Lecture 25: Analgesic drugs: OPIOIDS Flashcards
What type of receptors are Opioid receptors and what is their mechanism of action
They are GPCRs. Presynaptic neuron 1. Activate Gi proteins 2. Inhibit adenylate cyclase enzyme 3. Reduce Ca2+ channels permeability 4. Block transmitter release
Post synaptic neurons
- binding at the mu receptor leads to outflux of K+ from the post synaptic neuron
- Leads to hyperpolarisation
- Needs increased stimulation to depolarise and conduct signal
Therefore leads to reduced conduction of nociceptive and inflammatory pain signals
What are the 6 possible routes of administration of opiates
Oral, parenteral: injection, transmucosal, transdermal, nasal or sublingual
What is Opium and what is it made of
Opium is dried latex from opium poppies containing
- Narcotic alkaloids: eg. morphine, codeine
- Non-narcotic alkaloids (eg. papaverine, thebaine, noscapine)
What is the difference between an Opiate and Opioids
Opiates are
natural narcotic analgesic derived from opium poppy
Opioids are synthetic narcotics which mimic the poppy plant.
What are 3 commonly used opioids that are very strong, strong and weak.
Which are synthetic, semi synthetic and natural
- Very strong: Fentanyl; augments anaesthetic agents. synthetic used for operating table. It is 50-100x more potent that morphine.
Strong: Morphine: natural; for severe post operative pain.
Semisynthetic is heroin- diamorphine
Weak: Codeine: natural , tramadol: synthetic,
Where are opioid mu, kappa, delta opioid receptors and how many subtypes do they have
Mu and Kappa both have 3 subtypes.
Both are in the Spinal cord and periaqueductal grey of brainstem.
Mu is also in cortex and thalamus
Kappa is also in limbic system, hypothalamus,
Delta has 2 subtypes. It is in cerebral cortex, olfactory bulb, nuc. accumbens, amygdala, and pontine nucleus
How are opioid receptors produced in the periphery
- Certain inflam mediators are released from damaged tissues in the periphery
- Stimulates Dorsal root ganglia cell body to produce opioid receptors.
- Transported toward the central terminal in the dorsal horn and Distribute along the primary afferent fibre (peripheral nociceptor terminals)
- They are stimulated by endogenous (monocyte + macrophage delivered) & exogenous opioids within hours of local tissue damage.
What are the adverse effects of Opioids
generally given for sedation and analgesia,
and what conditions should you be aware of before you give them
AE:
- Respiratory depression
- Somnolence and dizziness
- Release of histamine causing itching, hypotension
- Ileus and Constipation
- Nausea + vomiting, - Vagally mediated bradycardia
Precautions:
- Patients with sleep apnea , COPD, and elderly patients
-Euphoric effect can lead to physical, psychological dependence, drug tolerance and addiction
What are the effects of mu1, mu2 and kappa opioid receptor stimulation and the adverse effects
All have analgesia for nociceptive and inflammatory pain- not neuropathic (pain due to nerve damage)
Kappa also has dysphoria
Mu2 have have side effects + euphoria and substance dependence
What does antagonist, agonist - antagonist and partial agonist opioids mean
Antago: no effect - good for overdose
Agonist-antagonist: they have both functions depending on the receptor type
Partial agonist has activity at one or more but not all receptor types.
What are the 4 Endogenous opioid peptides and their opioid receptors they activate
- Endorphins: mu
- Endomorphins: mu
- Enkephalins: delta
- Dynorphins: kappa
How should you choose which opioid to use in real life?
- To choose the most effective and comfortable route. Severe - IV
- Give opioids continuously for severe to moderate pain. Don’t leave patient to suffer
- Consider patient inter-variability
- Use of adjuvants (eg. NSAIDS) for enhancing opioids analgesia and reduce side effects bc don’t need high dose of opioids.
What are the 2 ways to help opioid addiction
- Firstly change the addicted opioid to ones that have less side/euphoric effects: eg. Methadone or Bup-re-norphine.
Then slowly over time the dose is reduced. - Rapid opiate detoxification:
Give high doses of naltrexone antagonist to the patient under anaesthetic for 5-6hrs where they are unable to feel the withdrawal symptoms.
After waking up they are kept on oral naltrexone for a long time to reduce risk of relapse.
What are 4 medications to manage opioid withdrawal symptoms
- To reduce autonomic symptoms of withdrawal (sweating, piloerection, increase HR, BP, RR, mydriasis, lacrimation) use Clonidine
- To reduce nausea and vomiting use promethazine
- To reduce muscle cramps use diazepam
- To reduce diarrhoea use antidiarrheal
What are the notable effects, side effects, half life, VD and route of administration relating to bioavailability of Morphine
Effects: Miosis (pinpoint pupil), euphoria, cough suppression
Side effect : aggravate biliary stones- sphincter of Oddi constriction.
Half life of 3 hours due to low lipid solubility- slower onset and longer duration.
Only 1/3 bound to plasma protein so large volume of distribution.
75% first pass metabolism for oral delivery so generally given through IV - can
Patient controlled analgesia.
IM possible
Epidural/intrathecally given to mix with lower dose of local anaesthetic.
