MORPHINE

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MORPHINE

  1. 1. Morphine was isolatedfrom raw opium in 1805 by aGerman pharmacologist,Friedrich Wilhelm AdamSerturner (1783-1841).Morphine is a potentsuppressor of pain and is avery useful drug in painfulconditions, especially insevere chest pain arisingdue to heart attacks. It alsoinduces sleep in no time
  2. 2. Barely eighteen yearsafter morphine wasdiscovered, it was usedfor homicide. In 1823, atwenty-seven year oldFrench doctor, EdmeCastaing, mixedmorphine in the winegiven to his friend,Auguste Ballet, to kill him
  3. 3. In fact the namemorphine comes from theGreek ‘god of dreams’,Morpheus. IncidentallyMorpheus was the son ofHypnos, the Greek ‘godof sleep’, and our word‘hypnosis’is derived fromit. Hypnos was also thebrother of Thanatos, the‘god of death’.Morphine not onlybrings sleep and dreamsbut may cause deathwhen taken in largedoses.Morpheus (The God Of Dreams)
  4. 4. Morphine is a natural opium alkaloidIt is a dried extract obtained from the capsules of the poppyplant known as papaver somniferumIt requires approximately 10 kg of raw opium to produce 1 kgof morphine
  5. 5. • Morphine• Thebaine• CodeinePhenanthrenederivatives• Papaverine• NoscapineBenzo-isoquinolinederivatives1. According to ring structure
  6. 6. • Morphine• CodeineA. Naturalopium alkaloids• Heroine• PholcodeineB. Semisynthetic opiumalkaloids• Pethidine• MethadineC. Syntheticopiods2.According to synthesis
  7. 7.  Opioids exert their major effects by interacting with opioidreceptors in the CNS Opioids activate 7- transmembrane GPCRs locatedpresynaptically and postsynaptically along pain transmissionpathways High densities of opioid receptors known as mu, delta andkappa are found in the dorsal horn of the spinal cord and higherCNS centers Most currently used opioid analgesics act mainly at mu- opioidreceptors Morphine acts at kappa receptors in lamina 1 and 11 of thesubstantia Granulose of the spinal cord and decreases therelease of substance p, which is modulates pain perception inthe spinal cordMechanism of action
  8. 8.  Opioids have an onset of action that depends on the route ofadministration Opioids causes hyper polarization of nerve cells , inhibition ofnerve firing and presynaptic inhibition of transmitter release Cellular effects of these drugs involve enhancement of neuronalpotassium efflux( hyperpolarizes neurons and makes them lesslikely to respond to a pain stimulus ) and inhibition of calciuminflux ( decreases neuro- transmitter release from neurons locatedalong the pain transmission pathway ) Brainstem opioid receptors mediate respiratory depressionproduced by opioid analgesics Constipation results from activation of opoioid receptors in theCNS and in the GITMechanism of action
  9. 9.  Absorption of morphine from GI T is slow and incompleteQuick effect is produced on subcutaneous injectionIt is partly bound to plasma proteinsIt is metabolized by conjugation with glucuronic acidIt is almost completely excreted in urine within 24 hoursBioavailability is 20 to 40 per centGiven sc , onset of action is in 15 – 20 min, peak effect in 1hrsDuration of action is 3 – 5 hrs
  10. 10. • Morphine causes analgesia• Morphine relieves severe deep seated pain like visceral pain andpain of trauma• Opioids relieve pain both by raising the pain threshold at thespinal cord level and more importantly by altering the brainsperception of pain• It alters the emotional reaction to pain• The analgesic action morphine is primarily due to its effect onendogenous opioid receptors in midbrain and brain stem areas• Inhibitory impulses from these areas to the dorsal horn constitutethe gating system• The morphine also acts directly on the dorsal horn where itinhibits the release of substance P
  11. 11. • Morphine produces euphoria in presence of pain• But in the absence of pain , it produces dysphoria & restlessness• With an increased dose, it produces sleep• Tolerance is noted to both euphoria (mu receptor ) anddysphoria (kappa receptors)• Morphine induces sedation in analgesic doses and is useful whenpain is accompanied by insomnia
  12. 12. • Morphine has anti-tussive property• Morphine depress the medularly cough centre , an effect notblocked by naloxone• It is not used clinically and related drugs like codeine, with lessrespiratory depressant and addictive liability are used• Nausea and vomiting are common features with analgesic dosesand induced by stimulation of the chemoreceptor tiger zone (CTZ)• Tolerance develops to vomiting on prolonged use• Higher doses of morphine inhibit the vomiting centre
  13. 13. • Morphine produces constriction of pupil ( miosis)• Miosis is induced by mu and kappa mediated stimulation of theoculomotor nucleus• The effect is blocked by atropine• Morphine addicts have constricted pupil• Tolerance to papillary constriction is not seen in addicts and pinpointpupils are indicative of morphine abuse and diagnostic in morphinepoisoning ( other respiratory depressants induce papillary dilatation)
  14. 14. • The action of morphine on the respiration is dose dependent• Analgesic doses of morphine induce depression of the respiratorycentre resulting in increase in plasma carbon dioxideconcentrations• Respiratory center depression is mediated by mu receptors and isthe cause of death in morphine poisoning• At higher doses it produces respiratory depression• Respiratory depression is the most common cause of death inacute overdose• Opioids shift the equilibrium point of heat – regulating centre sothat body temperature falls slightly
  15. 15. • Morphine decreases peristaltic propulsive movements• It produces spasm of intestinal smooth muscles and sphincters• Gastric emptying is delayed• It also increases absorption of water , So the feces get dried• All these effects leads t o constipation• Morphine increase billiary tract pressure due to contraction of thegallbladder and constrictor of the biliary sphincter• This produces increase in intrabiliary pressure• Atropine antagonizes this effect
  16. 16. • Normal dose of morphine produces no effect on heart rate ,blood pressure or circulation• But hypo tension and bradycardia may be produced at toxicdose• Hypotension is due to dilation of peripheral veins and arterioles,histamine release and reduced sympathetic activity and in largedoses due to depression of medularly vasomotor center’• Bradycardia is due to stimulation of the vagal nucleus• Because of respiratory depression and carbon dioxide retention,cerebral vessels dilate and increase the cerebrospinal fluidpressure• Morphine is usually contraindicated in individuals with severebrain injury
  17. 17. • Morphine releases histamine from mast cells, causing urticaria,sweating and vasodilatation• Morphine can cause the bronco-constriction , asthmatics shouldnot receive the drug• Morphine inhibits release of GRH and corticotrophic releasinghormone and it decreases the concentration of luteinizinghormone, FSH & ACTH• It increases prolactin and growth hormone release by diminishingdopaminergic inhibition• It increases antidiuretic hormone and leads to urinary retention
  18. 18. • No significant effect . May prolong labor in high doses• Tone and amplitude of contractions of the urters is increased ,tone of external sphincter and volume of the bladder are increased• Opioids inhibit urinary voiding reflex• All these result in urinary retention especially in orderly male withprostate hypertrophy• In high doses it produce convulsions. T hey may increases t heexcitability of the spinal cord
  19. 19. Do you know who is this?was an Austrianneurologist who founder ofpsychoanalysiswas a physiologist,medical doctor, psychologist
  20. 20. Do you know how he died?In September 1939, Freud, whowas suffering from cancer and insevere pain, persuaded his doctorand friend Max Schur to help himcommit suicideLater ,on 21 and 22 Septemberadministered large doses ofmorphine that resulted in Freudsdeath on 23 September 1939
  21. 21.  Acute morphine poisoning characterized by respiratorydepression, pin point pupil cyanosis, reduced body temperature,hypotension , shock and coma naloxone 0.4-0.8mg iv GIT Symptoms – Nausea, vomiting and constipation Central effects like dysphoria and mental clouding Intolerance like tremor, delirium and skin rashes Depression of fetal respiration
  22. 22. The depressant actions of morphine are enhancedby phenothiazines, monoamine oxidase inhibitors and tricycleantidepressantsRepeated use of drug produces tolerance to the respiratorydepressant, analgesic, euphoric and sedative effects of morphinePhysical and psychological dependence readily occur withmorphineWithdrawal produce a series of autonomic , motor andpsychological responses that incapacitate the individual and causeserious - unbearable symptomsTreatment of withdrawal syndrome is oral methadone
  23. 23.  Infants and elder people Respiratory conditions such as bronchial asthma Head injury Acute abdominal pain Hypothyroidism
  24. 24. Preparation DoseTincture opium - 0.3 to 2 ml by mouthMorphine sulphate - 8 – 20 mg by mouth or by injectionMorphine hydrochloride - 8 – 20 mg by mouth or by injection
  25. 25. 1. It is an analgesic for the relief of severepain2. Used as pre-anesthetic medication3. For producing sleep and sedation4. Used as anti-tussive5. For the treatment of diarrhea6. In the treatment of acute left ventricularfailure

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