HNS16 Narcotic Analgesics Flashcards
Local anaesthetic vs Opioid analgesic
LA:
- block Na channel —> may cause motor / sympathetic block as well
- ***block pain signals transduction
- work locally only
Opioid analgesic:
- just relieve pain without affecting other sensation e.g. thermoception / proprioception
- ***modify pain signals
- work systemically
Natural pain modulators (Endogenous opioid)
- Enkephalins
2. Endorphins
First guy to extract active ingredient from opium
Friedrich Wilhelm Serturner
2 main SE of opioid
- Respiratory depression
2. Dependence
Classification of opioids (based on chemical structure)
- Morphine related compounds
- Phenylpiperidines
- Pethidine - Methadone and propoxyphene
- Dextropropoxyphene - Mixed agonist antagonist (Partial agonist)
- Pentazocine, Buprenorphine, Butorphanol, Tramadol
Classification of opioids (based on strength)
- Strong
- Morphine
- Pethidine
- Fentanyl
- derivatives (e.g. Heroin, Codeine: prodrug) - Mild
- Partial agonists
- Dextropropoxyphene
—> Propoxyphene group
—> others: Doloxene, Dologesic (dextropropoxyphene + paracetamol)
—> NOT available in world now due to arrhythmia
—> mild opioid (much less respiratory depression)
Unique opioid: Methadone
- Physeptone
- Slow onset (lower addictive potential)
- Longest acting
- Opioid abuse (opioid detoxification)
- ***“Complex” analgesic —> action not only on opioid receptor
Giving agonist together with partial agonist
Overall weaker analgesic effect
—> since partial agonist (elicit <100% response) can displace agonist from opioid receptor
Mixed agonist / antagonist
- Pentazocine
- Buprenorphine
- Butorphanol
- ***Tramadol (complex pharmacological properties / MOA)
Opioid receptor classification
- **1. μ receptor
- responsible for ***pain control clinically
- responsible for ***respiratory depression
- primarily found in CNS (brain / spinal cord) —> opioid analgesic must be able to pass BBB (high lipid solubility / high non-ionised fraction at blood pH)
- κ receptor
- δ receptor
Routes for opioid analgesic administration
- Oral
- convenient - IV
- faster onset
- better absorption - SC injection
- fairly good absorption since opioids are lipid-soluble - Transmucosal (in US)
- lollipop - Epidural
- catheter into epidural space
- lower dose needed - Patient-control analgesia
- Transdermal
- Fentanyl patch - Inhalation
- military use
- hard to control dose
Plasma and effect site (CNS) concentration
When given IV:
Plasma conc ↓ —> CNS conc ↑ (drug diffuse into CNS) —> to a point where 2 curves meet —> equilibrium concentration —> beyond equilibrium point both conc starts ↓
Drugs that diffuse quickly to CNS (e.g. Alfentanil):
- reach equilibrium point in shorter time with ***higher equilibrium concentration
- faster onset —> more addictive
- less time lag between plasma conc and drug effect —> easier to titrate
Drugs that diffuse slowly to CNS (e.g. Fentanyl, Sufentanyl):
- reach equilibrium point in a longer time with ***lower equilibrium concentration
- slower onset —> less addictive
- more time lag between plasma conc and drug effect —> harder to titrate
When consider duration of action in IV infusion
- Elimination half-life
- only one fixed number for each drug - Context sensitive half time
- also consider how long infusion has been carried on before discontinuing / minutes since beginning of infusion (隻藥infuse左幾耐)
—> infuse得越耐 —> context sensitive half-time越長
- some drugs more context sensitive (當用耐左, context sensitive half-time升好多) —> ***Significance: Accumulation of drug in body
- less context sensitive (infuse耐左, context sensitive half-time都唔會變)
E.g. Fentanyl very context sensitive:
當infuse耐左 —> 要勁長時間先eliminate到
Alfentanyl less context sensitive:
當infuse耐左 —> half life都唔會點變
Morphine metabolism
Metabolised in liver by ***glucuronidation
—> mostly morphine-6-glucuronide (more water soluble for renally excreted)
—> active metabolite
—> can still enter CNS and exerts its effect
Pethidine metabolism
Pethidine
—> majority: **Esterase
—> minor metabolite: **Norpethdine (neurotoxic —> seizure / convulsion)
At risk patient:
- Normal liver function + Poor renal function
- repeatedly received Pethidine
***Side effects of opioids (acute use)
(more common, more severe —> less common, less severe)
- Sedation
- N+V
- Respiratory depression (dose dependent)
- Euphoria
- Miosis (瞳孔縮小) (can be beneficial —> diagnosis to see if patients have been on opioids e.g. drug addicts)
Therapeutic window of opioid
LD05 - ED95 (LD05: 5% die at the dose, ED95: 95% effective at the dose)
Opioid: ED95 = LD05 and ED50 close to LD50 (very narrow window)
—> but for each patient there is always an effective dose that will not kill him
Opioid dosing
Start at low dose
—> until get satisfactory pain control
Patient Controlled Analgesia (PCA)
Use patients’ own sensation of pain as feedback
—> self-administered dose of opioid
Side effects of opioids (prolonged use)
- All acute side effects
- Constipation (esp. oral use)
- Tolerance / dependence
Euphoria / Addictiveness
Pethidine > Morphine > Methadone
Tolerance
Physiological state characterised by decrease in effects of drug with chronic administration
—> **physiological change in body
—> patients require **larger dose over time
Dependence
- Physical dependence
- **physiological adaptation of body to presence of opioid
- development of **withdrawal symptoms when opioids are:
—> discontinued
—> dose reduced abruptly
—> when an antagonist (e.g. Naloxone) administered
—> when an agonist-antagonist (e.g. Pentazocine) administered - Psychological dependence (Addiction)
- **compulsive use of drugs for non-medical reasons
- characterised by **craving for mood altering effects but not pain relief
- should not happen with proper supervision
- dysfunctional behaviour:
—> denial of drug use
—> lying
—> forgery of prescription
—> theft of drugs
—> selling / buying drugs on the street
—> used prescribed drugs to get high
Regulations of opioids
- Classified as Dangerous drugs
- Medical practitioners are required to maintain proper records of ALL dangerous drugs, whether supplied, dispensed, administered
Tramadol
Complex MOA:
- ***Mixed agonist-antagonist at opioid receptor
- also ***inhibits uptake of serotonin and catecholamine in CNS —> DDI with antidepressants esp. SSRI
Indication:
- mild to moderate pain
SE:
- does not cause much sedation
- almost does not cause respiratory depression
- no euphoria —> very little addiction
Naloxone (Narcan)
- for opioid overdose
- opioid antagonist (pure antagonist)
- relatively short half-life (75 mins) —> shorter than most opioids —> wear off before opioid effects —> need to observe patients before discharging
Choosing an opioid
- Efficacy
- SE
- Onset and duration
- Route of administration and availability
- Safety
- Addictive potential
