SEDATIVES AND HYPNOTICS

OPIODSBy: Mrs. Kalaivani Sathish M. PharmAssistant Professor,PIMS - Panipat

OPIODSOpiod analgesics are one of the oldest remedies for relief pain.Opium is the dark brown gummy exudate obtained from the poppy capsule (papaver somniferum)Opium has been in use since 4000BC.

CLASSIFICATIONBased on receptor occupation1.AgonistsA.Natural opium alkaloidsMorphine ,codeine,B.Synthetic opioidsPethidine,Methadone

CLASSIFICATION2.Andagonists Naloxone,naltrexoneMixed agonist antagonistsPendazocine,nalpurine,butorphanol,Buprenorphine,nalorphine

CLASSIFICATIONCHEMICALLY THE OPIUM ALKALOIDS CAN BE GROUPED INTO1.THE PHENANTHRENE GROUPMorphine,codeine,thebaine2.The benzylisoquinoline groupPapaverine,noscapine,narcine

CLASSIFICATIONOpioids can also be classified depending on their sources as:A.Natural opium alkaloidsMorphine ,codeine,noscapineB.Semisynthetic derivativeHeroin,oxymorphone,pholcodeinec.Synthetic opioidsPethidine,Methadone,loperamidefentanyl

MORPHINEMorphine is the most important alkaloid of opium.many new opioids with actions similar to morphine have been synthesized.

Mechanism of actionMorphine and other opioids produce their effects by acting on specific opioid receptors mu( ),kappa( k)and delta( ).these receptors are present in the CNS and other tissues.Stimulation of opioid receptors finally results in a decrease in the intracellular calcium which in turn decrease the release of neurotransmitters.

In CNS mu ( ),kappa( k)and delta( ) receptors

Stimulation of opioid receptors (Morphine)

Decrease the Intra cellular Calcium Level

Decrease the release of Neurotransmitter

It decreases the visceral Pain

Pharmacological action1.Analgesia:Morphine is a potent analgesic and relieves pain without loss of consciousness.in higher doses it relieves severe pain as that of biliary colic.2.Euphoria ,sedation and hypnosisRapid IV inj of morphine produces a warm flushing of the skin and an immensely pleasurable sensation in the lower abdomen about 45 sec.it also produces drowsiness ,a calming effect,inability to concentrate ,indifferance to surroundings.

Pharmacological action3.Respiration Morphine produce respiratory depression. It directly depresses the respiratory center in the brain stem.Death from morphine poisoning is almost always due to respiatory arrest.4.Cough centerIt directly depress the cough center and thereby suppress cough.opioids should be used as antitussive only in the dry cough

Pharmacological action5.Nausea and emesisMorphine directly stimulates the CTZ in the medula causing nausea and vomitting.in higher doses it depress the vomitting center and hence there is no vomitting in poisoning .6.pupil Morphine produces miosis resulting in a characteristic pinpoint pupil in high doses.7.vagusMorphine stimulates vagal center causing bradycardia.

PHARMACOLOGICAL ACTION8.Heat regulationOpioids shift the equlibirium point of heat regulating center so that body temperature falls slightly.9.Truncal rigidityHigher dose of fentanyl found to enhance the tone of the large trunk muscles by acting at supraspinal levels.10.Excitatory effect In high doses opioids produce convulsion

PHARMACOLOGICAL ACTIONCardiovascular systemIn therapeutic dose morphine produces hypotension by;Direct peripheral vasodilatation.Inhibition of baroreceptor reflexes.In higher doses ,it causes depression of vasomotor center and histamine release both contributing to a fall in BP.

PHARMACOLOGICAL ACTIONGIT Opioids decrease the motility of the gut.Stomach:Gasric motility is decreased resulting in increased gastric empting time.gastric acid secretion is reduced.Intestine :Morphine diminises all secretions,delays digestion of food in the small intestine.

PHARMACOLOGICAL ACTIONOther Smooth MusclesBiliary tract Morphine causes spasm of the sphincter of Oddi. Atrophine partially antagonise this .Urinary Bladder and Ureter Opioids inhibit urinary voiding reflex, as a result of this urinary retention occurs especially in the elderly males with Prostatic hypertrophy.Uterus No significant effect, may prolong labour in high doses.Bronchi Morphine causes release of histamine from the mast cells leads to broncho constriction.

PHARMACOLOGICAL ACTIONOther Smooth MusclesBiliary tract Morphine causes spasm of the sphincter of Oddi. Atrophine partially antagonise this .Urinary Bladder and Ureter Opioids inhibit urinary voiding reflex, as a result of this urinary retention occurs especially in the elderly males with Prostatic hypertrophy.Uterus No significant effect, may prolong labour in high doses.Bronchi Morphine causes release of histamine from the mast cells leads to broncho constriction.

PHARMACOKINETICSGiven Orally, absorption of morphine is slow and incomplete.Morphine undergoes first pass metabolism.

Absorbed well in Orally

Metabolized in Liver

Excreted by kidney

ADVERSE EFFECTSNausea, VomitingRespiratory DepressionDysphoria (State of being Unhappy)DizzinessHypotensionSkin Rashes

TOLERANCETolerance is defined as the capacity of the body to endure or become less responsive to a substance.Lethal dose of Morphine is 250 mg, addict can tolerate morphine in gm.

DEPENDENCEIts ability to produce euphoria, makes it a drug of addiction.Opioids produce both psychological and physical dependence.

MANAGEMENT OF ADDICTIONMorphine slowly withdrawn over several days and substituted by oral Methadone. Later on methadone is gradually withdrawn.Acute Morphine PoisoningSymptoms includes respiratory depression, with shallow breathing, pinpoint pupils, hypotension, shock, coma and death.

Acute Morphine Poisoning TreatmentPositive Pressure RespirationMaintenance of BPGastric lavage with potttasim permanganate to remove unabsorbed drug.Specific antidote is Naloxone 0.4 to 0.8 mg IV repeated every 10 to 15 minutes.

OTHER OPIOIDSHeroinIt is converted to morphine in the body.It has higher lipid solubility.It gives euphoric effects faster and greater.It is used as analgesics and banned in most countries.

OTHER OPIOIDSCODEINEIt is Commonly used anti tussives. It is also available with Paracetamol for analgesia.

OTHER OPIOIDSDEXTROMETHORPHANIt acts centrally to elevate the threshold for coughing. It is effective as codeine.

OTHER OPIOIDSTRAMADOLIt is an effective analgesic, it is a weak opioid agonist.

OTHER OPIOIDSPETHIDINEIt produce corneal anesthesia.It has anticholinergic effects, it cause dry mouth and blurring of visionDose and Uses 25 100 mg IM. SC. Used as analgesics in visceral pain. Given as pre anesthetc medicationsAdverse Effects it is similar to morphine.

OTHER OPIOIDS fentanylIt is about 100 times more potent than morphine.It is highly lipid soluble and fast acting.Epidural fentanyl is used for postoperative and obstetric analgesiaIt can also used in chronic pain . ADVERSE EFFECTCough muscle rigidity,Nausea & VomitingRespiratory Depression

OTHER OPIOIDS (METHADONE)It is a synthetic opioids and mu receptors agonist. Its action is similar to morphine. It is an effective analgesic and is more effective when administered via oral, rectal, SC, IV and Spinal route.It is effective for certain Cancer Pain, which are not relieved by morphine.It has a long duration of action.Dose 10 mg oral or IM.

OPIOIDS ANTAGONISTSNaloxone It is a pure antagonist, does not produce any significant action.It antagonise the morphine action, especially respiratory depression, sedation and precipitate morphine withdrawal syndrome.Given orally, it undergoes first pass metabolism, hence it is given IV.Dose 0.4 mg IV.Uses Drug of choice for Morphine Over Dose.It can also be used for diagnosis of opioid dependence.

OPIOIDS ANTAGONISTSNaltrexone It is another pure opioid antagonist.It is more potent than naloxene.Orally EffectiveUses To prevent the relapse of heavy drinking of alcohol.

MIXED AGONIST & ANTAGONISTPentazocine are similar to morphine.20 mg pentazocine is equal to 10 mg morphine.Sedation and respiratory depression are less marked.Doses 50 100 mg oraL 30 50 mg IMUses Used as opioid analgesics especially in post operative and chronic pain.Adverse Effect Sedation, Sweating, Anxiety, Hallucination.

MIXED AGONIST & ANTAGONISTNalorphine is also an agonist antagonist.At low doses it is a good analgesics, but increase in dose no increase in analgesic effect.It causes dysphoria, respiratory depression.Uses It may be usesd in acute opioid poisoning and it is used for the diagnosis of opioid addiction.

NURSING IMPLICATIONSRespirations should be monitored closely while patients are in opioids.Watch for signs of tolerance in patients while patient is using this drug for a prolong periods.Antidote must be kept readily available for use in case of emergency.