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Pharm (Fall 2022) > Histamine & Serotonin (Exam IV) > Flashcards

Histamine & Serotonin (Exam IV) Flashcards

1
Q

What two types of pruritis exist?
Differentiate the two.

A
  • Neurogenic = Suppressed pain response or noxious stimuli.
  • Psychogenic = Imagined. (think of your nose being itchy so it then becomes itchy)
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2
Q

What are mediators of pruritis called?
What are the main members of this “group”

A

Autacoid Groups.
1. Histamine
2. Serotonin
3. Leukotrienes
4. Prostaglandins

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3
Q

What are histamines derived from?

A

Histadine (amino acid)

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4
Q

Where are the three main places where histamine is found?

A
  1. Mast cells (Immune system “vesicles”)
  2. Brain (as a neurotransmitter)
  3. Stomach (to create acid)
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5
Q

What are the two ways that histamine is released?

A
  1. Chemical Response
    - Morphine and Tubocurarine
  2. Mechanical Response
    - Mast Cell damage (particularly crush injuries)
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6
Q

Which two drugs cause an itchiness response by displacing histamine from mast cells?

A

Morphine and Tubocurarine

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7
Q

How many histamine receptor subtypes are there? (that we need to know about)

A

H1 - H4

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8
Q

Where are H1 receptors found?

A

Brain, smooth muscle, endothelium

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9
Q

Where are H2 receptors found?

A

Gastric Mucosa

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10
Q

Where are H3 receptors found?

A

Brain

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11
Q

Where are H4 receptors found?

A

WBC’s

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12
Q

What two ways exist to antagonize histamine?

A
  1. Physiologic reversal of effects with epinephrine.
  2. Histamine receptor antagonists.
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13
Q

Do 2nd generation H1-Antagonists cross the BBB?
What is the consequence of this?

A

No, less sedation is observed.

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14
Q

Do first generation H1-Antagonists cross the BBB?
What does this result in?
What is a drug example?

A
  • Yes
  • Sedation
  • Benadryl (diphenhydramine)
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15
Q

Which four first generation H1-antagonists should be known?
What is their respective use/effect?

A
  1. Dimenhydrinate (dramamine) - motion sickness
  2. Diphenhydramine (benadryl) - sedation
  3. Promethazine (phenergan) - antiemetic
  4. Cyproheptadine (periactin) - antiserotonin
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16
Q

What 2nd generation H1-antagonists should be known?

A
  • Fexofenadine
  • Loratadine
  • Cetirizine
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17
Q

What is an off-label use for H1-antagonists?

A

Pregnancy morning sickness

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18
Q

What would H1-antagonist toxicity symptoms be?

A
  • Sedation
  • Antimuscarinic effects (urinary retention & blurred vision)
  • Paradoxical (excitations, convulsions, paradoxical hypotension)
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19
Q

What are H2-antagonists used for?
What is their mechanism?

A
  • Decreasing stomach acid
  • Blocking histamine from binding to H2 receptors in the parietal cells of the stomach.
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20
Q

How is stomach acid made?

A
  1. Histamine binds to H2 receptors in stomach parietal cells
  2. H2 receptors = ↑ cAMP = PKA
  3. PKA = ↑ proton pumps = HCl acid.
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21
Q

What drug class is generally more effective for stomach acid reduction than H2-antagonists?

A

PPI

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22
Q

Where is 90% of serotonin?

A
  • GI tract
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23
Q

Where does serotonin target (produced?) in the GI tract?
What would cancer in this location cause?

A
  • Enterochromaffin cells
  • Diarrhea
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24
Q

Where does serotonin target (produced?) in the vasculature?

A

Platelets (constricts blood vessel at side of bleed where platelets are)

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25
Q

Where is serotonin produced in the brain?
What does it regulate in the brain?

A
  • Raphe Nuclei
  • Essentially everything
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26
Q

What is the precursor molecule of serotonin?
What type of molecule is this?

A

L-Tryptophan (an amino acid)

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27
Q

What drug class can precipitate serotonin syndrome?

A

MAOI’s

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28
Q

What enzyme metabolizes serotonin?
What is serotonin metabolized into?
How is this metabolite important?

A
  • Monoamine oxidase (MAO)
  • 5-hydroxindoleacetic acid (5-HIAA)
  • 5-HIAA is detectable in blood to test for enterochromaffin tumors.
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29
Q

Which serotonin receptor is not a GPCR?
What is this receptor and where is located?
What does this area regulate?

A
  • 5-HT₃
  • Ion channel located in Area Postrema
  • Area Postrema = vomiting reflex
30
Q

What is a 5-HT3 antagonist?

A

Ondansetron (Zofran)

31
Q

Which four serotonin effects on the nervous system were covered in lecture?

A
  1. Melatonin precursor
  2. Vomiting reflex
  3. Pain & itch (similar to histamine)
  4. Chemoreceptor reflex ( ↓ HR & BP )
32
Q

What does serotonin do in the respiratory system?

A
  • Facilitate ACh release = bronchoconstriction = ↑ respiratory rate.
33
Q

What does serotonin do in the cardiovascular system?

A
  • Causes contraction in smooth muscle
  • Platelet aggregation
34
Q

What does serotonin do in the GI tract?

A
  • ↑ intestinal tone
  • Facilitates peristalsis
35
Q

What does too much serotonin do to the GI tract?

A

Diarrhea

36
Q

What receptors do serotonin agonists target? Where are these receptors located?

A
  • 5-HT1a = Raphe Nuclei
  • 5-HT1b = Brain
  • 5-HT1c = Brain
37
Q

What receptors do serotonin antagonists target? Where are these receptors located?

A
  • 5-HT2a = Platelets
  • 5-HT3 = Area Postrema (N/V)
38
Q

What type of drug is Buspirone?
What is this drugs mechanism of action?
What disorders are indications for buspirone?

A
  • 5-HT1A partial agonist (non-benzo anxiolytic)
  • ↓ serotonin from Raphe Nuclei
  • GAD & OCD
39
Q

What is Sumatriptan?
What is the indication for sumatripan?
Is it prophylactic or just treatment of s/s?

A
  • 5HT1b/1d agonist
  • Migraines
  • Treatment of symptoms
40
Q

What three things are involved in Migraine disorder?
What are the major symptoms?

A
  • CGRP, Substance P, and the trigeminal nerve
  • Severe HA, N/V, photophobia, photophonia, speech problems.
41
Q

What pain relief drugs are most effective for migraines?

A
  • ASA or ASA/Caffeine
42
Q

What is the primary medication for treating migraines?
How do these drugs work?

A
  • Triptans - 5-HT1b/1d agonists
  • Bind to 5-HT1b/1d in cranial blood vessels preventing dilation and stretching.
43
Q

What drug can be prescribed for migraines but is often less effective than alternatives? This substance is what LSD is derived from.

A

Ergotamine

44
Q

What drugs are preventative for migraines?

A

Glucocorticoids (prednisone specifically)

45
Q

What 5 drugs are preventative for migraines?

A
  1. BB’s, CCBs, & ACEi (if BP is ↑)
  2. Antidepressants (SSRI’s, TCA’s)
  3. Anti-seizure drugs
  4. Botox (paralyzes blood vessels from dilating)
  5. MABs - (Aimovig - blocks CGRP receptors)
46
Q

What can Triptan toxicity cause?

A
  • Coronary vasospasm
  • Serotonin Syndrome (if taken w/ SSRI’s or MAOI’s)
47
Q

What serotonin-related weight loss drugs should be known?

A

None, they’ve all been recalled in the US.

48
Q
  • What drugs can precipitate Serotonin Syndrome?
  • What is the major sign/symptom in its clinical presentation?
  • What therapy is primarily indicated?
A
  • SSRI’s, MAOI’s, St. John’s Wort, Ginseng, etc.
  • Hyperthermia
  • Sedation, paralysis, intubation and ventilation, & cyproheptadine.
49
Q
  • What drugs can precipitate Neuroleptic Malignant Syndrome?
  • What is the major sign/symptom in its clinical presentation?
  • What therapy is primarily indicated?
A
  • D₂-Blocking Antipsychotics.
  • Hyperthermia
  • Diphenhydramine (Benadryl), & supportive care (cooling, sedation, etc.)
50
Q
  • What drugs can precipitate Malignant Hyperthermia?
  • What is the major sign/symptom in its clinical presentation?
  • What therapy is primarily indicated?
A
  • Volatile Anesthetics.
  • Hyperthermia
  • Removal of anesthetic and Dantrolene.
51
Q

What serious condition can cyproheptadine help treat?
Is it the primary therapy for this condition?
What is cyproheptadine’s mechanism of action?

A
  • Serotonin Syndrome
  • No, sedation with benzo’s, intubation/ventilation, & paralysis are the primary modalities of care.
  • Antihistamine that has 5-HT₂ block effects.
52
Q

What is the mortality of serotonin syndrome without proper care?

A

75%

53
Q

Which 5-HT₂ Antagonists should be known?
Do these drugs have any other effects?
What do these drugs treat?

A
  • Phenoxybenzamine (α1-antagonism) & Cyproheptadine (H1-antagonism)
  • Treatment of carcinoid tumors & cold-induced urticaria.
54
Q

Which 5-HT₃ antagonists should be known?

A
  • Ondansetron
55
Q

What molecule is the precursor to dopamine? What type of molecule is this?

A

Tyrosine (Amino acid)

56
Q

What is the biosynthesis pathway for dopamine?

A

Tyrosine → tyrosine hydroxylase → L-Dopa → dopa decarboxylase → Dopamine

57
Q

How many Dopamine receptors are there and what is their receptor type?
Where are these located?

A
  • D1 - D5
  • All are metabotropic
  • All are located in the CNS (D1 & D2 can be found peripherally as well)
58
Q

Where is dopamine produced in the brain?
What pathway is pertinent to reinforcement and addiction?

A
  • Substantia Nigra & Ventral Tegmental Area
  • Mesolimbic system.
59
Q

Are men or women more likely to be affected by depression and anxiety?

A

Women (twice as likely for both conditions)

60
Q

What is the fourth highest cause of disability worldwide?

A

Depression

61
Q

What are the four major classes of Antidepressant treatment?
Which of these is firstline therapy?
Which would be utilized last?

A
  1. SSRI’s (1st)
  2. SNRI’s
  3. TCA’s
  4. MAOI’s (last)
62
Q

How do SNRI’s differ from SSRI’s?

A
  • SNRI’s inhibit SERT (serotonin reuptake transporter) & NET (norepinephrine reuptake transporter).
  • SSRI’s only inhibit SERT.
63
Q

When are MAOI’s utilized?
Why are they not used more often?

A
  • Major Depression refractory to other care.
  • MAOI’s have lethal drug interactions.
64
Q

What are TCA’s mechanism of action?

A
  • Inhibition of SERT, NET, & some anticholinergic effects.
65
Q

What are NDRI’s?
Give some examples.

A
  • Norepinephrine/Dopamine Reuptake Inhibitors
  • Buproprion (Wellbutrin), Solfriamfetol (Sunosi)
66
Q

Which NDRI can promote wakefulness?

A
  • Solfriamfetol
67
Q

What type of drugs are anti-psychotics?
Give some examples.

A
  • D₂ Antagonists
  • Haloperidol, aripiprazole, Amisulpride
68
Q

What “Black Box” warning is found on many anti-anxiety/anti-depression medications?

A
  • Suicidal Tendency
69
Q

What alternative therapies exist apart from pharmacotherapies for depression/anxiety?

A
  1. Psychotherapy (seeing a therapist)
  2. Electroconvulsive therapy (severe depression)
  3. St. John’s Wort (mild depression)
70
Q

What is the #1 selling botanical product in the U.S.?

A

St. John’s Wort

71
Q

What drug is a 5-HT1a partial agonist?
What would this drug do?

A
  • Buspirone
  • ↓ Serotonin from Raphe Nucleus

Pharm (Fall 2022) (23 decks)

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