ergot alkaloids dr. naila abrar. learning objectives after this session, you should be able to: know...
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Ergot Alkaloids
Dr. Naila Abrar
LEARNING OBJECTIVESLEARNING OBJECTIVES
After this session, you should be able to:• know the source and classification of ergot
alkaloids;• describe pharmacological actions of ergot
alkaloids;• comprehend the clinical indications of ergot
alkaloids; and• describe the adverse effects & contraindications
of ergot alkaloids.
SOURCE:SOURCE: fungus - Claviceps purpurea
DISCOVERY:DISCOVERY:
ERGOTISM: ERGOTISM:
St. Anthony’s fire
Claviceps purpurea
CLASSIFICATIONCLASSIFICATIONAMINE ALKALOIDSAMINE ALKALOIDS6- Methylergoline, lysergic acid, lysergic acid
diethylamide, ergometrine (ergonovine), methysergide
PEPTIDE ALKALOIDSPEPTIDE ALKALOIDSErgotamine, dihydroergotamine, - ergocryptine, bromocriptine
CHEMISTRYCHEMISTRY
• Ergoline nucleus• Derivatives of tetracyclic compound 6-methylergoline• Substituent in beta configuration at position 8 and a
double bond in ring D• Natural alkaloids: ergotamine, ergonovine
(derivatives of d-lysergic acid)• Semisynthetic & synthetic: dihydroergotamine,
bromocriptine, LSD, methysergide
PHARMACOKINETICSPHARMACOKINETICS
• Variable absorption from GIT• Ergotamine- poor oral BA• Speed of absorption and peak blood levels of
ergotamine improved with caffeine• Routes: oral S/L, I/M, I/V, nasal, rectal• Extensive metabolism• Ergonovine & methylergonovine - rapidly
absorbed
MECHANISM OF ACTIONMECHANISM OF ACTION
• Multi-receptor function• Agonist, partial agonist, and antagonist at ,
serotonin • Presynaptic 5HT receptor (5HT1A/1D)
• Partial agonist at 5HT2 - uterus
• Partial agonist at CNS dopamine• Antagonist at blood vessels dopamine
PHARMACOLOGICAL ACTIONSPHARMACOLOGICAL ACTIONS
CNS CNS • Hallucinogenic • LSD – drug abuse (agonist at 5HT2 in CNS)
• Nausea, vomiting – CTZ D2
• Decrease extrapyramidal symptoms - striatum D2
Inhibition of prolactin secretion – pituitary D2
Bromocriptine, pergolide, cabergoline
VASCULAR SMOOTH MUSCLEVASCULAR SMOOTH MUSCLE• stimulation – VC – increase TPR & BP• Also vascular 5HT2
• Ergotamine- partial agonist• Vasospasm • Flow of blood to periphery decreases• Slow dissociation from receptors
UTERUSUTERUS• Stimulation of & 5HT2
• More in uterus at term• Ergonovine (ergometrine) more selective • Rhythmic contractions and relaxation in
small doses and prolonged contracture at higher doses
GITGIT• Stimulation of 5HT2 receptors
• Increase motility, diarrhea, abdominal cramps
• Dopamine receptors CTZ – anorexia, nausea, vomiting
CLINICAL USESCLINICAL USESMIGRAINEMIGRAINETriptan drugsProdrome of attack – ergotamine tartrate Increase absorption with caffeineS/L 2 mg half hourly till relief - No more than 6mg
for each attack or no more than 10mg /wk0.25-0.5mg I/V or I/M total dose of 2 -3mg in 24hrs0.5 mg nasal spray- repeated after 15 mins if req.
total dose of 2 mg in 24hrs
HYPERPROLACTINEMIABromocriptine, cabergoline, pergolidePARKINSONISMBromocriptine, decrease EP effectsPOST PARTUM HEMORRHAGEErgonovine maleate 0.2 mg I/MDIAGNOSIS OF VARIANT ANGINAErgonovine to localize reactive segments of
coronaries during angiographySENILE CEREBRAL INSUFFICIENCYAlzheimer’s disease
ADVERSE EFFECTSADVERSE EFFECTS
GIT:GIT: NVD, abdominal crampsVASOSPASM:VASOSPASM: Severe, gangreneCNS:CNS: Hallucinations, delirium, mania, drowsiness,
sedation, drugs of abuse - LSDRETROPERITONEAL FIBROSIS: RETROPERITONEAL FIBROSIS: MethysergideERYTHROMELALGIA:ERYTHROMELALGIA: with ergot derived
dopamine agonists like pergolide BP:BP: Raised UTERUS:UTERUS: Abortion
Erythromelalgia
CONTRAINDICATIONSCONTRAINDICATIONS
• Pregnancy• Renal disease• Hepatic disease• Psychotic illness• Collagen diseases• Peripheral Vascular disease
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