Analgesics Flashcards
Acute pain
Pain that usually starts relatively suddenly and has a specific cause or etiology. Generally doesn’t last more than about 3 months.
Chronic pain
Pain that persists beyond normal tissue healing time, which is assumed to be about 3 months. Pain signals remain active for weeks, months, or years.
Acetominiphen (Tylenol) is for ___
Mild to moderate pain
○ OTC, non-narcotic, non-NSAID
_____ is Commonly abbreviated APAP
Acetominophen (tylenol)
○ Acetyl-para-aminophenol (APAP)
○ Known as paracetamol outside the US
Acetominiphen MOA
Believed to cause inhibition of COX enzyme in various tissues, although it’s never been confirmed.
○ COX (cyclooxygenase) forms prostaglandins
● APAP may possibly inhibit prostaglandin E2 production in CNS
Where is acetominophen metabolized?
Metabolized in the liver – 90% by conjugation and 5% by CYP2E1 enzymes. 5%
excreted unchanged in the urine.
○ Toxic metabolites can accumulate in renal impairment.
Acetominophen Indications for use
Mild pain
Fever
Acetominophen Contraindications
● Severe active liver disease (IV)
● Severe hepatic impairment (IV)
In contrast to NSAIDs, ____ does not have antiplatelet or anti-inflammatory effects.
APAP
Black box warnings for Acetominophen
Hepatotoxicity
○ APAP has long been associated with acute liver failure, including cases of liver
transplant and death.
○ Generally seen with doses over 4000 mg per day.
Common side effects with acetaminophen
● Nausea
● Vomiting (IV use)
● Rash
● Headache
● Insomnia (IV use)
● Constipation (IV use)
● Agitation (peds IV use)
● Pruritus (peds IV use)
Adverse reactions with acetominophen
● Hepatotoxicity
● Acute renal tubular necrosis
Most commonly reported drug to Poison Control Centers in US
APAP (Acetominophen)
T/F There are no early symptoms that predict APAP toxicity
T
Risk for hepatotoxicity increases if presenting >____ hours after
24
If you suspect APAP overdose, ____ level is the most important diagnostic test (4+ hours after ingestion)
serum acetaminophen
Treatment of APAP OD is to _____
replenish Glutathione (GSH) by administering its precursor – N-acetylcysteine (NAC)
Toxic metabolite of APAP is reduced by natural antioxidant ______
Glutathione (GSH)
Max dose of acetominophen is ____ mg per day from all sources
4000
Three main neurotransmitters that Bind to and activate opioid receptors in the CNS
Endorphins, Enkephalins, Dynorphins
Activation of the CNS ______ results in efferent signals down into the
spinal cord, resulting in endogenous opioid release, blocking incoming pain signals
Analgesia System
Analgesia stystem structures
○ Periaqueductal gray – primary control center
○ Raphe nuclei neurons – extends down into spinal cord
○ Substantia gelatinosa – release endogenous opioids
____ is a natural occurring substance,
obtained from crude opium latex, extracted from the Opium Poppy
Morphine
____ is also found in crude opium along with morphine
Codeine
____ is a manufactured version of morphine
Heroin
____ is the prototype drug for strong Mu receptor agonists and all other opiates are compared to it.
Morphine
Opiates MOA
Bind to and stimulate the opioid receptors
○ Produce “morphine-like” effect
○ Mimic effects of endogenous opioids
All opioids stimulate ____ receptors to some degree
Mu
● Opioids are metabolized in _____
● Opioid metabolites are excreted by _____
liver (CYP3A4 or CYP2D6); kidneys
Opiate side effects
● Respiratory depression – dose dependent
● Sedation – due to decreased heart rate and respiratory rate
● Euphoria/Dysphoria – Possibly due to disinhibition of dopamine neurons
● Addiction
● Constipation – Can be severe
● Miosis – (pinpoint pupils) common
Opiate adverse reactions
● Respiratory depression and/or arrest
● Circulatory/cardiovascular depression
● Hypotension: Probably due to peripheral arterial and venous dilation
● Increased intracranial pressure
● Paralytic ileus
● Seizures (especially withdrawal)O
Opiate BBWs
● Appropriate use – ER formulations only when no good alternative for chronic pain
● Potential for drug addiction, abuse, and misuse.
● Medication error risk
● Life threatening respiratory depression can occur even with appropriate doses
● Neonatal withdrawal
● Avoid alcohol
● Risks of severe CNS depression with Benzodiazepines – Avoid combo!
Opiate follow up/monitoring
● Weigh risk/benefits in pregnancy
● Check baseline creatinine
● Monitor for respiratory depression with initiation and change in dose
Opiate contraindications
● Hypersensitivity to related drugs
● Respiratory depression
● Acute or severe asthma
● Paralytic Ileus
● GI obstruction or stricture
A _____ license is required in order to
prescribe narcotics, like opiate
medications
DEA
Codeine indications
Not usually prescribed by itself
○ Usually used in combo with another medication
■ Phenergan with Codeine, Tylenol #3, etc
Indications
● Moderate pain
● *Cough (Phenergan/codeine)
● Diarrhea (rarely anymore…just don’t, there are other options)
Codeine MOA
● Weak opioid receptor agonist that is actually a prodrug
○ Metabolized by CYP2D6 into Morphine
Unique codeine adverse reaction In addition to the common opioid reactions
○ Syncope
Contraindications for codeine In addition to the common opioid contraindications
○ Patients under 12 years, and 12-18 with respiratory disease
○ Post tonsillectomy or adenoidectomy in pediatric patients
BBWs for codeine In addition to the common opioid BBWs
Death related to ultra-rapid metabolism to Morphine.
Follow up and monitoring for codeine
● Weigh risks and benefits during pregnancy, especially for prolonged use; possible risk of birth defects based on conflicting human data
● Possibly unsafe with lactation – use alternative
● Check creatinine at baseline – cleared by kidneys
● Monitor signs and symptoms of respiratory depression, especially when initiating drug or increasing dose
Tramadol (Ultram) MOA
Tramadol has 2 mechanisms of action
○ Very weak Mu agonist
○ Blocks serotonin and norepinephrine reuptake (central analgesia)
Tramadol (Ultram) Indications
Moderate pain – Can be used in acute or chronic pain
Tramadol (Ultram) In addition to the common opioid side effects
○ CNS stimulation (with seizure
potential)
Contraindications for Tramadol (Ultram)
● Respiratory depression
● Acute alcohol/drug intoxication
● Suicide ideation or behavior
● History of addiction
Tramadol (Ultram) BBWs In addition to the common opioid BBWs
○ Risk of ultra-rapid metabolism of Tramadol – Respiratory depression and death have occurred in children who received Tramadol after a tonsillectomy and/or adenoidectomy
○ Great potential for CYP450-related drug-drug interactions
○ Profound sedation risk from concomitant use with Benzodiazepines
Adverse reactions of Tramadol (Ultram)
● Stevens-Johnson Syndrome (SJS)
● Toxic Epidermal Necrolysis (TEN)
● Suicidal ideation – Due to serotonin/NE mechanism
Follow up/monitoring for Tramadol (Ultram)
- Avoid during pregnancy
- Check creatinine at baseline
- monitor signs of respiratory depression
- Enquire of past Hx of seizures
Tapentadol (Nucynta) MOA
In addition to opioid agonism, it also inhibits reuptake of norepinephrine (central analgesia)
Tapentadol (Nucynta) indications
● Moderate to severe acute pain (regular tabs)
● Severe chronic pain (ER tabs)
● Severe diabetic neuropathic pain (ER tabs)
Tapentadol (Nucynta) Side effects
In addition to the common opioid side effects
○ Fatigue
○ Dyspepsia
○ Anxiety
○ Hot flashes
Tapentadol (Nucynta) contraindications In addition to the common opioid contraindications
○ MAO inhibitor in last 14 days
○ Coma or impaired consciousness
Tapentadol (Nucynta) BBWs In addition to the common opioid BBWs
○ Profound sedation risk from concomitant use with Benzodiazepines
Tapentadol (Nucynta) Major Adverse Reactions In addition to the common opioid reactions
○ Seizures and/or hallucinations
○ Androgen and/or Adrenal insufficiency (with long-term use)
Hydrocodone (Norco, Vicodin)
● Semisynthetic derivative of codeine
● Effect similar to PO morphine
Most commonly used as Hydrocodone-APAP combination
Hydrocodone (Norco, Vicodin) MOA
● Stimulates opioid receptors
● If combined with APAP, also utilizes APAPs MOA
Hydrocodone (Norco, Vicodin) Indications
● Moderate to severe pain
○ Commonly used, especially in acute injury pain or for post-op pain
○ Occasionally used for chronic pain (ER forms)
Hydrocodone (Norco, Vicodin) contraindications In addition to the common opioid contraindications
○ MAO inhibitor in last 14 days
Hydrocodone (Norco, Vicodin) BBWs In addition to the common opioid BBWs
○ Hepatotoxicity possible with APAP combinations if patient is inadvertently
taking more than 4000 mg of APAP per day
○ Opioid analgesic REMS program is FDA required and must be available
_____ commonly used in ER and hospital for severe pain
Morphine sulfate IV
Morphine MOA
Strong opioid receptor agonist
Morphine Contraindications In addition to the common opioid contraindications
Labor and delivery (PO form specifically)
Pearl for Morphine
Never, ever break, crush, or chew long-acting PO forms!
Oxycodone (OxyContin, Percocet) MOA
● Semisynthetic derivative of morphine
● PO analgesic effect 1.5 times that of PO morphine
● Commonly used as Oxycodone-APAP combination
Mechanism of Action
● Moderate to strong opioid agonist
● If combined with APAP, also utilizes APAPs MOA
Oxycodone (OxyContin, Percocet) Indications
○ IR form commonly used, especially in acute injury or post-op pain
○ ER form commonly used for chronic pain
■ Should be last resort due to tolerance and addiction potential
Oxycodone (OxyContin, Percocet) Contraindications In addition to common opioid contraindications
○ MAO inhibitor use within 14 days
Hydromorphone (Dilaudid) MOA
● Semi-synthetic derivative of morphine
○ 8-10 times more potent than morphine!
● IV form commonly used in hospital/ED for severe pain
MOA: Strong opioid agonist
Hydromorphone (Dilaudid) Indications for use
● Moderate to severe acute pain
● Severe chronic pain (ER PO form)
Hydromorphone (Dilaudid) Side effects
● In addition to the common opioid side effects
○ Hyperhidrosis – excessive sweating
Hydromorphone (Dilaudid) contraindications
● In addition to common opioid contraindications
○ Labor and Delivery (IR tab form)
Meperidine (Demerol) properties and MOA
● Synthetic opioid structure unrelated to morphine
● Has short duration and high potential for toxicity, so it should only be used short
term (less than 2 days)
● Toxic metabolite (Normeperidine) can accumulate in CNS if high dose or
concomitant renal failure
MOA: Opioid receptor agonist, but also has…
○ Anticholinergic (antimuscarinic) properties
○ Abilities to block neuronal reuptake of Serotonin
Meperidine (Demerol) Indications
● Acute severe pain
● Preoperative sedation
● Obstetric analgesia – caution advised
Maperidine (Demerol) Side Effects In addition to the common opioid side effects
○ Tachycardia and/or palpitations
○ Anxiety/agitation
○ Tremor or other involuntary movements
Meperidine (Demerol) Contraindications
In addition to the common opioid contraindications
○ MAO inhibitor use in past 14 days
○ Caution if QT prolongation
○ Caution if tachycardia
○ Caution if pheochromocytoma
Meperidine (Demerol) major adverse reactions In addition to the common opioid reactions
○ Hallucinations
○ Seizures – due to normeperidine accumulation in CNS
○ Syncope
Fentanyl (Duragesic, Actiq)
● For severe pain (Nasal, Transdermal, Transmucosal, IV, IM)
○ Fentanyl transdermal patch (Duragesic) is for chronic pain only, comes with a lot of BBWs
○ Fentanyl nasal (Lazanda) and Fentanyl transmucosal (Actiq), have restricted distribution and only for cancer pain
Fentanyl (Duragesic, Actiq) MOA
● Strong opioid receptor agonist
● Fast acting, short half-life, is often highly sedating
○ 100 times more potent than morphine, peaks in 5 minutes
Fentanyl (Duragesic, Actiq) Indications for Use
● Severe acute pain, anesthesia adjunct (general/regional)
● Transdermal (patch) for Severe chronic pain
● Transmucosal (lozenge) and Transnasal (spray) for Breakthrough cancer pain in opioid tolerant patients
Fentanyl (Duragesic, Actiq) Contraindications In addition to the common opioid contraindications
MAO inhibitor use in past 14 days
Fentanyl (Duragesic, Actiq) Adverse reactions In addition to the common opioid reactions
○ Severe truncal rigidity (IV, IM forms)
○ Arrhythmias and Cardiac Arrest (IV, IM forms)
○ Dental decay with abscess (lozenge form)
○ Pulmonary embolism (nasal form)
IM/IV forms appear to be safe in lactation for _____
Fentanyl (Duragesic, Actiq)
Methadone (Dolophine) can be use for what?
When used for treatment of opioid dependence (the more common use), it has to be dispensed only by opioid treatment centers (“Methadone clinics”) certified by the Substance Abuse and Mental Health Services
Methadone (Dolophine) MOA
Three mechanisms of action
○ Strong opioid receptor agonist
○ N-methyl-D-aspartate (NMDA) antagonist
○ Norepinephrine and serotonin reuptake inhibitor
Methadone (Dolophine) Pharmacokinetics
Very lipophilic, so accumulates in adipose tissue
○ Half-life ranges from 12 to 150 hours
○ Analgesic effects ranges from 4 to 8 hours
Go low and slow
Methadone (Dolophine) Indications
● Severe chronic pain
● Opioid dependence (short term detox or maintenance)
Methadone (Dolophine) Contraindications In addition to the common opioid contraindications
○ MAO inhibitor use within 14 days
○ Caution in QT prolongation (or risk of)
Methadone (Dolophine) BBWs
○ Appropriate use – Should only be prescribed by providers who have extensive experience in strong opioids, should only be prescribed when no good
alternative for chronic pain
○ Life-threatening QT prolongation can occur, causing arrhythmias.
Methadone (Dolophine) Major Adverse Reactions In addition to the common opioid reactions
○ QT prolongation, Torsades de pointes (form of V-tach), cardiac arrest, cardiomyopathy
○ Pulmonary edema
Methadone (Dolophine) Follow up and Monitoring
● Benefits outweigh risks for opioid dependence use, otherwise weigh the risk/benefits
during pregnancy.
● Requires daily doses and frequent visits with prescriber
Distribution is restricted in the US for___
Buprenorphine-Naloxone (Suboxone)
Buprenorphine-Naloxone (Suboxone) indications for use
Opioid dependence
Buprenorphine-Naloxone (Suboxone) MOA
Buprenorphine is an opioid agonist that has high binding affinity to Mu, but low intrinsic activity
○ Also a weak Kappa receptor antagonist
○ Slow to dissociate, making effects resistant to naloxone reversal
● Naloxone is added to help prevent illicit IV abuse or crushing tabs
Contraindications of Buprenorphine-Naloxone (Suboxone)
● Severe hepatic impairment
● Avoid abrupt withdrawal
Buprenorphine-Naloxone (Suboxone) Major Adverse Reactions In addition to the common opioid reactions
○ Hepatotoxicity
T/F you may use Buprenorphine-Naloxone (Suboxone) while breastfeeding
T
While also indicated for opioid dependence (like Suboxone), this medication is also indicated for
moderate-severe pain (IM and IV forms)
Buprenorphine (Subutex, Sublocade)
How is Buprenorphine (Butrans) used?
● Butrans is a buprenorphine only transdermal patch
● Indicated only for all-day, moderate-to-severe chronic pain
BBW for QT prolongation
Naloxone (Narcan) indications
Injectable medication for reversal of opioid agents
● Opioid overdose
● Opioid full reversal
● Opioid partial reversal
Naloxone (Narcan) MOA
● Strong opioid antagonist
● High affinity to opioid binding sites, especially Mu
● Produces marked antagonism of agonist opioid effects
○ When given IV to a morphine-treated patient, Naloxone completely and dramatically reverses opioid effects within 1-3 minutes
● Naloxone has a short duration of action (1-2 hours) but sometimes needs to be re-administered sooner than that
Naloxone (Narcan) Adverse reactions
● Ventricular fibrillation
● Ventricular tachycardia
● Cardiac arrest
● Seizures
● Severe opioid withdrawal
T/F Naloxone (Narcan) has no risk of fetal harm
T
MOA for Tricyclic Antidepressants (TCAs)
Block reuptake of both norepinephrine &
serotonin in the CNS (SSRI/SNRI)
Tricyclic Antidepressants (TCAs)
● Anticholinergic effects
Tricyclic Antidepressants (TCAs) indications for use
● Amitriptyline is often prescribed for
neuropathic pain
● Imipramine can be used in chronic pain
disorders as
Tricyclic Antidepressants (TCAs), SNRI and SSRIs BBW
Suicidality
Selective Serotonin Reuptake Inhibitors (SSRIs) MOA
● Blockage of serotonin reuptake increases the
amount of serotonin available in the synaptic cleft
Selective Norepinephrine Reuptake Inhibitors (SSRIs) Indications for use
Primary indication is for depression, panic disorders, etc.
○ Duloxetine (Cymbalta) is FDA approved for diabetic neuropathic pain, fibromyalgia, and chronic
musculoskeletal pain
○ Milnacipran (Savella) is indicated only for fibromyalgia
Antiepileptic Medications MOA
Not well understood. Believed to work on
presynaptic voltage-gated calcium channels
○ Believed to increase GABA release
○ Believed to decrease Glutamate release
Antiepileptic Medications Indication for Use
● Both Gabapentin and Pregabalin are commonly
used in the treatment neuropathic pain in general
Antiepileptic Medications contraindications
Renal impairment
Antiepileptic Medications Side effects
● Depression/suicidality
● Stevens-Johnson Syndrome
● Angioedema
● Dizziness/somnolence (initially)
Adaptive pain
Pain that acts as a warning or protective signal
Pathological pain
Pain that is itself a pathology, reflects damage or dysfunction of the nervous system
serves no benefit
Nociceptive pain
Type of adaptive pain that involves Noxious stimuli, has a maximum threshold
Inflammatory pain
A type of adaptive pain that is protective from further harm
Visceral pain
Type of nocioceptive pain that refers to internal organs and tissues, respond to stretch and inflammattion. poorly localized, deep, squeezing and dull
superficial pain
Type of somatic pain in Skin and superficial tissue that is sharp and easily localized
Deep somatic pain
Type of somatic pain that includes ligaments, tendons, bones, muscles, blood vessels. Pain that is poorly localized and dull
Peripheral neuropathic pain
Peripheral nerve damage.
Burning, tingling, electrical, shooting pain in peripheral nerves
Central neuropathic pain
Central nerve damage seen in stroke and parkinsons disease
Dysfunctional pain
Type of pathological pain that don’t fit in any other pain categories. Dysfunctional amplification of normal sensory signals (Fibromyalgia, IBS, TMJ disease, tension headaches)
Obstetric analgesia can be helped by which analgesic?
Meperidine
Which analgesic can cause adrenal insufficiency with long-term use?
Hydrocodone
The drug of choice for analgesic and antipyretic issues when pregnant and breastfeeding is
Acetominophen
Stevens-Johnson syndrom is a potential adverse reaction seen with ____
Tramadol
Severe truncal ridgidity and arrythmias can occur when taking this medication
Fentanyl
Analgesics that are considered safe with breastfeeding
Hydrocodone (use lowest dose possible)
Morphine
Fentanyl (IM/IV)
Buprenorphine-Naloxone
Naloxone
Naltrexone
SSRIs
____ and ____ should not be prescribed with Benzos
Tramadol and Tapentadol
