Opioid drugs Flashcards
What are opioids
They are substances which act at opioid receptors in rtes central and peripheral nervous system
Name the 3 families of naturally occurring opioids
- Beta-endorphins
- Enkephalins
- Dynorphins
What are opioids also known as
neuropeptides” aka “endogenous endorphins”
When were opioids discovered
in the 1970s
What properties do endorphins have
They have morphine like properties
What are endorphins responsible for
Responsible fro the feelings of euphoria elicited from physical or emotional pleasure, pleasure or stress
What are endorphins described as
Natural painkillers that are very potent
What roles do opioids play
Selective roles in:
- Pain modulation
- Neurotransmission
- Stress responses
- Reward processing
- Autonomic function regulation
In which system do opioid act in
CNS and PNS at the pre and post synaptic membranes to trigger their responses
Name the 3 families of opioid receptors
- Mu
- Delta
- Kappa
Where are Mu receptor found
Found in the brainstem and media thalamus
What do Mu receptors control
- Super spinal analgesia,
- respiratory depression
- Euphoria
- Sedation
- Decreased GIT motility
- Physical dependence
Where are delta receptors found
In the brain
Where are kappa receptors found
In the limbic system, diencephalon, brainstem, spinal cord
What are Kappa receptors responsible for
- Spinal analgesia
- Sedation
- Dyspnoae
- Dependence
- Dysphoral
- Respiratory depression
Describe all opioid receptors
They are G protein couples
What do opioid receptors cause
cAMP inhibition at intracellular targets which then act as second messenger to activate protein kinases and affect gene transcription
How do opioid receptors act on presynaptic membranes of A delta and C fibres neurones
They will inhibit voltage gated calcium channels decreasing cAMP levels blocking the release of pain transmitters like glutamate, substance p and calcitonin with the end result being analgesia
Name the 4 chemical classes of opioids
- Phenanthrenes
- Benzomorphans
- Phenylpiperidines
- Diphenylheptanes
Give examples of Phenanthrenes
- Morphine
- Codeine
- hydromorphone
- Oxycodone
- buprenorphine
Describe morphine
Is a hydroxyl containing opioid which has a higher incidence of nausea and hallucinations
Descrive codeine
Is a hydroxyl containing opioid which has a higher incidence of nausea and hallucinations
Give examples of Benzomorphans
Pentazocine
Give examples of Phenylpiperidines
- fentanyl,
- alfentanil,
- sufentanil,
- meperidine
Give examples of Diphenylheptanes
propoxyphene and methadone
Name the one opioid drug that is unique
Tramadol
Why is Tramadol unique
It doesn’t fit into the standard opioid classification system
Describe Tramadol
it is an atypical opioid as it is a partial mu agonist as well as having central GABAergic, catecholaminergic and serotonergic activities
How can we further classify opioids after chemical class
- Agonists
- Partial agonist
- Antagonist
What are agonists
They have affinity and efficacy
Give examples of agonist opioid drugs
morphine,
fentanyl,
methadone
What are partial agonists
They have affinity but only partial efficacy
Give examples of partial agonist opioid drugs
buprenorphine
What are antagonist
Have affinity but no efficacy
Give examples of antagonist opioid drugs
naloxone and naltrexone
What do we mean by affinity
Strength of the drugs bond to the receptor
What do we mean by efficacy
The strength of action is affected by the binding at this receptor
Where does opioid metabolism occur
In the liver
Which enzyme is in charge of opioid metabolism
glucuronidation or P450
What can effect the degree of opioid metabolism
- Genetic makeup
- Gender
- Age
- Diet
- Disease status
- Concurrent use of medications
What does the kidney do in terms of opioids
Excretes opioids but does not metabolise them
What can degree of sensitivity of opioids be controlled by
Polymorphic gene expression for Mu receptors
How do polymorphic gene expression of mu receptors affect degree of sensitivity of opioids
They will influence analgesic effects dependence and tolerance
What do the metabolites of opioids control
The undesirable effects seen
What does morphine treat
Moderatley severe to severe pain
How much of the morphine crosses the blood brain barrier
Less than half due to poor lipid solubility, rapid glucuronidation and ionisation of the drug at physiological pH
What is morphine metabolise by
demethylation AND glucuronidation
What are morphine side effect due to
Histamine release causing bronchospasm and hypotension and direct respiratory drive inhibition
What can morphine reduce
Peripheral sympathetic tone leading to venous pooling and orthostatic hypotension
What can morphine cause
- Spasms of digestive tract leading to decreased motility and resultant constipation as well as bladder spams
- Nausea and vomiting
What is Codeine
A weak opioid analgesic has partial agonist activity at Mu receptors
What is the half life of codeine
2.5 - 3 hours
Codeine is a ______ drug
Pro drug
What do we mean by pro drug
They just undergo some metabolism to be effective
What is codeine metabolised into
Morphine
Why is codeine a weak opioid analgesics
It is metabolised into morphine
Is codeine Susceptible to drug drug interaction
Yes due to its metabolism but the CYP450 chain
What is methadone
A synthetic Mu receptor agonist and NMDA antagonist
What is methadone used to treat
Heroin addicts but can we useful to treat neuropathic pain
What can methadone cause
Potentially serious cardiac arrhythmia and hypokalaemia and hypomagnesiumaemia
What can methadone interact with
SSRIs and TCAs as well as with venlafaxine (antidepressant/ antipsychotic drugs)
What do we mean by tolerance
having to take progressively higher doses of a drug in order to maintain the same effects as the initial dose
What do we mean by dependence
Having to continue taking the drug in order to prevent intolerable side effect produced but sudden cessation of ingestion
What do we mean by addiction
Is the compulsion to continue taking a substance and despite negative consequence, they are unable to stop doing so
What is the problem with opioid drugs and analgesia
Due to their pharmacology opioid drugs do not have an upper ceiling to how much analgesia they can achieve meaning a patient can build up tolerance
What is the problem with tolerance in opioid drugs
Increasingly higher and higher doses of opioid will need to be taken
This increases the risk of adverse side effects
What are the side effects of opioid withdrawal
- Cravings
- Restlessness and irritability
- Increased sensitivity to pain
- nausea,
- abdominal cramps,
- myalgia,
- dysphoria,
- insomnia and anxiety.
What are the clinical signs of opioids withdrawal
- Pupillary dilatation,
- sweating,
- piloerection,
- tachycardia,
- vomiting and diarrhoea,
- hypertension,
- yawning,
- fever,
- rhinorrhoea.
