Brainscape's Knowledge GenomeTM

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


See full index

PCM1 Exam 2 > RCS 12 - Autacoids & Autacoid Antagonists > Flashcards

RCS 12 - Autacoids & Autacoid Antagonists Flashcards

1
Q

Define autacoid and list the autacoids we need to know.

A

Autacoids - biological factors which act like local hormones, have a brief duration, and act near the site of synthesis

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

List the histamine receptors. What do they all have in common?

A

H1, H2, H3, and H4

  • They’re all G protein linked
  • They all have constitutive activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Where are the H1 and H2 receptors usually found? What is usually the key steps in their signal cascades?

A
  • H1 receptors are present in endothelium, smooth muscle, and nerve endings. These receptors are coupled to the activation of PLC
  • H2 receptors are present in the gastric mucosa, cardiac muscle, and some immune cells. These receptors are linked to the activation of adenylyl cyclase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe how the different histamine receptors effect the CVS.

A
  • Vasodilation
    • H2 receptors on vascular smooth muscle cause vasodilation via cAMP
    • H1 receptors on endothelial cells cause vasodilation via NO formation
  • Increased HR and contractility caused by H2 receptors
  • Increased capillary permeability caused by H1 receptors on the endothelium causing endothelial cell contraction.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe how the different histamine receptors affect the GIT, Respiratory system, Nervous system, and secretory tissues.

A
  • GIT
    • H1 in the smooth muscle causes contraction
    • H2 in gastric parietal cells stimulates gastric acid secretion
  • Respiratory - H1 in the bronchiolar smooth muscle causes bronchoconstriction
  • Nervous - H1 in sensory nerve endings stimulates pain and itching
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is anaphylaxis and what causes it?

A

Anaphylaxis is a serious allergic reaction which is rapid in onset

Caused by systemic mast cell degranulation (release of histamine)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is histamine used for clinically?

A

Some pulmonary function tests for nonspecific bronchial hyperactivity

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

List the types of histamine antagonists we need to know. Also list the specific drugs in each category that we need to know.

A
  • Physiological Antagonists - epinephrine
  • Release Inhibitors - cromolyn, nedocromil
  • Receptor Antagonists
    • H1 Antagonists
      • First Generation - dipenhydramine (benadryl), dimenhydrinate (dramamine), chlorpheniramine, hydroxyzine, meclazine (bonine)
      • Second Generation - fexofenadine (allegra), loratadine (claritin), ceterizine (zyrtec)
    • H2 Antagonists - cimetidine (tagamet), ranitidine (zantac), famotidine (pepcid), nizatidine (axid)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe how epinephrine acts as a histamine antagonist

A

Epinephrine has smooth muscle actions opposite to those of histamine, but acting at different receptors

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

Describe the MOA and effects of cromolyn & nedocromil

A

Release inhibitors

Reduce immunologic mast cell degranulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the primary differences between first generation and second generation H1 receptor antagonists?

A
  • The first generation drugs are more liposoluble which means they more readily enter the CNS and have a sedative effect. They are also more likely to block autonomic receptors.
  • In addition to being less liposoluble, the second generation drugs are also substrates of the P-glycoprotein transporter. This makes them even less likely to cross the BBB to have a sedative effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

List the MOA, uses, and adverse effects of H1 receptor antagonists.

A
  • MOA - actually not antagonists, they are inverse agonists. They also block cholinergic, α-adrenergic, and serotonine receptors as well as Na+ channels
  • Uses:
    • DOC for allergic rhinitis and urticaria
    • 1st generation are used for motion sickness & nausea (dramamine & bonine). Some are also used to treat insomnia
  • Adverse Effects - sedation (less common with 2nd generation) and dry mouth (due to anticholinergic effects)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

List the primary uses of H2 receptor antagonists.

A
  • Inhibitor gastric acid secretion
    • promotes healing of duodenal and gastric ulcers
    • treats acute stress ulcers
    • prevention and treatment of GERD
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

List the adverse effects of H2 receptor antagonists

A
  • Adverse effects only occur in <3% of patients
  • Confusion, hallucinations, and agitation when given IV. Especially in elderly ICU patients or patients who have renal or hepatic dysfuncion. More common with cimetidine
  • Headache
  • Dizziness
  • Diarrhea
  • Muscular pain
  • Constipation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which H2 anatagonist is more likely to cause side effects and why? Give the side effects

A

Cimetidine

It inhibits cP450, slowing the metabolism of several drugs. It also binds to androgen receptors to elicit an antiandrogenic effect: gynecomastia and reduced sperm count in men and galactorrhea in women

Also can cause confusion, hallucinations, and agitation in elderly ICU patients and patients with renal or hepatic dysfunction

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

How many types of serotonin receptors are there? List the different serotonin receptors we need to know and describe the types of receptor they are.

A
  • There are seven 5-HT receptor subtypes but we only need to know the following:
    • GPCRs
      • 5-HT1D
      • 5-HT1B
      • 5-HT2
      • 5-HT4
    • Ligand Gated Ion Channel
      • 5-HT3
17
Q

What are the typical clinical applications of serotonin?

A

There are none but several serotonin agonists are used clincally

18
Q

List the 5-HT1D/1B agonists we need to know. Describe what they’re used for and why.

A

Sumatriptan and other -triptan drugs

First-line therapy for actue severe migraine attacks

Most migraines are the result of a trigmenal nerve terminal releasing CGRP (calcitonin gene related peptide) onto blood vessels in the head which vasodilate when their CGRP receptors are activated. These nerve terminals have a 5-HT1D receptor that inhibits release of CGRP when activated. Those blood vessels have a 5-HT1B receptor that stimulate vasoconstriction when activated. Sumatriptan works by activating both the 5-HT1D and 5-HT1B receptors.

19
Q

What are the adverse effects and contraindications for Triptan drugs

A

These drugs can cause coronary vasospasms and are therefore contraindicated in patients with CAD or angina

20
Q

List the 5-HT4 agonists we need to know. What are they used for and why? What are their adverse effects

A

Metoclopramide and Cisapride

  • They are used as prokinetic agents (a drug that enhances GIT motility)
  • They work by stimulating ACh release from enteric nerve terminals while antagonizing D2 receptors (which inhibit motility)
  • Adverse Effects
    • Most Common - somnolence, nervousness, and dystonic reactions
    • Rare - extrapyramidal effects and tardive dyskinesia
    • Cisapride also prolongs QT interval so it is no longer generally available in the US
21
Q

List the 5-HT2 antagonists we need to know. What are their uses? Do they have other actions?

A

Cyproheptadine

  • Used
    • allergic rhinitis
    • vasomotor rhinitis (non allergic)
    • management of serotonin syndrome
  • Also a potent H1 blocking agent
22
Q

List the 5-HT3 antagonists we need to know. What are their uses and why?

A

Ondansetron (Zofran)

  • Used as an anti-emetic (especially for chemo patients) because it antagonizes the 5-HT3 receptors in the vomiting center of the brain
23
Q

What are the ergot alkaloids and their MOAs?

A
  • Ergotamine
  • Dihydroergotamine
  • Bromocriptine
  • Cabergoline
  • Ergonovine
  • Methylergonovine

They have a wide range of MOAs including agonist, partial agonist, and antagonist actions at α and 5-HT receptors, as well as agonist and partial agonist actions at CNS dopamine receptors. Some have higher affinity for presynpatic receptors while others prefer postsynaptic receptors

24
Q

Give the various uses for the ergot alkaloids

A
  • Migraines - ergotamine and dihydroergotamine (triptans are preferred)
  • Hyperprolactinemia - Bromocriptine and Cabergoline are effective in reducing high levels of prolactin
  • Postpartum Hemorrhage - ergonovine and methylergonovine (oxytocin preferred)
  • Diagnosis of variant angina - ergonovine provokes a coronary artery spasm in patients with variant angina
25
Q

What are the adverse effects and contraindications of the ergot alkaloids?

A
  • Adverse Effects - vasospasms
  • Contraindications
    • Pregnancy - may cause fetal distress and miscarriage
    • Peripheral Vascular Disease, CAD, HTN, and impaired Hepatic/Renal function
    • Also on drugs that cause vasoconstriction
26
Q

What is an eicosanoid and what are the main types of eicosanoids?

A
  • Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid
    • prostaglandins
    • prostacyclins
    • thromboxanes
    • leukotrienes
27
Q

Describe the structure of arachidonic acid and where it is usually found in the body

A

It is a 20 carbon PUFA with four double bonds and is usually found esterified in phospholipids in the cell membrane

28
Q

Name the primary pathways that synthesize eicosanoids from arachidonic acid and specify which eicosanoids are generated from which pathways.

A
  • Cyco-oxygenase Pathway - prostaglandins, prostacyclins, and thromboxanes
  • Lipoxygenase Pathway - leukotrienes
29
Q

List the differences between COX-1 and COX-2 that we need to know for this exam.

A

COX-1 is found in most cells as a constitutively active enzyme that produces prostaglandins involved in normal cell homeostasis

COX-2 is found mainly in inflammatory cells and is induced by inflammatory stimuli

30
Q

What are leukotrienes generally associated with? List the specific leukotrienes we need to know and what the specific tissue effects they have are.

A
  • Leukotrienes are associated with asthma, anaphylactic shock, and cardiovascular disease
  • LTC4 and LTD4 are potent bronchoconstrictors secreted in astma and anaphylaxis
31
Q

List the MOAs of eicosanoids. What mediates their contractile and relaxing effets on smooth muscle?

A
  • Eicosanoids act in an autocrine and paracrine fashion to activate GPCRs (Gs, Gi, and Gq)
  • Contractile effects are mediated by Ca++ (Gq pathway)
  • Relaxing effects are mediated by cAMP
32
Q

List the eicosanoid analog drugs we need to know and the eicosanoid they are an analog of.

A
  • Misoprostol and Alprostadil (PGE1)
  • Dinoprostone (PGE2)
  • Epoprostenol (PGI2 (aka - prostacyclin))
  • Latanoprost (PGF2α)
33
Q

List the uses of misoprostol

A
  • Prevention of peptic ulcers in patients taking high doses of NSAIDs
  • To ripen the cervix at or near term
  • Management of postpartum hemorrhage
  • Used in combination with an antiprogestin like mifepristone or methotrexate as an abortifacient (abortion inducing drug)
34
Q

List the uses of dinoprostone

A
  • To ripen cervix at or near term
  • abortifacient
35
Q

List the uses of alprostadil

A
  • To maintain patency of the ductus arteriosus
  • For impotence
36
Q

List the uses of epoprostenol

A
  • To treat severe pulmonary HTN
  • To prevent platelet aggregation in dialysis machines
37
Q

List the uses of latanoprost

A

Glaucoma

38
Q

List the classes and subclasses of eicosanoid antagonists. List the drugs we need to know from each class.

A
  • Leukotriene Pathway Inhibitors
    • 5-lypoxygenase inhibitors - zileuton
    • LTD4 receptor antagonists - zafirlukast and montelukast
  • Glucocorticoids
  • NSAIDs
39
Q

How do glucocorticoids act as an eicosanoid antagonist

A
  • They inhibit PLA2, thus blocking the release of arachidonic acid
  • They inhibit synthesis of COX-2

PCM1 Exam 2 (34 decks)

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