drugs used in management of pain

MCQs SAQs summary

:قادة فريق علم األدوية

عبدالرحمن ذكري &لي التميمي :الشكر موصول ألعضاء الفريق املتميزين

جواهر اخليال

سارة الشمراني روان سعد القحطاني

@pharma436pharma436@outlook.com

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Drug Morphine

Mech.of

actio

n

1. Bindingtopresynaptic opioidreceptorscoupledtoGi (inhibitoryGprotein)→↓AC(adenylatecyclase)&cAMP→↓N-typevoltage-gatedCa2+channels(inhibitinfluxofCa2+,→reducereleaseofneurotransmitter)→↓excitatorytransmitter.

2. Bindingtopostsynaptic receptors→increasingpostsynapticK+efflux(hyperpolarization)→↓neuronalexcitability

P.K

- T1⁄2is2-3h- Itisslowlyanderraticallyabsorbedorally(bioavailability10-40%)→GivenSC,IM,orIVinjection.- Metabolizedbyconjugationwithglucuronicacid

- Undergoesenterohepaticrecycling→ CrossesBBB.- CrossesPlacenta→Infantsbornofaddictedmothersshowphysicaldependenceonopiatesandexhibit

withdrawalsymptomsifopioidsarenotadministered

P.D

- Analgesia[inacute&chronicpain]moreeffectiveonvisceral&skeletalpain.- Euphoriarelievesanxietyofpatient.→that’swhypeoplemayaddictit.- Respiratorydepression→byreductionofthesensitivityofrespiratorycenterneuronstocarbondioxide.- Depressionofcoughreflexes→treatmentofnon-reproductivecough(antitussiveeffect).- Nausea&vomiting→↑excitationCRTZ(chemoreceptortriggerzoon)- Pinpointpupil(miosis)→Diagnosticfeatureofopioidaddiction.- EffectsonGIT:-- •↑intone,↓motilityofintestine→severeconstipation→)byreducingreleaseofAch→treatdiarrhea.- •↑biliarytractpressureduetocontractionofthegallbladderandconstrictionofthebiliary

sphincter→contraindicatedinbiliarycolic

TOLERA

NCE&

DEPEND

ENCE

- Toleranceoccurswhenthepersontakesahigherdoseofthedrugtoachievethesamelevelofresponseachievedinitially.

- Occursrapidlywithopioids(e.g.morphine12–24hours)- Developstorespiratorydepression,analgesia,euphoriaandsedation- Notoleranceformiosissoitisgoodindicatorforaddictpeople.

- Dependencedevelopswhentheneuronsadapttotherepeateddrugexposureandonlyfunctionnormallyinthepresenceofthedrug.

- Physical dependence→withdrawalmanifestationsdevelopuponstoppage.Orgivingopioidantagonist.- Lastsforafewdays(8-10days)informof↑bodyache,insomnia,diarrhea,gooseflesh,lacrimation.- Psychological dependencelastingformonths/years→craving.- Dependencedevelopedmainlywithmorphine.

Indicatio

ns

1. Pain Control:cancerpain,severeburns,trauma,Severevisceralpain(notrenalcolics(becauseitconstrictstheureter)/biliarycolics,acutepancreatitis becausethegallbladder&pancreashascommonsphincter

constrictedbymorphine)AcutePulmonaryEdema2. MyocardialIschemia

3. StressRelief:e.g.heartfailure(nonpainfulconditions)

4. Pre- anestheticmedication

ADRs

- Itching- ConstrictedPupil- Sedation- Nausea/Vomiting- RespiratoryDepression- Constipation

C.I

- HeadInjury,duetodilationincranialbloodvessels>intra-cranialPressure>bleeding- BronchialasthmaorImpairedPulmonaryFunction.Duetoreleaseofhistamine..- Biliarycolic→itincreasethepressureofbiliarytract.

- Elderly(moresensitivedueto→↓Metabolism,leanbodymass→Renalfunction)- PtstakeMAOIs(Monoamineoxidaseinhibitors).Becausedepressantactionsofmorphineareenhanced- Infants,neonates,orduringchildbirth→conjugatingcapacity→accumulate→respiratorylevel

IPunchedSimon’sNoseRepeatedly*Crack*

Drug

codeine TRAMADOlPethidine

(mepridine)FENTANYL METHADONE

P.D

- µAgonist-Dependence<morphine

- Synthetic,μ(mu)agonist-lesspotentthanMorphine.-

inhibitsNEand

5HT(serotonin)

reuptake.

- Synthetic,moreeffectivek agonist.

- Lessanalgesic,constipating,depressantonfetalrespirationthan

morphine.- No cough suppressant

effect.- Hasatropine-like action(smoothmusclerelaxant)

- Doesnotcausepinpointpupilsbut,rather,causesthepupilstodilatebecauseofananticholinergicaction.

- Synthetic,μ(mu)agonist,- morepotentthanPethidine

andMorphine

- Weakersyntheticμagonist.

- antagonistoftheN-methyl- D-

aspartate(NMDA)receptor.-Innon-addicts,itcauses

toleranceanddependencebutnotas

severeasthatofMorphine.

P.K ـ

Canbegivenorally(high

bioavailability)_ • Highlylipophilic.

• ShortDuration. T1/2=55hrs

Use

- Usedinmild&

moderatepain

- Drycough- Diarrhea

Mildtomoderateacuteandchronic

visceralpain.

Duringlabor(becauseit

doesnotinhibitrespiration).

• AsinMorphinebutnotincoughanddiarrhea.

• Better(preanaetheticmedication).

• Usedinobstetric

analgesia(nodecrease

inrespiration)

• Usedinseverevisceral

pain;renalandbiliary

colics(smooth

musclesrelaxant).

- Usedforacutepain

• Analgesicsupplementduringanesthesia(IVor

intrathecal=injectionintothespinalcanal).

• Induceandmaintain

anesthesiainpoor-riskpts

(stabilizingheart)

• UsedincombinationwithDroperidol as

NEUROLEPTANALGESIA.(whenwewantthepatientto

cooperatewithusduringsurgeryandbeconscious)

• - Incancerpainandseverepostoperativepain;

(transdermalpatchchangedevery72hrs)

Usedtotreat

andcontrol

opioid

withdrawal(in

peoplewho

havebecome

addictedto

opiatessuchas

heroin)

- neurogenicpain(NMDAantagonist.)

ADRs

ـ

- Seizures (notusewithepileptics)- Nausea

- Drymouth- Dizziness- Sedation

- LessADRsonrespiratoryand

CVS

- Tremors,convulsions,hyperthermia,hypotension.

- Blurredvision,drymouth,urineretention(atropine-likeeffects)- Toleranceand

addiction.

- Respiratorydepression(mostserious)

- CVeffectsareless.- Bradycardiamaystilloccur

Opioidantagonists

Drug NALOXONE NALTREXONE

Indicatio

ns • Usedtotreatandreverserespiratorydepressioncausedbyopioidoverdose.• Reverse theeffectofanalgesiaontherespirationofthenewbornbaby.• Precipitateswithdrawalsyndromeinaddicts.Butinnormalcanrelievethepainwithoutwithdrawal

symptoms)

Extrainfo.

- Pureopioidantagonist- Competitiveantagonisttoμ,κ,andδ.

PartiallyantagonistVerysimilartoNaloxone

WithLongerdurationofaction.T1/2=10hrs

(that’swhyweprefernaloxonebecauseithasshortdurationsolesswithdrawalsymptoms)

Antagonistsrapidlyreversetheeffectofagonistssuchas(respiratorydepression),butprecipitatethe

symptomsofopiatewithdrawal

1) Whichoneofthefollowingdrugsiscontraindicatedinpatients

takeMAOISsuchasphenelzine?

a) Aspirin.b)Morphine.c)Naloxone.

2)Whichoneofthefollowingdrugscannotbeusedasanalgesiain

newbornbaby?

a) Pethidine.b)Naloxone.c)Morphine.

3)Whichoneofthefollowingdrugsisusedinobstetricanalgesia?

a) Pethidine.b)Naloxone.c)Fentanyl.

4)Whichoneofthefollowingdrugsmetabolizedbyconjugationwith

glucuronic?

a) Thebaine. b)Anticonvulsants. c)Morphine.

5) Patientwithbiliarycolicshaveseverepainthatistreatedwithone

oftheanalgesicthatworkonKappareceptors,Whichofthe

followingisthedrugwithatropinelikeeffectcanbeused?

a) Pentazocine. b)Pethidine. c)Morphine.

6)PatientcomingtotheERcomplainingofseverpaininthemiddle

torightupperabdomen.Investigationsshows presenceofgallstones.

Thepatientwasdiagnosedwithbiliarycolic.Whichoneofthe

followingdrugsyoushouldnotgiveittothepatient?

a) Morphine.b)Methadone.c)Naloxone.

7)Whichoneofthefollowingdrugscanbeusedtorelievethepainin

patientwithacutepancreatitisduetoitsatropine-likeaction?

a) codeine.b)Pethidine.c)Naloxone.

8)Whichoneofthefollowingopioidsreceptorsisresponsiblefor

miosisinaddictedperson?

a)Delta.b)Mu1.c)Mu2. 1)B

2)C

3)A

4)C

5)B

6)A

7)B

8)C

9)Whichoneofthefollowingreceptorsmayinhibitthesynthesisof

dopamine?

a) Kappa.b)Mu.c)OLR- 1.

10)Ayoungwomanisbroughtintotheemergencyroom.Sheis

unconscious,andshehaspupillaryconstrictionanddepressed

respiration.Basedonreports,anopioidoverdoseofmorphine,Which

ofthelisteddrugscanbeusedasantidoteinhercase?

a)codeine. b)Fentanyl. c)Naloxone.

11)Whichofthefollowingstatementsaboutfentanyliscorrect?

a)Itis100timesmorepotentthanmorphine.b)Itcanbeusedwithpatientwithmyocardiuminfarctionorheartfailure.c)Itcanbeusedduringsurgerywhenweneedthepatienttocooperatewithdoctorsandbeconscious.D)Allofthem.

12)WhichoneofthefollowingdrugsinhibitNE&5HTreuptake?

a) Pentazocine. b)Fentanyl. c)Tramadol.

13)A27-year-oldmalecametotheERdepartment,hewassuffering

fromNausea,vomitingandconstipation.Thedoctordidthe

examinationandhenoticedthathispupilwasconstricted.Whichof

thefollowingdrugswashemostlytake?

a)Naltrexone. b)Pethidine.c)Morphine.

14)Whichoneofthefollowingisdiagnosticfeatureandgood

indicatorforaddictpeople?

a) Constrictedpupil.b)respiratorydepression.c)euphoria.

15)Whichoneofthefollowingopioidscanbeusedtotreatorcontrolthe

withdrawalsymptomswithpersonwhohasbecameaddictedtoHeroin?

a) Pentazocine.b)Fentanyl.c)Methadone.

9)C

10)C

11)D

12)C

13)C

14)A

15)C

Q1:Hudaa27-year-oldfemalecametotheERdepartment,shewas

complainingofseverpaininthemiddletorightupperabdomen.

Investigationsshows presenceofgallstones.Thepatientwas

diagnosedwithbiliarycolic.

1-WhichdrugyoushouldnotgiveittoHuda?

Morphine2-Whatisthemechanismofactionofthisdrug?

1. BindingtopresynapticopioidreceptorscoupledtoGi (inhibitoryGprotein)→↓ AC(adenylatecyclase)&cAMP→↓ N-typevoltage-gatedCa2+channels(inhibitinfluxofCa2+,→ reducereleaseofneurotransmitter)→↓ excitatorytransmitter.

2. Bindingtopostsynapticreceptors→ increasingpostsynapticK+efflux(hyperpolarization)→↓ neuronalexcitability.

3-WhythisdrugshouldgivenIVrepeatedly?

Morphinehasveryshorthalflifeabout2-3hours.4-Howdoesitmetabolize?

Metabolizedbyconjugationwithglucuronicacid.5-Whythisdrugiscontraindicationinelderlypatients?

Theybemoresensitivedueto1- decreaseinthelivermetabolism.2-impairmentofRenalfunction6- Whatisthediagnosticfeatureofthisdrugcanbeeasilydiagnosed?

Miosis(constructedpupil),thereisnotoleranceforit.7- Whatisthedrugofchoicetorelieveherpain,andwhy?

Pethidine,duetoitsatropinelikeactionwithsmoothmusclerelaxant.

Q2:Newbornbabysufferfromseverabdominalpain.Andhehad

givenanopioiddrugtorelievehispain.Suddenlyhedeveloped

respiratorydepression.

1-Whatismostlikelyanalgesicdrugwasusedinhiscase?

Morphine2-Whythisdrugiscontraindicatedwithnewbornbaby?Becausetheyhavelimitedconjugatingcapacityà whichleadtoaccumulateofmorphine→respiratorydepression3- Whichdrugcanbeusedtoreverserespiratorydepression?

OpioidAntagonistsuchasNaloxone&Naltrexone.ButwepreferNaloxone duetoitsshorthalflife.4-Isthereanydrugwhichrecommendedtobeusedinobstetricanalgesia?

Yes,Pethidine(meperidine)