Pain

An unpleasant sensory & emotional experience associated with actual or potential tissue damaged, or described in terms of such damage

Patient Assessment Opioid Allergies Opioid Withdrawal Symptoms

Non-Opioids are just as effective at
treating pain without the side effects
or addictive properties
The body is full of receptors other
than opioid receptors
Multi-Modal Analgesia = Best Analgesia
If Opioid Therapy Needed
Lowest dose for shortest duration
assess risk, changes, and monitor
arrange treatment for OUD if needed
Family History: alcoholism, recreational
drug use, substance use disorder
Social History: alcohol, tobacco,
recreational drug use
Medication Use History: past and current,
Caused by histamine release
any allergies/intolerances
occurring & semi-synthetic
Urine Drug Screening
Signs of Trauma/Distress
Comorbidities (mental health)
Sweating / Tachycardia
Myoclonus /Anxiety
Urticaria
Rhinorrhea /Myalgias – “Flu Like”
Puritis
Nausea / Diarrhea
Sneezing
Sleep Disturbance
Abdominal Cramping
from opioids. Naturally
Early Symptoms generally take 5-10 days
following reduction
are more potent. Risk of
cross-sensitivity â so can
Chronic fatigue, mental functioning, pain,
switch between the three.
general well-being may improve over time

CDC Chronic Pain Guidelines

Avoid Solo Opioid Therapy
Physical Therapy, Alternative Medications, Lifestyle Changes, Psychological Support
Assess Risk/Benefit
Assess Pain & Function
Establish realistic goals with patients including how opioid therapy will be discontinued
If no improvement, stop opioids
Abide by rules of opioid agreement Discuss with patients known risks and realistic benefits of opioid therapy
Avoid long-acting opioids
Low Dose: < 50 mg MME
Provide lowest effective dose of opioids Medium Dose: 50 – 90 mg MME
High Dose: > 90 mg MME
Prescribe 3 days or less supply for acute pain More than 7 days are rarely needed
Regular scheduled follow up is an expectation Evaluate benefits/harms within 1-4 weeks of starting opioid therapy then every 3 months
Consider offering naloxone when history of overdose, substance use disorder, high dosages, or concurrent
Evaluate for addiction and risk factors for overdose
benzodiazepine use are present
Regular review of PMP
Urine drug testing at least annually
Avoid use of opioids with benzodiazepines
1-833-2-FINDHELP
Arrange treatment for opioid use disorder if indicated Arrange evidence-based treatment for patients - Typically combination of meds and behavioral therapy
 Non-Opioid Analgesics
Dosing ADR
325 – 650 mg q 4-6 hrs Liver Dysfunction: lowest effective dose (max 2g/day) for shortest
Acetaminophen
Max: 3 or 4 g / day duration

Ibuprofen 200 – 400 mg q 4-6 hrs

CV Thrombosis
15 – 30 mg q 6 hrs Reduce Dose to 15mg to those with renal impairment, > 65 yo, or low
GI Bleeding
Ketorolac Max: 5 days body weight < 50 kg
Renal Impairment
Toradol
NSAIDs

Platelet
15mg just as effective Can be given IV
Dysfunction

Celecoxib 100 mg BID Least risk of GI toxicity within NSAIDs

Naproxen 250 – 500 q 6-12 hrs

Powerful antiemetic for cannabinoid induced hyperemesis

Haloperidol 2.5 – 5 mg IV QTc Prolongation Good for psychologic drivers of pain & those who perseverate on pain
antipsychotic Can start 1.25 and â PRN similar to Zofran
Only give diphenhydramine AFTER dystonic reactions occur

≤ 1.5 mg/kg IV over 10-60 min

5% transdermal patch QD
Lidocaine
Oral 2% viscous solution
Slowly over 10 minutes
Ketamine 0.1-0.3 mg/kg or 0.1mg/kg/hr IV
NMDA Receptor Antagonist
50 mg Intranasal
Abnormal rhythm Patch: great for neuropathic or localized nociceptive pain
Severe cardiac History on for 12 hours / off for 12 hours
Effect is dose dependent – á dose is psychomimetic (hallucinations)
X: PTSD Can be given adjunctively with opioids to â opioid requirements
Better than opioids because less respiratory depression

Dicyclomine 20 mg PO/IM
X: Elderly Alleviates smooth muscle spasms in GI tract – great for abdominal pain
Anti-Spasmodic / Anticholinergic Not IV: thrombosis
 Neuropathic Pain
- Burning, tingling, electric-shock like sensations

Gabapentin Bind voltage gated CA2+ channels which â CNS NT release

Anticonvulsant

300 – 900 mg TID Sedating (Up titration Reqd)

1st Neurontin Also for: alcohol use disorder (600 TID) & Anxiety
Line Pregabalin Renal Impairment Adjustment
50 – 150 mg BID - TID More potent than gabapentin, but often more expensive
s

Lyrica
Carbamazepine

X: those with depression when needed for

TCA

Amitriptyline analgesia
Sleeplessness
SNRI

60 mg QD Headache / Dizziness
Duloxetine 120 mg no more effective Dry Mouth
Constipation
Ketamine /
Lidocaine
Tizanidine Sedating Helpful in many OUD symptoms
Skeletal Muscle

Baclofen Dependence Risk “Most dangerous”

Relaxants

Sedating
Cyclobenzaprine Serotonin Syndrome Risk
Short-Term Only
Dependence Risk
Carisoprodol Withdrawal
Benzodiazepines High overdose risk with opioids

Opioid Taper Naloxone - Opioid Antagonist

Binds to brain opioid receptors in place of opioid drugs preventing opioids from binding
Compare Risk & Benefits
Can temporarily reverse an overdose
Onset: 2-3 minutes after administered
Most Common Taper
â by 5 – 20 % every 4 weeks with pauses in taper as needed Small Doses (0.02 – 0.08 mg IV/IM) as needed
Large Dose (0.4 – 2 mg IV/IM) as needed
Those who have been opioid dependent for years
â by 2-10% every 4-8 weeks with pauses as needed Repeat dosing often needed in heroin/fentanyl overdose due to short naloxone half life
 Common Opioids
- Can either be natural alkaloid (what drug screen captures), semi-synthetic, or fully synthetic (most potent)(does not appear on drug screen)
- Opioid Tolerant: Patients on high daily doses for > 1 week
Dosing Opioid Tolerant ADR

1/10 as Codeine IR X: Children < 12 Antitussive Properties

15 – 60 mg Q 4-6 Hrs
potent Tylenol with Codeine Caution: 12-17 yo Converted by CYP2D6
Natural

IR: 5-15 mg Q4H Itching can add hydroxyzine ½ life: 150 minutes
Morphine ER: 15-30 mg Q12H or or diphenhydramine
Base > 60 mg / day Low Lipid Sol. = slow to enter BBB
ER: MS Contin 24H
X: Severe Renal Impairment Renal Adjustment Needed
IV: 1-2 mg Q4H

Hydrocodone IR: 5 – 10 mg Q 4 H
= > 60 mg / day Itching
Norco / Vicodin ER: 10-20 mg Q12 or 24 H
Semi-Synthetic

1.5 x
Oxycodone IR: 5-15 mg Q4H Metabolized through CYP34A
More > 30 mg / day
Potent Percocet / OxyContin ER: 10-20 mg Q12H Renal Adjustment Needed

4x IR: 2-4 mg Q4H

Hydromorphone
More ER: 8-32 mg Q24H > 8 mg / day Less pruritus and nausea
Potent Dilaudid
IV: 0.2-2 mg Q4H

100 x 25 – 50 mcg Q4H Highly Lipid soluble = quick affects

Chest Wall Rigidity
More Fentanyl Patch: 25-200 mcg/hr Short ½ life but long duration (fat deposit)
Ineffective Ventilation
Synthetic

Potent Patch = Chronic Pain Metabolized by CYP34A

Used for OUD Lose Tolerance Quickly

Methadone 2.5-10 mg Q8-12H QT Prolongation
Centrally
Cancer/Chronic Titrate slowly – first dose titration day 5
Acting
Opioids Serotonin Syndrome â Respiratory Depression
Tramadol Weakly Inhibits NE (acts like SNRI)
Seizures â CYP2D6 Effect = NO/low analgesic effect

May be combined with Naloxone

Analgesia: TID/QID
Mixed Buprenorphine 1mg SL = 30mg MME Used for OUD
Acting Partial MU agonist á Affinity for receptors – Must wait for full
Max 32 mg daily
agonist to clear from their system
 Treatment for Withdrawal / Assistance with Taper Withdrawal Symptoms
Indication First Line Alternatives
Re-Evaluate in 3-7 days
Clonidine – 0.1– 0.2 mg Q6-8H Baclofen 5mg TID (á 40mg) Average duration: 15 days
Autonomic Symptoms Taper to discontinue
Sweating / Myoclonus Hold if BP < 90/60 mmHg Gabapentin 100 – 300 mg BID/TID Can help reduce withdrawal symptoms &
Tachycardia Test Dose: 0.1 with blood work check 1 hour post dose Up to 1800 – 2100 BID-TID Help with pain, anxiety, sleep
Reevaluate in 3-7 days; taper to stop
Tizanidine 4mg TID (á 8mg TID)

Anxiety / Dysphoria
Hydroxyzine - 25 – 50 mg TID PRN Diphenhydramine 25mg Q6H PRN Can be sedating
Lacrimation / Rhinorrhea
Topical Medications
Myalgias NSAIDS or Acetaminophen 650 mg Q6H PRN Less systemic effects
Menthol / Lidocaine
Sleep Disturbances Trazodone - 25 – 300 mg HS
Prochlorperazine 5-10mg Q4H PRN
Nausea Ondansetron 4mg Q6H PRN
Promethazine 25 mg Q6H PRN

Abdominal Cramping Dicyclomine - 20 mg Q6-8H PRN

Bismuth Subsalicylate
Loperamide - 4mg initial then 2mg with each loose stool
Diarrhea Not to exceed 16mg Daily
524 mg Q0.5-1H
Not to exceed 4192 mg/day

ALTO Pathways
Immediate / 1st Line Alternatives Discharge Medications

Ketorolac 15mg IV Lidocaine 1.5mg/kg (max 200mg)

APAP 1000mg Q6H PRN
Renal Colic APAP 1000 mg PO Desmopressin 40mcg intranasal
IBU 600mg Q6H PRN
0.9% NaCl 1000mL Ketamine 0.1-0.3 mg/kg IVPB

APAP 1000mg PO + Cyclobenzaprine 5mg OR Diazepam 5mg APAP 1000 mg Q6H PRN + NSAID
Opioid-Naïve Ibu 600 mg or Ketorolac 15mg IV/IM Ketamine 0.1-0.3 mg/kg IVPB Cyclobenzaprine 5-10 mg Q8HPRN
Musculoskeletal Pain Lidocaine 1% Trigger Point Injection Lidoderm 5% Patch
Lidoderm Patch 4 or 5% (max 3 patches) Gabapentin 300-600mg Gabapentin 300mg HS

Dicyclomine 20mg Q6H

Haloperidol 5mg IV
Chronic Abdominal Pain Lidocaine 1.5mg/kg in 100mL NS APAP or NSAID
Dicyclomine 20mg PO/IM
or Gastroparesis Ketamine 0.1-0l3 mg/kg IVPB Metoclopramide 10mg Q6H
Ketorolac 15mg IV
Bismuth Subsalicylate 524 mg PRN
 Opioid Conversions
1. Determine 24-hour opioid use (TDD)
2. Determine equianalgesic dose of new agent converting to
3. Convert current opioid dose to new opioid dose
a. Incomplete Cross Tolerance: â by 25% and round down
Formulations

BR is on morphine solution 15mg PO Q6H. You recommend switching him to MS Contin (ER) tablets because
Changing

TDD: 15 x 4 (Q6H) = 60 mg MME

he would rather take his mediation twice daily.
No conversion factor needed
60 / 2 (twice daily) = 30 mg
MS Contin comes as 15mg, 30mg, 60mg, 100mg, & 200mg

BR is on morphine solution 15mg PO Q6H. You recommend switching him to Oxycontin (ER) because his TDD: 15 x 4 (Q6H) = 60 mg MME
Changing
Opioid

insurance only covers oxycodone products 60mg MME x (20mg/30mg) = 40mg

40mg x 0.75 = 30mg
Oxycontin comes in 10mg, 15mg, 20mg 30 mg, 40mg, 60mg, 80mg 160mg 30mg / 2 = 15mg

Give 5-15% of total daily dose Q4-6H PRN (IR

Breakthrough

BR begins Oxycontin 15mg Q12H with good relief… except when he goes out for a long walk with his dog
Only)
sparky. He notices towards the end of his walk he has more pain in his leg than normal.
Pain

30mg daily x 5-15% = 1.5 – 4.5

Oxycodone comes in 5mg & 10mg 5mg Q6H for breakthrough pain
Fentanyl

60 mg MME
Fentanyl Patch comes in 12, 25, 50, 75, 100 mcg/hr
Patch

60/2 = 30
Frequency: Q72H Give 25 mcg Patch

Patient Controlled Analgesia (PCA)

Determine 24 Hour Requirement
12mg x 12 = 144 mg

Convert TDD to PCA Medication

40-year-old with lung cancer has order for
144 mg x (1mg/3mg) = 48 mg TDD IV
morphine PO 12mg Q2H PRN in hospital and
receives 12 doses over 24 hours. Design
Bolus Dose: amount patient can self-administer Determine basal rate if desired
morphine PCA with 50% of TDD basal rate and
48mg x 50% = 24 mg or 1mg/hr
a 4mg/hr max dose with 10-minute lockouts.
Lock Out Period: Normally 10 minutes
Provide remainder of daily dose as bolus
Basal Dose: Continuous infusion of opioid Max 4mg/hr – 1mg/hr basal = 3mg/hr
1 hr / 10 minutes = 6 doses
Hourly Max: How much basal they get per hour 3mg / 6 doses = 0.5 mg per dose
 Opioids TYR — GLY — GLY —PHE — MET/LEU
Thalamus
HO
Tyrosine (Tyr)
Enkephalin Methionine (Met) Neutral

or
Acidic pKa 10 Leucine (Leu) Neutral

O Glycine O
H H
N-Terminus N N O C-Terminus
H 3N N N
H H
O Glycine O O
Dorsal Horn
Phenylalanine (Phe) of
Neutral Spinal Cord

Biosynthesis Storage Release Receptor Interaction Termination

Cell Nucleus Vesicles

Supply for later

Large peptides (peptidase) In response to action Hydrolysis of amide bond
are broken down into & potential due to pain between Glycine 3 &
smaller peptides impulses Phenylalanine
Protect from Metabolism
Morphine - 4,5-epoxymorphinian
CH3
17-Amino – Required for Binding
A: Aromatic Tertiary Amine – Ionized – Basic
N
B: Cyclohexane
*D C: Cyclohexane á Potency
B * D: Piperidine NCH3 à NH
A * C E: Tetrahydrofuran
E
O
* * (-)-Morphine has 5 chiral carbons:
â Potency â Intrinsic Activity = Antagonists
HO OH 5R, 6S, 9R, 13S and 14R
Steric Bulk = k agonism

Add 14-OH
3-OH and 6-OH à Esters
á Binding Potency

á potency
Enters CNS Faster and
in á concentration Remove 7-8 Double Bond

á Potency

6-OH
3-OH 2 Alcohol – Neutral
Phenol – Ionized – Acidic

ether ester OCOCH3

OCH3 H neutral
neutral
H3CO H H3COCO
ether ester á Potency
neutral neutral
Removal of 4,5 epoxy linkage
â Potency = â analgesic effects
á Potency
â Activity á Activity
 4,5-epoxymorphinans Morphine Rule – Pharmacophore

Tertiary Amino Group

N

the bare minimal

structural requirement Two Carbon Chain
to produce morphine-
C
like analgesia

Quaternary Carbon
linked to phenyl ring
Binding

H
N
CH3 CH3

N N N-Demethylation
Oxidative-O-Dealkylation
O-Demethylation CYP CH3 O
CYP2D6 N HO Normorphine OH
Conjugation Less Active

Glucuronidation
O O
H3CO OH HO OH
Codeine Morphine O
Less Active Active Metabolite ConjO OGluc
More Polar - hard to get into CNS
Phenol = Shorter Duration More H20 Soluble - easily excreeted
Easily inactivated

Morphine Analogs
Binding Affinity
 Morphinan - μ receptor agonist
(-)-3-hydroxy-N-methylmorphinian
Analgesic
6x more
potent than
morphine
á Potency
Benzomorphan - mixed acting
4-Phenylpiperidine - μ receptor agonist Meperidine
CH3
N
O CH3
10 x less potent than morphine
4’ Ester = short acting
Piperidine ring with aromatic ring at 4 position inactive metabolite / use IV
OND metabolite (2 amine):
seizures in prolonged use
Morphinan Derivatives
(+)-3-hydroxy-N-methylmorphinian
Antagonist
3-OH à
Methyl mixed acting
μ antagonist / k agonist
â analgesic
á antitussive
Mild – Moderate Pain
Benzomorphan Derivatives- μ antagonist / k agonist
Antagonist
Mild – Moderate Pain
Kappa Agonist Side Effects: dysphoria
μ agonism in the gut -- Treats Diarrhea - â GI motility
Oral Administration = rapid ester hydrolysis
Lipophilic = poor H20 soluble in gut Amphoteric = both acid and base – localized in gut
Difenoxin (active metabolite) = Zwitterionic Nature
limits crossing BBB and causes central mu agonism
4-anilidopiperidines - μ receptor agonist Fentanyl Modifications of Fentanyl
CH3 EWG Thiophene
H 3C Ester Hydrolysis
N tetrazol-5-one
O
N O
Basic N N
S
pKa: 8.5 N O N
R N N pKa: 8.1 N
CH3 pKa: 7.2 - 32% ionized N CH3
H O Lower pKa: 6.5 penetrates BBB - faster onset N
N CH3
N mostly unionized O
Neutral penetrates BBB N H3CO O O
CH3 H3CO
R faster onset / shorter duration
O 4-methoxymethyl
Short Acting: H3CO
H 3C O
distribution not metabolism
Prolonged = toxicity Alfentanil Remifentanil Sufentyl
Exception to Morphine Rule 100-200 x more potent than morphine 800 x more potent than morphine
100 x more potent than morphine 25 x more potent than morphine
AR Ring not directly attached to 4 C â respiratory depression

Open Chain Derivatives - μ receptor agonist Methadone – Dolophine Tramadol - Ultram Nucynta – Tapentadol

Synthetic Codeine Analog Synthetic Codeine Analog

Resides in (-) isomer / á Duration Weak Agonism / SSRI Activity
Useful in treatment of heroin opioid More potent / SSRI Activity
OOD Metabolite is 2 – 4 x more potent
addiction

Antagonist
Opioid Analgesics
Opiate: naturally derived from poppy opium – Codeine, Morphine, Heroin
Opioid: any drug with effect at opioid receptor

Side Effects Withdrawal Symptoms Tolerance

Insomnia
Jitteriness/Anxiety Opioid dose must be increased in order to
Dilated Pupils
have same effect
Itching / Sedation / Nausea Rapid Heart Rate
Dysphoria / Bradycardia Excessive Sweating
Rapid Respirations could be due to:
Constipation
Urinary Retention locus coeruleus
Immune Suppression opioid receptors becoming less sensitive
principal site in brain for NE synthesis
Respiratory Depression
With regular use of CNS Depressants, brain will downregulation where less receptors are
preemptively go above homeostasis in anticipation available for biding due to their removal
of drug lowering affects
 MOA Clinical Uses Kinetics Adverse Effects
Oral Dizziness / Drowsiness
Sigma Receptor Agonists Dextromethorphan
Medulla Cough Center Antitussive CYP2D6 Metabolism Restlessness / Nausea / Vomiting
Delsym, Mucinex DM t½: 29.5 hours Serotonin Syndrome
X: CHFF
KOR Agonist Butorphanol Drowsiness / Nausea / Sweating

MOR / KOR
MOR Antagonist Moderate Pain Weakness / Floaty Feeling /
Stadol
Mixed Psychomimetic
Pentazocine X: CHF
Mild – Moderate Pain IV Injection
Weak

Talwin Psychomimetic Effect

Tramadol Oral Bioavailability: 68% Seizures
Mild – Moderate Pain
Ultram CYP2D6 / CYP3A4 Metabolism Serotonin Syndrome
SNRI

Tapentadol ER Formulation Serotonin Syndrome

Moderate – Severe Pain Glucuronidation Metabolism Pregnancy Category C
Nucynta
Mild – Moderate Pain Oral / Weak Morphine Prodrug
Mod

Codeine
Opiates
Natural

Antitussive CYP2D6 Metabolism

Morphine Moderate – Severe Pain

High 1st Pass Metabolism
Commonly Abused Adjunct to Anesthesia
Respiratory Depression
Hydrocodone Moderate – Severe Pain
Oral / t½: 4 hours Nausea / Vomiting / Pruritis
Vicodin, Lortab Cough Suppressant
Constipation / Urinary Retention
Oxycodone Mental Clouding / Dysphoria
MOR Agonist

Percocet, OxyContin Moderate – Severe Pain

Commonly Abused Potential for withdrawal symptoms
Hydromorphone
Moderate – Severe Pain
Potent

Dilaudid
Fentanyl Severe Pain Rapid Onset / Shorter
Sublimaze Postoperative Labor Analgesia Duration Nausea / Confusion
Sufentanil – Sufenta Sedation / Constipation
Severe Pain Respiratory Depression
Alfentanil – Alfenta Fentanyl Analogs
s–anesthetic adjuvant
Remifentanil – Ultiva
Meiosis / Seizures / Sedation
Meperidine Analgesia
t½: 15-20 hours Respiratory Depression
Demerol Post-Anesthesia Shivering Muscle Twitches / CNS Excitation
Methadone Anticholinergic Effects
Long QT Syndrome
Dolophine Long Acting - t ½: 27 hours
Analgesia
CYP3A4 Metabolism Sedation / Nausea / Vomiting
Partial

Buprenorphine Opioid Use Disorder

20 – 50x more potent than Dizziness / Sweating
Suboxone, Subutex
morphine Withdrawal Symptoms

Loperamide Oral - ½ Life = 7-14 Hours Nausea / Constipation

Anti - Diarrheal
Imodium AD Poor BBB Penetration Urinary Retention
 MOA Clinical Uses Kinetics Adverse Effects

Methylnaltrexone
Reliston Diarrhea / Gas / Nausea / Headache
Stomach Pain / Chills
MOR / DOR / KOR Antagonist

Naloxegol Sweating / Hot Flashes

Opioid Induced Constipation Does not cross BBB
Movantik

Alvimopan Sour Stomach / Bloating / Convulsions

Entereg â Urine / á Thirst

Naltrexone Opioid Use Disorders Nausea / Headache / Dizziness / Anxiety

CI in hepatitis or liver failure
ReVia Alcohol Use Disorder Tiredness / Trouble Sleeping

Nausea / Vomiting / Diarrhea / Chills

Nalmefene - Revex Alcohol Use Disorder Caution if history of liver or
Stomach Pain / Muscle and Joint Pain
*Not in USA* Opioid Overdose kidney disease
Anxiety / Depression
Acute Opioid Withdrawal
Naloxone Rapid onset / Short Acting
Opioid Overdose Agitation / Nausea / Vomiting / Diarrhea
Narcan Autoinjector available
“Goose Flesh” / Tearing / Runny Nose
]
Tylenol -- Acetaminophen (APAP)
Effective analgesic & antipyretic
*not anti-inflammatory*

Choice of Analgesic in older adults due to fewer adverse drug reactions

Adult Dosing Onset & Duration Pediatric Dosing

Weight base preferred
325 – 1000 mg PO Q 4 – 6 H Onset: < 1 hour
10-15 mg/kg/dose Q 4-6 H PRN
MAX: 3000 mg/day when OTC Duration: 4 – 6 hours
MAX: 5 doses / 24 hours

Centrally blocks prostaglandin synthesis

MOA

Peripherally blocks pain impulse generation

Excessive or chronic APAP use

Hepatotoxicity Risk Factors

Consumption of >3 alcoholic drinks / day

Poor nutrition

Concurrent with hepatotoxic drugs

- Isoniazid, phenytoin, zidovudine

Hepatic Impairment: avoid or < 2 g / day

Stevens – Johnson Syndrome (SJS)

Serious ADR

Discontinue at first signs of rash

Could happen with first or second dose when taking APAP for the first time

Warfarin
Drug Interaction

APAP is safest choice for pain/fever only if used appropriately and monitored
Dose: <2g / day for shortest possible duration and monitor if using > 3 consecutive days

X May enhance anticoagulant effect when taken at doses >1.3 or 2 g / day for consec. days
X May increase INR / bleeding risk
P Monitor and Educate
 Ibuprofen / Naproxen
Non-Steroidal Anti-Inflammatory Drugs – NSAIDS
Effective analgesic & antipyretic & anti-inflammatory
Inhibits prostaglandin synthesis by peripheral & reversible inhibition of COX1 / COX2
MOA

Non-selective COX inhibitors – why so many side effects

Reduces sensitivity to pain impulses

Advil / Motrin -- Ibuprofen

Adult Dosing Pediatric Dosing
Weight base preferred
Renal Impairment: NOT
200 – 400 mg Q 4-6 H PRN 6 months – 11 years old recommended for self-care
5-10 mg/kg/dose Q 6-8 H PRN
MAX: 1200mg / day for OTC MAX: 4 doses / day Geriatric: consider starting with
lower dose
< 6 months: NOT recommended
Aleve -- Naproxen
Adult Dosing Pediatric Dosing
Renal Impairment: NOT
220 – 240 mg Q 8-12 H recommended for self-care
Not recommended < 12 years old
MAX: 660 mg / day for OTC Geriatric: consider starting with
lower dose

GI: peptic ulcers / GI bleeding – COX 1 inhibitors

Serious ADR

Kidney: NA/Water retention, hypertension, hemodynamic acute kidney injury – COX 1 & 2
Cardiovascular: stroke, myocardial infarction – COX 1 & 2 / Aspirin
COX 2 > COX 1 inhibition

Large doses or longer duration of treatment with NSAIDs Concurrent use increases risk:
GI Risks / IXNs

≥60 years of age

Previous history of ulcer disease or bleeding Other NSAIDs
Consumption of ≥3 alcoholic drinks/day Anticoagulants/antiplatelets
Untreated Helicobacter pylori infection Glucocorticoids
Rheumatoid Arthritis SSRIs
NSAID related dyspepsia bisphosphonates

Acute renal failure due to vasoconstriction Risk Factors

Renal Toxicity

Modest worsening of underlying HTN

(antihypertensive inhibited with concurrent use) Advanced age, hypertension,
Hyperkalemia, hyponatremia, and edema diabetes, atherosclerotic
(concurrent use of ACE-inhibitors worsen hyperkalemia) cardiovascular disease, use of
Increased risk of renal cell cancer diuretics
 OTC Pain

Pain: unpleasant sensory and emotional experience associated with actual or potential tissue damage
Chronic Pain: pain lasting at least 3 months

Approx. 12% of all prescriptions are for pain management

>100 million individuals in pain related to long term disability

Approx. 80% use (often inappropriately) an OTC pain relieve at least 1x/week

20-30% of patients >65 yo take OTC analgesics

Prostaglandins: Primary target of OTC analgesics

- Key role in inflammatory response
- Synthesized by cyclooxygenase (COX)
o COX 2 plays greater role in synthesis during inflammatory response

Common Medications
 Assessing and Evaluating for Self-Care

Everyone has different pain tolerance and threshold

What is unbearable for someone might be baseline for another
]
Tylenol -- Acetaminophen (APAP)
Effective analgesic & antipyretic
*not anti-inflammatory*

Choice of Analgesic in older adults due to fewer adverse drug reactions

Adult Dosing Onset & Duration Pediatric Dosing

Weight base preferred
325 – 1000 mg PO Q 4 – 6 H Onset: < 1 hour
10-15 mg/kg/dose Q 4-6 H PRN
MAX: 3000 mg/day when OTC Duration: 4 – 6 hours
MAX: 5 doses / 24 hours

Centrally blocks prostaglandin synthesis

MOA

Peripherally blocks pain impulse generation

Excessive or chronic APAP use

Hepatotoxicity Risk Factors

Consumption of >3 alcoholic drinks / day

Poor nutrition

Concurrent with hepatotoxic drugs

- Isoniazid, phenytoin, zidovudine

Hepatic Impairment: avoid or < 2 g / day

Stevens – Johnson Syndrome (SJS)

Serious ADR

Discontinue at first signs of rash

Could happen with first or second dose when taking APAP for the first time

Warfarin
Drug Interaction

APAP is safest choice for pain/fever only if used appropriately and monitored
Dose: <2g / day for shortest possible duration and monitor if using > 3 consecutive days

X May enhance anticoagulant effect when taken at doses >1.3 or 2 g / day for consec. days
X May increase INR / bleeding risk
P Monitor and Educate
 Ibuprofen / Naproxen
Non-Steroidal Anti-Inflammatory Drugs – NSAIDS
Effective analgesic & antipyretic & anti-inflammatory
Inhibits prostaglandin synthesis by peripheral & reversible inhibition of COX1 / COX2
MOA

Non-selective COX inhibitors – why so many side effects

Reduces sensitivity to pain impulses

Advil / Motrin -- Ibuprofen

Adult Dosing Pediatric Dosing
Weight base preferred
Renal Impairment: NOT
200 – 400 mg Q 4-6 H PRN 6 months – 11 years old recommended for self-care
5-10 mg/kg/dose Q 6-8 H PRN
MAX: 1200mg / day for OTC MAX: 4 doses / day Geriatric: consider starting with
lower dose
< 6 months: NOT recommended
Aleve -- Naproxen
Adult Dosing Pediatric Dosing
Renal Impairment: NOT
220 – 240 mg Q 8-12 H recommended for self-care
Not recommended < 12 years old
MAX: 660 mg / day for OTC Geriatric: consider starting with
lower dose

GI: peptic ulcers / GI bleeding – COX 1 inhibitors

Serious ADR

Kidney: NA/Water retention, hypertension, hemodynamic acute kidney injury – COX 1 & 2
Cardiovascular: stroke, myocardial infarction – COX 1 & 2 / Aspirin
COX 2 > COX 1 inhibition

Large doses or longer duration of treatment with NSAIDs Concurrent use increases risk:
GI Risks / IXNs

≥60 years of age

Previous history of ulcer disease or bleeding Other NSAIDs
Consumption of ≥3 alcoholic drinks/day Anticoagulants/antiplatelets
Untreated Helicobacter pylori infection Glucocorticoids
Rheumatoid Arthritis SSRIs
NSAID related dyspepsia bisphosphonates

Acute renal failure due to vasoconstriction Risk Factors

Renal Toxicity

Modest worsening of underlying HTN

(antihypertensive inhibited with concurrent use) Advanced age, hypertension,
Hyperkalemia, hyponatremia, and edema diabetes, atherosclerotic
(concurrent use of ACE-inhibitors worsen hyperkalemia) cardiovascular disease, use of
Increased risk of renal cell cancer diuretics
 Case 1: MJ a 17-year-old will use an NSAID to relieve her ankle pain / swelling

What common, minor GI ADR’s should you counsel her about?

Dyspepsia, heartburn, nausea, anorexia, and epigastric pain

What is an important counseling point to minimize these ADRs?

Take NSAIDs with food, milk, or antacids to minimize stomach upset

MJ asks if there are any serious complications with NSAID use. What would you tell her?

GI ulceration, perforation, and bleeding (more with aspirin)

Upper GI bleeding risk à iron deficiency anemia

MJ asks how she can minimize her risks for these serious ADRs. What would you tell her?

Screen her for risks / concurrent meds – ASA > Naproxen > Ibuprofen

Case 2: Mr. AB is 70-year-old male picking up diabetes medications and a diuretic that helps him with his leg
swelling. He also wants to pay for OTC ibuprofen

Is Mr. AB at risk for renal toxicity with NSAID use?

Yes

What are his risk factors?

Age, diabetes, diuretic use

What are some other risk factors that may increase NSAID associated renal toxicity?

See above -- avoid use with history of impaired renal function, congestive heart failure, disease that
compromises renal hemodynamics
\
ADD IN LECTURE TIME STAMP 1:01 SLIDES 39 – 41

CV Risks – Naproxen safer vs ibuprofen

Naproxen/ibuprofen contraindicatied in recetn history of bypass
Lowest dose forTime
rhosrtes duration
 Aspirin / Magnesium Salicylate
Salicylate (NSAIDs)
Effective analgesic & antipyretic & anti-inflammatory (at 4-6 g / day dosing)

Inhibits prostaglandin synthesis by peripheral & reversible inhibition of COX1 / COX2

MOA

Reduces sensitivity to pain impulses

Bayer, St. Joseph, Ecotrin -- Aspirin (ASA)

Adult Dosing
Low Dose: 85 mg – CV protection
325 mg – 650 mg Q 4-6 H
MAX: 4000 mg / day
Pediatric Dosing
Renal dosing: not recommended
if CrCl <10mL/min:
NOT recommended
Hepatic Dosing: avoid in
advanced disease stages

Doan’s – Magnesium Salicylate

Adult Dosing Pediatric Dosing

650 mg Q 4 H or 1000 mg Q 6 H
Not recommended < 12 years old
MAX: 4000 mg / day

Reye’s Syndrome
- Acute, potentially fatal illness exclusive to children < 19 years old
- Leads to progressive neurologic damage, hepatic injury, hypoglycemia
- Onset follows a viral infection with influenza or chickenpox
- Vomiting, lethargy, rigidity, fixed pupils, seizures, respiratory arrest
- Salicylates increase risk x 35 fold
- Avoid in children < 19 years old who have or are recovering from flu/chickenpox
Toxicity:
- Associated with risk of 90-100mg/kg/dose x 2 days
- Risk factors:
o Renal/hepatic impairment
o Metabolic disorders
o Unstable disease
o Multiple cormorbidities
- Symptoms: dizziness, tinnitus, ….
Avoid in patients with history of gout or hyperuricemia
Intolernace within 3 hours, High cross reaction with other NSAIDS, APAP preferred alternative
 Case: AB is 70-year-old male who reports taking “baby” Aspirin daily

What is most likely indication for his daily aspirin use?

CVD protection / prevention

What does he mean by “baby” Aspirin?

Is there another dose of Aspirin that is also used for similar

indication mentioned above?

325 mg

Topical analgesics
Cannabis1
Derived from hemp and marijuana plants
Mostly used for Chronic Neuropathic Pain

Medical vs Recreational Use

Delta-9-tetraydrocannabinol (THC) & Cannabidiol (CBD)

THC leads to High / CBD does not

Hemp derived ≤ 0.3% THC
Marijuana contains > 0.3% THC
Patient Education

ADR’s
- CBD: decreased appetite, weight loss, diarrhea, dizziness, drowsiness, and fatigue
- THC: psychoactive effects such as feeling drunk, disturbance in attention, dizziness, sedation,
disorientation, dissociation, paranoia, and euphoric mood

Withdrawal Symptoms: anxiety, headache, hypersomnia, restlessness, depression, irritability, insomnia / odd
dreams, tremors, decreased appetite

Drug Interactions; THC and CBD are primarily metabolized by CYP P450 enzymes
- Severity based on route of administration (sublingual > topical)

Encourage product quality

- Buy from regulated medical dispensary
- Look for USDA certification
- Product label showing dosage guidelines

1
file:///Users/jennadant/Desktop/Thera/CBD vs THC (1).pdf
 Acute Musculoskeletal Pain – Lower Back Pain / Sprain
APAP or NSAIDs recommended in doses/intervals
Topical counterirritants can be used as an adjunct to systemic analgesics

Self-Care Exclusions

Severe pain (pain score >6)

Pain that lasts >7 days
< 2 years old
Increased intensity or change in character of pain
Pelvic or abdominal pain (other than dysmenorrhea)
Accompanying nausea, vomiting, fever, or other signs of systemic infection or disorder
Visually deformed joint, abnormal movement, weakness in any limb, or suspected fracture
Back pain and loss of bowel and/or bladder control
Pregnancy

Lower Back Pain

Most frequently reported MSP

Most common work injury

Common Causes
Lumbar sprain or strain
Sciatica (warrants medical reference)

Relapse in 40% of patients

Heat Therapy
Non-Inflammatory Pain or Lower Back Pain
Never in acute phase (<48 hours)

Apply for 15-20 mins, 3-4x/day

May use moist compress, heating pads, hot water

bottles, heat-generating wraps

Remove heating wraps or pads if pain or discomfort,

itching, or burning occurs, may apply wrap/pad over
layer of clothing

Avoid using wraps while sleeping, over broken skin,

or in conjunction with topical analgesics

If the injured area has diminished pain perception or

decreased sensation, heat therapy can result in burns
 Osteoarthritis (OA)
Degenerative joint disease: insidious onset over years
Potential factors: genetic, metabolic, environmental
Warrants initial evaluation by MD
Monthly follow-up recommended

Location Signs Symptoms

Weight-bearing joints Joint swelling Dull, deep, localized joint

Narrowing of joint space pain often relieved by rest
Knees Joint deformities
Hip Joint stiffness in morning for
Low back Absence of Inflammation 20-30 minutes
Hands

Non-Pharmacologic Measures

Weight Loss à reduce stress on weight bearing joints

Aerobic and muscle strengthening exercises à improve joint flexibility and biomechanics
Assistive devices to help ambulation
First Line

ICE/HEAT Therapy: may provide temporary relief and some benefit from alternating

Pharmacologic Measures
APAP
- Start with non-pharmacologic measures / use in conjunction
- Titrate up to appropriate max dose prior to initiating NSAIDs
- Use in conjunction with topical analgesic

Topical Capsaicin or methyl salicylate

NSAID’s
- If no relief from APAP and no counterindications

Glucosamine + Chondroitin
- Herbal supplement that works slowly (up to 2 months before improvement)
- Building blocks of articular cartilage
- Use in combination with methylsulfonylmethane (MSM)
- Dosing: Glucosamine 1500mg/day and Chondroitin 1200mg/day
- ADRs: nausea, stomach upset, constipation, diarrhea
- Drug Interaction: Warfarin
 Headaches (HA)
Primary Secondary

Not associated with underlying illness Due to underlying condition

Most amendable to self-treatment (head trauma, vascular defects,

substance abuse/withdrawal, etc)
Tension HA, Migraine, Sinus HA
Warrant’s referral

Self-Care Exclusions

Severe pain (pain score >8)

HA that persists >10 days with or w/out treatment
< 8 years old
3rd trimester of pregnancy

High fever or signs of serious infection

History of liver disease / consumption of >3 alcoholic beverages per day
Secondary HA, except sinus HA
Symptoms consistent with migraine but no formal diagnosis

Butterbur (Petasites hybridus)

Migraine Prevention
Reduces frequency, intensity, and duration

MOA: smooth muscle relaxant activity on vascular walls in cerebral blood vessels
Dosing:
- Adult: 50-75 mg po bid up to 4 months
- Child: 25-50 mg bid up to 4 months
ADRs: GI distress, burping, itching, rash, hot flushes, headaches, skin discoloration

Self-Care Exclusions: < 8 years old, pregnancy/lactation, undiagnosed/ongoing migraine