Nacrotic Analgesics (Opoids) Flashcards
What does somniferum means?
somnus - sleep
ferre - bring
What does phenanthrenes include?
- morphine (10% of opium, strong opioid agonist)
- codeine (0.5% of opium, weak opioid agonist)
- thebaine (0.2% of opium; precursor for syn of naloxone, buprenorphine, and other opioid drugs)
What are the 3 major families derived from opioid precursors? (endogenous opoid peptides = found in our body naturally)
- b-endorphin (30aa)
- enkephalins (5 aa pentapeptides)
- dynorphins (~18-20aa)
What are endorphins also known as?
opioid peptides
What is the psychophysiology of pain?
- modulatory circuits to regulate the perception of pain
- attitude, mood and physical exercise can influence perception of pain
- better to control pain before it becomes severe
How does the pain goes to the brain?
Signal tissue damage/ noxious stimuli (periphery) –> primary afferent neurone (Asigma-/C-fibre) –> Dorsal root ganglion of spinal cord and synapse –> spinothalamic tract –> Efferent pathway, goes back to spinal cord –> Reduce depolarisation and reduces signal –> Perception of pain lessen/ modify the perception
Afferent - periphery, the start
Efferent - the end
How does the opioid analgesia reduce the perception of pain?
- inhibit of the propagation of pain signals (efferent)
- alter the emotional perception of pain
- elevate the pain threshold (so that level of noxious stimuli need to inc to a certain amt before actually feeling the pain)
Which opioid receptors sites can be used to regulate pain?
- peripheral nociceptive terminals (peripheral analgesia)
- spine (spinal analgesia)
- brain (supraspinal analgesia)
What are the 3 major opioid receptors types?
- mu
- delta
- kappa
- all belong to G-protein coupled receptors
What are the different tissue expression and dose dependence of effects?
Good (at low doses)
Nociceptive terminals - peripheral analgesia
Spine - spinal analgesia
Brainstem - supraspinal analgesia and sedation, dangerous severe sedation
Resp nuclei - cough suppression
Caution (at higher doses) "emotional" brain - euphoria, dysphoria oculomotor - pupil constriction GIT - Reduced gut motility, constipation Resp nuclei - resp depression
What do we need to take note about dosing features and dosing to effect in individuals?
- elderly pts lower dose
- neuropathic pain require higher opioid doses than nociceptive pain
- lower doses for continuous maintenance of pain relief than adm in response to recurrence of pain
- start low, then titrate to adequate level of analgesia or until persistent and unacceptable SE warrant for re-evaluation
- if no partial analgesia w incremental dosing in opioid-naive pt may indicate pain syndrome is unresponsive to opioid therapy
- for chronic pain pts, opioids dont exert an appreciable analgesic effect until threshold dose achieved
What are the clinical uses of opioid agonists?
- analgesia: codeine, morphine, pethidine
- anaesthetic adjuvant: fentanyl
- cough suppressant/antitussive: codeine
- anti-diarrhoeal: diphenoxylate
What are the properties of morphine?
- strong opioid agonists
- strong mu agonist (weaker delta and kappa agonist)
- high max analgesic efficacy
- high liability for addiction/abuse
What are the properties of methadone and fentanyl?
- strong opioid agonists
- strong mu agonist (no sig delta and kappa affinity)
- high max analgesic efficacy
- high liability for addiction/abuse
- methadone: long-acting (plasma t1/2 > 24h)
- fentanyl: short-acting (anaesthetic adjuvant)
What are the properties of pethidine?
- strong opioid agonists
- strong mu agonist (weaker delta and kappa agonist)
- shorter duration of action than morphine (esp in neonate thus used in labour)
- N-demethylated in liver to norpethidine (hallucinogenic and convulsant effects at HIGH dose)
- restlessness > sedation
- antimuscarinic (parasympatholytic); dry mouth, blurring vision, but NO MIOSIS and less spasm of smooth muscle
What are the properties of codeine/ dihydrocodeine?
- Moderate opioid agonists
- weak mu and delta agonist (probably not kappa agonist)
- low max analgesic efficacy
- moderate liability for addiction/abuse
- ~10% converted to morphine/dihydromorphine
- ~10% population show reduced analgesic effect due to lack of demethylating enzyme
What are the properties of tramadol?
- Moderate opioid agonists
- weak mu agonist
- weak inhibitor of 5-HT and NA re-uptake
Ondansetron: 5-HT3 antagonist activity (anti-emetic), blocks analgesic effect
If give tramadol; the effect of tramadol analgesic is reduced; might have analgesic effect mediated by 5-HT3; maybe that is why ondansetron reduces the effect of tramadol
How does respiratory depression occur?
actions in nucleus tractus solitarius and nucleus ambiguus:
- reduce responses to CO2 and H+
- suppress voluntary breathing
Respiratory depression can be lethal in which populations?
(normally should not occur in normal therapeutic doses but can be lethal in)
- overdose
- respiratory disease
- hepatic dysfn
- combi w other CNS depressants
- young children
opioid AVOIDED in INFANTS
What are the common adv effects of opioids?
- N/V: actions on chemoreceptor trigger zone in the area postrema of the medulla (usually reduces w repeated or chronic use)
- constipation due to reduced GI motility (esp w chronic use)
- drowsiness (caution when machinery use)
- MIOSIS (pinpoint pupils) actions in oculomotor nucleus (pinpoint pupil DIAGNOSTIC feature of opioid overdose)
- MYDRIASIS can also follow if hypoxia occurs - urinary retention due to inc bladder sphincter tone (esp in pts w prostatic hypertrophy)
If the person collapse hypoxia result; it is going to damage the brain, the usual miosis wont be there –> mydriasis, the pupils have become dilated
- postural hypotension and bradycardia actions in cardioregulatory nuclei in medulla
- immunosuppressant effect w long-term use, most likely through CNS effects on immune system
- morphine can also trigger histamine release from mast cells –> urticaria, itching, bronchoconstriction, hypotension due to vasodilation
MORPHINE CAUTION IN ASTHMATICS
What is heroin
acetylated morphine (diamorphine)
What is the definition of tolerance?
- less effective after prolonged use
- dose-escalation required
addiction and tolerance can lead to risk of overdose
What is the definition of addiction?
- psychological craving
- compulsive use
- loss of control over use
addiction and tolerance can lead to risk of overdose
What is the definition of physical dependence?
- physiological dependence such that stopping the drug leads to physical withdrawal smx
What are the opioid withdrawal symptoms?
- anxiety
- irritability
- chills
- hot flushes
- joint pain
- lacrimation (tears)
- rhinorrhoea (runny nose)
- N/V
- Abdominal cramps
- diarrhoea
What are the opioid antagonists?
Naloxone
Naltrexone
Nalmefene
Strong mu antagonism, also delta and kappa antagonism
used to counteract opioid overdose; Remove opioid from binding sites; competitor but no effect on body
use with extreme caution in pts w opiate dependency as they can precipitate potentially fatal withdrawal syndrome
What is naloxone?
short-acting (IV) for acute overdose
What is naltrexone?
long-acting (PO), after immediate situation resolved
Acute overdose; - use immediate situation naloxone
Once immediate situation resolved; need to ensure all opioid cleared from body; naltrexone (for opioid overdose and clear opioid from body)
What is nalmefene?
Long-acting (IV)
THIS IS NOW THE FIRST LINE
