NARCOTIC (OPIOID) ANALGESIC Flashcards
Raw opium contains _
20 alkaloids (aka opiates)
4 main classes of opioids
- Phenanthrenes
- Benzylisoquinolines
- Tetrahydroisoquinolines
- Cryptopines
Phenanthrenes
- Morphine (10%)
- strong opioid - Codeine (0.5%)
- weak opioid - Thebaine (0.2%)
- used for the synthesis of naloxone (opioid antagonist)
Endogenous opioid peptides (3)
- Beta-endodorphins
- from preproopiomelanocortin (POMC)
- 30 aa - Enkephalins
- from preproenkephalin
- pentapeptides (5) - Dynorphin
- from preprodynorphin
- 18-20 aa
Last time known as endorphins, now called opioids peptides
Factors that can affect pain perception
- Attitude
- Mood
- Physical exercise
Transmission of pain
Pain to brain
- Primary Afferent Neuron (A delta- / C-fibre)
- Spinothalamic tract
Brain to pain
1. Efferent Neuron (modulate pain)
MOA of pain modulation
- Inhibit the propagation of pain signals
- Alter emotional perception of pain
- Elevate pain threshold
Sites of opioid receptors regulating pain (3)
- Peripheral nociceptive terminals
- peripheral analgesia - Spine
- spinal analgesia - Brain
- supraspinal analgesia
3 major opioid receptors
- mu
- delta
- kappa
all G-protein coupled receptors
Euphoria vs Dysphoria
Euphoria
- intense happiness and excitement
Dysphoria
- very unhappy, uneasy or dissatisfied
Miosis vs Mydriasis
Miosis
- pupil constriction
- pinpoint pupil
- ADR of opioid analgesic
- signs of opioid overdose (short term)
Mydriasis
- pupil dilation
Individual dosing features (3)
- Elderly patients require lower dose to achieve effective pain relief than younger patients
- Neuropathic pain require higher doses than nociceptive pain
- Lower doses are usually required for continuous maintenance of pain relief than administration only in response to recurrence of pain
Dosing to effect considerations (3)
- Start with low dose and carefully titrate until adequate level of analgesia is obtained or until persistent and unacceptable side effects warrant a re-evaluation of therapy.
- Failure of a least partial analgesia with incremental dosing in opioid-naive patient may indicate that the pain syndrome is unresponsive to opioid therapy
- Some patients with chronic pain, opioids do not exert an appreciable analgesic effect until a threshold dose has been achieved
Clinical uses of opioid agonists (4)
- Analgesia
- morphine
- codeine
- pethidine (used in labor) - Adjunctive anaesthetic
- fentanyl - Cough-suppressant/anti-tussive
- codeine - Anti-diarrhoeal
- diphenoxylate
Strong opioid agonist (4)
- Morphine
- Methadone
- Fentanyl
- Pethidine (Meperidine)
Morphine
- strong opioid agonist
- strong mu, weak delta & kappa
- maximum analgesic efficacy
- high liability for addiction/abuse
Methadone
- strong opioid agonist
- strong mu, no significant delta & kappa
- long acting (plasma half life >24h)
- high liability for addiction/abuse
Fentanyl
- strong opioid agonist
- strong mu, no significant delta & kappa
- short acting (hence adjuvant anaesthetic)
- high liability for addiction/abuse
Pethidine (Meperidine)
- strong opioid agonist
- strong mu, weak delta & kappa
- shorter duration of action than morphine (esp in neonates, hence used in labour)
ADR :
- restlessness > sedation
- N-demethylated in the liver to give norpethidine (hallucinations & convulsive)
- anti-muscarinic (dry mouths & blur vision but no miosis & less spasm of smooth muscle)
Moderate opioid agonists (2)
- Codeine
2. Tramadol
Codeine
- moderate opioid agonist
- weak mu & delta, no kappa
- low maximum analgesic efficacy
- 10% converted to morphine/dihydromorphine by demethylation.
10% of ppl shows reduced analgesic efficacy due to lack of demethylating enzymes - moderate liability for addiction/abuse
Tramadol
- weak mu
- weak 5-HT & noradrenaline reuptake inhibitor (SNRI)
- Ondansetron (5-HT antagonist), reduce analgesic efficacy of tramadol - shows tramadol is 5-HT agonist to cause analgesic effect?
ADR of opioid agonists (9)
- Respiratory depression
- N/V
- Drowsiness
- Constipation
- Miosis (pinpoint pupil)
- Urinary retention
- Postural hypotension & bradycardia
- Immunosuppression
- Histamine release (morphine)
Respiratory depression
- actions in nucleus tractor solitarius & nucleus ambiguus
- reduce response to CO2 & H+
- suppress voluntary breathing
should not occur at normal therapeutic doses but can be lethal in :
- overdosage
- respiratory disease
- hepatic dysfunction
- combination with other CNS depressants
- young children
Can opioid agonists be used in infants?
No.
N/V
- due to actions on the chemoreceptor trigger zone (CTZ) of medulla
- reduces with repeated doses
Constipation
- due to reduced GI motility (esp w chronic use)
Miosis
- pinpoint pupils
- actions in oculomotor nucleus
- pinpoint pupil is a diagnostic feature of opioid overdose. HOWEVER, if hypoxia occurs due to respiratory depression, mydriasis of eyes follows
Urinary retention
- increased bladder sphincter muscle tone (esp males with prostatic hypertrophy)
Postural hypotension & bradycardia
- actions in cardioregulatory nuclei in the medulla
Immunosuppressant
- due to long-term use
- effect on CNS system on immune system
Histamine release from mast cells by morphine
- urticaria & itching
- bronchoconstriction
- hypotension from vasodilation
Hence, morphine should be used in caution in asthmatic patients
Tolerance
- less effective after prolong use
- dose escalation required
Physical dependence
- physiological dependence
- stopping the drug lead to physical withdrawal symptoms
eg joint pain, rhinorrhea, lacrimation
anxiety, irritability, chills, hot flushes, n/v, abdominal cramps & diarrhea
Addiction
- psychological craving
- compulsive use
- loss of control over use
Addiction and tolerance can lead to _
opioid overdose
Opioid antagonists (3)
- Naloxone
- Naltrexone
- Nalmefene
- strong mu antagonist
- used to conteract opioid overdose
- use in caution with patients with opiate dependency as they can precipitate potentially fatal withdrawal symptoms
Naloxone
- short acting
- IV
- made from thebaine
Naltrexone
- long acting
- PO
Nalmefene
- long acting
- IV
Pethidine ADR (3)
ADR :
- Restlessness > sedation
- N-demethylated in the liver to give norpethidine (hallucinations & convulsive)
- Anti-muscarinic (dry mouths & blur vision but no miosis & less spasm of smooth muscle)
Morphine ADR (3)
Histamine release resulting in :
- Urticaria & itching
- Bronchoconstriction (use in caution in asthmatics)
- Hypotension due to vasodilation
Morphine should be used in caution in patients with __
Asthma
Opioid antagonists should be used in caution in patients with __
Physical dependency
- use of opioid antagonist can precipitate potentially fatal withdrawal syndrome
Respiratory depression results in __ and __
- Reduce response to CO2 and H+ stimulation
2. Suppress voluntary respiration
Respiratory depression should not occur at normal therapeutic doses unless __ (5)
- Overdosage
- Respiratory disease
- Hepatic dysfunction
- Concurrent use with other CNS depressants
- Young children
- Codeine to morphine/dihydromorphine
vs - Pethidine to norpethidine
- Demethylation
2. N-demethylation
Tramadol pharmacological activities
- Moderate opioid agonist
2. Weak SNRI effect
