27-10-23 - Opioids Flashcards
Learning outcomes
- To explain the role of opioids in the management of pain, including named examples of opioids and their utility
- To explain the mechanism of action of opioids at a cellular level
- To relate the principles of pharmacodynamics and pharmacokinetics to the therapeutic outcomes and side effects of the opioids
- To identify the need for adjuvant prescribing for patients taking opioid analgesics
- To discuss the major concerns and implications of opioid use and relate this to their legal requirements as a controlled drug
Describe the WHO analgesic ladder (in picture)
What is opium, opioids, and opiates?
What effects do they produce?
- Opium: Natural extract of the poppy Papaver somniferum. It contains morphine and other related compounds.
- Opioid: any substance (natural or synthetic) that produces morphine like effects which are blocked by a morphine antagonist
- Opiates: naturally occurring substances that produce morphine like effects which are blocked by a morphine antagonist
What are 7 parts of the structure for thinking about any drug?
- 7 parts of the structure for thinking about any drug:
1) What is it? (class of drug)
2) How is it given?
3) What is its mechanism of action?
* (Pharmacodynamics: what does the drug do to the body?)
4) What are its main clinical uses?
5) How is it metabolised?
* (Pharmacokinetics: what does the body do to the drug?)
6) Consider the effect on each system in turn.
7) Should I know anything else about the drug?
What are opioids?
Why are they administered?
What are the 3 different types of opioids?
How can opioids differ in terms of their action?
- Opioids area huge family of drugs
- They are administered principally for their analgesic action
- 3 different types of opioids:
1) Strong
2) Intermediate
3) Weak - Opioids can differ in terms of duration of action and potency (e.g fentanyl is very potent compared to morphine)
What is the action of strong opioids?
What are 9 examples of strong opioids?
- Strong opioids have no ceiling effect and are pure MU agonist
- 9 examples of strong opioids
1) Morphine
2) Oxycodone
3) Diamorphine (heroine)
4) Pethidine
* Give dilated pupils instead of restricted pupils like the rest
5) Fentanyl
6) Remifentanil (short half-life)
7) Methadone (long half-life)
8) Buprenorphine
9) Tramadol
* Strong opioid, more towards intermediate
How do weak opioids function?
What are 3 examples of weak opioids?
- Weak opioids have a “ceiling effect” where escalation of the dose typically causes side effects without improving analgesia
- 3 examples of weak opioids:
1) Codeine
2) Dihydrocodeine
3) Loperamide
* Aka Imodium
* Can be used to inhibit GI motility (treatment for diarrhoea)
* Weak opioids, but highly ionised
* Doesn’t get absorbed into the blood very well
What are 2 antagonists for opioids?
- 2 antagonists for opioids:
1) Naloxone
2) Naltrexone
Describe the conversion of oral morphine (mg/day / mg) prescription to the following opioids (in picture):
1) Oral oxycodone (mg)
2) IV morphine (mg)
3) Tramadol (mg)
4) Fentanyl patch (mcg/h – micrograms per hour)
5) Buprenorphine (mcg/h)
6) Tapentadol (mg)
7) Codeine (mg)
What are 5 ways opioids can be given?
- 5 ways opioids can be given:
1) Oral medication
2) Oral patches (e.g fentanyl)
3) Injection (e.g remifentanil)
4) Oral lozenges (fentanyl)
5) Patient control analgesia (PCA)
What is oral bioavailability?
Describe the oral bioavailability for the following opioids:
1) Morphine
2) Oxycodone
3) Fentanyl
4) Codeine
5) Tramadol
6) Methadone
What is codeine? What is it metabolised by?
- Oral bioavailability (F%) is the fraction of an oral administered drug that reaches systemic circulation
- Oral bioavailability for the following opioids:
1) Morphine – 30%
2) Oxycodone – 60%
3) Fentanyl – 50% (lozenge)
* Can bypass portal vein drainage is it is absorbed in the mouth, not swallowed
4) Codeine – 60%
5) Tramadol – 80%
6) Methadone – 80%
- Codeine is a pro-drug, so needs to be metabolised by liver CYP P450 enzymes to be activated
What is the site of action for opioids?
Which OP is responsible for analgesic action?
Where are they located?
What are the 3 other types of opioid peptide receptors (Ops)?
What are these opioid receptors responsible for?
- The site of action for opioids are Opioids peptide receptors (Ops)
- Mu opioid peptide receptor (MOP) is responsible for main analgesic action of opioids
- They are located all around the body, meaning opioids have wide-spread effects
- 3 other types of opioid peptide receptors (Ops):
1) Kappa (KOP)
2) Delta (DOP)
3) Nociception (NOP) - Theses 3 receptors underpin the side-effects from opioids
What are the 3 main types of endogenous opioids?
What do exogenous opioids mimic?
- 3 main types of endogenous (natural) opioids:
1) Endorphins
2) Dynorphin
3) Encephalin - Exogenous opioids mimic the actions of these endogenous opioids, and act as substrates on the MOP receptors in the body
What type of receptors are opioid receptors?
What 2 effects do opioids have on opioid receptors?
- Opioid receptors (OPs) are G-protein coupled receptors
- 2 effects do opioids have on opioid receptors:
1) Close presynaptic voltage sensitive calcium channels
* Reduces neurotransmitter release
2) Open postsynaptic potassium channels
* Hyperpolarises neurone, inhibiting neural excitability
What are 4 CNS effects of opioids?
What cranial nerve do they each affect?
What is an exception to this?
- 4 CNS effects of opioids:
1) All have analgesic effects (clinically relevant)
2) All have sedative effects (may be desirable, may not be)
3) All can cause euphoria
* Potential for abuse
* Disinhibition of dopamine-containing neurones in ventral tegmental area
* Increased dopamine in nucleus accumbens
4) Most have effect on 3rd cranial nerve nucleus
* “Pin-point pupils” / meiosis
* Pethidine is the exception due to the anticholinergic effects
What are 10 adverse effects of opioids?
What are adverse effects of opioids caused by?
How are adverse effects of opioids affected by tolerance?
What side-effects are more resistant to this?
- 10 adverse effects of opioids:
1) Urinary retention
2) Nausea
3) Potential for addiction
4) Respiratory distress
5) Hypotension
6) Dysphoria (anxiety, depression, unease)
7) Sedation
8) Constipation
9) Dry mouth
10) Urticaria and itch - Due to histamine release
- Can be quite a disabling side effect, particularly with intrathecal injection
- Urticaria (hives) is a raised, itchy rash that appears on the skin.
- Adverse effects of opioids are caused by actions on different opioid receptors
- Adverse effects will diminish with time as tolerance develops
- Constipation and dry mouth are more resistant
Describe 6 effects of morphine on the innate immunity (in picture).
Describe 3 effects of morphine on adaptive immunity.
What do these effects lead to?
What are 8 side-effects from opioid impact on the endocrine system?
- 8 side-effects from opioid impact on the endocrine system:
1) Weight gain
2) Decreased muscle mass
3) Osteoporosis
4) Possible infertility
5) Sexual dysfunction
6) Fatigue
7) Hot flashes
8) Depression
What 3 factors affect how opioids are metabolised?
- 3 factors affect how opioids are metabolised
1) Pharmacogenetics
* Can produce big variation with some opioids
* Codeine is a prodrug - needs CPY2D6 activity to activate
* CYPSD6 polymorphisms present in different races can lead to fast and slow metabolism of drugs such as morphine (in picture)
2) Age
* Codeine not for under 18s due to variation in metabolism
* An opioid naïve 80–90-year-old may only need a few mgs
3) Renal failure
* Can be an issue due to accumulation of active metabolites
* Exception is remifentanil (plasma esterases)
Withdrawal syndrome.
What are the symptoms in the first 12 hours of withdrawal largely due to?
How can it be alleviated?
What manifests after this period?
How does time course of development and resolution vary?
How does morphine withdrawal develop and resolve?
Describe the 3 stages of withdrawal (in picture)
- Withdrawal syndrome
- Approximately the first 12 hours is largely psychological and can be alleviated by placebo
- Physiological dependence manifests after that
- Time course of development and resolution varies
- Morphine, maximum severity in 1-2 days, subsides rapidly (5-10 days).
- 3 stages of withdrawal (in picture)
