10/23/2016

Autacoids
Local Hormones / autopharmacological
agents
“auto”
Autacoids “akos”
Local release  action on specific sites
Rowel Catchillar, MS

Autocoids Autocoids
Biologically active amines Vasoactive Peptide Dilators
(1) Bradykinin
(2) atrial natriuretic peptide
Eicosanoids vasoactive intestinal polypeptide
(1) Neurotensin, substance P
(2) Vasoactive Peptide Constrictors
(3) Angiotensin II
(4) Vasopressin
 Endothelins
neuropeptide Y
urotensin

Prostaglandin Analogs Eicosanoids

Precursor: Arachidonic acid Prostaglandin
COX Isoforms PGD
□ COX 1: constitutive form, “housekeeping”  for PGE
basal production of PG, PC and TX
PGF2
□ COX 2: “inducible form”
LOX Prostacyclin
Thromboxane

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PGE2 PGD2
Vasodilation Bronchoconstriction
gastric secretion Vasoconstriction or vasodilation
Uterine contraction
platelet aggregation “niacin flush”
Bronchodilation Scalp of bald people

Alprostadil
Misoprostol
Dinoprostone

PGF2 TXA2 (Thromboxane)

Uterine contraction Vasoconstriction
Bronchoconstriction platelet aggregation
Aqueous humor drainage bronchoconstriction

Carboprost (abortifacient)
Latanoprost, Travoprost, Bimatoprost,
Unoprostone

Prostacyclin Prostaglandin Blockers

Vasodilation NSAIDS
platelet aggregation Analgesic
Antipyretic
Bronchodilation
Anti-inflammatory
Gastric cytoprotection Antiplatelet (ASA)
MOA: __both COX isoforms (except –
Epoprostenol coxibs)

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Prostaglandin Blockers Salicylates

Adverse effects
GI upset (ulcer)
Platelet (prolonged bleeding time)
Fluid retention (Na and H2O)
Hypersensitivity
Delayed parturition (dystocia)
Aspirin
Standard drug (for NSAID studies)
Antiplatelet (75-325 mg/day)
Analgesic & antipyretic (325-650 mg q6h)
Anti-inflammatory (3-5 g/day)
Uricosuric (high dose)
S/E:
□ (1)______: tinnitus, bronchospasm, vertigo
□ (2)______
□ (3)Aspirin-induced asthma
Kinetics
□ first-order, 600-1000mg/day
□ zero-order, >2-4g/day)

Propionic acid derivatives Anthranilic acid derivatives or fenamates

Ibuprofen Mefenamic acid
Fenoprofen Primary dysmenorrhea
Recommendation:
Naproxen
Ketoprofen
Flurbiprofen
Oxaprozin

Aryl-acetic acid derivatives Enolic acids

Ketorolac Piroxicam
(1)
(2) Meloxicam
Recommendation Phenylbutazone
Etodolac Antipyrine
Tolmetin Antipyrine + Benzocaine: otic drop
Diclofenac
Indomethacin
Nabumetone: 6-methoxy-2-naphtyl-acetic
acid
Sulindac: sulfide metabolite

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Sulfonylphenyl derivatives/ Selective COX-2

inhibitors
Leukotriene
Celecoxib Bronchoconstriction (LTC4, LTD4, LTE4)
Valedocoxib  slow-reacting substance of
anaphylaxis (SRS-A)
Rofecoxib (withdrawn)
Neutrophil chemotaxis (LTB4)

Leukotrienes Histamine
Precursor:
Zileuton (Zyflo) Inhibits 5-LOX
Receptor Subtype Distribution Prototypic Antagonist
S/E: sinusitis H1 (allergic & Smooth muscle Diphenhydramine
Zafirlukast (Accolate), Blocks Cysteinyl anaphylactic responses)
H2 (increased secretion Stomach, heart, Cimetidine
Montelukast (Singulair) leukotriene receptor of acid & pepsin) mast cells
S/E: eosinophilic H3 Nerve endings, Clobenpropit
CNS (investigational)
vasculitis H4 Leukocytes —

Anti-histamines (H1-Blockers) Serotonins

5-HT1 CNS Buspirone (partial 5-HT1a receptor
(Inhibitory) agonist)
Smooth Sumatriptan /”triptans” (5-HT1d
muscles (Both) receptor agonist)
5-HT2 CNS Trazodone activator of 5-HT1B and
(excitatory) 5-HT2 receptors

Olanzapine and other atypical anti-

psychotics (5-HT2a receptor
antagonist)
Cyproheptadine (5-HT2 antagonist)
Ketanserin & phenoxybenzamine
are effective 5-HT2 blockers

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Serotonins ERGOT alkaloids

5-HT3 Postrema  Ondansetron and “setrons”
N/V (antagonists) NOT autocoids, but interact with
Alosetron  IBS-D serotonin receptors
5-HT4 GIT (⬆ Tegaserod (partial 5-HT4 agonist)
Source: C. purpurea
peristalsis)  IBS-C
Toxicity: Ergotism: “St. Anthony’s Fire”

ERGOT alkaloids DMARDs

CATEGORY MUST-KNOW INFORMATION
Methylergonovine most uterine-selective agent  Methotrexate (1) S
(1) (2) C
Ergonovine (1) (3) R
(2) (4) I
Ergotamine (+caffeine) (1) (5) P
(6) Sarcoidosis
(2)  Sulfasalazine active metabolites:
Methysergide, Migraine prophylaxis  (1)
dihydroergonovine  (2)
Bromocriptine and pergolide  Antimalarials
lysergic acid diethylamide  Leflunomide pyrimidine synthesis inhibitor
(LSD)  TNF- Inhibitors Etanercept (Enbrel)
Infliximab
 Interleukin-1 Anakinra (Kineret)
Antagonists
 Gold Compounds Auranofin

Anti-Gout
Drug MOA Notes
Colchicine DOC for acute gout
Uricosoric agents ⬇ proximal tubular Colchicine first before
-probenecid reabsorption of urate uricosoric agent
-Sulfinpyrazone (large dose)

Allopurinol ⬇ xanthine oxidase DOC for chronic gout

Active:
Phenylbutazone Has uricosuric effect Acute gouty arthritis
Indomethacin Acute gouty arthritis