Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology > Autacoids > Flashcards

Autacoids Flashcards

1
Q

What are autacoids?

Examples?

A
  1. Endogenous substances that mediate inflammation

2. Histamine, Serotonin, Lipid-derived eicosanoids, bradykinin, cytokines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Histamine-general

A

z Stored in mast cells and basophils, released by antigen binding to IgE antibodies on cell surface

z Produces vasodilation, flushing, vascular permeability, bronchoconstriction, pain, and itch

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

serotonin-general

A

Main role in inflammation is vasodilation, but can produce vasoconstriction and platelet
aggregation if tissue is damaged

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Lipid-derived eicosanoids: prostaglandins, leukotrienes

-general

A

Modulate pain, bronchial tone, vascular tone, platelet function, inflammatory cell function,
uterine tone, GI function, renal function, CNS function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Bradykinin and related peptides

general

A

Produce pain, vasodilation, vascular permeability, stimulate prostaglandin biosynthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q
  1. Synthesis of Histamine

2. metabolism of histamine

A
  1. Biosynthesized from histidine via histidine decarboxylase
  2. metabolized by:
    - Diamine oxidase (phase I)
    - Histamine-N-methyltransferase (phase II)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Storage of histamine

A

z Mast cells (tissues, especially skin, lung mucosa, intestinal mucosa)

z Basophils (blood)

z Enterochromaffin-like cells in stomach

z Neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Histamine Receptors

A

G protein-coupled Receptors:

  1. H 1 : peripheral nerve endings, CNS, smooth muscle of blood vessels, bronchi, and intestine; G q -coupled
    - #1 most important is breathing
  2. H 2 : gastric mucosa, heart, mast cells, CNS; G s -coupled
    - I have to go #2=stomach
    - Gs b/c s is for sh*t
  3. H 3 : autoreceptors on histaminergic neurons in CNS and PNS; G i -coupled
  4. H 4 : Eosinophils, neutrophils, CD4 T-cells; G i -coupled
    - H4=CD4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What causes histamine release?

A

1) mast cells and basophils degranulate if surface IgE bind w/antigen
2. Substances released during IgG/IgM rxns that activate complement cascade

  1. Certain drugs: benzylisoquinoline, NMJ blockers, opioids, succinylcholine)
    - thus these drugs can cause itchiness

neutrophils, basophils, and others are attarcted to histamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Ways to antagonize histamine

A
  1. Physiological antagonism
    - Example: epinephrine to reverse effects of anaphylaxis
  2. Inhibit histamine release
    - Cromolyn sodium
    - Nedocromil
    - above drugs used for asthma
  3. Histamine receptor antagonists
    - many are inverse agonists
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Histamine H1 Receptor effects

A

1) Vasodilation of small blood vessels
- Most important vascular effect in humans
- Flushing
- Decreased total peripheral resistance
- Decreased blood pressure

2) Increased capillary permeability → edema, urticaria
3) Bronchoconstriction and bronchospasm
4) Nerve endings: pain and itch
5) Contraction of intestinal smooth muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

H1 Antagonists

  1. Indications
  2. 1st vs. 2nd generation
A

Introduced in the 1940s and today are among the most
widely used drugs

H1=I PUMA 
1. Indications: 
 z Allergic conditions
 z Urticaria
 z Insomnia
 z Motion sickness
 z Parkinsonian syndrome

a) 1st generation-more sedation

b) 2nd-less likely to cause drowsiness
* **Low CNS accumulation; effluxed from the CNS via the P-glycoprotein pump system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

H1 antagonist drugs

A
  1. Diphenyhydramine (Benadryl, Sominex)-1st
  2. Certirizine (Zyrtec)-2nd
  3. Fexofenadine (Allegra)-2nd
    - active metabolite: terfenadine
  4. Loratidine (Claritin, Tavist ND)-2nd
    - active metabolite: desloratidine (clarinex)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

H1 antagonist Drugs:

Shared general mechanism

A

All the ones we are studying are INVERSE agonists!

H 1 receptor inverse agonist, stabilizes the inactive conformation of H 1 receptors; blocks the effects of histamine on H 1 receptors in the GI tract, uterus, large blood vessels, and bronchial muscle and suppresses the formation of edema, flare, and pruritus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

H1 antagonist Drugs:

Shared TX

A

TX for allergic rhinitis, sneezing, itching, urticaria

***1st generation (diphenyhydramine) add TX for motion sickness, insomnia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Histamine H2 Receptor Effects

A

1)Vasodilation of small blood vessels
2) Increased heart rate: reflex tachycardia and direct
stimulation
-tachycardia due to baroreceptor reflex to vasodialtion

3) Gastric acid secretion due to activation of PARIETAL cell H2 receptor activation

17
Q

H2 Receptor Antagonists and gastric acid

A

Drug: Cimetidine (Tagamet)
Mechanism: inverse agonist, reduces constitutive activation of H 2 receptors on parietal cells

  • 1970s to treat peptic ulcer disease

-Not as efficacious as proton pump inhibitors but cheap,
very safe, and available OTC
** Get 60-70% decrease in 24 hr acid secretion

  • Especially effective at inhibiting nocturnal acid secretion, but less effective on meal-stimulated acid secretion
18
Q

Serotonin

  1. Synthesis
  2. Storage
  3. Receptors
A
  1. Biosynthesized from tryptophan
  2. Storage sites:
    a)Most 5-HT in the body is in enterochromaffin cells in GI
    epithelium

b) In blood, 5-HT is stored in platelet vesicles
- platelet aggregation and activation

b) In brain, 5-HT is in synaptic vesicles
- sex, temp, mood, sensory, appetite

  1. At least 14 receptor subtypes:
    a) Most are G protein-coupled
    - mostly Gq
    b) One, the 5-HT 3 receptor, is a ligand-gated ion channel
19
Q

Serotonin Synthesis and metabolism

A
  1. Synthesis:
    a) tryptophan + ttryptophan hydroxylase (TPH) = 5HTP
    b) 5HTP + Aromatic Amino Acid decarboxylase (AAAD) = SEROTONIN!!!
  2. metabolism
    a) melatonin!!! Formed from 2 Phase 2 enzymes: Arylalkylamine-N-acetyltransferase (AANAT) + ASMT
20
Q

Some Effects of 5HT

A
  1. CNS neurotransmitter
    a) Serotonin receptors in the CNS affect mood, appetite, sexual activity, thermoregulation, sensory perception, sleep, memory,
    cognition
    b) Mediates vomiting in the chemoreceptor trigger zone (5-HT 3 receptors)
  2. GI tract
    a) 5-HT 3 activation suppresses GI motility
    b) 5-HT 4 activation promotes motility (“4 let it Pour”
  3. CV system
    a) Released from platelets to initiate blood clotting
    b) Vasoconstriction (5-HT 1 , 5-HT 2 , 5-HT 7 )
    • **Blood pressure
    • **Migraine
21
Q

Migraines and 5HT

A

1) Pathophysiology likely involves neurogenic origin followed by
vasodilation

2) 5-HT is a key mediator of migraine pathogenesis
* **Plasma and platelet 5-HT concentrations vary with the different phases of a migraine episode
* **Urine concentrations of 5-HT and its metabolites are elevated during most migraine attacks
* **Agents that release 5-HT from intracellular stores precipitate migraine

Drugs: Ergotamine (partially both) and Sumatriptan (agonist)

Ergotamine also used to induce labor and for vasoconstriction post partum

22
Q

Ergotism

A

From Ergotamine (Ergomar):

angina, asthenia, coronary vasospasm, cramps, myalgia,
paresthesias, changes in HR; vasoconstriction may result in hypothermia or tissue necrosis

23
Q

Serotonin Receptor Migraine Drugs: General Precautions

A

CV: angina, arteriosclerosis, coronary artery disease, hypertension, peripheral
vascular disease, Raynaud’s disease, thrombophlebitis, MI, stroke

Hepatic disease

Renal insufficiency

24
Q

Migraines and…

  1. various anti-seizure drugs (valproic acid)
  2. Feverfew (Tanacetum parthenium, Migraban)
A

Both prophylactic for migraines

  1. questionable
  2. also has antiinflammatory effects; prevents release of 5HT, inhibits vasospasm
25
Q

Serotonin Syndrome

A

1) Serotonin syndrome is caused by excessive serotonin
concentrations at its receptors

2) Can be precipitated by the concomitant use of drugs (SSRIs, MDMA-ecstasy) that enhance synaptic serotonin concentrations, usually developing in less than 12 hr

3)Symptoms
 z Agitation
 z Hyperthermia
 z Flushing
 z GI disturbances
 z Myoclonus
 z Rhabdomyolysis
 z Tremor and seizures

See slide 34

26
Q

Management of Serotonin Syndrome

A

*Remove precipitating drugs

*Supportive care
z Monitor vital signs
z IV fluids

*Control agitation
z Benzodiazepines-anti-seizure and for anxiety so helps calm patient and treat myoclonus

*Antagonize 5-HT actions
z Cyproheptadine: H 1 , 5-HT 2, D 3 , M 1-5 blocker

*Control hypertension and tachycardia
 z Sodium nitroprusside (NO brings down BP right away) 
 z Esmolol (IV Beta-1 receptor blocker to reduce tachycardia )

*Control hyperthermia
z Vecuronium-NMJ blocker to reduce heat produced by the
monoclonus
z No role for antipyretic agents

Pharmacology (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions