Narcotics

Question 1

Four steps of Pain

Answer 1

1. Pain sensory fibres activated by noxious stimuli
2. Release of pain mediators
3. Binding of mediators to receptors
   - stimulate neurons that project to various areas of spinal cord and brain
4. Sensation of pain

Question 2

Pain mediators that promote pain

Answer 2

Substance P

Glutamate

Question 3

Pain mediators that inhibit pain

Answer 3

Serotonin

Norepinephrine

Question 4

Pain mechanism

Answer 4

• noxious stimuli
• propagation of action potential
• Calcium channel opens
• prompt release of pain mediators
• pain mediators bind postsynaptic receptors

Question 5

Endogenous Opioids found in the body

Answer 5

Beta-endorphin
Enkephalins
Dynorphin

Question 6

Opioid Receptor subtypes

Answer 6

Mu, Kappa, Delta

Question 7

Effects of Mu receptor subtype

Answer 7

• analgesia
• sedation and euphoria
• inhibition of respiration
• reduced GI peristalsis

Question 8

Kappa and Delta subtype effects

Answer 8

• Primarily analgesia

- most opioids are primarily Mu agonists

Question 9

Mu agonists and analgesia

Answer 9

• inhibition transmission of pain signals

- alter response to pain (in CNS, alter mood)

Question 10

Opioid receptor mechanism

Answer 10

1. Opioid binds to receptor (primarily Mu)
2. Presynaptically inhibits Calcium channel opening
3. Inhibits release of pain mediators
4. Also inhibits post-synaptic response to pain mediators

Question 11

Drug design includes (4)

Answer 11

Full agonists (morphine)
Partial Agonists (buprenorphine)
Reuptake inhibitors (tramadol)
Antagonists (naloxone)

Question 12

Opioid Routes of Administration

Answer 12

• oral
• buccal, sublingual
• rectal
• transdermal
• inhaled
• Parenteral (subcutaneous, intramuscular, intravenous)

Question 13

Highly Potent Opioid

Answer 13

Fentanyl (100X morphine)

Question 14

Intermediate potent Opioid

Answer 14

Morphine

Question 15

Low potent opioid

Answer 15

Codeine (1/10th of morphine)

Question 16

Three uses of Opioids

Answer 16

Pain
- various forms of pain
Diarrhea 
- few are used as anti-diarrheals 
Cough
- Codeine is the opioid typically used for cough

Question 17

Opioid Pharmacokinetics

Answer 17

Some have active metabolites
- Codine -> CYP2D6 -> morphine
Are metabolized in the liver and Eli mated by kidney
Renal impairment can lead to accumulation of metabolites and toxicity

Question 18

Side Effects of Opioids

Answer 18

• Nausea
• Constipation
• Sedation
• Euphoria
• Miosis
• Respiratory depression

Question 19

Nausea Mechanism

Answer 19

• Opioids stimulate the chemoreceptor trigger zone

- Anti-nauseants are used

Question 20

Constipation mechanism

Answer 20

• stimulation of mu receptors in the gut

- slows peristalsis, reduces secretions

Question 21

Sedation Mechanism

Answer 21

Inhibits the reticular activation system in brain

Question 22

Euphoria

Answer 22

Occurs due to actions in the limbic region of the brain

Question 23

Miosis

Answer 23

• Pinpoint pupils
• likely parasympathetic effect
• Can be used to confirm opioid use

Question 24

Respiratory Depression

Answer 24

• Opioids attenuate CO2 sensors in respiratory centre
• main cause of death with opioid toxicity
• drug interaction with Benzodiazepines which also cause respiratory depression

Question 25

Opioid overdose treatment

Answer 25

Opioid antagonist Naloxone administered by injection

Question 26

Tolerance in Opioids (Pharmacokinetic and Pharmacodynamic)

Answer 26

Kinetic: enhanced ability to eliminate opioids Dynamic: Reduction in the number of Mu receptors, increase the number of pain mediating receptors

Question 27

Heroin

Answer 27

- associated with addiction - injected intravenously - highly lipophilic - relatively short duration of action (enhances withdrawal symptoms)

Question 28

Treatment for Opioid withdrawal

Answer 28

Methadone, administered orally and has a half life of 35 hours, causes less euphoria

Question 29

Opioid partial agonists

Answer 29

Buprenorphine - partial agonist at Mu receptors - antagonist at Kappa receptors - management of addiction (with naloxone) - moderate pain, chronic use

Question 30

Advantages of Partial over Full agonist

Answer 30

- Safer in overdose (respiratory depression plateaus) | - Lower risk of abuse (euphoria plateaus)

Question 31

Opioid Reuptake inhibitors

Answer 31

Tramadol - Weak Mu agonist so less respiratory depression, constipation and less abuse potential - inhibits reuptake of serotonin and NE