NSGl 533/l NSG533l Examl 2l –l Advancedl
Pharmacologyl Guide|l Wilkesl (Latestl
2026/l 2027l Update)l 100%l Verifiedl
Questionsl &l Answersl |l Gradel A
Q:l NOCICEPTIVEl PAINl (Tissuel Injury)
Answer:
l Pathophysiology
Tissuel damagel →l inflammatoryl mediatorsl (prostaglandins,l bradykinin)l →l peripherall
nociceptorl activation.
l Describedl As
Aching,l throbbing,l sharp,l localized.
l First-Linel Treatment
NSAIDsl -l ↓l prostaglandinsl (inflammation-drivenl pain)
Acetaminophen-l Centrall analgesicl effect
Opioidsl (ifl severe)-l Mul receptorl modulationl ofl ascendingl pain
Examples
OA
Sprain
Post-opl pain
Q:l INFLAMMATORYl PAINl (Subsetl ofl Nociceptive)
Answer:
l Mechanism
Prostaglandin-mediatedl inflammation.
l Bestl First-Line
NSAIDs
Why?
Theyl directlyl targetl COXl enzymesl →l ↓l prostaglandins.
NOTl First-Line
Gabapentinl TCAs
Becausel therel isl nol nervel hyperexcitability.
,Q:l NEUROPATHICl PAINl (Nervel Damage)
Answer:
l Pathophysiology
Nervel injuryl →l abnormall sodiuml channell firingl →l centrall sensitizationl →l
hyperexcitability.
l Describedl As
Burningl Electricl Shootingl Tingling
l First-Line
Duloxetine-↑l serotoninl &l NEl →l modulatesl descendingl inhibition
Amitriptyline-l Samel mechanism
Gabapentin-l ↓l calciuml channell neurotransmitterl release
Pregabalin-l Samel asl gabapentin
Examples
Diabeticl peripherall neuropathy
Postherpeticl neuralgia
Radiculopathy
⚠l Important
NSAIDsl arel usuallyl ineffective.
Q:l CENTRALl SENSITIZATIONl /l NOCIPLASTICl PAIN
Answer:
l Pathophysiology
Amplifiedl CNSl painl signalingl withoutl clearl tissuel damage.
Examples
Fibromyalgia
Chronicl widespreadl pain
l Bestl Choices
Duloxetine
Milnacipran
Pregabalin
Amitriptyline
NOTl Effective
NSAIDsl Opioidsl (limitedl role)
,Q:l MALIGNANTl (CANCER)l PAIN
Answer:
l Mechanism
Oftenl mixed:
Inflammatory
Neuropathic
Bonel destruction
l Treatment
Followl WHOl ladderl BUTl oftenl startl atl Stepl 3.
Morphine
Hydromorphone
Fentanyl
Plus:
Adjuvants
Corticosteroidsl (ifl spinall cordl compression)
Bisphosphonatesl (bonel mets)
Q:l ACUTEl SEVEREl TRAUMAl PAIN
Answer:
Mechanism:l Tissuel injuryl +l inflammatoryl cascade.
Treatment:
IVl opioids
NSAIDsl (ifl safe)
Multimodall therapy
Q:l Clinicall Decisionl Flowl (Howl Youl Thinkl onl Exam)l forl Pain
Answer:
Whatl typel ofl painl isl it?
Whatl mechanisml isl drivingl it?
Whatl drugl targetsl thatl pathway?
Arel therel contraindications?
Doesl patientl havel GI,l renal,l CVl risks?
, Q:l Ultral High-Yieldl Pearlsl forl Painl MGMT
Answer:
Burningl pain?l →l Nervel →l SNRIl orl gabapentin.
Swollenl joint?l →l Prostaglandinl →l NSAID.
Widespreadl fatiguel +l pain?l →l Centrall →l Duloxetine.
Severel cancerl pain?l →l Strongl opioidl early.
Q:l Mechanisml ofl Actionl ofl Acetaminophenl (APAP)
Answer:
Acetaminophenl worksl primarilyl centrallyl (inl thel CNS).
Whatl itl does:
Inhibitsl centrall cyclooxygenasel (COX)l activityl inl thel brain
Decreasesl prostaglandinl synthesisl inl thel CNS
Reducesl painl perceptionl andl fever
Whatl itl doesl NOTl do:
Doesl notl significantlyl inhibitl peripherall COX
Doesl notl reducel inflammation
Doesl notl affectl platelets
Doesl notl causel gastricl irritation
So:
APAPl =l Centrall analgesicl andl antipyreticl only
Q:l Whyl APAPl isl differentl froml NSAIDs
Answer:
NSAIDs:
Blockl COX-1l andl COX-2l peripherally
Decreasel prostaglandinsl atl sitel ofl inflammation
Anti-inflammatory
APAP:
Worksl inl CNSl only
Nol meaningfull anti-inflammatoryl effect
Q:l Whenl isl APAPl Indicated?
Answer:
Pharmacologyl Guide|l Wilkesl (Latestl
2026/l 2027l Update)l 100%l Verifiedl
Questionsl &l Answersl |l Gradel A
Q:l NOCICEPTIVEl PAINl (Tissuel Injury)
Answer:
l Pathophysiology
Tissuel damagel →l inflammatoryl mediatorsl (prostaglandins,l bradykinin)l →l peripherall
nociceptorl activation.
l Describedl As
Aching,l throbbing,l sharp,l localized.
l First-Linel Treatment
NSAIDsl -l ↓l prostaglandinsl (inflammation-drivenl pain)
Acetaminophen-l Centrall analgesicl effect
Opioidsl (ifl severe)-l Mul receptorl modulationl ofl ascendingl pain
Examples
OA
Sprain
Post-opl pain
Q:l INFLAMMATORYl PAINl (Subsetl ofl Nociceptive)
Answer:
l Mechanism
Prostaglandin-mediatedl inflammation.
l Bestl First-Line
NSAIDs
Why?
Theyl directlyl targetl COXl enzymesl →l ↓l prostaglandins.
NOTl First-Line
Gabapentinl TCAs
Becausel therel isl nol nervel hyperexcitability.
,Q:l NEUROPATHICl PAINl (Nervel Damage)
Answer:
l Pathophysiology
Nervel injuryl →l abnormall sodiuml channell firingl →l centrall sensitizationl →l
hyperexcitability.
l Describedl As
Burningl Electricl Shootingl Tingling
l First-Line
Duloxetine-↑l serotoninl &l NEl →l modulatesl descendingl inhibition
Amitriptyline-l Samel mechanism
Gabapentin-l ↓l calciuml channell neurotransmitterl release
Pregabalin-l Samel asl gabapentin
Examples
Diabeticl peripherall neuropathy
Postherpeticl neuralgia
Radiculopathy
⚠l Important
NSAIDsl arel usuallyl ineffective.
Q:l CENTRALl SENSITIZATIONl /l NOCIPLASTICl PAIN
Answer:
l Pathophysiology
Amplifiedl CNSl painl signalingl withoutl clearl tissuel damage.
Examples
Fibromyalgia
Chronicl widespreadl pain
l Bestl Choices
Duloxetine
Milnacipran
Pregabalin
Amitriptyline
NOTl Effective
NSAIDsl Opioidsl (limitedl role)
,Q:l MALIGNANTl (CANCER)l PAIN
Answer:
l Mechanism
Oftenl mixed:
Inflammatory
Neuropathic
Bonel destruction
l Treatment
Followl WHOl ladderl BUTl oftenl startl atl Stepl 3.
Morphine
Hydromorphone
Fentanyl
Plus:
Adjuvants
Corticosteroidsl (ifl spinall cordl compression)
Bisphosphonatesl (bonel mets)
Q:l ACUTEl SEVEREl TRAUMAl PAIN
Answer:
Mechanism:l Tissuel injuryl +l inflammatoryl cascade.
Treatment:
IVl opioids
NSAIDsl (ifl safe)
Multimodall therapy
Q:l Clinicall Decisionl Flowl (Howl Youl Thinkl onl Exam)l forl Pain
Answer:
Whatl typel ofl painl isl it?
Whatl mechanisml isl drivingl it?
Whatl drugl targetsl thatl pathway?
Arel therel contraindications?
Doesl patientl havel GI,l renal,l CVl risks?
, Q:l Ultral High-Yieldl Pearlsl forl Painl MGMT
Answer:
Burningl pain?l →l Nervel →l SNRIl orl gabapentin.
Swollenl joint?l →l Prostaglandinl →l NSAID.
Widespreadl fatiguel +l pain?l →l Centrall →l Duloxetine.
Severel cancerl pain?l →l Strongl opioidl early.
Q:l Mechanisml ofl Actionl ofl Acetaminophenl (APAP)
Answer:
Acetaminophenl worksl primarilyl centrallyl (inl thel CNS).
Whatl itl does:
Inhibitsl centrall cyclooxygenasel (COX)l activityl inl thel brain
Decreasesl prostaglandinl synthesisl inl thel CNS
Reducesl painl perceptionl andl fever
Whatl itl doesl NOTl do:
Doesl notl significantlyl inhibitl peripherall COX
Doesl notl reducel inflammation
Doesl notl affectl platelets
Doesl notl causel gastricl irritation
So:
APAPl =l Centrall analgesicl andl antipyreticl only
Q:l Whyl APAPl isl differentl froml NSAIDs
Answer:
NSAIDs:
Blockl COX-1l andl COX-2l peripherally
Decreasel prostaglandinsl atl sitel ofl inflammation
Anti-inflammatory
APAP:
Worksl inl CNSl only
Nol meaningfull anti-inflammatoryl effect
Q:l Whenl isl APAPl Indicated?
Answer:
