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OPIOID ANALGESICS

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ANTAGONISTS

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MAINLY OBTAINED FROM OPIUM POPPY.ACT BY BINDING TO SPECIFIC OPIOID

RECEPTORS IN THE CNS.MAINLY USED FOR RELIEVING INTENSE

PAIN.EUPHORIC PROPERTIESANTAGONISTS IMPORTANT IN OVERDOSE.

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OPIOID RECEPTORS5

4 TYPES Mu ( µ )Kappa ( к )Delta ( δ )Sigma ( σ )

Mu ( µ )6

Location : supraspinal areas of pain modulation (periaqueductal gray, medial thalamic nuclei, hypothalamus, limbic system)

Response : Supraspinal analgesia, euphoria, respiratory depression, sedation, physical dependence, pupil constriction, decreased GI motility.

Abuse potential : High

Kappa ( к )

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Location: Dorsal horn of spinal gray matter (substantia gelatinosa ); deep layers of cerebral cortex.

Response: Spinal analgesia, sedation, depressed flexor reflexes, pupillary constriction.

Abuse potential: Low

Delta ( δ )

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Location : Substantia nigra, globus pallidus, corpus striatum, other limbic structures.

Response: Euphoria, sedationAbuse potential : Low

Sigma ( σ )9

Location : Hippocampus.Response : Dysphoria, Hallucinations,

cardiovascular stimulation, pupil dilatation.Abuse potential : Low

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Other than these responses, Some of them are involved in depression of

cough , ↑ nausea, ↑ vomiting, neuroendocrine actions, maintainance of B.P, control of stomach secretions, and also anti-inflammatory effects.

Strong Agonists11

MorphineFentanylHeroinMeperidineMethadoneSufentanil

Moderate Agonists12

Codeine

Propoxyphene

Mixed agonist - antagonist13

Buprenorphine

Pentazocine

Antagonists14

Naloxone

Naltrexone

MORPHINE15

Main agonist actions on Mu, and also for Kappa and Sigma receptors

ACTIONS:- Analgesia – relief of pain without loss of

consciousness.- Euphoria- Causes Respiration Depression (This is the

most common cause of death in acute opioid overdose)

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- Depression of cough reflex- MIOSIS – PINPOINT PUPIL.- Stimulation of the edinger westphal nucleus

of oculomotor nerve which causes parasympathetic stimulation of the eye.

- Emesis.—stimulates chemoreceptor trigger zone (CTZ) in area postrema

- - GIT : ↓ motility, relieves diarrhea and dysentery

- CVS : high doses cause hypotension and bradycardia

17- Cerebral vessels dilate - ↑ CSF pressure

( CI – severe brain injury)- Histamine release causes

bronchoconstriction, urticaria, sweating and vasodilation.

- Hormonal actions – ( increase in prolactin, GH and ADH)

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Morphine is used legally:As an analgesic in hospital settings to

relieve Pain in Myocardial Infarction Pain after surgery Pain associated with trauma

In the relief of severe chronic pain, e.g. Cancer pain Pain from kidney stones Severe Back pain

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As an adjunct to general anesthesia In epidural anesthesia or intrathecal

analgesia For palliative care (i.e. to alleviate pain

without curing the underlying reason for it, usually because the latter is found impossible)

As an antitussive for severe cough In nebulised form, for treatment of dyspnea,

although the evidence for efficacy is slim. Evidence is better for other routes .

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As an anti-diarrheal in chronic conditions (e.g., for diarrhea associated with AIDS), although loperamide (a non-absorbed opioid acting only on the gut) is the most commonly used opioid for diarrhea.

contraindications21

acute respiratory depression acute pancreatitis (this may be a result of

morphine use as well) because morphine may cause spasm of the sphincter of Oddi and worsen the pain

renal failure (due to accumulation of the metabolite morphine-6-glucuronide)

chemical toxicity (potentially lethal in low tolerance subjects)

raised intracranial pressure, including head injury (exacerbation due pCO2 increases from respiratory depression)

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SE23

SedationConstipationNauseaVomitingUrinary retentionPotential for addictionResp. depression

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Drug interactions:MAO Inhibitors (monoamine oxidase

inhibitors )TCA’s(tricyclic antidepressant)Antipsychotic

MEPERIDINE (Pethidine )25

MECH : Binds to Kappa receptors.Actions :AnalgesiaResp. depressionIV route can cause increase in H.R.Dilates pupilDecreases GI motility ↑ CSF pressure

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USES:Any kind of analgesia – preferred for labor

analgesiaNot used for diarrhea or coughCan replace morphine or heroin in addicts.Route : oral and parental Met : liverExe : Urine

SE27

TremorsMuscle twitchesConvulsionsDilates pupilNot given with other neuroleptics and MAO

inhibitors.Cause hypotension – postoperative.

METHADONE28

MECH: More on Mu receptorsEqual potency to Morphine, but less

euphoric and longer duration of action.Actions:Mostly same as morphine.Route : oralMet: LiverExe: Urine

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USES :AnalgesiaAddicts of heroin and morphine – for

withdrawal .

SE:Less severe than morphine.

FENTANYL30

AROUND 100 TIMES MORE POWERFUL ANALGESIC THAN MORPHINE, SO USED during ANESTHESIA

Rapid action and short duration of action.Main action is on Mu, and also on kappa

sigma receptors.

HEROIN31

2-3 times more potent than morphine.More euphoriaNo therapeutic usesAddiction

PROPOXYPHENE32

Derivative of MethadoneAnalgesic for mild to moderate painSometimes used in combination with aspirin

or acetaminophen - ↑ analgesiaAlso has antitussive action (used for cough)

SE33

Nausea, ConstipationHigh doses can causeResp depression, ConvulsionConfusion, HallucinationsCardiotoxicity, Pul. edema These effects can be antagonized by

Naloxone.

CODEINE34

Good antitussive,Less analgesic than morphineCauses euphoriaSedationAddictionSo, many of the newer cough medications

do not contain codeineIt has been replaced by dextrometharphan

PENTAZOCINE35

AGONIST ON Kappa AND Partial ANTAGONIST ON Mu & delta.

Moderate painOral or parentalLess euphoric than morphineNot used with morphine.

SE36

At high dosesIncrease B.PHallucinationsNight maresTachycardiaDizzinessResp depression

BUPRENORPHINE37

AGONIST Mu receptorsParenteralModerate painMorphine withdrawalSE:Resp depressionNausea, dizziness

NALOXONE38

OPIOID ANTAGONISTRapidly reverse the effects of opioids,

which can increase withdrawal symptoms

Reverse the coma and resp depression of opioid overdose.

IV route – In 30 sec shows significant changes in resp depression and coma.

Precipitates the withdrawal symptoms in morphine and heroin abusers.

NALTREXONE39

SAME AS NALOXONELonger duration of action than naloxoneOral routeUsed in opiate dependence maintainance

programs.