Narcotic Analgesia J.K

8/14/2019 Narcotic Analgesia J.K

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Narcotic analgesiaNarcotic analgesia

Compiled byCompiled by

Dr . Jahangir KaboutariDr . Jahangir KaboutariDVM, PhD Assistant professor of PharmacologyDVM, PhD Assistant professor of Pharmacology

Faculty of Veterinary Medicine, University ofFaculty of Veterinary Medicine, University ofShahrekord, Shahrekord .IranShahrekord, Shahrekord .Iran


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DefinitionDefinition

NarcoticsNarcotics::Those chemical alkaloid compoundsThose chemical alkaloid compounds

which binds stereo specifically to the Opiatewhich binds stereo specifically to the Opiate

receptors and used to alleviate severe and visceralreceptors and used to alleviate severe and visceralpainspains

OpioidOpioid ::refer to drugs in a generic sense, natural orrefer to drugs in a generic sense, natural or

synthetic, with morphine- like actionssynthetic, with morphine- like actions


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Opioids classificationOpioids classification

NaturalNatural::

PhenathrenesPhenathrenes: morphine 10%: morphine 10%

Codeine 5%Codeine 5%

Thebaine 0.2%Thebaine 0.2%

Bezylisoquinolines:Bezylisoquinolines:papverinpapverin

NoscapineNoscapine

Semi synthetics :Sem

i synthetics : Heroin, Oxymorphone,Heroin, Oxymorphone,

HydromorphoneHydromorphone

Synthetics :S

ynthetics : Meperidine, Methadone,Meperidine, Methadone,Morphinians, BenzomorphansMorphinians, Benzomorphans


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Morphine chemistryMorphine chemistry

pentacyclic alkaloidpentacyclic alkaloid

oxygen bridge at 4,5 positionoxygen bridge at 4,5 position

)three major rings )a, b, c)three major rings )a, b, c

phenolic groups )s/a hydroxyl, alcoholic, OHphenolic groups )s/a hydroxyl, alcoholic, OHat position 3 and 6, modifications at thoseat position 3 and 6, modifications at those

positions changes pharmacokinetics andpositions changes pharmacokinetics and

. potency of drug. potency of drug

changing nitrogen at 16 position )n16 bychanging nitrogen at 16 position )n16 by

adding an alkyl group converts it to Naloxaneadding an alkyl group converts it to Naloxane

))i.e. go from a agonist to an antagonist))i.e. go from a agonist to an antagonist


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Sulfate saltSulfate salt

Spp response variation due to difference inSpp response variation due to difference in

number, distribution &sensitivity of opiatenumber, distribution &sensitivity of opiate.receptors in the body.receptors in the body

General CSN effects:General CSN effects:AnalgesiaA

nalgesia, sedation, sedation

. &respiratory depression. &respiratory depression

: Generally: Gene

rally

CNS depressantCNS depressant:human, monkey& dog:human, monkey& dog

CNS stimulatorCNS stimulator: goat, cat, sheep, horse & cow: goat, cat, sheep, horse & cow


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Receptor StimulationReceptor Stimulation

Gi protein mediated increase in K conductance, neuralGi protein mediated increase in K conductance, neural

hyperpolarization & decrease synaptic transmission.hyperpolarization & decrease synaptic transmission.

Endogenous ligand: EnkephalineEndogenous ligand: EnkephalinePP hysical dependencehysical dependence

EE uphoriauphoria

AAnalgesia )nalgesia )11 supraspina,supraspina,)2 spinal analgesia)2 spinal analgesiaRRespiratory depressionespiratory depression

GGasrtointestinal upset


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G protein mediated decrease in Ca inward,G protein mediated decrease in Ca inward,

.decrease NT release.decrease NT release

Endogenous ligand: DynorphinEndogenous ligand: Dynorphin

SSedationedation

AA )nalgesia )spinal)nalgesia )spinal

MM iosisiosis

DD ysphoriaysphoria


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Gi protein mediated increase in K conductance, neuralGi protein mediated increase in K conductance, neural

hyperpolarization & decrease synaptic transmission,hyperpolarization & decrease synaptic transmission,interactive molecular complex withinteractive molecular complex with..

Endogenous ligand: Enkephaline

AA )nalgesia )spinal & supra spinal)nalgesia )spinal & supra spinal

RRee lease oflease ofgg rowthrowthhh ormoneormone

Excitatory ,no analgesic, insensitive to NaloxaneExcitatory ,no analgesic, insensitive to NaloxaneDD )ysphoria )opposite of euphoria)ysphoria )opposite of euphoria

HH)allucination )both visual & auditory)allucination )both visual & auditoryRRespiratory and vasomotor stimulationespiratory and vasomotor stimulation

MM ydriasisydriasis

PPshycotomimetic & maniashycotomimetic & mania


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Opiate receptorsOpiate receptors

.CNS distribution is not uniform.CNS distribution is not uniform

.they are at areas concerned with pain.they are at areas concerned with pain

receptor locations beginning with highest concentrationreceptor locations beginning with highest concentration:areas:areas

cerebral cortex .1cerebral cortex .1amygdala .2amygdala .2

septum .3septum .3

thalamus .4thalamus .4hypothalamus .5hypothalamus .5

midbrain .6midbrain .6

spinal cord .7spinal cord .7


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Endogenous Opioid PeptidesEndogenous Opioid Peptides

Three distinct families of peptides have beenThree distinct families of peptides have been

identified: theidentified: theEnkephalinsEnkephalins,, thetheEndorphinsEndorphins,,

and theand theDynorphinsDynorphins.. Each family is derivedEach family is derived.from a distinct precursor polypeptide.from a distinct precursor polypeptide

These precursors are now designated asThese precursors are now designated as

proenkephalin )also proenkephalin A,proenkephalin )also proenkephalin A,proopiomelanocortin )POMC, andproopiomelanocortin )POMC, and

)prodynorphin )also proenkephalin B)prodynorphin )also proenkephalin B


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Endogenous Opioid Peptides :Endogenous Opioid Peptides :

EnkephalinsEnkephalins

met enkephalinmet enkephalin )methionine at 5' position &)methionine at 5' position &leu enkephalinleu enkephalin. ) )leucine at 5' position. ) )leucine at 5' position

Neuromodulators in Thalamus ,hypothalamus,Neuromodulators in Thalamus ,hypothalamus,

brain stem, dorsal horn of spinal cord,brain stem, dorsal horn of spinal cord,plasma, PNS, G.I.Tplasma, PNS, G.I.T

short interneurons in substantia gelatinosa atshort interneurons in substantia gelatinosa at

the ending of the efferent neurons whichthe ending of the efferent neurons whichinhibit release of P. substanceinhibit release of P. substance


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: Endogenous Opioid Peptides: Endogenous Opioid Peptides

.Endorphin.Endorphin

.Neurohormone.Neurohormone

hypothalamus, hypophysis, placenta, smallhypothalamus, hypophysis, placenta, small

.intestine & plasma.intestine & plasma

.Analgesia and pain decrease while stress

.Analgesia and pain decrease while stress

. conservation between species. conservation between species

. little difference in humans. little difference in humans


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Endogenous Opioid Peptides :Endogenous Opioid Peptides :

DynorphinDynorphin

Central control of CVSCentral control of CVS

Neuromodulator of CNSNeuromodulator of CNSSpinal analgesiaSpinal analgesia


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ImportantImportant

Synergism withSynergism with2 adrenergic agonists due to2 adrenergic agonists due to

activation of presynaptic inhibitory receptor ofactivation of presynaptic inhibitory receptor of

.nociceptive fibers.nociceptive fibers

PotencyPotency.: affinity for opiate receptors.: affinity for opiate receptors

EfficacyEfficacy. : a function of analgesic property. : a function of analgesic property

Involvement of Serotoninergic & GABAergicInvolvement of Serotoninergic & GABAergic

.pathways in opioid analgesia.pathways in opioid analgesia


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PharmacokineticsPharmacokinetics

AbsorptionAbsorptionReadily absorbed from GI tract )smallReadily absorbed from GI tract )small

intestine, nasal mucosa, lung subcutaneous,intestine, nasal mucosa, lung subcutaneous,

.intramuscular, IV route & Sc.intramuscular, IV route & Sc

.Dermal absorption especially in damaged skins.Dermal absorption especially in damaged skins

CNS is primary site of action: analgesia&CNS is primary site of action: analgesia&

.sedation.sedation

.Intensive distribution to almost tissues.Intensive distribution to almost tissues


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Metabolism/ExcretionMetabolism/Excretion

.Hepatic metabolism, glucuronide conjugation.Hepatic metabolism, glucuronide conjugation

.Renal excretion.Renal excretion

Plasma half life : 2.5 to 3 h, analgesic timePlasma half life : 2.5 to 3 h, analgesic time

.h 4-5.h 4-5

.250mg IT: up to 24h in obstetrics.250mg IT: up to 24h in obstetrics

morphine 3 glucuronide : main metabolitemorphine 3 glucuronide : main metabolite

morphine 6 glucuronide : active metabolitemorphine 6 glucuronide : active metabolite.which accumulate while hepatic failure.which accumulate while hepatic failure

Intensive 1Intensive 1stst. pass effect. pass effect


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AdministrationAdministration

Oral morphine not given due to erratic oralOral morphine not given due to erratic oral.availability.availability

Significant variable first pass effect fromSignificant variable first pass effect from

person to person and have intraspecies effectperson to person and have intraspecies effect

.))same dose will vary in person day to day.))same dose will vary in person day to day

IV morphine acts promptly and its main effectIV morphine acts promptly and its main effect

.is at the CNS.is at the CNS


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CNS is primary site of action ofCNS is primary site of action of

morphinemorphine

analgesiaanalgesia

sedationsedation

euphoriaeuphoria

mood changemood change

mental cloudinessmental cloudiness


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Morphine analgesiaMorphine analgesia

****Changes our reaction and our perceptionChanges our reaction and our perceptionof painof pain

severe cancer pain is tolerated more whensevere cancer pain is tolerated more when. person is given morphine. person is given morphine

relieves all types of pain, but most effectiverelieves all types of pain, but most effective. against continuous dull aching pain. against continuous dull aching pain

sharp, stabbing, shooting pain also relieved bysharp, stabbing, shooting pain also relieved bymorphinemorphine

Morphine given to a pain free individualMorphine given to a pain free individual

first experience is dysphoricfirst experience is dysphoric

not experienced in person in painnot experienced in person in pain


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SedationSedation

morphine causes sedation effect, but no loss ofmorphine causes sedation effect, but no loss of

consciousnessconsciousness

EuphoriaEuphoria

sense of well beingsense of well being

reason why morphine is abusedreason why morphine is abused


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Effects of morphine on respirationEffects of morphine on respiration

There is a primary and continuous depressionThere is a primary and continuous depression

of respiration related to doseof respiration related to dose

decrease ratedecrease rate

decrease volumedecrease volume

decrease tidal exchangedecrease tidal exchange

Dog : at firstDog : at first stimulation cause panting, thenstimulation cause panting, then

22stimulation cause respiratory depressionstimulation cause respiratory depression


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receptor activation produces respiratoryreceptor activation produces respiratory

depression; with increase in dose can causedepression; with increase in dose can cause.further respiratory depression.further respiratory depression

CNS becomes less responsive to pCO2 therebyCNS becomes less responsive to pCO2 thereby

. causing a build up of CO2. causing a build up of CO2rhythm and responsiveness causes irregularrhythm and responsiveness causes irregular

breathing patterns; one will see periods ofbreathing patterns; one will see periods of

. apnea

. apnea


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Nausea and vomitingNausea and vomiting

Stimulation of CTZ, in area postrema ofStimulation of CTZ, in area postrema of

medullamedulla

stimulation by stretch receptors causes nauseastimulation by stretch receptors causes nausea

and vomiting , afferents from gut and earand vomiting , afferents from gut and ear

involved in motion sicknessinvolved in motion sickness

Dog is more sensitive than catDog is more sensitive than cat

min after Sc injection: emesis 5-10min after Sc injection: emesis 5-10


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pupil sizepupil size

Miosis )pinpoint pupils: human, dog , rabbit &rat viaMiosis )pinpoint pupils: human, dog , rabbit &rat via

kappa receptorkappa receptorMydriasis: cat, sheep, horse, monkey via sigmaMydriasis: cat, sheep, horse, monkey via sigmareceptors variation due to number or distribution ofreceptors variation due to number or distribution of.sigma receptors in Oculomotor nucleus.sigma receptors in Oculomotor nucleus

Birds: no sensitiveBirds: no sensitivepinpoint pupils still responsive to bright lightpinpoint pupils still responsive to bright light

oculomotor nerve )CN3 is stimulated by kappaoculomotor nerve )CN3 is stimulated by kappareceptorreceptor

if kappa receptor is blocked, mydriasis from sigmaif kappa receptor is blocked, mydriasis from sigmaeffect will resulteffect will result

atropine partially blocks effect indicatingatropine partially blocks effect indicatingparasympathetic system involvedparasympathetic system involved


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CVS effectsCVS effects

Vascular effects more than cardiacVascular effects more than cardiac

coronary vasodilatation in human while ccoronary vasodilatation in human while cvasoconstriction in dogvasoconstriction in dog

Human :used in cardiac diseases : post acuteHuman :used in cardiac diseases : post acute

MI pain, acute pulmonary edemaMI pain, acute pulmonary edema.&postoperative pain.&postoperative pain

Release of histamineRelease of histamine ,,suppression of centralsuppression of central

adrenergic tone ,decrease catecholamine secretion,adrenergic tone ,decrease catecholamine secretion,suppression of reflex vasoconstriction:suppression of reflex vasoconstriction:

Vasodilation , hypotension & decrease MDFVasodilation , hypotension & decrease MDF

Dog : vagotonic ,sedative &protective against vent.Dog : vagotonic ,sedative &protective against vent.

fibrillationfibrillation


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Morphine effects on the G.I.TMorphine effects on the G.I.T

increase in tone and decrease in mobilityincrease in tone and decrease in mobility leads toleads toconstipationconstipation

Initially excitation of myenteric plexus& defecation, thenInitially excitation of myenteric plexus& defecation, then

increased tone in stomach, small intestine, large intestineincreased tone in stomach, small intestine, large intestine

,spasm of anal sphincter &suppression of deification reflex,spasm of anal sphincter &suppression of deification reflexin brain result in constipation.in brain result in constipation.. decreased concentration of HCl secretion. decreased concentration of HCl secretion

delay of passage of food )gastric contents so more reabsorptiondelay of passage of food )gastric contents so more reabsorptionof water ,used in diarrheaof water ,used in diarrhea

tolerance does not develop )i.e. same amount of effect each**tolerance does not develop )i.e. same amount of effect each**time to this constipation effecttime to this constipation effect


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Morphine effects on smooth musclesMorphine effects on smooth muscles

biliary tractbiliary tract

marked increase in pressure in the biliary tract upmarked increase in pressure in the biliary tract upto 10 fold, due to contraction of Sphincter ofto 10 fold, due to contraction of Sphincter of

OddiOddi

bronchial musclebronchial muscle

bronchoconstriction can resultbronchoconstriction can result

contraindicated in asthmatics, particularly before**contraindicated in asthmatics, particularly before**

surgerysurgery

uterusuterus

contraction of uterus can prolong laborcontraction of uterus can prolong labor


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Morphine effects on smooth musclesMorphine effects on smooth muscles

contcont

:Urinary system:Urinary system

Initially contraction of smooth muscles of theInitially contraction of smooth muscles of the

wall of U .bladder & urether and urinationwall of U .bladder & urether and urinationthen, Increase in ADH secretion &then, Increase in ADH secretion &

contraction of the sphincter of the U .bladdercontraction of the sphincter of the U .bladder

result in urinary retention up to 10%result in urinary retention up to 10%


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Neuro endocrine EffectsNeuro endocrine Effects

inhibit the release of GnRH , CRF thusinhibit the release of GnRH , CRF thusdecreasing circulating concentrations of LH,decreasing circulating concentrations of LH,

FSH, ACTH, and b- endorphin; theFSH, ACTH, and b- endorphin; the

concentrations of testosterone and cortisol inconcentrations of testosterone and cortisol in plasma decline disturbance of oesrtus plasma decline disturbance of oesrtus

.cycle.cycle

Secretion of thyrotropin is relativelySecretion of thyrotropin is relatively

.unaffected.unaffected

Modulator agent in Hypothalamus, HypophysisModulator agent in Hypothalamus, Hypophysis

& Dopaminergic- Serotoninergic nuclei& Dopaminergic- Serotoninergic nuclei

Addi tiAddi ti


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AddictionAddiction.Physical &mental dependence.Physical &mental dependence

.Mental dependence: tolerance to euphoria.Mental dependence: tolerance to euphoria

Physical dependence: withdrawal signs which start 8hPhysical dependence: withdrawal signs which start 8h:after last dose, peak in 36-72h:after last dose, peak in 36-72h

lacrimation,nasal discharge, sweating, yawning,lacrimation,nasal discharge, sweating, yawning,.nausea, diarrhea, muscular pain.nausea, diarrhea, muscular pain

.h later: uncalm sleep 13.h later: uncalm sleep 1324h later: goose flesh, pupil dilation, tremor24h later: goose flesh, pupil dilation, tremor.&agitation.&agitation

h later peak of signs: insomnia, tremor, 48-72h later peak of signs: insomnia, tremor, 48-72

intestinal cramps, nausea ,vomiting, diarrhea, severeintestinal cramps, nausea ,vomiting, diarrhea, severeyawning, muscular pain in leg, severe pain in loweryawning, muscular pain in leg, severe pain in lowerpart of vertebral column, hypertension, sweating &part of vertebral column, hypertension, sweating &.goose flesh.goose flesh

signs last for 7-10days, mild sings last for monthssigns last for 7-10days, mild sings last for months


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Addiction contAddiction cont

Negative feedback of exogenous opioidsNegative feedback of exogenous opioids

especiallyespecially-endorphine &receptor down-endorphine &receptor down

.regulation.regulationCa accumulation in some parts of neurons andCa accumulation in some parts of neurons and

inhibition of NT release during use of drug ,inhibition of NT release during use of drug ,

after stoping use of drug Ca release and NTafter stoping use of drug Ca release and NT.secretion cause withdrawal signs.secretion cause withdrawal signs


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Tolerance to morphineTolerance to morphine

Depends on: type of Opioid ,amount of use, times ofDepends on: type of Opioid ,amount of use, times of

. use. useNauseaNausea

AnalgesiaAnalgesia

SedationSedation

Respiratory depressionRespiratory depression

CardiovascularCardiovascular

EuphoricEuphoric

:not to:not toMiosisMiosis

ConstipationConstipation


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IndicationIndication

.Decrease severe &visceral pains.Decrease severe &visceral painsAs pre anesthetic: 30-50%decraese in anesthetic doseAs pre anesthetic: 30-50%decraese in anesthetic dose

.especially in preoperative pains.especially in preoperative pains

As post operative drug: decrease incidence & relapseAs post operative drug: decrease incidence & relapse

of hallucination of Pentobarbital anesthesiaof hallucination of Pentobarbital anesthesia

.recovery.recovery

. Acute pulmonary edema. Acute pulmonary edema

.Constipating effect.Constipating effect

. Anti tussive. Anti tussive

Obstetrical analgesiaObstetrical analgesia


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AdvantagesAdvantages

No inhibition of motor activity orNo inhibition of motor activity or

.consciousness.consciousness

Increase pain threshold: suppress moderateIncrease pain threshold: suppress moderate

.pains, decrease severe& sharp pains.pains, decrease severe& sharp pains

.Anti anxiety.Anti anxiety

.Control visceral& traumatic pains.Control visceral& traumatic pains

C i di iC i di i


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ContraindicationsContraindications.Uremia &toxemia : increase ADH secretion.Uremia &toxemia : increase ADH secretion

.Traumatic shocks : hypertension.Traumatic shocks : hypertension

. Head trauma &injuries :increase ICP. Head trauma &injuries :increase ICP

Strychnine poisoning & epileptic seizures:Strychnine poisoning & epileptic seizures:

spinal cord stimulation & increase centralspinal cord stimulation & increase central.seizures.seizures

CautionsCautions

C. section: fetal respiratory depression &C. section: fetal respiratory depression &

.interference with uterine contractions.interference with uterine contractions

.Large animals: restlessness & excitation.Large animals: restlessness & excitation

T i it f hiT i it f hi


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Toxicity of morphineToxicity of morphine

Primarily: Cold pale skin then cyanotic, slow surfacePrimarily: Cold pale skin then cyanotic, slow surfaceirregular breath, bradycardia& hypotension up toirregular breath, bradycardia& hypotension up to

shock and then bilateral pin point pupil, respiratoryshock and then bilateral pin point pupil, respiratory.depression &coma.depression &coma

excitatory and spinal reflexesexcitatory and spinal reflexes

high doses of many OPIOID cause convulsionshigh doses of many OPIOID cause convulsionsdue to stimulation at sigma receptordue to stimulation at sigma receptor

TreatmentTreatment

establish adequate ventilation .1establish adequate ventilation .1

1a. 4 point restraints needed1a. 4 point restraints needed

giving OPIOID antagonist :Naloxane .2giving OPIOID antagonist :Naloxane .2

Heathing the body, fluid therapy, artificial.3Heathing the body, fluid therapy, artificial.3

respirationrespiration


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Drug interactions with OpioidsDrug interactions with Opioids

in general, the coadministration of CNS**in general, the coadministration of CNS**

depressants with OPIOID often produces atdepressants with OPIOID often produces at

)least an additive depression )potentiation)least an additive depression )potentiation


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OPIOID and phenothiazinesOPIOID and phenothiazines

produces an additive CNS depression as well asproduces an additive CNS depression as well as

enhancement of the actions of OPIOID )respiratoryenhancement of the actions of OPIOID )respiratorydepression . this combination may also produce adepression . this combination may also produce a

greater incidence of orthostatic hypotensiongreater incidence of orthostatic hypotension

OPIOID and tricyclics antidepressantsOPIOID and tricyclics antidepressants

. can produce increased hypotension. can produce increased hypotension

meperidine and MOA inhibitors : severe andmeperidine and MOA inhibitors : severe and

immediate reactions that include excitation, rigidity,immediate reactions that include excitation, rigidity,hypertension, and severe respiratory depressionhypertension, and severe respiratory depression


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OPIOID and barbituratesOPIOID and barbiturates

Increased clearanceIncreased clearance

morphine and amphetaminemorphine and amphetamine

Enhanced analgesic effectEnhanced analgesic effect


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CodeineCodeine

.Semi synthetic.Semi synthetic

.change in the methyl group on 3 position

.change in the methyl group on 3 position

. 0.1the potency )analgesic properties of morphine. 0.1the potency )analgesic properties of morphine

absorbed readily from GI tract more regular and moreabsorbed readily from GI tract more regular and more. predictable than morphine. predictable than morphine

. given orally. given orally.metabolized like morphine through glucuronic acid.metabolized like morphine through glucuronic acid

physical dependence is necessity of drug so you don'tphysical dependence is necessity of drug so you don't.go through withdrawal.go through withdrawal

tolerance and physical dependence is protracted fromtolerance and physical dependence is protracted from.morphine since potency of codeine is low.morphine since potency of codeine is low

withdrawal from codeine is mild in relation towithdrawal from codeine is mild in relation to. morphine. morphine

Anti tussive drug as phosphate &sulfate saltsAnti tussive drug as phosphate &sulfate salts


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)Heroin )diacetylmorphine)Heroin )diacetylmorphine

Severely addictive, no therapeutic usage, mostSeverely addictive, no therapeutic usage, most.lipophilic of all the OPIOID.lipophilic of all the OPIOID

More euphoria, rapidly hydrolyzed, better penetrationMore euphoria, rapidly hydrolyzed, better penetration

.to brain &more rapid acting.to brain &more rapid actingIV use: tremor in the lower region of abdomen withIV use: tremor in the lower region of abdomen with

.warmth & itching like sexual orgasm.warmth & itching like sexual orgasm

it is anywhere from 3 to 4 times the analgesic potencyit is anywhere from 3 to 4 times the analgesic potency

of morphineof morphine


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When heroin is ingested, it crosses the blood brainWhen heroin is ingested, it crosses the blood brainbarrier rapidly )morphine crosses slow where it isbarrier rapidly )morphine crosses slow where it ishydrolyzed to monoacetyl morphine )acetyl grouphydrolyzed to monoacetyl morphine )acetyl group

got cleaved off and then it is hydrolyzed togot cleaved off and then it is hydrolyzed tomorphine making more of the drug in the brainmorphine making more of the drug in the brain.making it 3 to 4 times more potent.making it 3 to 4 times more potent

withdrawal symptoms of heroin similar to morphine,withdrawal symptoms of heroin similar to morphine,

.)but more intense )rebound effect.)but more intense )rebound effectmydriasismydriasis

diarrheadiarrhea

vasoconstrictionvasoconstrictiondysphoriadysphoria

.etc.etc


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)Hydromorphone HCl )trade name : dilaudid)Hydromorphone HCl )trade name : dilaudid

.Semi synthetic.Semi synthetic

.times more potent than morphine 5.times more potent than morphine 5

more sedation than morphine so less euphoric feelingmore sedation than morphine so less euphoric feeling

.so not abused much.so not abused much

.less constipation.less constipation

.does not produce miosis.does not produce miosis

tolerance and physical dependence is more intensetolerance and physical dependence is more intense

. than morphine because of its high potency. than morphine because of its high potency.respiratory depression &narcosis > morphine.respiratory depression &narcosis > morphine


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)Fentanyl citrate )Sublimaze)Fentanyl citrate )Sublimaze

synthetic drug activesynthetic drug active

More lipophilic: 80 - 100 times > morphine, rapidlyMore lipophilic: 80 - 100 times > morphine, rapidly. acting drug. acting drug

.Sympatholytic with the least cardiac depression.Sympatholytic with the least cardiac depression

Preoperative medication with Butyrophenones as:Preoperative medication with Butyrophenones as:.Neurolepanalgesia.Neurolepanalgesia

.short acting )30-45 min, onset of action is 5 minutes.short acting )30-45 min, onset of action is 5 minutes

Transdermal patchTransdermal patch

highly abused ,known ashighly abused ,known aschina whitechina white as street nameas street name

less histamine release than morphineless histamine release than morphine


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Sufentanil citrateSufentanil citrate

More lipophilic than fentanyl&5-10 times moreMore lipophilic than fentanyl&5-10 times more

.potent.potent

.Safety margin>6.Safety margin>6

Excellent anesthesia with excellent CVSExcellent anesthesia with excellent CVS

.stability.stability


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Carfentanil citrateCarfentanil citrate

.more potent than morphine 10000.more potent than morphine 10000

.Hunting wild animals.Hunting wild animals

Intensive care when use, always with anIntensive care when use, always with an.antagonist such as: Dipernorphine.antagonist such as: Dipernorphine


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Alfentanil HClAlfentanil HCl

More lipophilic than Fentanyl but less potencyMore lipophilic than Fentanyl but less potency

.&half life.&half life

. Redistribution& short action period: infusion. Redistribution& short action period: infusionRapid hepatic metabolism not accumulates inRapid hepatic metabolism not accumulates in

.body.body


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Ramifentanil citrateRamifentanil citrate

.times more potent than Fentanyl 20-30.times more potent than Fentanyl 20-30

.Half life:7.5minutes.Half life:7.5minutes

TI:33000TI:33000

)Meperidine )Pethideine BP

)Meperidine )Pethideine BP


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)Meperidine )Pethideine BP)Meperidine )Pethideine BP

Synthetic, efficacy same as morphineSynthetic, efficacy same as morphine..

Op: rapid absorption, Sc: pain &irritation, IVOp: rapid absorption, Sc: pain &irritation, IV.the best route.the best route

.Histamine release& hypotension, spasmolytic.Histamine release& hypotension, spasmolytic

Less fetal respiratory depression: C. section&Less fetal respiratory depression: C. section&.delivery pain.delivery pain

Horse : C. section, colic especially acute colicHorse : C. section, colic especially acute colic

.superior to: Xylazine, Dipyrone, Pentazocine.superior to: Xylazine, Dipyrone, Pentazocine

.Cattle: calming nervous heifers.Cattle: calming nervous heifers

. Safe up to 750 morphine dose. Safe up to 750 morphine dose


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Hepatic metabolism :Normeperidine can cause:Hepatic metabolism :Normeperidine can cause:

epilepsy &myclonus ,accumulates in body inepilepsy &myclonus ,accumulates in body inrenal insufficiency so not suitable for chronicrenal insufficiency so not suitable for chronic

.use.use

.Caution in patients receiving MAO inhibitors.Caution in patients receiving MAO inhibitors

.Toxicity: fetal seizure treated with Barbiturates.Toxicity: fetal seizure treated with Barbiturates

:unlike morphine:unlike morphine


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pp

more respiratory depressionmore respiratory depression

more bronchoconstriction activitymore bronchoconstriction activity

less constipationless constipationno anti tussive activityno anti tussive activity

)it causes mydriasis )not miosis**)it causes mydriasis )not miosis**

toxic effects similar to atropinetoxic effects similar to atropinedry as a bone, blind as a bat, red as a beet,dry as a bone, blind as a bat, red as a beet,mad as a hattermad as a hatter

have dry mouthhave dry mouth

drug absorbed orallydrug absorbed orally

drug most abused by health care professionalsdrug most abused by health care professionalsdue to its availabilitydue to its availability

withdrawal similar to morphinewithdrawal similar to morphine

MethadoneMethadone


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Synthetic substitute for morphine in Germany.Synthetic substitute for morphine in Germany.Efficacy similar to morphine, less 1Efficacy similar to morphine, less 1stst passpass

.effect.effect

. long duration of activity ,cumulative. long duration of activity ,cumulative

.Absorbed well orally.Absorbed well orally

.to 20 hour duration of action 16.to 20 hour duration of action 16powerful pain reliever, longer duration butpowerful pain reliever, longer duration but.milder withdrawal signs.milder withdrawal signs

maintenance program for narcotic treatment,maintenance program for narcotic treatment,. chronic severe pains. chronic severe pains

LA substitute: L-LA substitute: L--acetyl methadone )LAAM-acetyl methadone )LAAM.a single PO dose 2-4 days duration.a single PO dose 2-4 days duration

Diphenoxylate HClDiphenoxylate HCl


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Diphenoxylate HClDiphenoxylate HCl

.Synthetic ,derivative of Meperidine, OTC drug.Synthetic ,derivative of Meperidine, OTC drug

Combined with Atropine: Lomotil for treatmentCombined with Atropine: Lomotil for treatment. of severe diarrhea. of severe diarrhea

has very little analgesic properties at therapeutichas very little analgesic properties at therapeutic

. dose , no anti tussive effect. dose , no anti tussive effect

at high doses it has analgesic problems,at high doses it has analgesic problems,

. respiratory depression and euphoria. respiratory depression and euphoria

Metabolites: Diphenoxyne, Loperamide: an OTCMetabolites: Diphenoxyne, Loperamide: an OTC.anti diarrhea agent.anti diarrhea agent


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Etorphine HClEtorphine HCl

.Up to1000 times more efficacy then morphine.Up to1000 times more efficacy then morphineCombined with Acepromazine )large animal :Combined with Acepromazine )large animal :.capturing wild animals.capturing wild animals

Combined with Methotrimeprazine in smallCombined with Methotrimeprazine in small.animal.animal

Contra indication in human food producingContra indication in human food producing.animals.animals

Caution when use due to accidental human useCaution when use due to accidental human use.and death.and death


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Agonist-antagonistsAgonistic effect on kappa while antagonisticAgonistic effect on kappa while antagonistic

.effect on mu receptors.effect on mu receptors

Nalbuphine HClNalbuphine HCl

Pentazocine lactatePentazocine lactateButorphanol tartrateButorphanol tartrate


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Nalbuphine HClNalbuphine HCl

Limited analgesic& respiratory depression , theLimited analgesic& respiratory depression , the.least CVS activity.least CVS activity

Used in cardiac diseases & reversion of opioidsUsed in cardiac diseases & reversion of opioids

.induced respiratory depression.induced respiratory depression


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Pentazocine lactatePentazocine lactate

Synthetic, no addictiveSynthetic, no addictiveEfficacy: 25-50% of morphine, Less emesis,Efficacy: 25-50% of morphine, Less emesis,

.constipation &respiratory depression effects.constipation &respiratory depression effects

.No euphoria& excitation.No euphoria& excitationCross placenta reach 60% of maternal bloodCross placenta reach 60% of maternal blood

. concentration. concentration

.Used in ophthalmic surgeries.Used in ophthalmic surgeries

B h lB h l


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Butorphanol tartrateButorphanol tartrate

When dose increases response reach a plateau thenWhen dose increases response reach a plateau then

.decreases.decreases

.Efficacy 4-7 > morphine, similar to Nalbuphine.Efficacy 4-7 > morphine, similar to Nalbuphine

.Potent cough center depressant.Potent cough center depressant

&Combined in H with Detomidine :sedation-analgesia&Combined in H with Detomidine :sedation-analgesiaIn small animals: with Tranquilizers as a part ofIn small animals: with Tranquilizers as a part of

preanesthetic regimen to control mild to moderatepreanesthetic regimen to control mild to moderate

.pains.pains

.In cat :unlike other opioids no excitatory property.In cat :unlike other opioids no excitatory property


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Partial narcotic agonistsPartial narcotic agonists

In the presence of Opioids act as AntagonistIn the presence of Opioids act as Antagonist.while in their absence act like Agonist.while in their absence act like Agonist

Bupernorphine HClBupernorphine HCl

Tramadol HClTramadol HClNalorphine HClNalorphine HCl

Levallorphane tartrateLevallorphane tartrate


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Bupernorphine HClBupernorphine HCl

A derivative of Thebaine with high affinity forA derivative of Thebaine with high affinity for.Mo receptors.Mo receptors

Highly lipophilic, slow attachment Highly lipophilic, slow attachment detachment to opiate receptors: slow onset&detachment to opiate receptors: slow onset&.long acting.long acting

Efficacy 30>morphine , little emetic &Efficacy 30>morphine , little emetic &

.digestive effects.digestive effects

.Appropriate post operative analgesic agent.Appropriate post operative analgesic agent

ll hL ll h


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Levallorphan tartrateLevallorphan tartrate

In the absence of Opioids induces respiratoryIn the absence of Opioids induces respiratory

.depression.depression

.Antagonist for CNS effects of Opioids.Antagonist for CNS effects of OpioidsNot only ineffective in reversal of respiratoryNot only ineffective in reversal of respiratory

depression of : anesthetic agents,depression of : anesthetic agents,

barbitutates& non narcotic agents but alsobarbitutates& non narcotic agents but also.facilitates it.facilitates it


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Nalorphine HClNalorphine HCl

Administration Sc, Im, Iv but Iv route is theAdministration Sc, Im, Iv but Iv route is the.best.best

.Shorter acting than morphine.Shorter acting than morphine

No constipative, little CVS effects, decrease orNo constipative, little CVS effects, decrease orinhibit narcotics induced respiratoryinhibit narcotics induced respiratory

.depression.depression

If 1If 1stst dose failed to reverse narcotic effects.dose failed to reverse narcotic effects..later doses not recommended.later doses not recommended


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Tramadol HClTramadol HCl

A metabolite of anti depressant drug:A metabolite of anti depressant drug:

.Trazodone.Trazodone

Weak agonist of Mu receptors& weak inhibitorWeak agonist of Mu receptors& weak inhibitor.of NEP reuptake.of NEP reuptake

.Less& better side effects than other Opioids.Less& better side effects than other Opioids

.Post operative analgesic agent.Post operative analgesic agent


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Antagonism of MorphineAntagonism of Morphine

NaloxaneNaloxane

NaltrexoneNaltrexone

NalmefeneNalmefeneNalmexoneNalmexone

DipernorphineDipernorphine


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NaloxaneNaloxane

Competitive antagonist for all opiate receptors except.)of sigma )also endogenous Opioid angents

.Receptor affinity: Mu> Delta20-30> Kappa

.Antagonistic doseagonist dose

Duration is 30-45 minutes :must be reinjected every15)minutes, effects are immediate )3-5 min.

Drug of choice: reverse narcotics induced respiratory. depression, use in morphine poisoning DX

.Increase catecholamine release: MCF

Antagonizes inhibition of LH secretion due to.Opioids

N l d i h kN l d i h k


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Naloxane advantages in shockNaloxane advantages in shock

Inhibits hypotension due toInhibits hypotension due to..endorphine..endorphine

.Increases catecholamine release.Increases catecholamine release

Decreases amount of Myocardial DepressantDecreases amount of Myocardial Depressant

.Factor.FactorDecreases release of lysosomal enzymes,Decreases release of lysosomal enzymes,

.proteolysis &toxic material production.proteolysis &toxic material production

Totally : increases CVS efficacy in endotoxicTotally : increases CVS efficacy in endotoxic.& hemorrhagic shocks.& hemorrhagic shocks


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NaltrexoneNaltrexone


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Same effect of Naloxone except it is used orally soSame effect of Naloxone except it is used orally so

.can't use it if for person with acute toxicity.can't use it if for person with acute toxicity

.Long duration of action.Long duration of action

Single dose block action of heroin effects for 24 hours,Single dose block action of heroin effects for 24 hours,

Patient get no euphoric effect from heroin so personPatient get no euphoric effect from heroin so person

)gets off heroin )negative reinforcement)gets off heroin )negative reinforcementUsed for emergency treatment, once stabilized, giveUsed for emergency treatment, once stabilized, give

. patient Naltrexone. patient Naltrexone

.Approved for use by the FDA

.Approved for use by the FDA

.Also used for treatment of alcoholism.Also used for treatment of alcoholism

Documents

Narcotic Analgesia J.K