Narcotics analgesics Flashcards
Three major opioid receptor types that are potential targets for narcotic analgesics
- µ (Mu)
- δ (Delta)
- k (Kappa)
What type of receptors are opioid receptors?
G-protein coupled receptors
Sites of opioid receptors regulating pain
- Peripheral nociceptive terminals (peripheral analgesia)
- Spine (spinal analgesia)
- Brain (Supraspinal analgesia)
Generally, how do opioid analgesics reduce pain?
- Inhibit propagation of pain signals
- Alter emotional perception of pain
- (possibly) elevate pain treshold
The opioid receptor most involved in pain mediation
µ receptor
The opioid receptor that is most associated with Dysphoria
k receptor
List the dose dependence effects of narcotic analgesics as dose increases, from therapeutic to toxic.
- –Therapeutic—
1. Peripheral Analgesia (Nociceptive terminals)
2. Spinal Analgesia (Spine)
3. Supraspinal Analgesia, (Brainstem)
4. Sedation (Brainstem)
5. Euphoria (Emotional Brain)
6. Cough suppression (Brainstem, Resp Nuclei) - –Toxic—
1. Pupil constriction (Oculomotor)
2. Constipation, Reduced gut motility
3. Dysphoria (Emotional Brain)
4. Severe Sedation (Brainstem)
5. Respiratory depression (Respiratory Nuclei)
What are some dosing considerations for:
- Elderly
- Type of pain
- Chronic pain
- Elderly: require lower dose to achieve effective pain relief than younger patients
- Type of pain: Neuropathic pain rq higher dose than nociceptive
- Chronic pain: Lower doses with continuous maintenance rather than administration in response to pain recurrence
General rule for dosing opioids
Start low, titrate carefully until sufficient analgesia is obtained, or until persistent unacceptable SE requires therapy re-evaluation
Characteristics of opioids in some patients with chronic pain
Opioids do not exert appreciable analgesic effect until threshold dose achieved
What does failure of partial analgesia with incremental in opioid-naive patient indicate?
Pain syndrome is unresponsive to opioid therapy. Other medications or procedures may be required, and opioids should not be used
OR
higher doses of opioids are rqeuired
List the clinical uses of opioid agonists, and name some drugs associated with each usage
- Analgesia: Codeine, morphine, pethidine
- Anaesthetic adjuvant: Fentanyl
- Cough suppressant/antitussive: Codeine
- Anti-diarrhoeal: Diphenoxylate
Name some strong Opioid Agonists
- Morphine
- Fentanyl
- Methadone
- Pethidine
Describe the properties of Morphine, methadone and Fentanyl such as:
- Opioid receptor binding
- Analgesia efficacy
- Concerns
- Strong µ agonist. Weaker agonist of other opioid receptors
- High Maximum analgesic efficacy
- Concern: High liability for addiction or abuse
Compare the duration of action between Methdaone and Fentanyl
Methadone is long-acting (half life > 24h) while Fentanyl is short-acting and used as an anaesthetic adjuvant
Which opioid receptor does pethidine bind strongest to?
µ
Compare the duration of action between Morphine and Pethidine. What is the usage of pethidine
Pethidine has shorter Duration of Action than Morphine. Used in labour and delivery
Possible SE of Pethidine at high doses, and what is it caused by?
SE: Hallucination, Convulsant
Cause: Pethidine is N-demethylated in the liver to norpethidine, which has these effects
Unlike other opioid agonists, what is the SE that may be unique to pethidine?
Restlessness (rather than sedation)
Other SE of Pethidine?
Antimuscarinic side effets: Dry mouth, blur vision
- No miosis, less spasm of smooth muscle
Name some moderate opioid agonists
- Codeine/Dihydrocodeine
2. Tramadol
Why does Codeine/dihydrocodeine show various effectiveness between individuals?
- 10% population lack demethylating enzyme
- Cannot convert codeine/dihydrocodeine to higher efficacy morphine/dihydromorphine
Describe the binding of codeine/dihydrocodeine to opioid receptors
- Weak µ and δ agonist
- Probably not a k agonist
Describe the binding of Tramadol to opioid receptors
Weak µ agonist
When Ondansetron, a 5-HT3 antagonist, is taken with tramadol, the effect of tramadol is reduced. What does this show about tramadol?
Tramadol may be a weak agonist of 5-HT3, and hence a weak inhibitor of 5-HT and NE re-uptake
Describe the mechanism of opioid overdose that leads to the fatal AE of Respiratory Depression
- Actions in Nucleus Tractus Solitarius and Nucleus Ambiguus
- Causes reduction to responses to CO2 and H+
- Hence suppresses voluntary breathing
Risk factors leading to Respiratory Depression in patients taking Opioid agonists
- Overdose
- Respiratory disease
- Hepatic dysfunction (hence increased opioids elvel)
- Combination with other CNS depressants (e.g. BZD)
- Young Children (hence avoided in infants)
Generally, what are the common AE of opioid agonists, and the possible mechanism that causes the AE?
- Nausea/vomiting due to chemoreceptor trigger zone in postrema of medulla (reduces with repeated or chronic use)
- Drowsiness
- Constipation due to reduced GI motility (especially with chronic use)
Generally, what are the other AE of opioid agonists, and the possible mechanism that causes the AE?
- Miosis due to actions in oculomotor nucleus
- Urinary retention due to increased bladder sphincter tone (esp. in BPH)
- Postural Hypotension and Bradycardia due to actions in cardioregulatory nuclei in medulla)
- Immunosuppressant when used long-term, due to CNS effects on immune system
- Morphine: Trigger histamine release from mast cells causing allergy reactions
Can morphine be used in asthmatics?
Yes (or not at all), but with caution as morphine trigger hsitamine release from mast cells that can cause allergic reactions
Allergic SEs of Morphine
- Urticaria and itching
- Bronchoconstriction
- Hypotension due to Vasodilation
One possible diagnostic feature of opioid overdose
Pinpoint pupil (constricted pupil) due to actions in oculomotor nucleus
In a patient with opioid overdose, what is a possible diagnostic feature?
Miosis (pinpoint pupils) , but mydriasis if patient alr has hypoxia
Define:
- Tolerance
- Addiction
- Physical Dependence
Of drugs
- Tolerance: where a certain dose of drug becomes less effective after prolonged use, and dose escalation is required to achieve the same effect
- Addiction: Psychological craving for a drug, or compulsive and loss of control over use
- Physical Dependence: Stopping drug leads to physical withdrawal sx
Why is Heroin no longer used?
High risk of addiction and tolerance leads to risk of overdose
Name some examples of opioid withdrawal sx
- Anxiety
- Irritability
- Chills
- Hot flushes
- Joint pain
- Lacrimation
- Rhinorrhea
- Nausea
- Vomiting
- Abdominal cramps
- Diarrhea
Drugs to treat Opioid overdose, and their Mechanism of Action
Drug: Naloxone, Naltrexone, Nalmefene
MoA: Strong µ antagonism, some δ and k antagonism, displaces opioid agonists from receptors
Route of Administration and Duration of Action of the Opioid Antagonists
- Naloxone: Short-acting, usually IV
- Naltrexone: Long-acting, PO
- Nalmefene: Long-acting, IV
Can Opioid Antagonists be used in patients with opiate dependency?
Yes, but with extreme caution: may precipitate fatal withdrawal syndrome when used
