Non-opioids Therapeutics Flashcards
What is considered a statistically significant improvement in pain?
2 points or 30% improvement on the NRS in pain and functioning
What is the treatment goal in pain management
Decrease in pain
INCREASE in functioning/QOL
Acetaminophen max dose, toxic liver dose
MDD: 4g
Toxic Liver dose: 5-7g
What is the antidote for acetaminophen toxicity? MOA? When to administer
N-acetylcysteine (NAC)
- glutothione precurser and can quickly replenish glutathione levels
- administer within 8 hours
Who should be on 2g acetaminophen as a MDD (5)
- Elderly patients
- Fasting patients (could have depletion in GSH)
- Heavy drinkers
- Warfarin use
- Active liver/cardiac/renal impairment
Who should have MDD of acetaminophen
4g/day
3g/day
2g/day
<4g/day Healthy patient, short term use
<3g/day Healthy patient, long term use
<2g/day Unhealthy patient, long term use
NSAIDs MOA
Inhibit PGs for inflammation but ALSO PG’s necessary for desirable homeostatic effects
- GI mucosal integrity, platelet function, proper renal blood flow
T/F NSAIDs and coxibs are equivalent in efficacy
True
What group of patients do we avoid NSAIDs?
Elderly, cardiac, renal, GI Patients
- IHD, MI history, Stroke, CHF, CABG
- GI risk factors (ulcer, IBD, H.pylori)
- Low CrCl <40mL/min
- Asthma (hx of rxn to ASA)
- Concurrent meds that increase bleeding (ASA, warfarin, corticosteroids)
- Age 60+
What are ADRs of NSAID use in GI risk (3)
- Sx: heartburn, dyspepsia, GERD, stomach pain
- GI ulcers (can be asymptomatic)
- Perforated ulcers, obstruction, bleeding
Which NSAID as the greatest risk of fatal GI bleeding? Duration? Indication
Ketorolac MAX 7 days
Indications
- 5 days for severe acute pain following surgery (dental, ortho)
- 7 days for severe acute musculoskeletal pain (pain with trauma, post-birth uterine cramps)
Which NSAID is the safest in CV risk
Naproxen
T/F COX 2 inhibitors are safer than ibuprofen and diclofenac in CV risk
False
What are ADRs of NSAIDs in CV risk (3)
- Sodium retention and fluid retention
- Acute worsening of HTN
- Acute worsening of CHF due to fluid retention
T/F COX-2 inhibitors increase stroke risk
False
What dose of celecoxib has increased risk of MI
400mg per day
Do not exceed 200mg
NSAIDs in pregnancy
1st trimester
2nd trimester
3rd trimester
Lactation
1st trimester
- AVOID.
- malformations, oral clefts, cardiac defects, possible miscarriage
2nd trimester
- Low dose ok.
3rd trimester
- AVOID.
- premature closure of the ductus arteriosus, persistent pulmonary HTN, inhibit labor/prolong pregnancy
Lactation
- Ok to use.
Which conditions do antidepressants have the best effect in that was researched? (2)
Diabetic neuropathy
Post-herpetic neuralgia (post shingles)
Which type of antidepressants are favourable for pain
Ones that increase 5-HT (serotonin) AND NE
What are the tricyclic antidepressants used for pain
Tertiary amines
- Amitriptyline
- Imipramine
Secondary amines
- nortriptyline
- desipramine
What is MOA of antidepressants on pain
5-HT/NE bind presynaptically and reduce the influx of calcium which prevents the release of glutamate (don’t like this)
TCA’s
Dose
Onset for pain
Dose
- 30-50% lower than depression dose
- 10-25mg qhs
Onset
- 1-2 weeks for pain (quicker than 4 weeks for mood)
TCAs side effects
A1 receptor: Cardiac effects
- Qtc
H1 receptors
- sedation, weight gain
M1 receptors: ACh effects
- SLUD (salivation, lacrimation, urination, defecation)
NE reuptake blockade
- tremors, tachycardia, HTN, sweating, insomnia
5-HT
- nausea, anorexia, sexual dysfunction
What side effects does blocking 5-HT and NE at high doses cause?
GABA blockade
- it is a natural relaxant, it is good
- can lead to seizures at high doses
people with insomnia have low GABA levels
Which TCA is preferred?
Nortriptyline
- however if patient has insomnia you can choose amitriptyline for the sedation effect
T/F History of suicide is a contraindication for TCA
True
What other drugs can lead to serotonin syndrome when using TCAs
SSRIs
NSRIs
Tramadol
Cyclobenzaprine
Linezolid
Which SNRI has better efficacy for neuropathic pain?
Duloxetine over venlafaxine
What dose is required in venlafaxine to achieve pain relief
150mg minimum
What are side effects of duloxetine? (4)
Suicidal ideation
Sexual dysfunction
Hyperhidrosis (increased sweating)
Weight (more weight neutral)
bioavailability reduced 30% in smokers
Venlafaxine has the side effects + BP, HR, Na+
Define antidepressant discontinuation syndrome
Abrupt interruption, drastic dose reduction or d/c of antidepressant
Symptoms
- CNS and flu-like symptoms
- electric-shock-like
T/F anticonvulsants and antidepressants cannot be combined
False
When are gapaentinoids particularly useful?
In co-existing sleeping and anxiety disorders (sedating and axiolytic effects)
ADRs of gapaentinoids
Well-tolerated
- no serious organ toxicity
- Sedation, dizziness, confusion
- Weight gain, dry mouth
- Peripheral edema (STOP DRUG)
Which drug has a warning for respiratory depression when combined with opioids
Gabapentin
- risk is dose related. Keep it low
When is Ketamine used (NMDA receptor)
Relief of neuropathic cancer pain, or
severe refractory NeP conditions
What is cyclobenzaprine and methocarbamol used for
Skeletal muscle relaxant
- very sedative
3rd line in MSK pain after acetaminophen/NSAID
Methocarbamol
- less sedating, used in combo with acetaminophen
- Robaxin, Robaxacet
What anti-spasticity meds are used for pain?
Baclofen
- indicated for muscle relaxation but off-label used for pain
Dantrolene
What is serotonin syndrome
life-threatening drug reaction that leads to increased serotonin in the brain
- watch for med combos
- usually starts within 24hrs of a new med
- reversible upon stopping
What effects do serotonin syndrome have on
cognitive effects
autonomic effects
Somatic effects
Cognitive
- headache, agitation, hypomania, mental confusion
Autonomic
- sweating, fever, hypertension, nausea
Somatic
- muscle twitching (myoclonus), hyper-reflexia, muslce rigditiy and tremor
What are cannabinoids contraindicated in?
- IHD
- uncontrolled HTN
- Arrhythmias
- severe liver and kidney function
- schizophrenia/psychosis
- pregnancy
