Narcotics Flashcards
Four steps of Pain
- Pain sensory fibres activated by noxious stimuli
- Release of pain mediators
- Binding of mediators to receptors
- stimulate neurons that project to various areas of spinal cord and brain - Sensation of pain
Pain mediators that promote pain
Substance P
Glutamate
Pain mediators that inhibit pain
Serotonin
Norepinephrine
Pain mechanism
- noxious stimuli
- propagation of action potential
- Calcium channel opens
- prompt release of pain mediators
- pain mediators bind postsynaptic receptors
Endogenous Opioids found in the body
Beta-endorphin
Enkephalins
Dynorphin
Opioid Receptor subtypes
Mu, Kappa, Delta
Effects of Mu receptor subtype
- analgesia
- sedation and euphoria
- inhibition of respiration
- reduced GI peristalsis
Kappa and Delta subtype effects
- Primarily analgesia
- most opioids are primarily Mu agonists
Mu agonists and analgesia
- inhibition transmission of pain signals
- alter response to pain (in CNS, alter mood)
Opioid receptor mechanism
- Opioid binds to receptor (primarily Mu)
- Presynaptically inhibits Calcium channel opening
- Inhibits release of pain mediators
- Also inhibits post-synaptic response to pain mediators
Drug design includes (4)
Full agonists (morphine) Partial Agonists (buprenorphine) Reuptake inhibitors (tramadol) Antagonists (naloxone)
Opioid Routes of Administration
- oral
- buccal, sublingual
- rectal
- transdermal
- inhaled
- Parenteral (subcutaneous, intramuscular, intravenous)
Highly Potent Opioid
Fentanyl (100X morphine)
Intermediate potent Opioid
Morphine
Low potent opioid
Codeine (1/10th of morphine)
Three uses of Opioids
Pain - various forms of pain Diarrhea - few are used as anti-diarrheals Cough - Codeine is the opioid typically used for cough
Opioid Pharmacokinetics
Some have active metabolites
- Codine -> CYP2D6 -> morphine
Are metabolized in the liver and Eli mated by kidney
Renal impairment can lead to accumulation of metabolites and toxicity
Side Effects of Opioids
- Nausea
- Constipation
- Sedation
- Euphoria
- Miosis
- Respiratory depression
Nausea Mechanism
- Opioids stimulate the chemoreceptor trigger zone
- Anti-nauseants are used
Constipation mechanism
- stimulation of mu receptors in the gut
- slows peristalsis, reduces secretions
Sedation Mechanism
Inhibits the reticular activation system in brain
Euphoria
Occurs due to actions in the limbic region of the brain
Miosis
- Pinpoint pupils
- likely parasympathetic effect
- Can be used to confirm opioid use
Respiratory Depression
- Opioids attenuate CO2 sensors in respiratory centre
- main cause of death with opioid toxicity
- drug interaction with Benzodiazepines which also cause respiratory depression
Opioid overdose treatment
Opioid antagonist Naloxone administered by injection
Tolerance in Opioids (Pharmacokinetic and Pharmacodynamic)
Kinetic: enhanced ability to eliminate opioids
Dynamic: Reduction in the number of Mu receptors, increase the number of pain mediating receptors
Heroin
- associated with addiction
- injected intravenously
- highly lipophilic
- relatively short duration of action (enhances withdrawal symptoms)
Treatment for Opioid withdrawal
Methadone, administered orally and has a half life of 35 hours, causes less euphoria
Opioid partial agonists
Buprenorphine
- partial agonist at Mu receptors
- antagonist at Kappa receptors
- management of addiction (with naloxone)
- moderate pain, chronic use
Advantages of Partial over Full agonist
- Safer in overdose (respiratory depression plateaus)
- Lower risk of abuse (euphoria plateaus)
Opioid Reuptake inhibitors
Tramadol
- Weak Mu agonist so less respiratory depression, constipation and less abuse potential
- inhibits reuptake of serotonin and NE
