Autocoids and Autocoid Antagonists

Question 1

What are three autacoids?

Answer 1

• Histamine
• Serotonin
• Eicosanoids

Question 2

HISTAMINE: MECHANISM OF ACTION?

Answer 2

• Four histamine receptors: H1, H2 , H3 & H4
.
• All are G protein-linked.
• All four receptors have constitutive activity in
some systems.

Question 3

H1 AND H2 RECEPTORS, how are they activated and where are they found?

Answer 3

• H1 receptors are present in endothelium, smooth
muscle cells and nerve endings.
• H1 receptors are coupled to activation of PLC
• H2 receptors are present in gastric mucosa,
cardiac muscle cells and some immune cells.
• H2 receptors are linked to activation of adenylyl
cyclase.

Question 4

H1 RECEPTOR ANTAGONISTS first generation?

Answer 4

Examples of First Generation:
• Chlorpheniramine
• Cyclizine
• Diphenhydramine
• Dimenhydrinate
• Hydroxyzine
• Meclizine
• Promethazine

Question 5

H1 RECEPTOR ANTAGONISTS second generation?

Answer 5

Examples of Second Generation:
• Fexofenadine
• Loratadine
• Cetirizine

Question 6

Histamines effect on cardiovascular system?

Answer 6

Vasodilation
Vasodilation involves both H1 and H2 receptors. H1 receptors have the higher affinity for histamine and
mediate a dilator response that is rapid and short lived. By contrast, activation of H2 receptors causes dilation that develops slowly and is more sustained. H2 receptors are located on vascular smooth muscle cell, and the vasodilation is mediated by cAMP; H1
receptors reside on endothelial cells and their stimulation leads to formation of NO. The
decrease in blood pressure is usually accompanied by reflex tachycardia.

Question 7

RELEASE INHIBITORS of histamine?

Answer 7

Cromolyn & nedocromil
• Reduce immunologic mast cell degranulation.
• beta2-agonists also appear capable of reducing
histamine release.

Question 8

name the H2 receptor antagonists

Answer 8

Cimetidine
• Ranitidine
• Famotidine
• Nizatidine

Question 9

Cimetidine AE

Answer 9

Cimetidine inhibits cytochrome P450 and can
slow metabolism of several drugs.
• Cimetidine binds to androgen receptors and has
antiandrogenic effects: gynecomastia and
reduced sperm count in men and galactorrhea in
women.

Question 10

5-HT1D/1B RECEPTOR AGONISTS?

Answer 10

• Sumatriptan is the prototype.
• Triptans are first-line therapy for acute severe
migraine attacks.
• Triptans may cause coronary vasospasm.
• They are contraindicated in patients with
coronary artery disease or angina.

Question 11

5-HT4 RECEPTOR AGONISTS?

Answer 11

METOCLOPRAMIDE
• Prokinetic agent.
• Its administration results in coordinated
contractions that enhance transit.
• The most common adverse effects are
somnolence, nervousness and dystonic reactions.
• Extrapyramidal effects and tardive dyskinesia,
although rare, may occur.

CISAPRIDE
• Prokinetic agent.
• Prolongs QT interval.
• Due to serious cardiac adverse effects it is no
longer generally available in the US.
• The drug is available only on a limited basis.

Question 12

5-HT2 RECEPTOR ANTAGONISTS?

Answer 12

CYPROHEPTADINE
• Also has potent H1 blocking actions.
USES
• Allergic rhinitis
• Vasomotor rhinitis
• Management of serotonin syndrome.

Question 13

5-HT3 RECEPTOR ANTAGONISTS?

Answer 13

ONDANSETRON
• Anti-emetic.
• Particularly for the severe nausea and vomiting
that occurs with cancer chemotherapy.

Question 14

THE ERGOT ALKALOIDS?

Answer 14

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

Question 15

THE ERGOT ALKALOIDS: MOA?

Answer 15

• Their effects include:
• Agonist, partial agonist, and antagonist
actions at -adrenoceptors and 5-HT
receptors
• Agonist or partial agonist actions at CNS
dopamine receptors.
• Some have a high affinity for presynaptic
receptors, whereas others are more selective for
postsynaptic receptors.

Question 16

THE ERGOT ALKALOIDS: USES?

Answer 16

Migraine
• Ergot derivatives are highly specific for migraine
pain.
• Triptans are preferred, but therapy with
ergotamine or dihydroergotamine can be
effective.

Hyperprolactinemia
• Bromocriptine and cabergoline are effective in
reducing the high levels of prolactin that result
from pituitary tumors.

Postpartum Hemorrhage
• Oxytocin is the preferred agent for control of
postpartum hemorrhage, but if it is ineffective,
ergonovine or methylergonovine IM can be
tried.

Diagnosis Of Variant Angina
• Ergonovine IV provokes coronary artery spasm
in patients with variant angina.

Question 17

THE ERGOT ALKALOIDS:

ADVERSE EFFECTS?

Answer 17

• Vasospasm.
• Contraindicated in pregnant women because the
drugs may cause fetal distress and miscarriage.
• Contraindicated in patients with peripheral
vascular disease, CAD, hypertension, and
impaired hepatic or renal function.
• Should not be used concurrently with other drugs
that can cause vasoconstriction.

Question 18

(PGE1 analog) name and use?

Answer 18

Misoprostol (PGE1 analog)
• Prevention of peptic ulcers in patients taking high
doses of NSAIDs.
• To ripen the cervix at or near term.
• Management of postpartum hemorrhage.
• Abortifacient in combination with the antiprogestin
mifepristone or methotrexate.

Question 19

(PGE2) drug name and use?

Answer 19

Dinoprostone (PGE2)
• To ripen cervix at or near term.
• Abortifacient

Question 20

PGE1 drug name and use?

Answer 20

Alprostadil (PGE1)
• To maintain patency of the ductus arteriosus.
• For impotence.

Question 21

(PGI2) drug name and use?

Answer 21

Epoprostenol (PGI2)
• Used in severe pulmonary hypertension
• To prevent platelet aggregation in dialysis
machines.

Question 22

PGF2alpha drug name and use?

Answer 22

Latanoprost (PGF2alpha derivative)

• Used for glaucoma.

Question 23

LEUKOTRIENE PATHWAY INHIBITORS?

Answer 23

• Two classes:
• Inhibitors of 5-lypoxygenase: zileuton
• Antagonists of LTD4 receptors: zafirlukast,
montelukast