Lecture 25: Analgesic drugs 1 Flashcards
What are narcotic analgesics?
Analgesics that cause narcosis:
- > Narcosis
- > Impaired consciousness
What are the types of pain after injury?
Surgical trauma:
- Nocioceptive pain
- Inflammatory pain
= Opioids/opiates sensitive
Neuropathic pain (not sensitive)
What are routes of administration?
Oral Parenteral (jab) Transmucosal Transdermal Nasal Sublingual
What is opium?
Opium is the dried latex from opium poppies containing:
- Narcotic alkaloids
- Non-narcotic alkaloids
What is narcotic alkaloids used to create?
Morphine
Codiene
What are non-narcotic alkaloids used for?
Papaverine
Thebaine
Noscapine
Dont need to know this
What are opiates vs opiods?
Opiates = Natural
Opioids = Chemically synthesised
Describe the opioid receptor;
Opioid receptors are essentially pre-synaptic, belong to the G protein coupled family of receptors (GPCRs)
Describe the mechanism of action of opioid receptors:
- Activated Gi proteins -> Inhibition of adenylate cyclase enzyme -> Decreased Ca channels permeability (-> Blocked transmitter release)
- Increased K conductance -> Hyperpolarization of post synaptic neuron -> Decreased response
What are the different types of opioid receptor?
Mu
Kappa
Delta
What are Mu receptors found?
Spinal cord
Brainstem (peri-aqueductal grey)
Thalamus
Cortex
Where are kappa receptors found?
Limbic system
Hypothalamus
Brainstem (peri-aquaductal grey)
Spinal cord
Where are delta receptors found?
Olfactory bulb Cerebral cortex Nucleus accumbens Amygdala Pontine nucleus
Are opioids primarily central?
There is evidence to suggest after tissue damage opioids can act on peripheral nociceptor terminals.
These opioid receptors are synthesised in the cell body (DRG) and transported towards the periphery.
What are some opioid agonists and what are there actions?.
Morphine, Fentanyl, Pethide
Activation of all receptor subclasses though with varying affinitites
What are some opioid antagonists, what are their actions?
Naloxone, Naltrexone
Devoid of activity in all receptor classes
What are some opioid agonist-antagonist, what are their actions?
Nalorphine, Petazocine
Agonist activity one one type and antagonist on other receptors
What are some partial agonists, what are their actions?
Bup-re-norphine
Activity at one or more, but not all receptor types
What are the adverse effects of opioids?
- Resp. depression
- Somnolence (drowsiness)
- Dizziness
- Constipation
- Ileus
- Itching
- Nausea and vomiting
- Vagally mediated bradycardia
- Hypotension (morphine)
What are the precautions for opioid use?
- Sleep apnea
- COPD (chronic hypocapnic)
- Elderly
What are natural opioids?
Morphine
Codiene
What are semi-synthetic opioids?
Bup-re-norphine
Oxycodone
Di-acetyl-morphine (dimoprhine) (Heroin)
What are some fully synthetic opioids?
Fentanyl
Pithidine
Methadone
Tramadol
What are some endogenous opioid peptides?
Endorphins
Endomorphins
Enkephalins
Dynorphins
What are some notes for using opioids?
- To be administered through the most effective and comfortable route
- Round the clock for severe to moderate pain
- Consider inter-patient variability
- Use of adjuvants for enhancing opioids analgesia and reducing side effects i.e NSAIDS
What are the two main effects of opioids?
Analgesia
Euphoria
It is the euphoric effect that can lead to abuse
What are the adverse conditions of opioid use?
- Physical dependence i.e not addicted, withdrawl symptoms.
- Psychological/emotional dependence (cravings)
- Drug tolerance (consider opioid rotation), larger doses required to achieve the same effect
- Opioid addiction (addiction is a disease, compulsive use despite harm)
What are the symptoms of opioid withdrawl?
Mostly autonomic
- Altered HR
- Altered BP
- Altered RR
- GI, Nausea, vomiting, cramps, diarrhoea
- Sweating
-> Irritability, restlessness, tremor, yawning
How do you manage opioid withdraw?
- > Give methadone or bup-re-norphine (cross tolerance, then slowly withdraw)
- > Clonidine, reduce ANS symptoms
- > Promethazine for N&V
- > Diazepam (for muscle cramps)
- > Anti-diarrheal
How is rapid opiate detox done? ~6hrs
- Under GA pt not subject to withdraw discomfort
- High doses of nal tre xone used
- Oral dose can be continued to reduce the risk of relapse
Give the relative potencies of some opioids:
Fentanyl is 50-100x more potent than Morphine
What are the pharmacokinetics of morphine?
- Low lipid solubility (Slower onset and longer duration)
- 1/3 bound to plasma proteins
- Large VoD
What are the routes of administration for morphine?
Oral (Bioavailability ~25%)
IV, IM, Epidural
What is the metabolism of morphine?
Liver
- > 70% to Morphine-3-glucuronide
- > Morphine-6-glucuronide (half as potent, longer half life)
Write some notes on pethidine:
Pethidine
- > Converted to norpethidine (active form)
- > 8-12hr half life
NB: Can accumulate in renal failure-> Hallucination, Seizures
Can interact with anti-depressants
- Coma, convulsions, labile circulation, hyperpyrexia
Write some notes on Fentanyl:
- Stronger Mu receptor agonist
- 80-100 times more potent
- Predominantly metabolised in the liver to nor-fentanyl which is inactive
- Excreted in liver over days
How is fentanyl administerd?
IV most common
Can do transdermal patches but
- Slow onset
- Inability to rapidly change doses
Transmucosal lozenges
Nasal and sublingual spray
sublingual tablets
Describe fentanyl HCl ionto-phoretic transdermal system:
Iontophoresis is a method of transdermal PCA administration of ionizable drugs in which the electrically charged components are propelled through the skin by an external electric field
Write some notes on methadone:
Oral: Bioavailability 70%, can be administered in other ways
- No significant cognitive impairments
- No euphoria
- Safe in renal and liver failure
What is methadone used for?
For chronic pain patients (Due to its NMDA antagonsim)
For neuropathic pain
For opioid withdrawal
For detox
Write some notes on tramadol:
- Oral bioavailability greater than 70%
- Inhibits uptake of noradrenaline and serotonin
Whats a risk specific to tramamdol?
May causes serotonin syndrome if administered with SSRI antidepressants
What are some consideration for codiene?
Codeine is metabolised to morphine by Cytochrome P450
Ultra rapid metabolisers are at higher risk of toxic opioid effects
Slow metabolisers may not experience adequate analgesic effect with codeine
What are opioid antagonists?
Naloxone
Nal tre xone
Devoid of all activity
What are coanalgesics and some examples?
- Shown to enhance the analgesic effect, but devoid of analgesic function
i. e
Tricyclic antidepressants Anticonvulsants i.e gabapentin Anxiolytics Corticosteroids Others i.e Ketamine, clonidine
