Lecture 24: analgesic drugs 1

Question 1

Opoids/Opiates analgesics cause?

Answer 1

Analgesia and a state of imparied consciousness

Question 2

3 types of pain after injury?

Answer 2

1. Nociceptive Pain
2. Inflammatory Pain
3. Neuropathic Pain

1 and 2 areeasily treated with opiates but 3 is not as easy

Question 3

Routes of administration?

Answer 3

1. oral
2. parenteral
3. trans-mucosal
4. transdermal

Question 4

Opiate vs Opioid?

Answer 4

Opiate is a narcotic analgesic dervied from opium poppy (natural)

Opioids are synthetic narcotics that mimic the natural poppy plant

Question 5

What are opioid receptors?

Answer 5

They are essentially pre-synaptic, belonging to the G-protein coupled family of receptors.

Activate Gi proteins inhibits adenylate cyclase enz causing decreased Ca channel permeability decreasing response.

also increases K+ conductance hyperpolarising synaptic neuron decreasing response

Question 6

Synthesis of Opioid receptors?

Answer 6

Synthesised in the cell body (DRG) and transported towards the central terminal i the dorsal horn and towards the periphery. Peripheral receptors become active within hours or local tissue damage. This happens around the same time that immunocompetent cells that posess opioid receptors and have the ability to synthesize opioid peptides.

Question 7

Opioids, agonists and antagonists?

Answer 7

Agonists - Activation of ALL receptor subclasses, though with different affinities (eg. Morphine, Fentanyl, Pethidine)

Antagonists - devoid of activity in ALL recpetor classes, just attach themselves. (Eg. Naloxone, Naltrexone) -can reverse overdose and/or the analgesic effects

Agonist-Antagonist - Agonist on one type and antagonist on others (eg. Nalorphine, pentazocine)

Partial Agonist - Activity on one or more but not all receptor types (eg. Bup-re-norphine)

Question 8

Uses of Opioids?

Answer 8

Sedation and treatment of severe and moderate pain

Relatively ineffective for neuropathic pain

NB: marked individual variations in amount required - will need to titrate up until pain is gone but not too much to give respiratory depression.

Question 9

Adverse effects of Opioids?

Precautions?

Answer 9

1. Resp depression
2. Drowsiness
3. Constipation
4. Itching
5. N and V
6. Vagally mediated bradycardia
7. Hypotension via vasodilation

Precautions: Sleep apnea, COPD, elderly

Question 10

Natural Opiates?

Semi-synthetic opioids?

Fully Synthetic opioids?

Endogenous opioid peptides?

Answer 10

1 - Morphine and codeine

2 - Bup-re-norphine, Oxycodone, Di-acetyl codeine (heroin)

3 - Fentanyl, pethidine, Methadone, tramadol

4 - Endorphins, endomorphins, Enkephalins, Dynorphins

Question 11

Considerations when using Opioids?

Answer 11

Most effective and comfortable route

Round the clock for sever to moderate pain

Consider inter-patient variability

Use of adjuvents for enhancing opioid analgesia and reducing side effects - NSAIDS or antiemetics

Question 12

Considerations regarding abuse?

Answer 12

It is the euphoric effect that leads to abuse

1. physical dependence - withdrawal
2. psychological/emotional dependence - leads to physical
3. drug tolerance - use opioid rotation
4. opioid addiction - compulsive use despite harm

Question 13

Management of opioid withdrawal? slow method?

Answer 13

Replace with Methadone or Bup-re-norphine that have less chance of addiction

Clonidine blocking noradrenaline decr. tachycardia and high BP

Promethazine for N + V

Diazepam for muscle cramps

Anti diarrheal for diarrhoea

Question 14

Management of opioid withdrawal? fast?

Answer 14

Under GA th patient is not subject to withdrawal discomfort

High dose of naltrexone to remove drug from recpetors and then oral dosing afterwards to continue to reduce the risk of relapse.

Question 15

Morphine features?

Answer 15

1. Powerful analgesic and sedation
2. Cough supression
3. Miosis (pin point pupil)
4. Altered mood (euphoria and tranquility)
5. Half life of approx 3h
6. low lipid solubility = slow onset long duration
7. metabolised in the Liver and excreted in the urine

Question 16

Side effects of morphine?

Answer 16

1. Resp depression
2. N + V
3. constipation
4. addiction
5. Biliary colic (constricts sphincter of oddi)
6. Bradycardia and hypotension

Question 17

Pethidine features?

Answer 17

1. Synthetic analgesic
2. Dry mouth, tachycardia but less biliary spasm
3. give in tablet (bioavail. = 50%) or injection
4. High lipid solubility = fast action
5. same SE as the other opioids.

Question 18

Fentanyl features?

Answer 18

1. High lipid solubility = fast onset
2. Strong Mu receptor agonist
3. analgesic and anaesthetic
4. SE similar to opioids
5. IV, IM or transderman patches (for slow onset long acting)

Question 19

Iontophoresis?

Answer 19

A method of transdermal PCA (patient controlled analgesia) administration of ionizable drugs in which the electrically charged components are propelled through the skin by an external electric field.

Question 20

Methadone features? Uses?

Answer 20

1. Well absorbed from all routes of administration
2. Rapid onset (30-60min)
3. No significant cognitive impariment and no euphoria
4. Safe in renal failure as it can be secreted by other methods.
5. For chronic and neuropathic pain as well as opioid withdrawal and detox

Question 21

Tramadol features?

Answer 21

1. Synthetic codeine analog
2. good oral bioavailability
3. inhibits noradrenaline and serotonin uptake - (both stimulate inhibitory inter-neuron)
4. SE: N+V, dizziness, sedation, constipation, Seritonin syndrome if given with SSRI (antidepressants), reduces threshold of epilepsy.

Question 22

Codiene features?

Answer 22

1. treats mild to moderate pain
2. supress cough and an anti diarrhoeal
3. Is metabolised to morphine by cytochrome P450

Question 23

Nitrous Oxide features?

Answer 23

1. Powerful analgesic
2. ENTONOX - 50% N₂O in oxygen good for in the field pain relief
3. N + V
4. non addictive
5. Euphoric effect