Pharmacology - chapter 42 - Autocoids & autocoid antagonists Flashcards
Autacoids are produced by …………….. and act ………………
Autacoids are produced by tissues and act locally
Three endogenous compounds that belong to the group of autacoids?
1 prostaglandins
2 histamine
3 serotonin
Prostagalndins are derivatives of ……….. ?
unsaturated fatty acids(arachidonic acid)
Mifepristone, areas of use?
1 an antiprogestational abortifacient
2 inhibits HCL secretion and enhances mucosal resistance.
In what tissues do we find the highest levels of histamine?
sites where the “inside” of the body meets the outside
1 lungs
2 GI tract
3 skin
How is histamine synthesized?
by decarboxylation of histidine
What factor involving histamine decides whether its release will induce a local allergic reaction or a anaphylactic one?
The rate of secretion. If it’s slow the histamine will be inactivated before it reaches the blood stream. If it’s too fast to be inactivated, a full blown anaphylactic reaction occurs.
H1 receptors are associated with?
exocrine glands - inreased mucus production
bronchial smooth muscle - induce bronchial constriction
intestinal smooth muscle - cause cramps and diarrhea
sensory nerve endings - causes itching and pain
H1 & H2 receptors are coexpressed in ……….?
1 cardiovascular sytem - positive ionotropism and chronotropism and reduces peripheral resistance.
2 skin - the tripple response: flare, reddening and wheal
H2 receptors are expressed?
stomach - stimulates HCL secretion
What is the most prominent side effect of first generation antihistamines?
CNS sedation
What receptors can H1 antihistamines ineract with?
1 cholinergic receptors
2 alpha-adrenergic
3 serotonin receptors
4 histamin H1 receptors
Chlorpheniramine, diphenhydramine, doxylamine, hydroxyzine and promethazine are all ………… ?
first generation antihistamines with marked potential for producing sedation.
drugs of choice to treat allergic rhinitis and urticaria?
antihistamines
drug of choice to treat systemic anaphylaxis?
epinephrine
Antihistamines used in motion sickness?
dimenhydrinate, cyclizine, meclizine, hydroxyzine ++
Most antihistamines are metabolized by ……….. ?
P450 system
drug interactions related to antihistamines?
potentiation of other CNS depressants, such as alcohol. People who take MAOi should not take antihistamines, as MAOi may exacerbate the cholinergic properties of antihistamines
H2 receptor blockers, clinical use?
inhibition of HCL secretion in treatment of ulcers and heartburn
What underlying pathomechanism separates migraine with and without aura.
Patients who have migraine without aura do not show hypoperfusion.
triptans and dihydroergotamine?
5-ht receptor agonists induce vasoconstriction in the cerebral arteries. Used in treating migraine.
Sumatriptan, naratriptan, rizatriptan, almotriptan, frovatriptan, zolmitriptan all work by…..?
acting on a subgroup of serotonin receptors found on small peripheral nerves that innervate intracranial vasculature - producing vsaoconstriction.
Agents used in prophylaxis of migraine?
B blockers: propanolol and nadolol
TCA: amitriptyline
Anticonvulsant: Dicalproex
Ca-channel blocker: verpamil
What agents are used in the prodromal phase of a migraine attack?
Triptans and dihydroergotamine - vasoconstrictors
what are the signs and syptoms of the prodromal phase of a migraine attack?
sensory distrubances, especially visual.
Analgesic agents used in the headache phase of a migraine attack?
anti-inflammatory drugs(aspirin, naproxen, ibuprofen). Severe pain may require administration of opioids(e.g. codeine sulfate or merperidine)
The major metabolite of Histamine is …?
zoleacetic acid
Which protein are H1 and H2 receptors coupled with?
H1 - Gq protein
H2 - Gs protein
What is a major problem with the first generation histamine blockers?
Their structure closely resembles muscarinic blockers and alpha adrenoreceptor blockers, producing a wide aray of undesireable adverse effects.
Ranitidine, famotidine, nizatidine and cemitidine: clinical application?
H2 antagonist used to lower gastric secretions.
Substrate in serotonin synthesis?
tryptophan
What is the enzyme responisble for metabolizing serotonin, and what is the major metabolite from this reaction?
MAO degrades serotonin to 5-HIIA(5-hydroxyindoleacetic acid) which can be meassured in the urine.
Three types of serotonin receptors, location and associated protein structures?
5-HT1: Gi protein coupled receptor that increase potassium conductance, located primarily in CNS.
5-HT2: Gq protein coupled receptors. Present in CNS & PNS.
5-HT3: cation-gated channel present in CNS, esp. chemoreceptve areas and vomiting center.
Clinical application of serotonin and histamine?
None
Ergot alkaloids may be classified into three subgroups based on the organ or tissue in which they have their primary effects. These three groups are?
1 Vessels - prolonged alpha mediated vasoconstriction
2 Uterus - produce powerful contraction
3 Brain - some ergots are potent dopamine-like agonists that bind D2 receptors in the pituitary and the basal ganglia.
Ergot alkaloids: three areas of clinical use?
1 Migraine
2 Obstetric bleeding
3 Hyperprolactinemia and Parkinsonism
Two x adverse effects of cementidine?
1 antiandrogenic effects in some patients
2 significant CYP3A4 inhibiting effects
Useful drug for reversing severe ergot-induced vasospasm?
Nitroprusside
Two abortifacients?
1 PGF 2alpha
2 PGE2
Prostaglandin ued to maintain a patent ductus arteriosus?
PGE1
Prostaglandin used in pulmonary hypertension and dialysis?
PGI2 - prostacyclin
Major mechanism of the anti-inflammatory effects of corticosteroids?
Inhibition of COX synthesis
Zileuton moa?
Inhibits Lipooxygenase
drug that have shown to be effective in closing a patent ductus arteriosus in newborns?
Ibuprofen - reversible binding of COX lowers prostaglandin levels, which is responsible for maintianing the duct.
