Topic 35 - Opioids, Nitrous Oxide and Carbamazepine Flashcards
What types of opioids are there?
Put simply, what is the use of opioids - what is the problem with this both for the patient and in the dental setting?
There are natural and synthetic opioids.
Opioids are used for the management of mod-severe pain and can be used recreationally or prescribed for pain. The problem with this is that patients can develop tolerance and dependence, and that after a difficult dental procedure, post-op analgesia can be difficult to determine as patients already have high tolerance so you’ll struggle to find ordinary low level analgesia for their pain.
Put simply, what does nitrous oxide do?
It’s an agent used in inhalation sedation.
What are the uses of carbamazepine? What’s important to know about it?
Used to treat trigeminal neuralgia but is also an anti-convulsant.
It has a lot of drug-interactions which are important to know before prescribing.
Define opioid. Is there another name for it?
Any agent that acts at an opioid receptor in the CNS and PNS. They can act at pre-synaptic and post-synaptic membranes to trigger a response.
Endogenous opioids are called neuropeptides.
Can you give some examples of endogenous opioids?
Can you give some examples of exogenous opioids?
The three main endogenous opioids are beta-endorphins, enkephalins and dynorphins.
Those made in a pharmaceutical lab include morphine, fentanyl and codeine.
Are endogenous opioids potent?
Yes - they’re natural painkillers and have a potency similar to synthetic morphine.
How do both endogenous and exogenous opioids work?
These opioids act at opioid receptors in the brain and spinal column. The opioid receptors are called mu, delta and kappa.
The opioids can act in different ways and can either upregulate, partially upregulate or downregulate activity in the target cells.
The effects are pain relief, autonomic function control, stress response, reward processing and can also act as neurotransmitters.
Once they bind to receptors, they are G-protein coupled and inhibit cAMP at intracellular targets (enzymes and ion channels). These acts as second messengers and activate protein kinase, affecting gene transcription.
How can you classify opioids?
Agonists (morphine, fentanyl), antagonists (naloxone) and partial agonists.
Most clinically relevant opioids are active primarily at mu
receptors and therefore are termed “mu agonists”.
The affinity and efficacy at each receptor is varied for each opioid encountered.
What controls the sensitivity a patient has to opioids and what effects can this have?
Polymorphic gene expression at mu receptors.
Gender, age, diet, comorbid disease, other medications.
It effects the amount of analgesia a patient gets from opioids, the likelihood of getting dependent/tolerant.
Where does metabolism and excretion of opioids occur and through which methods?
Opioids are metabolised in the liver using the P450 cytochrome pathway, demethylation and glucorodination.
There is no metabolism at the kidneys - here opioids are secreted in urine.
What causes the side effects of opioids?
The metabolites rather than the drug itself. E.g. morphine metabolism can result in bronchospasm, hypotension, constipation and urinary retention.
Define tolerance
Having to take progressively higher doses of a drug to maintain the same effect as the first initial dose
Define dependence
Having to continue to take a drug to prevent intolerable side effects from occurring on sudden cessation of ingesting the drug e.g. patients dependent on a drug may experience a physiological withdrawal
Define addiction
A person feeling a compulsion to still keep taking a drug even when there’snegative consequences but they can’t stop doing so.
You don’t need to be addicted to be dependent or tolerant.
Define withdrawal.
What is it a response to?
Physiological response to ceasing a drug on which you are dependent
It’s a response to taking recreational drugs, but also can occur after a patient has been prescribed opioids long term or in high dosage for chronic pain.
If a tolerance is built up over time, increasingly higher and higher doses may be taken with less _______________??
Negative side effects occurring.
What are some things you may see during withdrawal?
Responses can include cravings, restlessness, irritability, vomiting, diarrhoea, hypertension, abdominal pain, increase in anxiety and insomnia, and extremely emotionally vulnerable - so it’s advised to stop using potent drug when under medical supervision. Can cause morbidity and mortality.
Clinically you’d see tachycardia, pupillary dilation, vomiting, diarrhoea, sweating, piloerection, rhinorrhoea.
What are some uses of NO?
Nitrous oxide is used in sedation in dentistry for children and anxious adults.
It’s used in obstetrics during childbirth.
It’s used in the emergency dept when repositioning limbs e.g. after trauma.
It also has an anaesthetic and analgesic effect so is used as one of the initial gases in GA - but it has a short half life so other gases and drugs are used too.
What does nitrous oxide feel like? How does it do this?
Analgesic effect - can stimulate opioid receptors
Anaesthetic effect - NDMA glutamate receptor blockade
Feels like it slows your body’s reaction time down.
Does NO work fast/slow and how long do the effects stay?
Rapid duration.
Effects short lived.
Can NO cause addiction and side effects?
You’re very unlikely to become addicted to NO as the effect is very short lived. However, if you use high amounts over a long amount of time, you may develop side effects such as megaloblastic anaemia and spinal cord degeneration.
Can you talk about the pharmacokinetics of NO?
Is highly water soluble so readily enters the bloodstream in the alveoli of the lungs.
Here, it enters so rapidly that it sucks out in the alveoli, so even more NO is taken up, which is referred to as the second gas effect.
Can you talk about the pharmacodynamics of NO?
- Reduces tidal volume
- Increases respiratory rate
- Has mild effects on heart rate and pulmonary vascular resistance
- Reduces hepatic and renal blood flow
- Increases cranial blood flow metabolism and intracranial pressure
What pre-screening should you do before prescribing carbamazepine?
Han Chinese and Thai patients may struggle to clear the drug so it can become very toxic. Can be prescribed in an emergency with HLA typing. But avoid.
