💥 Module 4 · Pain, Inflammation & Substance Use

21 drugs · 7 concepts · tested on Exam 3

💡 The big idea

One pain ladder plus two neurodegenerative side quests. Pain sorts into non-opioid (acetaminophen, NSAIDs), opioid (full agonist to partial agonist to antagonist), and adjuvants that treat the nerve pain the first two cannot touch. Bolted onto that are the Parkinson's drugs (add dopamine or block acetylcholine), the Alzheimer's drugs (add acetylcholine or block glutamate), and the substance-use drugs.

🧠 How to think about this module

Pain drugs stack by mechanism: acetaminophen works centrally with no anti-inflammatory effect, NSAIDs block prostaglandins so they DO reduce inflammation, opioids block the pain signal in the CNS, adjuvants quiet the nerve itself.
Every opioid question is really a respiratory and sedation question. Sedation comes BEFORE respiratory depression — a client who is hard to rouse is the warning sign, not the number on the monitor.
Parkinson's = too little dopamine and relatively too much acetylcholine. Every PD drug either adds dopamine or blocks acetylcholine.
Alzheimer's = too little acetylcholine (donepezil raises it) plus too much glutamate (memantine blocks it).
Migraine has two separate drug lists: abort the headache you have (triptans, NSAIDs) vs prevent the next one (beta blockers, TCAs, topiramate, valproate). Exams love to swap them.

🏷️ The whole module in 10 classes

Learn these groups and the drug list stops being 21 separate names.

Class	What it does	Examples	What gets tested
Non-opioid analgesic	Pain and fever only — no anti-inflammatory effect and no bleeding risk.	acetaminophen	Maximum 4,000 mg in 24 hours for a healthy adult, 3,000 mg for an older adult, and 2,000 mg with chronic alcohol use. Count the hidden acetaminophen in combination products like Percocet and cold remedies. Antidote is acetylcysteine.
NSAIDs	Block COX so you get less inflammation, pain, and fever. Aspirin also blocks platelets irreversibly.	ibuprofen, naproxen, aspirin, ketorolac, indomethacin, celecoxib (COX-2)	GI bleeding is the big one — take with food and teach the client to report black tarry stools or coffee-ground emesis. Also nephrotoxicity, fluid retention, and higher BP. Never give aspirin to a child with a viral illness (Reye syndrome).
Opioid agonists	Bind mu receptors in the CNS and block the pain signal. No ceiling on effect — or on respiratory depression.	morphine, hydromorphone, fentanyl, oxycodone, hydrocodone, codeine, tramadol, methadone	Hold and call if respiratory rate is under 12 in an adult or the client cannot be roused. Constipation never improves with time — start a bowel regimen with the first dose.
Partial agonists and antagonists	Occupy the receptor but produce less effect, or none at all.	buprenorphine (partial agonist), naloxone and naltrexone (antagonists)	Naloxone lasts only about 30 to 90 minutes — shorter than most opioids. The client can re-sedate after it wears off. Stay with them and be ready to repeat the dose.
Adjuvant analgesics	Drugs from other classes that treat neuropathic pain opioids don't reach.	pregabalin, gabapentin, amitriptyline, duloxetine, carbamazepine	Sedation, dizziness, and ataxia mean fall precautions. Amitriptyline is strongly anticholinergic — dry mouth, urinary retention, constipation, and confusion, especially in older adults.
Muscle relaxants	Reduce spasm centrally or directly at the muscle.	baclofen, cyclobenzaprine, tizanidine (central); dantrolene (direct)	Never stop baclofen abruptly, especially intrathecal — rebound spasticity, high fever, and rhabdomyolysis can be fatal. Dantrolene is the malignant hyperthermia antidote and is hepatotoxic with chronic use.
Antiparkinson drugs	Restore the dopamine-to-acetylcholine balance.	levodopa/carbidopa, pramipexole, entacapone (COMT inhibitor), selegiline (MAO-B inhibitor), benztropine (anticholinergic), amantadine	Orthostatic hypotension is universal — teach the client to change position slowly. Timing matters more than dose: the 'on-off' phenomenon is treated by tightening the schedule, so these doses are not flexible.
Anti-Alzheimer drugs	Slow the decline; they do not reverse it.	donepezil, rivastigmine, galantamine (cholinesterase inhibitors); memantine (NMDA antagonist)	Cholinesterase inhibitors are cholinergic — bradycardia, syncope, nausea, diarrhea, and weight loss. Check the pulse before giving, and give at bedtime if it causes GI upset.
Antimigraine agents	Abortive drugs constrict dilated cranial vessels; preventives are taken daily.	sumatriptan and other triptans, ergotamine, NSAIDs (abortive); propranolol, amitriptyline, topiramate, valproate, CGRP antibodies (preventive)	Triptans constrict vessels everywhere — contraindicated in coronary artery disease, uncontrolled hypertension, and prior stroke. Chest tightness after a dose needs an ECG, not reassurance.
Substance use agents	Reduce craving, block reward, or create aversion.	varenicline, bupropion, nicotine replacement (smoking); disulfiram, naltrexone, acamprosate (alcohol); buprenorphine, methadone (opioid)	Disulfiram plus ANY alcohol — including mouthwash, cough syrup, sauces, and even cologne — causes flushing, vomiting, chest pain, and hypotension. Bupropion and varenicline both lower the seizure threshold.

⚖️ Acetaminophen vs NSAIDs

Acetaminophen	NSAIDs (ibuprofen, aspirin, naproxen)
Pain and fever only	Pain, fever, AND inflammation
No effect on platelets, no stomach irritation	Bleeding risk, GI ulcers, kidney injury, higher BP
Organ at risk: liver	Organs at risk: stomach and kidneys
Max 4,000 mg/day adult, 3,000 older adult, 2,000 with alcohol use	Take with food; avoid with anticoagulants and in CKD; no aspirin in children with viral illness
Antidote: acetylcysteine	No antidote — stop the drug and protect the gut with a PPI

🚨 Red flags DANGER

Respiratory rate under 12, pinpoint pupils, and a client who will not wake: hold the opioid, stimulate, apply oxygen, call, and give naloxone. Act on the sedation before the respiratory rate falls.
Naloxone wears off before the opioid does. Never leave a reversed client unattended and never discharge them early.
Sumatriptan in a client with chest pain, known coronary disease, or within 24 hours of an ergot: do not give it.
Malignant hyperthermia (masseter/jaw rigidity, rising end-tidal CO2, then a temperature spike): stop the trigger, give dantrolene 2.5 mg/kg IV, and cool aggressively. Temperature rise is a LATE sign.
Abrupt withdrawal of intrathecal baclofen or of levodopa can be fatal. Never 'just hold it' without calling the provider.

🧵 Exam traps ⭐ HIGH YIELD

Tramadol looks like a mild analgesic but it is an opioid AND serotonergic — added to an SSRI it causes serotonin syndrome, and it lowers the seizure threshold.
Celecoxib is a sulfonamide, so ask about sulfa allergy. It spares the stomach but not the kidneys or the cardiovascular system.
Carbidopa has no therapeutic effect of its own. It stops levodopa being broken down before it crosses into the brain, which means less levodopa is needed and there is less nausea.
Benztropine treats drug-induced parkinsonism and tremor, not the disease itself — and it is anticholinergic, so it is a poor choice in older adults.
Donepezil raises acetylcholine and benztropine blocks it. Seeing both on one MAR is the question, and the answer is to call the provider.
Aspirin appears here as an analgesic but is dosed as an antiplatelet elsewhere in the course. The dose tells you which job it is doing: 81 mg is antiplatelet, 325-650 mg is analgesic.

🧠 Ways to remember it

Pain ladder: acetaminophen, then an NSAID, then an opioid, and add an adjuvant for nerve pain.
Opioid overdose triad: pinpoint Pupils, Poor respirations, Passed out. Naloxone.
Naloxone is short, opioids are long — watch for the second overdose.
Parkinson's = Dopamine Down, ACh Up. Add dopamine or block acetylcholine.
Disulfiram: 'drink and you'll wish you hadn't.'

🧠 The concepts 7

What are the adverse effects of opioid agonists?🚨 DANGER

RESPIRATORY DEPRESSION is the one that kills; CONSTIPATION is the one that never goes away. Also sedation, hypotension and light-headedness, dizziness, nausea and vomiting, sweating, pruritus, urinary retention, miosis, plus tolerance and physical dependence.

SEDATION ALWAYS PRECEDES RESPIRATORY DEPRESSION. Rising drowsiness is your early warning. Assess sedation level along with respiratory rate, and hold the dose for excessive sedation rather than waiting for the respiratory rate to fall.
Tolerance develops to nearly every effect EXCEPT constipation and miosis. Start a stimulant laxative plus a stool softener at the same time as the opioid, not after the patient is impacted.
Overdose triad: pinpoint pupils, respiratory depression, and decreased level of consciousness. Naloxone is the reversal agent.
Boxed warning: combining an opioid with benzodiazepines, alcohol, or any other CNS depressant markedly increases the risk of profound sedation, respiratory depression, and death.
Highest-risk patients: opioid-naive, older adults, obesity or sleep apnea, renal or hepatic impairment, and the first 24 hours after starting or increasing a dose.
Meperidine is generally avoided: its metabolite normeperidine is neurotoxic and causes seizures, especially in older adults and renal impairment. Morphine is a Schedule II controlled substance with real diversion risk; follow waste and countersign policy exactly.

Sedation before respiration. Pinpoint pupils, pinpoint breathing. And they will be constipated forever.

What are the treatment options for acute opioid overdose?🚨 DANGER

NALOXONE (Narcan), an opioid antagonist that displaces the opioid off its receptors, PLUS airway and ventilatory support. Airway first: bag-mask ventilation and oxygen while the naloxone is drawn up. Titrate naloxone to adequate respirations, not to full wakefulness.

Naloxone has a SHORTER DURATION OF ACTION THAN MOST OPIOIDS, so repeat doses or a continuous infusion are often needed. Never leave the patient or discharge them after one dose - re-narcotization is the classic exam answer.
Routes: IV (fastest), IM, subcutaneous, and intranasal. Take-home intranasal naloxone should be prescribed to anyone on high-dose or long-term opioids and to their household.
Giving too much too fast produces ACUTE WITHDRAWAL: agitation, pain, hypertension, tachycardia, vomiting, diaphoresis, and tremors. In postoperative patients the textbook warns of hypotension, hypertension, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest.
In a chronic-pain or postop patient, dilute and give small increments, watching the respiratory rate. In a street overdose, the priority is simply reversing apnea.
It works on opioids ONLY. It will not reverse benzodiazepines, alcohol, or stimulants. If the patient does not respond, look for another cause. (Flumazenil reverses benzodiazepines but is rarely used because it can precipitate seizures.)
Naltrexone is a different drug: long-acting, oral or monthly IM, used for maintenance treatment of opioid and alcohol use disorder, NOT for acute overdose.

Airway, then Narcan, then stay: the antidote wears off before the opioid does.

What are the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs)?🚨 DANGER

GI ULCERATION AND BLEEDING is the classic (from COX-1 inhibition removing gastric protection). Also renal impairment and fluid retention, increased blood pressure, increased CARDIOVASCULAR thrombotic risk (boxed warning), bleeding from antiplatelet effect, hypersensitivity, and tinnitus with aspirin.

GI risk is higher with: high dose, long duration, more than one NSAID at a time, age 60 and over, prior ulcer or GI bleed, concurrent anticoagulant or corticosteroid, and three or more alcoholic drinks a day. Take with food or milk and consider a PPI for high-risk patients.
Teach the patient to report black tarry stools, coffee-ground emesis, or new abdominal pain. GI bleeding from NSAIDs is often PAINLESS until it is severe.
RENAL: NSAIDs block the prostaglandins that keep the afferent arteriole dilated, so they cause acute kidney injury, sodium and water retention, edema, hyperkalemia, and worsening heart failure. The 'triple whammy' of an NSAID plus an ACE inhibitor or ARB plus a diuretic is a common cause of AKI.
CARDIOVASCULAR boxed warning: all NSAIDs except aspirin increase the risk of MI and stroke, even in the first weeks. Contraindicated for pain after coronary artery bypass grafting.
ASPIRIN specifics: irreversible platelet inhibition for the life of the platelet (7 to 10 days), tinnitus as an early sign of salicylism, and REYE SYNDROME - never give aspirin to a child or teenager with chickenpox or a flu-like illness.
KETOROLAC is limited to 5 DAYS TOTAL by any route because of GI and renal toxicity. Celecoxib is COX-2 selective, so less GI injury, but it still carries the cardiovascular and renal risks and is avoided in sulfonamide allergy. Aspirin-exacerbated respiratory disease (the 'aspirin triad': asthma, nasal polyps, aspirin sensitivity) means all NSAIDs must be avoided.

NSAIDs: Bleeding stomach, Beat-up Kidneys, Blood pressure up, and Blood clots. Aspirin adds ringing ears and Reye's.

How does the pharmacological treatment differ for an acute migraine compared to the prophylaxis of migraines?⭐ HIGH YIELD

ACUTE (abortive) treatment is taken AT THE ONSET of a migraine to stop the attack in progress: TRIPTANS, ergot alkaloids, NSAIDs, acetaminophen, and antiemetics. PROPHYLAXIS is taken EVERY DAY whether or not there is a headache, to reduce how often attacks happen: beta blockers, topiramate, valproate, amitriptyline, and CGRP monoclonal antibodies.

Triptan rules (textbook): give at the ONSET of the migraine, may repeat ONCE after 2 hours, not to exceed 200 mg of sumatriptan per day. Routes are oral, subcutaneous, and nasal spray. Adverse effects: dizziness, vertigo, somnolence, nausea, vomiting, chest discomfort, and angina.
Triptans and ergots are VASOCONSTRICTORS, so both are contraindicated in coronary artery disease, uncontrolled hypertension, peripheral vascular disease, and stroke history. Ergotamine is additionally contraindicated in renal or hepatic dysfunction. NEVER give a triptan and an ergot within 24 hours of each other.
Triptans plus SSRIs, SNRIs, or other serotonergic drugs raise SEROTONIN SYNDROME risk. Chest tightness after a triptan is usually not cardiac, but it must be evaluated the first time.
MEDICATION OVERUSE (rebound) HEADACHE: using abortive drugs more than 2 to 3 days a week makes headaches more frequent. That frequency is itself the trigger for starting prophylaxis.
Prophylaxis is indicated at roughly 4 or more migraine days a month, or when attacks are disabling despite abortive therapy. It takes 4 to 8 WEEKS to judge whether it is working, so tell the patient not to quit early.
Non-drug measures matter for both: identify and avoid triggers, regular sleep and meals, hydration, stress management, and a headache diary. Newer options: gepants (ubrogepant, rimegepant) and lasmiditan for acute attacks, which do not vasoconstrict, and onabotulinumtoxinA for chronic migraine.

ACUTE / abortive	PROPHYLAXIS / preventive
Taken at the first sign of an attack	Taken every day regardless of symptoms
Triptans: sumatriptan, rizatriptan, zolmitriptan	Beta blockers: PROPRANOLOL, metoprolol, timolol
Ergot alkaloids: ergotamine, dihydroergotamine	Anticonvulsants: TOPIRAMATE, valproate/divalproex
NSAIDs, acetaminophen, aspirin-acetaminophen-caffeine	Antidepressants: amitriptyline, venlafaxine
Antiemetics: metoclopramide, prochlorperazine	CGRP monoclonal antibodies: erenumab, fremanezumab, galcanezumab; atogepant
Gepants (ubrogepant, rimegepant), lasmiditan	Candesartan; onabotulinumtoxinA for chronic migraine
Goal: stop THIS headache	Goal: fewer and milder headaches over months

Abortive = at the onset, once, maybe twice. Preventive = every day, and give it 8 weeks.

Define opioid agonist, opioid partial agonist, and opioid antagonist. Give examples of drugs in each pharmacological category.⭐ HIGH YIELD

AGONIST: binds the opioid receptor and fully activates it, producing full analgesia with no ceiling (morphine, fentanyl, hydromorphone, oxycodone, hydrocodone, codeine, methadone). PARTIAL AGONIST/agonist-antagonist: activates the receptor only partially, so there is a CEILING effect (buprenorphine, butorphanol, nalbuphine, pentazocine). ANTAGONIST: binds and blocks with no activation (naloxone, naltrexone).

The ceiling effect is the point of partial agonists: past a certain dose, more drug gives no more analgesia AND no more respiratory depression, so the overdose risk is lower. They also have lower abuse potential.
THE TRAP: giving a partial agonist or agonist-antagonist to someone who is physically dependent on a full agonist DISPLACES the full agonist and PRECIPITATES ACUTE WITHDRAWAL. Always ask about current opioid use before giving nalbuphine, butorphanol, or buprenorphine.
Buprenorphine (with or without naloxone, as Suboxone) is a mainstay of opioid use disorder treatment; methadone is the full-agonist alternative and requires a certified program plus QT monitoring.
Naloxone is short-acting and used for ACUTE overdose. Naltrexone is long-acting (daily oral or monthly IM) and used for MAINTENANCE in opioid and alcohol use disorder. Naltrexone requires 7 to 10 opioid-free days first or it will precipitate withdrawal.
Peripherally acting antagonists (methylnaltrexone, naloxegol, alvimopan) treat opioid-induced constipation without reversing analgesia, because they do not cross the blood-brain barrier.
Receptor shorthand: mu receptors give analgesia, euphoria, respiratory depression, constipation, and dependence. Kappa gives analgesia and sedation with less euphoria, which is why kappa agonist / mu antagonist drugs like nalbuphine and butorphanol behave the way they do.

Category	What it does at the receptor	Examples
Full agonist	Fully activates mu; no analgesic ceiling	morphine, hydromorphone, fentanyl, oxycodone, hydrocodone, codeine, methadone, meperidine, tramadol (weak)
Partial agonist / agonist-antagonist	Partial mu activation or kappa agonist + mu antagonist; CEILING effect; can precipitate withdrawal	buprenorphine, butorphanol, nalbuphine, pentazocine
Antagonist	Binds and blocks, no activation; reverses effects	naloxone (acute overdose), naltrexone (maintenance), methylnaltrexone (constipation only)

Full agonist = no ceiling. Partial = ceiling, and it will yank a dependent patient into withdrawal. Antagonist = pure block.

Disulfiram🚨 DANGER

Disulfiram (Antabuse) is an aversion therapy for ALCOHOL USE DISORDER. It blocks aldehyde dehydrogenase, so acetaldehyde accumulates and drinking causes a violently unpleasant reaction. It does not reduce craving; it works purely by deterrence.

THE DISULFIRAM REACTION starts within 10 to 30 minutes of any alcohol: intense flushing, throbbing headache, nausea and copious vomiting, sweating, palpitations, tachycardia, dyspnea, chest pain, blurred vision, weakness, confusion, and hypotension. Severe reactions cause respiratory depression, arrhythmias, seizures, MI, and death.
TEACH EVERY HIDDEN SOURCE OF ALCOHOL: mouthwash, cough and cold syrups, elixirs, vanilla and other flavoring extracts, sauces, vinegars, aftershave, colognes, hand sanitizer, and some topical preparations. Even skin exposure can trigger it.
The effect persists for up to 14 DAYS after the last dose, so the alcohol ban continues for two weeks after stopping.
The patient must be ABSTINENT for at least 12 hours (and free of alcohol on the breath) before the first dose, and must consent knowingly. Never give it to someone who is intoxicated or who does not know they are getting it.
Also causes a metallic or garlic aftertaste, drowsiness, headache, and rarely hepatotoxicity and peripheral neuropathy. Monitor LFTs at baseline and periodically. Contraindicated in severe cardiac disease and psychosis.
Interactions: raises phenytoin, warfarin, and isoniazid levels. Metronidazole and some cephalosporins cause a disulfiram-LIKE reaction with alcohol on their own; so do sulfonylureas. Other options for alcohol use disorder work differently: naltrexone reduces craving and reward, and acamprosate helps maintain abstinence.

Disulfiram doesn't stop the craving, it punishes the drink. And 'alcohol' includes the mouthwash.

Levodopa/carbidopa⭐ HIGH YIELD

Levodopa is a dopamine precursor that crosses the blood-brain barrier and is converted to dopamine to treat Parkinson's disease. Carbidopa blocks that conversion in the PERIPHERY, so more levodopa reaches the brain and there is far less nausea.

Avoid HIGH-PROTEIN meals with the dose: dietary amino acids compete with levodopa for absorption and blunt the effect.
Harmless but alarming: sweat, saliva, and urine may turn dark red, brown, or black. Warn the patient in advance.
Orthostatic hypotension is common. Rise slowly and use fall precautions.
Long-term: dyskinesias, wearing-off, and the on-off phenomenon (abrupt loss of effect). Doses must be given ON TIME, to the minute.
Do NOT stop abruptly: risk of a neuroleptic malignant-like syndrome. Avoid with MAOIs (hypertensive crisis) and with antipsychotics or metoclopramide, which are dopamine blockers that cancel it out. Report hallucinations, confusion, sudden sleep attacks, and impulse-control behaviors such as gambling, spending, and hypersexuality.

Carbidopa is the bodyguard: it keeps levodopa from being mugged before it reaches the brain.

💉 The drugs 21

💉 AcetaminophenBLACK BOX

Nonopioid analgesic, antipyretic, Nonsalicylate, paraaminophenol derivative

What it is for

Mild to moderate pain or fever, arthralgia, dental pain, dysmenorrhea, headache, myalgia, osteoarthritis Unlabeled: Migraine

How it works

Activates descending serotonergic inhibitory pathway in CNS; antipyretic action results from (hypothalamic heat-regulating center)

Watch for

CNS Agitation (child) (IV); headache, fatigue, anxiety (IV)
RESP Dyspnea (IV), atelectasis (child) (IV)
CV Hyper- and hypotension (IV)
GI Nausea, vomiting, abdominal pain …

Antidote / reversal: 1

💥 Module 4 · Pain, Inflammation & Substance Use

💡 The big idea

🧠 How to think about this module

🏷️ The whole module in 10 classes

⚖️ Acetaminophen vs NSAIDs

🚨 Red flags DANGER

🧵 Exam traps ⭐ HIGH YIELD

🧠 Ways to remember it

🧠 The concepts 7

What are the adverse effects of opioid agonists?🚨 DANGER

What are the treatment options for acute opioid overdose?🚨 DANGER

What are the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs)?🚨 DANGER

How does the pharmacological treatment differ for an acute migraine compared to the prophylaxis of migraines?⭐ HIGH YIELD

Define opioid agonist, opioid partial agonist, and opioid antagonist. Give examples of drugs in each pharmacological category.⭐ HIGH YIELD

Disulfiram🚨 DANGER

Levodopa/carbidopa⭐ HIGH YIELD

💉 The drugs 21

💉 AcetaminophenBLACK BOX

💉 AmitriptylineBLACK BOX

💉 AspirinHIGH ALERTBLACK BOX

💉 BaclofenBLACK BOX

💉 Benztropine

💉 BuprenorphineHIGH ALERTBLACK BOX

💉 BupropionBLACK BOX

💉 CelecoxibHIGH ALERTBLACK BOX

💉 DantroleneHIGH ALERTBLACK BOX

💉 Donepezil

💉 Entacapone

💉 IbuprofenBLACK BOX

💉 Memantine

💉 MorphineHIGH ALERTBLACK BOX

💉 Naloxone

💉 Pramipexole

💉 Pregabalin

💉 SelegilineBLACK BOX

💉 Sumatriptan

💉 TramadolHIGH ALERTBLACK BOX

💉 Varenicline