2nd generation H1-Antagonists cross the BBB?
What is the consequence of this?
No, less sedation is observed.
Do first generation H1-Antagonists cross the BBB?
What does this result in?
What is a drug example?
- Yes
- Sedation
- Benadryl (diphenhydramine)
Which four first generation H1-antagonists should be known?
What is their respective use/effect?
- Dimenhydrinate (dramamine) - motion sickness
- Diphenhydramine (benadryl) - sedation
- Promethazine (phenergan) - antiemetic
- Cyproheptadine (periactin) - antiserotonin
What 2nd generation H1-antagonists should be known?
- Fexofenadine
- Loratadine
- Cetirizine
What is an off-label use for H1-antagonists?
Pregnancy morning sickness
What would H1-antagonist toxicity symptoms be?
- Sedation
- Antimuscarinic effects (urinary retention & blurred vision)
- Paradoxical (excitations, convulsions, paradoxical hypotension)
What are H2-antagonists used for?
What is their mechanism?
- Decreasing stomach acid
- Blocking histamine from binding to H2 receptors in the parietal cells of the stomach.
How is stomach acid made?
- Histamine binds to H2 receptors in stomach parietal cells
- H2 receptors = ↑ cAMP = PKA
- PKA = ↑ proton pumps = HCl acid.
What drug class is generally more effective for stomach acid reduction than H2-antagonists?
PPI
Where is 90% of serotonin?
- GI tract
Where does serotonin target (produced?) in the GI tract?
What would cancer in this location cause?
- Enterochromaffin cells
- Diarrhea
Where does serotonin target (produced?) in the vasculature?
Platelets (constricts blood vessel at side of bleed where platelets are)
Where is serotonin produced in the brain?
What does it regulate in the brain?
- Raphe Nuclei
- Essentially everything
What is the precursor molecule of serotonin?
What type of molecule is this?
L-Tryptophan (an amino acid)
What drug class can precipitate serotonin syndrome?
MAOI’s
What enzyme metabolizes serotonin?
What is serotonin metabolized into?
How is this metabolite important?
- Monoamine oxidase (MAO)
- 5-hydroxindoleacetic acid (5-HIAA)
- 5-HIAA is detectable in blood to test for enterochromaffin tumors.
Which serotonin receptor is not a GPCR?
What is this receptor and where is located?
What does this area regulate?
- 5-HT₃
- Ion channel located in Area Postrema
- Area Postrema = vomiting reflex
What is a 5-HT3 antagonist?
Ondansetron (Zofran)
Which four serotonin effects on the nervous system were covered in lecture?
- Melatonin precursor
- Vomiting reflex
- Pain & itch (similar to histamine)
- Chemoreceptor reflex ( ↓ HR & BP )
What does serotonin do in the respiratory system?
- Facilitate ACh release = bronchoconstriction = ↑ respiratory rate.
What does serotonin do in the cardiovascular system?
- Causes contraction in smooth muscle
- Platelet aggregation
What does serotonin do in the GI tract?
- ↑ intestinal tone
- Facilitates peristalsis
What does too much serotonin do to the GI tract?
Diarrhea
What receptors do serotonin agonists target? Where are these receptors located?
- 5-HT1a = Raphe Nuclei
- 5-HT1b = Brain
- 5-HT1c = Brain
What receptors do serotonin antagonists target? Where are these receptors located?
- 5-HT2a = Platelets
- 5-HT3 = Area Postrema (N/V)
What type of drug is Buspirone?
What is this drugs mechanism of action?
What disorders are indications for buspirone?
- 5-HT1A partial agonist (non-benzo anxiolytic)
- ↓ serotonin from Raphe Nuclei
- GAD & OCD
What is Sumatriptan?
What is the indication for sumatripan?
Is it prophylactic or just treatment of s/s?
- 5HT1b/1d agonist
- Migraines
- Treatment of symptoms
What three things are involved in Migraine disorder?
What are the major symptoms?
- CGRP, Substance P, and the trigeminal nerve
- Severe HA, N/V, photophobia, photophonia, speech problems.
What pain relief drugs are most effective for migraines?
- ASA or ASA/Caffeine
What is the primary medication for treating migraines?
How do these drugs work?
- Triptans - 5-HT1b/1d agonists
- Bind to 5-HT1b/1d in cranial blood vessels preventing dilation and stretching.
What drug can be prescribed for migraines but is often less effective than alternatives? This substance is what LSD is derived from.
Ergotamine
What drugs are preventative for migraines?
Glucocorticoids (prednisone specifically)
What 5 drugs are preventative for migraines?
- BB’s, CCBs, & ACEi (if BP is ↑)
- Antidepressants (SSRI’s, TCA’s)
- Anti-seizure drugs
- Botox (paralyzes blood vessels from dilating)
- MABs - (Aimovig - blocks CGRP receptors)
What can Triptan toxicity cause?
- Coronary vasospasm
- Serotonin Syndrome (if taken w/ SSRI’s or MAOI’s)
What serotonin-related weight loss drugs should be known?
None, they’ve all been recalled in the US.
- What drugs can precipitate Serotonin Syndrome?
- What is the major sign/symptom in its clinical presentation?
- What therapy is primarily indicated?
- SSRI’s, MAOI’s, St. John’s Wort, Ginseng, etc.
- Hyperthermia
- Sedation, paralysis, intubation and ventilation, & cyproheptadine.
- What drugs can precipitate Neuroleptic Malignant Syndrome?
- What is the major sign/symptom in its clinical presentation?
- What therapy is primarily indicated?
- D₂-Blocking Antipsychotics.
- Hyperthermia
- Diphenhydramine (Benadryl), & supportive care (cooling, sedation, etc.)
- What drugs can precipitate Malignant Hyperthermia?
- What is the major sign/symptom in its clinical presentation?
- What therapy is primarily indicated?
- Volatile Anesthetics.
- Hyperthermia
- Removal of anesthetic and Dantrolene.
What serious condition can cyproheptadine help treat?
Is it the primary therapy for this condition?
What is cyproheptadine’s mechanism of action?
- Serotonin Syndrome
- No, sedation with benzo’s, intubation/ventilation, & paralysis are the primary modalities of care.
- Antihistamine that has 5-HT₂ block effects.
What is the mortality of serotonin syndrome without proper care?
75%
Which 5-HT₂ Antagonists should be known?
Do these drugs have any other effects?
What do these drugs treat?
- Phenoxybenzamine (α1-antagonism) & Cyproheptadine (H1-antagonism)
- Treatment of carcinoid tumors & cold-induced urticaria.
Which 5-HT₃ antagonists should be known?
- Ondansetron
What molecule is the precursor to dopamine? What type of molecule is this?
Tyrosine (Amino acid)
What is the biosynthesis pathway for dopamine?
Tyrosine → tyrosine hydroxylase → L-Dopa → dopa decarboxylase → Dopamine
How many Dopamine receptors are there and what is their receptor type?
Where are these located?
- D1 - D5
- All are metabotropic
- All are located in the CNS (D1 & D2 can be found peripherally as well)
Where is dopamine produced in the brain?
What pathway is pertinent to reinforcement and addiction?
- Substantia Nigra & Ventral Tegmental Area
- Mesolimbic system.
Are men or women more likely to be affected by depression and anxiety?
Women (twice as likely for both conditions)
What is the fourth highest cause of disability worldwide?
Depression
What are the four major classes of Antidepressant treatment?
Which of these is firstline therapy?
Which would be utilized last?
- SSRI’s (1st)
- SNRI’s
- TCA’s
- MAOI’s (last)
How do SNRI’s differ from SSRI’s?
- SNRI’s inhibit SERT (serotonin reuptake transporter) & NET (norepinephrine reuptake transporter).
- SSRI’s only inhibit SERT.
When are MAOI’s utilized?
Why are they not used more often?
- Major Depression refractory to other care.
- MAOI’s have lethal drug interactions.
What are TCA’s mechanism of action?
- Inhibition of SERT, NET, & some anticholinergic effects.
What are NDRI’s?
Give some examples.
- Norepinephrine/Dopamine Reuptake Inhibitors
- Buproprion (Wellbutrin), Solfriamfetol (Sunosi)
Which NDRI can promote wakefulness?
- Solfriamfetol
What type of drugs are anti-psychotics?
Give some examples.
- D₂ Antagonists
- Haloperidol, aripiprazole, Amisulpride
What “Black Box” warning is found on many anti-anxiety/anti-depression medications?
- Suicidal Tendency
What alternative therapies exist apart from pharmacotherapies for depression/anxiety?
- Psychotherapy (seeing a therapist)
- Electroconvulsive therapy (severe depression)
- St. John’s Wort (mild depression)
What is the #1 selling botanical product in the U.S.?
St. John’s Wort
What drug is a 5-HT1a partial agonist?
What would this drug do?
- Buspirone
- ↓ Serotonin from Raphe Nucleus
