Pain PHARM Flashcards
Opioid
Agonist-antagonists
Examples
Butorphanol
Nalbuphine
Pentazocine
SE:
cause withdrawal if given with pure opioids
psychotomimetic reactions
MOA:
agonist kappa receptor
antagonist mu receptor
*Exception
Buprenorphine (partial agonist mu, antagonist kappa)
SE Opioids
Sedation
Respiratory depression
bradycardia
Hypotension
Urinary retention
*No Tolerance to below:
Constipation
Miosis (pinpoint pupils)
How long does it take to develop physical dependence and tolerance?
1-2 weeks
Require wean and WAT-1 score
Example
Pure opioids
Strong
Morphine
fentanyl
methadone
hydromorphone, oxymorphone, levorphanol
Moderate
Codiene
Oxycodone
Hydrocodone
MOA
agonist at mu receptors (analgesia, euphoria, sedation, respiratory supression, physical dependence)
Agonist at kappa receptors (analgesia, sedation, psychomimetic effects)
Equianalgesic dose
cross tolerance to opioids
dose for different route and/or different opioid
start lower than equianalgesic dosage, cross tolerance is incomplete
Why do you. not prescribe meperidine
Toxic metabolite - normeperidine
AE:
Psychogenic - hallucinations, dysphoria, agitation, seizures
serotonin syndrome
Breakthrough dose of opioids
1/6 the total daily opioid dose
Q2H PRN
strong opioid, short acting, rapid onset
Decrease SE from opioid
reduce dosage by 1/4
opioid rotation
add non opoioid adjuvant
mu receptor
Function
sedation
euphoria
respiratory depression
decrease GI motility
- decrease peristalsis
- decreased secretions
- increase rectal sphincter tone
analgesia
physical dependence and tolerance
- decrease receptor number
- decrease receptor activation
kappa receptor
Less agonist activity
Examples
sedation
analgesia
Decreased GI motility
psychomimetic effects - hallucinations, nightmares etc.
Pure opioid antagonist
Examples
Naloxone
Naltrexone
Morphine MOA
binds endogenous opioid receptors
mu agonist
kappa agonist
mu receptor
- respiratory depression, sedation, GI motility decreaes, physical dependence
- sedation, analgesia, euphoria (majority effect)
kappa receptor
- sedaiton
- analgesia
- psychomimetic effects - hallucinations
*receptors exist in the dorsal horn/posterior horn in teh substantia gellatinosa
modulation pain - decrease afferent sensory neurons from sending pain signals to the brain
Morphine SE
Respiratory depresion
- caution opoioid naive, swithcing opioid, or increasing dosage
Contradinicated
- pregnancy and breast feeding
SE:
respiraotry depresison
sedation
hallucinations
hypotension
*blunts baroreceptor reflex
*release histamine
bradycardia
urinary retention
constipation
- decrease peristalsis
- increase sphincter tone
- decrease secretions
pruritis
*releases histamine
emesis
- stimulate chemoreceptor trigger zone
physical dependence and tolerance
- decrease receptor number
- decrease receptor activity
Codeine
moderate strength opioid
pure opioid
agonist mu and agonist kappa
Codiene
pharmacokinetics
Liver converts codiene to morphine (10%)
CYP2D6
ultrametabolizers (higher proportion converted) dangerous (leads to respiratory supression and death)
Codiene contraindications
ultra metabolizers
children
pregnancy and breast feeding
Codiene ultrametabolizers
Why?
They have multiple copies of teh CYP2D6 gene
they convert way more than 10% to morphine
leads to respiratory supression and death
Fentanyl
Indications, SE, duration action
INdications
- chronic pain, cancer pain
- Severe pain
MOA
- 100x affinity for mu and kappa receptors compared to morphine
SE
- severe respiratory sedation and death
- same as morphine
Duraiton action
- transdermal patch
- 24 hours reach peak
- 48 hours duraiton
Contraindications
- children < 18 years
- weight < 110lbs
- post operative pain/perioperative pain
- CYP3A4 inhibitors (results in toxicity)
Pharmakokinetics
Fentanyl
100x affinity for mu and kappa receptors
metabolized by CYP3A4
- inhibitors result in toxicity (respiratory depresison and death)
Methadone
Indication, SE, contraindications
Indication
- chronic pain
- long acting strong opioid
- duration 72 hours
SE
- QT prolonged interval, torsades de pointes
- respiratory depression if combined with CNS depressant (black box warning)
Contraindications
- do not combine with CNS depressant
- QT interval prolonged
Prescribing considerations
Methadone
ECG baseline, 1 month, anually
- looking for prolonged QT interval
Do not prescribe iwth CNS depressants
- toxicity, respiratory depresison and death
Moderate Opioids
Examples
Multi-modal therapy
Percocet
- tylenol + oxycodone
Perdocan
- ASA + oxycodone
Vicodin
- Hydromorphone + tylenol
*risk abuse potential when crushed
increases onset
rapid onset = addiction
Tramadol
MOA, SE, contraindications
MOA
- synthetic opioid
- codiene analog
- weak agonist mu receptor
- inhibits reuptake of NE and serotonin
- neurmodulation of pain in the dorsal horn/posterior horn
- inhibit release excitatory NT
- promote release inhibitory NT
- promote activation inhiitory interneurons
SE
- HTN crisis (combined with MAO innhibitor)
- serotonin syndrome (MAOi, SSRI, SNRI, TCA, triptan etc.)
Contraindications
- banned from prescription in canada
- CLass I opioid
DEATH WHEN COMBINED WITH CNS DEPRESSANT
Opioid tolerance
pathophysiology
decreased number receptors
decreased intrinsic activity of receptors
opioid physical dependence
high dose
long duraiton therapy 1-2 weeks
will develop physical dependence and abstenience syndrome when withdrawal
Buphrenorphine
MOA, Indication, SE
MOA
- partial mu agonist
- kappa antagonist
Indication
- opioid withdrawal
- addiction
SE
- naloxone/naltrexone does not work
- binds too tightly to the mu receptor
- there is no reversal agent
- renal or hepatic disease (too much drug in system)
- prolonged QT interval (similar to methadone)
Saboxone
Example
Saboxone = buphrenorphine + naloxone
used in withdrawl/detoxification opioids
induction agent to stablize withdrawal
- naloxone to kick off opioid
- buphrenorphine to partially antagonize the mu receptors (binds tightly)
Embeda
Example
morphine + naltrexone
PO formulae
prevents abuse - naltrexone will block euphoria if it is crushed
Opioids that prolong the QT interval
- methadone
- buphrenorphine
- saboxone
opioids that result in toxicity with CYP
- fentanyl
- CYP3A4 inhibitors result in toxicity - Codiene
- CYP2D6 ultrametabolizers increase amount converted to morphine > 10%
Neuropathic pain
Adjuvants
SNRI
- venlafaxine
- duloxetine
SSRI
- paroxetine
- fluoxetine
- citalopram
TCA
- amytriptyline
- nortriptyline
AED
- topiramate
- divalproex (VPA)
- gabapentin
- pregabalin
- carbamazepine
Trigeminal neuralgia
Treatment
Carbamazepine
SE
- neuro: diplopia, nystagmus, blurred, ataxia, sedation
- bone: bone marrow supression, bleeding
- liver/kidney: hepatitis, kidney disease
- teratogenic
- hyponatremia and water retention
- Skin: TENS, DRESS, SJS (HLA1502 asian)
Cannabinoid examples
Nabilone = THC
Sativex (nabiximol) = THC + cannabidiol
Marinol = Dronabinol = THC
Medical Marijuana
Cannabinoid
MOA, SE
bind endogenous cannabinoid receptors
release endogenous opioids
Capsaicin cream
block C fibre transmission
