Narcotic Analgesics Flashcards
Tolerance
Requiring higher doses to achieve the same effects of opioid
- Constipation is an exception
Stupor
Reduced consciousness
- Do not use heavy machinery
Classification
Chemical: Opioids and Opiates
Pharmacological: Narcotic Agonists
- Full or partial agonists of multiple specific opioid receptors
Therapeutic: Narcotic Analgesics for severe pain when NSAIDs are ineffective
Chemical Nomenclature: Opioids or Opiates
Opiates: Naturally occurring compounds in the botanical opium poppy (morphine, and codeine)
Opioids: Synthetic or semi-synthetic compound that are structurally similar to morphine
- bind to opiate receptors in the bind and mimic morphine
- Synthetic: Meperidine, fentanyl, methadone, tramadol, tapentadol
- Semi-synthetic: Hydrocodone, benzhydrocodone, oxycodone, heroin, hydromophone, oxymorphone, buprenorphine
Opioids is used to refer to ALL narcotic analgesics
Chemical Nomenclature
- Phenanthrene: Morphine, Codeine, Heroin, Hydromorphone, Hydocodone
- Phenylpiperidines: Oxycodone, Oxymorphone, Levorphanol, Naloxone, Buprenorphine
- Diphenylheptanes: Methadone
- Benzomorphans: Diphenoxylate, Loperamide, Pentazocine
- Synthetic Opioid like Compounds: ADOL drugs: Tramadol and Tapentadol
Pharmacological Effects of Opioids
- Analgesia: Pain relief»_space; NSAIDs; no cardio protective, anti-inflammatory or antipyretic effect
- Euphoria/Dysphoria: Happy/high feeling Vs dissatisfaction
- Respiratory Depression: Most dangerous side effect
- Physical Dependence: Major component of opioid addiction
- Sedation: Side effects due to CNS depression
- Miosis: Pupillary constriction, autonomic nervous system
- Reduction of GI motility: Related to side effect of constipation
Pharmacological: Relative Strengths
Strong Agonists: AlfenTANYL, Heroin, Morphine, LevorPHANOL, SufenTANIL
Moderate/Low Agonists: Codeine, OxyCODONE, HydroCODONE, BenzhydroCODONE
Mixed Agonists/Antagonisits: Buprenorphine, Butorphanol, Pentazocine
Antagonists: Naloxone, Naloxegol, Naltrexone, Methylnaltrexone
Other Analgesics: Tramadol/Tapentadol
Therapeutic Nomenclature
Used for variety of indications
- Acute pain: using immediate release (IR)
- Non-Cancer chronic pain: when non responsive to alternative agents such as NSAIDs
- Chronic cancer pain: When alternative agents are insufficient, Preference toward extended release (ER) formulation
- Neuropathic pain: when non responsive to agents used for neuropathic pain (anti epileptic or antidepressant agents)
Therapeutic Applications
Anesthesia
- Adjunct to general anesthetics
- Morphine or fentanyl
Palliative sedation
- End of life sedation (focuses on relief of pain, anxiety and depression but is not curative)
Therapeutic Applications II
Antidiarrheals: Slows down GI motility and Use of opioid side effect for treatment of severe non infectious diarrhea
- Deodorized Tincture of Opium “Opium Tincture”*
– High alcoholic content of liquid form of drug
– CII used for non-infectious diarrhea
- Loperamide Hydrochloride (Imodium A-D) available OTC
– Potential abuse: euphoric effect in high doses
– Cardiac arrhythmias with excessive doses
Anti-tussives: Suppression of the cough reflex in brain
- Codeine: CII unless combined with acetaminophen; most effective
- Hydrpcpdpne bitrate: CII
- Dextromethorphen: mostly OTC - non controlled but has abuse potential
Dosage Guidelines
- Opioids doses vary widely from one patient and one compound to another
- Start with lowest available strength of an immediate release opioid and titrate dose upward for effect
- Consideration:
– Patient Factors (age/weight, pain, tolerances, illness)
– Immediate Vs controlled release dosage
– Route of administration (PO, IV, IM, transdermal and transmucosal)
– Properties of specific drug (potency and average dose)
Dose Equivalent
Morphine: PO/IV/IM
Codeine: considered weak opioid
- Limited use alone due to ADE
Hydrocodone: similar potency to morphine
Hydromorphone: more potent than morphine
- 1mg = 5mg morphine
Oxycodone: more potent than morphine
Fentanyl: MOST potent and short acting
Methadone: More potent than morphine
- Used for OUD/Pain management
Meperidine: Less potent than morphine
- Quick onset of action
Abuse Deterrent Formulation
- Alone or in combination with naloxone/naltrexone
- Purpose: prevent abuse of opioid when crushed or injected
- No generic available
- Utilizes one or more mechanism to make their intentional recreational use more difficult
- Mechanisms: Resist crushing, Resist dissolving, Release opioid antagonist
Short vs long-acting dosage
Immediate release dosage forms
- Preferred use to prevent pain tolerance
- Q4-6H PRN breakthrough pain
Long acting dosage forms
- To maintain pain relief throughout the day
Transdermal dosage forms
- considered a controlled release formulation
- Not for sever ACUTE pain
Transmucosal dosage forms
- Sublingual or buccal
– SL: under tongue absorbed directly by bloodstream bypassing liver for faster absorption
– Buccal: Absorbed through cheek; fast acting for chronic or breakthrough pain
Black Box Warning of Opioids
- Hypoventilation
- Extended release formulation
- Not for children
- Abuse & addiction potential
- Avoid splitting of LA/ER/transdermal
- Routes of administration
- Abrupt treatment effects
- Chronic use in pregnancy
Contraindication
- Patients with significant respiratory depression
- Patients with bronchial asthma
- Patients with convulsive disorders
- Addiction prone patients
- Treatment of diarrhea
Warning and Precautions
- Adverse dug reaction are DOSE dependent and specific to individual compounds
- Pregnancy category C: Due to withdrawal syndrome in neonates (NAS: Neonatal abstinence syndrome) and evidence of birth defects in animal trials
– If not essential => not recommended
Somnolence - Recommendation of avoid driving or use of heavy machinery when initiated
FDA and Storage Requirements
FDA on LA/ ER Formulations
- Company required to have post-marketing surveillance on LA/ER formulation
- Only for sever pain
- Mandate to warn patient of greater risk for addiction
Storage Requirements
- Stored within a secured cabinet or safe within the department
- C-III-C-V dispersed throughout non controlled substances o the shelf
Drug-Drug Interaction
- Avoid combination with opioids that can increase respiratory depression (alcohol, benzodiazepines, MAOls)
- Medication that are enzyme inducers or inhibitors cause potential DDI since metabolized by liver enzymes (hydrocodone, codeine, tramadol, fentayl)
- Specific enzyme inhibitors that can cause DDI with opioids (antibiotics: Clarithromycn, ketoconazole, CCB: Diltiazem and varapemil, Linezolid)
Narcotic Antagonists - NAL
Naloxone HCI (Narcan): IV, IM, IN (Not PO)
- Reverses effect of severe opioid toxicity
- Should be made available for patients at risk of overdose
- Short half life so repetitive doses may be required (especially with LA/ER opioids)
- New Jersey overdose prevention act of 2013 (requires a prescription but may be dispense without one if standing order/collaborative practice exist)
Naltrexone: Systemically active with oral administration
- Not effective for overdose
- Treatment of alcohol withdraw and opioid use disorder as maintenance
Naloxegol (Movantik) 12.5 or 25 mg tablets
- Opioid induced constipation (OIC) for patients with chronic non cancer pain
- Chemically released to naltrexone but without crossing the blood brain barrier
Narcotic Antagonists - NAL II
Methylnaltrexone (Registro)
- Subcutaneous
- OIC: quick onset of action with bowl movement within 30 min
Alvimopan (Entereg)
- 12mg for post operative ileus (intestinal obstruction due to loss of peristalsis)
Naldemedine (Symproic):PO
- OIC once daily dose
Nalmefene - IV, IM, SubQ
- Longer duration of action and higher affinity for opioid receptor than naloxone
Morphine Sulfate (Narcotic Agonists)
- PO various strengths, IR and ER) 10-200 mg, suppositories, IM, IV, subcutaneous, epidural injection
- Abuse deterrent formulations:
– Arymo
– Embeda
– Kadian
Codeine Sulfate - C-11 (Narcotic Agonists)
- IV available but commonly used as oral
- Weak opioid, commonly used in combination with acetaminophen or NSAIDs
Hydromorphone - Dilaudid (Narcotic Agonists)
- PO, IV, IM, Subcutaneous, Suppositories
- Frequently used IV/IM in hospital setting
Fentanyl and Fentanyl Citrate (Narcotic Agonists)
- IV, IM, transdermal, transmucosal (buccal and sublingual), Intranasal
- Heroin frequently laced with fentanyl and difficult to reverse with opioid antagonists
- Not available/effective OP
- Citrate=injection:IV, IM, Subcutaneous (Adjunct to regional anesthesia or pain management in critical care patients
ActiQ - Lozenge on a stick for sever breakthrough pain
Fentora - Transmucosal
Abstral - Transmucosal
Lazanda - Nasal spray
Duragesic - transdermal patch - Lasting 72H (change every 3 days)
- Precautions (avoid wounded skin, no heat (increase absorption), do not cut into smaller pieces, Fold patch and flush down toilet)
- Transitioning from PI to transdermal patch: may take 12-24 hours for onset of patch effect
Hydrocodone - bitartrate (Narcotic Agonists)
- PO only; C-II
- Vicodin and Vicodin HP (high potency)
- Hysingla ER tablets: once daily; abuse deterrent formulation
Oxycodone HCL (Oxycontin CR tabs) (Narcotic Agonists)
- C-II only reformulated, hard to crush
- Oxycontin ER capsules - abuse deterrent formulations
- Xyampza ER capsules
- Percocet tablets (with acetaminophen)
– CII
(Narcotic Agonists)
- Alfentanil (alfenta) injection - IV only
- Lecorphanol Tartrate (Levo-Dromoran)
– PO, IV, IM
– Adjunct to anesthesia preoperatively - Remifentanil HCI (Ultiva): IV, Adjunct to anesthesia
- Sufentail Citrate: IV, Adjunct to anesthesia
- Tapentadol HCI (Nucynta) PO: C-II similar to tramadol but more potent
- Pentazocine (Talwin):C-IV
Meperidine HCI - Demerol (Narcotic Agonists)
- PO, IV
- Similar to hydromorphone
- C-II; less favored due to side effect of nausea
Tramadol HCI - Ultram (ER), Ryzolt (ER) - (Narcotic Agonists)
- Dual analgesic narcoticL opioid agonist and inhibits reuptake of norepinephrine and serotonin responsible for pain pathway
- Opioid effect intended for short term
- Used for moderate/severe pain; weaker than opioid agonist but stronger than NSAID
- Less sedation/constipation
Methadone- Dolophine (Narcotic Agonists)
- Commonly used as oral form for maintenance treatment of opioid use disorder, addiction and pain
–Dosed 60-120 mg PO daily
– Suspension»_space;> tablet/wafers
– Closest monitored for two weeks - Prescribed for moderate to sever pain (lower cost)
– Should be reseed for treating terminal cancer pain
Narcotic Partial Agonists
Buprenorphine HCL (CIII) - Subutex
- Tablets (2 or 8mg), IV/IM, Transdermal
- Semi-synthetic; alternative option for OUD to methadone
- Less respiratory depression
Buprenorphine/Naloxone
- Sublingual: Zubsolv; Buccal film: Bunavail; SL film
- Combination with naloxone to prevent abuse potential - Naloxone PO is inactive
Combination Products
- Opioid + ASA + Acetaminophen + NSAID
- Acetaminophen –Tylenol with codeine (CIII), Vicodin, Percocet (CII), Ultracet (CIV)
- ASA (empirin, percodan)
- Ibuprofen (Combunox)
- B&O supprettes: Belladone & Opium suppositories
Legal and Regulatory: Monitoring
- Prescription Drug Monitoring Program (PDMPs)
- Risk Evaluation and Mitigation Strategy (REMS)
- DEA (Drug Enforcement Agency) Status
PDMPs
- Tracks every CDS prescription dispensed by any outpatient pharmacy
- Patient name/address, prescriber identity, and pharmacy data available to health care provider and law enforcement personnel
- Required programs exist in all states
- New Jersey-PDMP: state wise database for monitoring CDS (C-II to C-V)
- Pharmacies Required to report to New Jersey-PDMP at least Biweekly
REMS
- Available for many high risk meedication
- REMS for Opioids
– Morphine, hydromorphone, methadone, oxycodone, oxymorphone, transdermal fentanyl, and byprenorphine; immediate release transmucosal fentanyl products
– Focus mostly on long acting or extended release (LA or ER) opioids due to propensity for addiction
– Educational resources for perscribers
– Medication guides
DEA
- Responsible in overseeing all CDS
- Responsible for enforcing the controlled substances law and regulation in US
- Review of controlled substance schedule: CI, CII, CII, CIV, CV
– CI = no legitimate therapeutic use; illegal to prescribe and abuse
Practical Consideration(CII
- Prescription: Must include DEA + NPI number of prescriber in New Jersey - Serial number of blank - Limited to one CDS per script
- Telephone/Electronic Scripts: Telephone orders not allowed for CIIs, E-Scribing is permitted
- Post-Dated CIIs: Commonly occurs for CII that require > 30 day supply
- Limits: 30 day limit form date of issue for RX to be valid (quant limits: NJ = QID for 30 days (120 units)
- Refills: C-II CANNOT be refilled regardless - C-III to C-V: 5 refills within 6 month from date of issue
- Partial Filling: DEA allow partial of C-II filing but remainder of RX MUST be filled within 72 hours
Red & Green flags
Red Flags: Specialty doctor, Cash paying, Direction incorrect, Doctor shopping, Pharmacy shopping, Traveling far for RX
Green Flags: Physician/Patient know to pharmacy, Known chronic pain/terminal illness, Pain Management prescriber
Prescription Requirement
Perception Requirement:
- Date of Issue
- Patient name/address
- MD name/address and DEA number (a MUST)
- Drug name, strength, and dosage form,
- Quantity prescribed
- Direction
- Number of refiles
- Signature of prescriber
Labeling Requirement
- Name/adress of pharmacy
- Serial number of Rx
- Date of fill / Date of issue
- Patient name
- MD name
- Direction of use
- Refill information
- Cautionary label (PRN)
- Caution Label
