PH3113 - Pain and Analgesia 4 Flashcards
How can pain be treated?
Nociception
- NSAIDs
- reduce prostaglandin activity
Pain gaiting
- opiates
- mu receptors
- afferent C-fibres in dorsal horn
Pain perception
- opiates
- mu receptors
- improve mood
- forebrain
- midbrain
- mu receptors
- control pain
- periaqueductal gray
- locus coeruleus
What are dynorphins and enkephalins?
Endogenous peptides which are widely distributed in CNS and found in areas which control
- the perception of pain
- modulation of affective behaviour
- modulation of motor control
- regulation of ANS
- neuroendocrine function
What are the three types of opioid receptors?
All G-protein coupled receptors
- all G-protein linked
- all inhibit adenyl cyclase
- all release Gi alpha subunit
Mu
- met/leu-enkephalin beta-endorphin
Kappa
- dynorphins
Delta
- met/leu-enkephalin beta-endorphin
How do the opioid receptors mediate different effects?
Mu
- analgesia
- euphoria
Delta
- analgesia
- euphoria
Kappa
- peripheral analgesia
- spinal analgesia
Where are mu opioid receptors found?
Hypothalamus
- homeostasis
- endocrine function
Medulla
- cough centre
- codeine for dry cough
- anti-tussive
Chemoreceptor Trigger Zone
- medulla
- nausea
- emesis
- morphine
Respiratory centre
- medulla
What effect do opioid receptors have in the limbic system?
Most receptors found in amygdala probably do not exert analgesic action
- may influence emotional behaviour
- fear
- memories
What effect do peripheral opioid receptors have?
Gut motility
- constipation
Cardiovascular
- peripheral vasodilation
- reduced peripheral resistance
- inhibition of baroreceptor reflexes
What are the three types of opiates?
Full mu agonist
- naturally occurring
- morphine
- codeine
- synthetic
- diamorphine
- pethidine
- methadone
Partial agonist
- nalorphine
- pentazocine
- buprenorphine
- meptazinol
Antagonist
- naloxone
- naltrexone
Give some examples of opiates
Co-codamol
Co-dydramol
Codeine phosphate
Diamorphine
Dihydrocodeine
Dipipanone HCl with cyclizine
Fentanyl
Cyclizine with morphine
Hydromorphone
Meptazinil
Morphine
Oxycodone with naloxone
Pentazocine
Pethidine
Tapentadol
Tramadol
How is morphine metabolised?
Glucuronidation by the liver
- morphine-3-glucuronide
- major
- morphine-6-glucuronide
- minor
What are the pharmacological effects of morphine?
Good
- anti-nociceptive at spinal and supra-spinal sites
- mood elevating
- anxiolytic in forebrain
- hypogenic
- kappa receptor
- thalamic
- forebrain
- anti-tussive
- cough centre
- medulla
Bad
- respiratory depressant
- respiratory centre
- medulla
- nauseant and emetic
- chemoreceptor trigger zone
- medulla
- antihomeostatic
- hypothalamus
- pharmacological tolerance
- physical dependence
What are the side effects of opioids?
Constipation
Dizziness
Dry mouth
Vomiting
Confusion
Oedema
Respiratory depression
Sweating
Allergic reactions
- respond to antihistamines
When should opioids not be given, or used under caution?
Caution
- acute respiratory depression
- raised intracranial pressure
- head injury
- masking
Hepatic impairment
- may precipitate coma
Renal impairment
- increased and prolonged effects
- use with care
Pregancy
- pethidine in labour
- dihydromorphine now preferred
What are the critical interactions with opioids?
Absolute contraindication
- MAO inhibitors
- high incidence hyperpyrexic coma
Caution
- sedative hypnotics
- increased CNS depression
- respiratory
- tricyclic antidepressants
- antipsychotic drugs
- increased sedation
- variable effects on respiration
- enhanced pain relief
What are the problems of using opioids for chronic pain?
Doesn’t treat source of pain
Tolerance
Dependence
- treated as drug addicts
Withdrawal
Expensive
Medical
- endocrine
- immune system
How does opiate tolerance take place?
Most treatments are very short term
- only a few days
Pharmacokinetic
- may occur after 10 - 18 days treatment
- avoid confusion with greater opiate need
- disease progression
- may be related to enzyme induction
- more rapid production of morphine-3-glucuronide
Pharmacodynamic
- changes in receptor density
- release of neurotransmitter
- underlying mechanism linked to up-regulation of adenylyl cyclase
- down regulation of mRNA not significant
Pharmacodynamic tolerance associated with high doses, drug-seeking behaviour, break-through pain and genetic pre-disposition
- exceeding therapeutic requirement
How can opioid dependence take place?
Opiate addiction fears have influenced its prescription over the years
Addiction following acute treatment unlikely but depends on dose and use and withdrawal symptoms can occur
Physical and psychological dependence can develop when using opiates to treat chronic pain
Little evidence that opioids are help for long-term pain
- small proportion may obtain good pain relief with opioids long term if dose can be kept low and its use is intermittent
- difficult to identify at the start of the treatment
When do opioids become harmful to use?
Risk of harm increases substantially at doses above an oral morphine equivalence of 120 mg/day but no increased benefit
- therefore no point
Opioids should be discontinued if person is still in pain despite using opioids
- even if no other treatment is available
Assessment of the emotional influences on the person’s pain experience is essential for people with chronic pain who have refractory and disabling symptoms
- particularly if they are on high opioid doses
