Narcotics analgesics

Question 1

Three major opioid receptor types that are potential targets for narcotic analgesics

Answer 1

1. µ (Mu)
2. δ (Delta)
3. k (Kappa)

Question 2

What type of receptors are opioid receptors?

Answer 2

G-protein coupled receptors

Question 3

Sites of opioid receptors regulating pain

Answer 3

1. Peripheral nociceptive terminals (peripheral analgesia)
2. Spine (spinal analgesia)
3. Brain (Supraspinal analgesia)

Question 4

Generally, how do opioid analgesics reduce pain?

Answer 4

1. Inhibit propagation of pain signals
2. Alter emotional perception of pain
3. (possibly) elevate pain treshold

Question 5

The opioid receptor most involved in pain mediation

Answer 5

µ receptor

Question 6

The opioid receptor that is most associated with Dysphoria

Answer 6

k receptor

Question 7

List the dose dependence effects of narcotic analgesics as dose increases, from therapeutic to toxic.

Answer 7

• –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)

Question 8

What are some dosing considerations for:

1. Elderly
2. Type of pain
3. Chronic pain

Answer 8

1. Elderly: require lower dose to achieve effective pain relief than younger patients
2. Type of pain: Neuropathic pain rq higher dose than nociceptive
3. Chronic pain: Lower doses with continuous maintenance rather than administration in response to pain recurrence

Question 9

General rule for dosing opioids

Answer 9

Start low, titrate carefully until sufficient analgesia is obtained, or until persistent unacceptable SE requires therapy re-evaluation

Question 10

Characteristics of opioids in some patients with chronic pain

Answer 10

Opioids do not exert appreciable analgesic effect until threshold dose achieved

Question 11

What does failure of partial analgesia with incremental in opioid-naive patient indicate?

Answer 11

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

Question 12

List the clinical uses of opioid agonists, and name some drugs associated with each usage

Answer 12

1. Analgesia: Codeine, morphine, pethidine
2. Anaesthetic adjuvant: Fentanyl
3. Cough suppressant/antitussive: Codeine
4. Anti-diarrhoeal: Diphenoxylate

Question 13

Name some strong Opioid Agonists

Answer 13

1. Morphine
2. Fentanyl
3. Methadone
4. Pethidine

Question 14

Describe the properties of Morphine, methadone and Fentanyl such as:

• Opioid receptor binding
• Analgesia efficacy
• Concerns

Answer 14

1. Strong µ agonist. Weaker agonist of other opioid receptors
2. High Maximum analgesic efficacy
3. Concern: High liability for addiction or abuse

Question 15

Compare the duration of action between Methdaone and Fentanyl

Answer 15

Methadone is long-acting (half life > 24h) while Fentanyl is short-acting and used as an anaesthetic adjuvant

Question 16

Which opioid receptor does pethidine bind strongest to?

Answer 16

µ

Question 17

Compare the duration of action between Morphine and Pethidine. What is the usage of pethidine

Answer 17

Pethidine has shorter Duration of Action than Morphine. Used in labour and delivery

Question 18

Possible SE of Pethidine at high doses, and what is it caused by?

Answer 18

SE: Hallucination, Convulsant

Cause: Pethidine is N-demethylated in the liver to norpethidine, which has these effects

Question 19

Unlike other opioid agonists, what is the SE that may be unique to pethidine?

Answer 19

Restlessness (rather than sedation)

Question 20

Other SE of Pethidine?

Answer 20

Antimuscarinic side effets: Dry mouth, blur vision

• No miosis, less spasm of smooth muscle

Question 21

Name some moderate opioid agonists

Answer 21

1. Codeine/Dihydrocodeine

2. Tramadol

Question 22

Why does Codeine/dihydrocodeine show various effectiveness between individuals?

Answer 22

• 10% population lack demethylating enzyme

- Cannot convert codeine/dihydrocodeine to higher efficacy morphine/dihydromorphine

Question 23

Describe the binding of codeine/dihydrocodeine to opioid receptors

Answer 23

• Weak µ and δ agonist

- Probably not a k agonist

Question 24

Describe the binding of Tramadol to opioid receptors

Answer 24

Weak µ agonist

Question 25

When Ondansetron, a 5-HT3 antagonist, is taken with tramadol, the effect of tramadol is reduced. What does this show about tramadol?

Answer 25

Tramadol may be a weak agonist of 5-HT3, and hence a weak inhibitor of 5-HT and NE re-uptake

Question 26

Describe the mechanism of opioid overdose that leads to the fatal AE of Respiratory Depression

Answer 26

- Actions in Nucleus Tractus Solitarius and Nucleus Ambiguus - Causes reduction to responses to CO2 and H+ - Hence suppresses voluntary breathing

Question 27

Risk factors leading to Respiratory Depression in patients taking Opioid agonists

Answer 27

1. Overdose 2. Respiratory disease 3. Hepatic dysfunction (hence increased opioids elvel) 4. Combination with other CNS depressants (e.g. BZD) 5. Young Children (hence avoided in infants)

Question 28

Generally, what are the common AE of opioid agonists, and the possible mechanism that causes the AE?

Answer 28

1. Nausea/vomiting due to chemoreceptor trigger zone in postrema of medulla (reduces with repeated or chronic use) 2. Drowsiness 3. Constipation due to reduced GI motility (especially with chronic use)

Question 29

Generally, what are the other AE of opioid agonists, and the possible mechanism that causes the AE?

Answer 29

1. Miosis due to actions in oculomotor nucleus 2. Urinary retention due to increased bladder sphincter tone (esp. in BPH) 3. Postural Hypotension and Bradycardia due to actions in cardioregulatory nuclei in medulla) 4. Immunosuppressant when used long-term, due to CNS effects on immune system 5. Morphine: Trigger histamine release from mast cells causing allergy reactions

Question 30

Can morphine be used in asthmatics?

Answer 30

Yes (or not at all), but with caution as morphine trigger hsitamine release from mast cells that can cause allergic reactions

Question 31

Allergic SEs of Morphine

Answer 31

1. Urticaria and itching 2. Bronchoconstriction 3. Hypotension due to Vasodilation

Question 32

One possible diagnostic feature of opioid overdose

Answer 32

Pinpoint pupil (constricted pupil) due to actions in oculomotor nucleus

Question 33

In a patient with opioid overdose, what is a possible diagnostic feature?

Answer 33

Miosis (pinpoint pupils) , but mydriasis if patient alr has hypoxia

Question 34

# Define: 1. Tolerance 2. Addiction 3. Physical Dependence Of drugs

Answer 34

1. Tolerance: where a certain dose of drug becomes less effective after prolonged use, and dose escalation is required to achieve the same effect 2. Addiction: Psychological craving for a drug, or compulsive and loss of control over use 3. Physical Dependence: Stopping drug leads to physical withdrawal sx

Question 35

Why is Heroin no longer used?

Answer 35

High risk of addiction and tolerance leads to risk of overdose

Question 36

Name some examples of opioid withdrawal sx

Answer 36

1. Anxiety 2. Irritability 3. Chills 4. Hot flushes 5. Joint pain 6. Lacrimation 7. Rhinorrhea 8. Nausea 9. Vomiting 10. Abdominal cramps 11. Diarrhea

Question 37

Drugs to treat Opioid overdose, and their Mechanism of Action

Answer 37

Drug: Naloxone, Naltrexone, Nalmefene MoA: Strong µ antagonism, some δ and k antagonism, displaces opioid agonists from receptors

Question 38

Route of Administration and Duration of Action of the Opioid Antagonists

Answer 38

1. Naloxone: Short-acting, usually IV 2. Naltrexone: Long-acting, PO 3. Nalmefene: Long-acting, IV

Question 39

Can Opioid Antagonists be used in patients with opiate dependency?

Answer 39

Yes, but with extreme caution: may precipitate fatal withdrawal syndrome when used