Opioids Flashcards
How much money is spent in Scotland each year on drugs to treat pain?
£127 million
What is the WHO Analgesic ladder?
An analgesic ladder for Acute pain, chronic pain without control and acute crises of chronic pain, chronic pain, non-malignant pain and cancer pain
Start at bottom and work your way to the top
Step 1;
- Non opioid analgesics, NSAIDS
Step 2;
- Weak opioids
Step 3;
- Strong opioids (methadone, oral admission, transdermal patch)
Step 4;
- Nerve block (epidurals, PCA pump, neuroleptic block therapy, spinal stimulators)
Neurological procedures can reduce the step of the ladder you are on
Can also use NSAIDs with or without adjuvants for each step
What significant discovery was made in 2015 about Opioid use in the US?
The US Centers for Disease Control
and Prevention (CDC) reports that
prescription and illicit opioid misuse
caused more than 52,000 deaths in
2015, a fourfold rise since 1999
Opioids were killing more young people in US than motorcycle accidents - became an epidemic
What happened court case happened with OxyContin ?
OxyContin maker Purdue Pharma pled guilty to criminal charges and for violating health laws around opioids - contributed to the opioid crisis in America, made bankrupt and shut down
People worked out if you chewed before swallowed you’d get an increased effect, giving a peak conc toxic in many of them
What do Opioid prescription related deaths look like in the UK?
Tramadol related deaths have started rising in recent years - almost 250 deaths a year from it
What is “Opium”?
Opium is a natural extract of the poppy Papaver somniferum. It contains morphine and other related compounds.
What it an “Opioid”?
Opioid is any substance (natural or synthetic) that produces morphine like effects which are blocks by a morphine antagonist
What are “Opiates”?
Opiates are naturally occurring substances that produce morphine like effects which are blocked by a morphine antagonist
What structure should you use when thinking about a 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 of each system in turn
7). Should I know anything else about the drug ?
What are opioids and why do we have so many ?
- Huge family of drugs (20 in the UK)
- Administered principally for their analgesic action
- Strong, intermediate or weak (Intermediate usually used to wean people off opioids)
- Weak opioids have a “celling effect” where escalation of the dose typically causes side effects without improving analgesia
- Duration of action (Seconds to mins, up to 24 hours)
- Potency
Morphine is our reference drug (not most potent)
What are the different Opioids you should know?
Strong opioids (no celling affect, pure MU agonist);
- Morphine
- Oxycodone
- Diamorphine
- Fentanyl
- Pethidine
- Remifentanil
- Methadone
(All cause constipation)
Tramadol - Does have receptor activity at opioid receptors also acts on noradrenergic receptors in CNS and is an antidepressant
Weak opioids;
- Codeine (Pro-drug, metabolised into morphine by different people)
- Dihydrocodeine
(Ioperamide) - Isn’t CNS acting, its anti-diarrhoea
Side effect of most of these give pin point pupils, apart for pethidine see dilation due to muscarinic
Antagonist: Naloxone (& naltrexone)
- Can reverse respiratory depression
How can opioids be given ?
Tablets, injection (IM or SC), fentanyl patches, fentanyl oral transmucosal lozenges
If rested hot water bottle on fentanyl patch increased blood flow, etc. Opposite with cold, not enough pain relief
What is the Oral Bioavailability of each drug?
IV is 100% and the standard as it bypasses 1st pass effect
Oral Bioavailability of Opioids;
Tramadol - 80%
Methadone - 80% (Low clearance high distribution hence high half life)
Codeine - 60%
Oxycodone - 60%
Fentanyl - 50% (lozenge)
Morphine - 30%
Codeine is a pro-drug, so needs to be metabolised by liver CYP P450 enzymes to be activated
What are the different Site of Actions / Opioid receptors ?
Site of Actions / Opioid receptors;
- MU opioid peptide receptor (MOP)
- Kappa (KOP)
- Delta (DOP)
- Nociception (NOP)
Mu most important so learn this mechanism
Opioids receptors at all of these locations so modulate pain effectively
What are the Endogenous opioids ?
Encephalin, Endorphin and Dynorphin
Modifiy through Mu, KOP, DOP etc
What do Opioids do at a cellular level?
All are G-protein coupled receptors
Close voltage sensitive calcium channels
- reduces neurotransmitter release
Open potassium channels
- Hyperpolarises neurone, inhibiting neural excitability
Act on Mu receptors which inhibit voltage ca+ channels stopping vesicle release and decreasing vesicle release. Hyperpolarising post synaptic cell as stimulating post synaptic making less likely to by excited
See image attached
What are the adverse effects of opioids ?
Adverse effects of opioids
Due to actions on different opioid receptors;
- Many will diminish with time as tolerance develops
- Constpation and dry mouth are more resistant (may co-prescrbe laxative)
Urticaria and itch
- Histamine release
- Can be quite a disabling side effect particularly with intrathecal injection
(Common with morphine)
Long-term impact of impairment of hypothalamic function
Possible side effects;
- Urinary retention
- Nausea
- Potential for addiction
- Respiratory depression
- Hypotension
- Dysphoria (anxiety, depression, or unease)
- Sedation
- Constipation
- Weight gain
- Decrease muscle mass
- Osteoporosis
- Possible infertility
- Sexual dysfunction
- Fatigue
- Hot flashes
- Depression
Some of these will translate into signs patients can look for so know their dose is too high (See image)
What is withdrawal syndrome?
Approx. first 12 hour is largely psychological - 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)
Stage 1 - Up to 8 hours;
- Anxiety
- Drug craving
Stage 2 - 8 - 24 hours;
- Anxiety
- Insomnia
- GI disturbance
- Rhinorrhea
- Mydriasis
- Diaphoresis
Stage 3 - Up to 3 days;
- Tachycardia
- Nausea, vomiting
- Hypertension
- Diarrhoea
- Fever
- Chills
- Tremors
- Seizure
- Muscle spasms
Should ween off rather than go cold turkey
