Opiods - Strong Flashcards
What are indications for strong opioids?
- Acute severe pain
- Relief of chronic pain
- Relief of breathlessness in the context of end of life care
- Relieve anxiety and breathlessness in acute pulmonary oedema
What is the mechanism of action of strong opiods?
Act against mu receptors in the CNS. Activation of these G protein-coupled receptors has several effects that, overall, reduce neuronal excitability and pain transmission.
How do opioids cause respiratory depression?
In the medulla, they blunt the response to hypoxia and hypercapnoea, reducing respiratory drive and breathlessness.
How do opioids reduce sympathetic activity?
By relieving pain, breathlessness and associated anxiety, opioids reduce sympathetic nervous system (fight or flight) activity
What are the main opioid receptors?
- Mu receptors
- Delta Receptors
- Kappa receptors
What type of membrane protein are opioid receptors?
G-protein coupled transmembrane receptors
How does binding of opioids to opioid receptors dull pain?
Causes reduction of synaptic transmission
- Closing of presynaptic Ca2+ channels → hyperpolarization → reduced release of acetylcholine, noradrenaline, serotonin, glutamate, nitric oxide, and substance P (presynaptic inhibition)
- Opening of postsynaptic K+ channels → hyperpolarization (postsynaptic inhibition)
What are the two main mechanisms by which opioids relieve pain?
- Raise pain threshold
- Change in pain perception
What is the mechanism of action of tramadol?
A synthetic analogue of codeine - best classified as a ‘moderate’ strength opioid. Once made active, acts against:
- µ-receptor agonists
- Serotonergic pathways
- Adrenergic pathways
Due to Sertonergic and Adrenergic activity, acts as serotonin and norad reuptake inhibitors - contributes to effect
What are the therapeutic effects of opioids which act against mu receptors?
- Analgesia
- Slowed GI transit
What are side effects of mu receptor agonism?
- Respiratory depression with subsequent rise in CO2 (and possibly ICP)
- Constipation
- Miosis
- Bradycardia
- Strong addiction
- Euphoria
What are therapeutic effects of delta receptor agonism?
Analgesia
What are the side effects of delta receptor agonism?
- Respiratory depression
- Tolerance
- Addiction
What are therapeutic effects of kappa receptor agonism?
- Analgesia
- Sedation
- Slowed gastrointestinal transit
What are side effects of kappa receptor agonism?
- Dysphoria
- Sedation
- Constipation
What is meant by receptor affinity in terms of opioids?
Certain opioids have a stronger receptor affinity than comparatively stronger opioids - the weaker opioid inhibits the stronger opioid competitively, which has no effect
What is meant by intrinsic activity of opioids?
Substances that bind to a receptor but have no intrinsic activity can antagonise the effect of the agonists, if the receptor affinity of the antagonist is higher
What does the strongly lipophilic nature of fentanyal mean in terms of onset and penetration in the CNS?
Rapid onset of action and penetration into the CNS
What are examples of strong opioids?
- Morphine
- Morphine sulphate modified release tablets (MST)
- Morphine PCA
- Fentanyl PCA
- Oxycodone
- Tramadol
What are side effects of strong opioids?
- Respiratory depression
- Neurological depression
- Nausea and vomiting
- Pupillary constriction
- Constipation
- Tolerance
- Dependence
- Withdrawal reaction
How would you treat acute severe pain in a high dependency area?
IV morphine for rapid effect - 2-10mg
How might you treatacute severe pain in a ward setting?
Morphine IM/SC
What is the brand name given to short acting morphine tablets?
Sevredol
What is oromorph?
Morphine Oral solution - short acting morphine
What is MST?
Long acting (modified release) morphine
What is shortec?
Short-acting oxycodone capsules
How is fentanyl administered?
- Sublingual tablets
- Nasal spray
- Transdermal patches
What is the most appropriate route of administration of strong opiates in chronic pain?
Oral
If prescribing morphine for chornic pain, what would you initially start with?
Oromorph 5mg every 4 hours - immediate release
When prescribing opioids for chronic pain, what would you you prescribe following initially titrating oromorph dose?
MST
How would you calculate dosing for breakthrough analgesia?
Prescribe immediate release morphine at 1/10th to 1/6th of the regular 24 hour dose, as required.
Why can partial opioid agonists cause withdrawal symptoms in patients with strong opioid/full potency opiates?
Receptor affinity: certain opioids have a stronger receptor affinity than comparatively stronger opioids → the weaker opioid inhibits the stronger opioid competitively, which then has no effect → opioids of different potencies must not be combined
When converting opioids from one opioid to another, what is used as the reference potency?
Morphine (relative potency: 1) → a higher relative potency allows a lower dose for the same analgesic effect
How much stronger is oxycodone than morphine?
2x stronger
How much more potent is fentanyl than oral morphine?
Approximately 100-150 times more potent than oral morphine
How much more potent is alfentanil than oral morphine?
Approximately thirty times more potent than oral morphine
What are indications for prescribing alfentanil?
- Third line for moderate to severe opioid responsive pain in patients unable to tolerate morphine, diamorphine or oxycodone due to persistent side effects
- Injectable analgesic for moderate to severe, opioid responsive pain in patients with Stage 4-5 CKD, or severe acute renal impairment.
- Episodic/ incident pain.
What are indications for prescribing fentanyl?
- Second line opioid for moderate/severe opioid responsive pain.
- Pain that is stable.
- Oral and subcutaneous routes are not suitable.
- Patient unable to tolerate morphine/ diamorphine due to persistent side effects.
- Compliance is poor, but supervised patch application is possible.
What would you consider giving to someone on strong opiates?
Antiemetics and Laxatives
How would you titrate dose of oral morphine to control pain?
- Increase regular oromorph dose each day in steps of about 30% (or according to breakthrough doses used) until pain is controlled or side effects develop.
- Increase laxative dose as needed.
- Convert to MST when stable.
- Divide 24 hour dose of immediate release morphine by 2.
- Prescribe as MST - 12 hourly.
- Prescribe breakthrough analgesia at correct dose (1/10th to 1/6th of 24 hour morphine dose).
What are features of opioid toxicity?
- Altered mental status (euphoria to apathy)
- Bilateral miosis (pinpoint pupils)
- Respiratory depression (decreased RR and tidal volume)
- Seizures
- Decreased bowel sounds
- Decreased heart rate and blood pressure, hypothermia
- Rhabdomyolysis
How would you manage opioid toxicity?
- Airway management
- IV naloxone
- Manage complications - e.g. seizures
What is the classic triad of opioid toxicity?
- Altered metnal status
- Respiratory Depression
- Miosis
What is important to remember about the administration of naloxone?
Quickly metabolised - effect can wear off
What is the mechanism of action of naloxone?
Binds to opioid receptors (particularly mu receptors), where it acts as a competitive antagonist. It has little to no effect in the abscence of an exogenous opioid. It is used to restore an adequate level of consciousness and RR
What are side effects to naloxone use?
Opioid withdrawal reaction
What are features of opioid withdrawal?
- Flu-like symptoms: rhinorrhea, chills, piloerection, myalgia, arthralgia, leg cramps
- Gastrointestinal complaints: nausea, vomiting, abdominal pain, diarrhea, hyperactive bowel sounds
- Features of sympathetic hyperactivity: mydriasis, tachycardia, hypertension, hyperreflexia
- Features of CNS stimulation: insomnia, yawning, irritability, anxiety, agitation, aggression
What are the flu like syptoms of opioid withdrawal?
- Rhinorrhoea
- Chills
- Piloerection
- Myalgia
- Arthralgia
- Leg cramps
What are GI symptoms of opioid withdrawal?
- Nausea
- Vomiting
- Abdominal pain
- Diarrhoea
- Hyperactive bowel sounds
What are sympathetic features of opioid withdrawal?
- Mydriasis
- Tachycardia
- Hypertension
- Hyperreflexia
How would you treat opioid withdrawal?
Buprenorphine/methadone
What side effects of opioids diminish with chronic use?
Sedative, orthostatic and emetic effects
What side effects of opioid use persist with chornic use?
Miosis and constipation
