Autacoids Flashcards
Definition of Autacoids
They are heterogeneous group of locally acting hormones or inflammatory mediators that apear during inflammation or tissue injury
T or F
Autacoids act systemically
F
They do not act systemically
classification of Autacoids
Amine autacoid
Lipid-derived autacoid
Peptide autacoid
Other autacoid
Histamine is derived from?
Histidine—》Decaboxylase—–》histamine
Where histamine is storage?
In mast crll and basophil in a complex with heparin.
Is there histamine in the brain
Non mast cell histamine presents in the brain as a neurotransmitter
Histamine is abundant in :
GIT mucosa, skin epidermis, lung, brain
When is histamine released?
Type 1 hypersensitivity Trauma Snake venom Basic Drugs: Succinyl choline, atropine, morphine D-tubocurarin
Fate of histamine
Distructed by histaminase.
T or F
Histamine acts on G protein coupled receptor
T
What the 4 subtype of histamine receptors?
H1—CNS, Smooth muscle, skine
H2—heart, stomach, mast cell
H3—CNS
H4—Immune cells
Action of H1 receptor:
+ Ach, glutamate release
Spasmogenic
Triple Response
Action of H2 receptor:
+ inotropic
+ Hcl secretion, pepsin, Intrinsic factor
-ve feedback of histamine release
Histamine antagonists
1.Physio..: adrenaline
2.Mast cell stabilizer: cromolyn, nedocromil
3.Immunotherapy
H Receptors blockers
How mast cell stabilizers works?
They prevent Ca+ entry to mast cell during immune reaction
Why adrenaline is given in anaphylactic shock?
It causes bronchodilatation and vasoconstriction.
Which H1-R blockers can cross BBB?
First generation: Diphenhydrate, Chlorpheniramine, Promethazine, Cyproheptadine
H1-R blockers classification:
1st gen: highly lipid soluble, cross BBB, less potent, short duration and cheap
2nd gen: no CNS effect, more potent, long duration, Expensive
1st gen H1-R blockers can cross BBB
Can cause sedation, but in children less than 6 years cause paradoxical excitation and convulsion
1st gen H1-Blockers examples:
Diphenhydrate
Chlorpheniramine
Promethazine
Cyproheptadine
2nd gen H1-Blocker examples:
Terfenadine
Certizine
Astimazole
Fexofenadine
Why 1st gen H1-blockers have an atropine like action?
Due to blocking of muscarinic receptors.
1st gen H1-blockers cause orthostatic hypotension
Due to blocking of alpha1 receptors
1st gen H1 blockers increas appetite:
Due to Blocking of 5HT
1st gen H1 Blockers cause local anesthetic effect
Due to blocking of Na+ channel of excitable membrane.
H2-R Antagonist examples:
Cimitidine
Rantidine
Famotidine
What are the Ergot Alkaloids?
They are produced from fungus that infects grain
Mechanism of action of E.Alkaloids
Their effects include agonist, partial agonist, and antagonist action at alpha adrenoceptors and serotonin receptors.
And agonist or partial agonist actions at CNS dopamine receptors.
E.Alkaloid effect on serotonin receptors especially:
5-HT1A and 5-HT1D
less for 5-HT2 and 5-HT3
Effects of E.Alkaloid on CNS:
Powerful hallucingen
Suppress prolactine secretion from pituitary
Why E.alkaloid supress prolactine?
Because of stimulatory effect on D-R
Examples of E.Alkaloid that effect on CNS:
bromocriptine
pergolide
cabergoline
Effects of E.alkaloid on the Vascular S.M:
VC of BV :partial agonist at alpha-R
VC of cerebral BV: by acting on 5HT-2-R (BV)
What are the E.alkaloids that effect on Vascular S.M
ergotamine
ergonovine
methysergide
Which E.alkaloid is more selective than other ergot alkaloids in affecting the uterus?
Ergonovine
Effects of E.alkaloids on Uterine S.M:
causing uterine contraction, vasospasm of uterine blood vessels.
as on vascular S.M, apears to combine alpha agonist, serotonin agonist
T or F
No significant effect on bronchial or urinary muscles.
T
E.Alkaloid induce vomiting due to:
Its effect on smooth muscle
Its effect on 5HT-R
E.alkaloids effects on S.M
GIT—》 nausea, vomiting, diarrhoea.
Which E.alkaloid that use in Mograine
Ergotamine
Ergotamine routes of administration:
Oral, inhaler, sublingual, rectal, suppository
Ergotamine is often combined with caffeine (100 mg caffeine for each 1 mg ergotamine tartrate)
To facilitate absorption of the ergot alkaloid
T or F
The vasoconstriction induced by ergotamine is long-lasting and cumulative when the drug is taken repeatedly.
T
Which E.alkaloids use in Hyperprolactinemia?
Bromocriptine
Cabergoline
v.v.v.i
Which E.alkaloid use in Postpartum Hemorrhage?
Ergonovine
Used only for control of postpartum uterine bleeding and should never be given before delivery
It is given at the time of delivery of the placenta or immediately afterward if bleeding is significant.
Which E.alkaloid that use in Diagnosis of variant angina?
Methylergometrine
It used to produce prompt vasoconstriction during coronary angiography to diagnose variant angina
Not use now.
Which E.alkaloid that use in senile cerebral insufficiency (alzehimer’s dementia) ?
Dihydroergotoxine
Toxicity of E.alkaloids:
1_GIT: N,V,D.
2_Prolong vasospasm—-》gangrene, bowel infarction.
3_Drowsiness
4_C.T proliferation in retroperitoneal space
Treatment of prolonged vasospasm caused by E.alkaloid toxicity:
Large doses of nitroprusside or nitroglycerine
Contraindication of E.alkaloids:
Obstructive vascular disease
Collagen disease
What are the Eicosanoids?
They are Fatty acid derivative that release in inflammation and tissue injury
20 carbon double bound molecules.
Name some eicosanoids
Prostaglandine
Thromboxane
Leukotrienes
How eicosanoids synthesis?
Arachidonic acid is derived from phospholipid of the cell membrane under effect of phospholipase A2, which then further metabolised by cyclo-oxygenase (COX) to prostaglandine and thromboxane.
Phospholipase inhibitors?
Corticosteroids
Cyclo-oxygenase inhibitors
NSAID acetylesalicylic acid (aspirin)
Lipoxygenase metabolises arachidonic acid to:
Leukotrienes
Which cox type is ubiquitous?
Cox-1
Cox-2 is inducible by :
Pro-inflammatory stimuli (LPS, TNFalphan IL2, IFNgamma etc)
Where cox-2 localizes?
Inflammatory and neoplastic sites (small amounts in kidney, uterus, ovary, CNS [neocortex, hippocampus])
Why aspirin is contraindicated in peptic ulcer?
Aspirin inhibits prostaglandine synthasis which protects mucosal wall thus aggrevating and causing ulceration
Role of Cox-2
Pro-inflammatory and mitogenic functions (neuronal plasticity)
How corticosteroids effect on eicosanoid synthesis?
They block all the known pathways of eicosanoid synthesis and inhibit phospholipase A2 activity, thus preventing the release of arachidonic acid.
How NSAIDs effect on eicosanoid synthesis?
Block both of PG and TX formation by reversibly inhibiting cox activity
Aspirin is an ireversible.
5-LOX inhibitor that use for bronchial asthma
Zileuton
Selective antagonists of receptor for leukotrienes that used clinically in mild to moderate asthma:
Zafirlukast
Montelukast
Pranlukast
Synthetic preparation of PGE2, is administered vaginally for oxytocic use:
Dinoprostone
Dinoprostone functions
Stimulate of the contraction of the uterus throughout pregnancy.
Directly effects the collagenase of the cervix, resulting in softening.
it is approved for inducing abortion in the second trimester of pregnancy, for missed abortion
and for repening of the cervix for induction of labor in patients at or near term
Adverse effect of Dinoprostone:
Diarrhea
Oral oxytocic synthetic analog of PGE1
It prevents of NSAID-induced peptic ulcers
Misoprostol
Adverse effect of misoprostol
Diarrhea
An analog of PGF2alpha
used in second trimester abortion
Control postpartum hemorrhage
Second-line treatment for erectile dysfunction
Carboprost tromethamine
Adverse effect of Carboprost tromethamine:
Bronchospasm
PGI2 analog
Treatment of Pulmonary hypertension
Epoprostenol
PGE1
treatment of certain types of congenital heart disease (transposition of the great arteries, pulmonary atresia, pulmonary artery stenosis
Alprostadil
It is important to maintain the patency of the neonate’s ductus arteriosus until corrective surgery can be carried out.
Which drug?
Alprostadil
Adverse effects of alprostadil:
Penile pain, urethral burning, vaginal itching in partner (locally), dizziness and tachycardia (if absorbed systemically)
A stable long-acting PGF2alpha derivative:
Latanoprost
First prostanoid used for glucoma
Latanoprost
Other prostanoids used now for glucoma:
Bimatoprost
Travoprost
Adverse effects of Latanoprost:
Gradual change in iris color, keratopathy, comeal erosion (rare)
Effects of PGs inhibition
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