Intro to pharmacology of analgesic agents - Pharmacology

Question 1

Define pain

Answer 1

An unpleasant sensory and emotional experience which we primarily associate with tissue damage or describe in terms of tissue damage or both (IASP definition).

Question 2

List the sources of pain

Answer 2

Injury

Disease

Question 3

What is the sensory pathway?

Answer 3

Transduction
Transmission - sensory fibres  (touch, pain)
Transmission - spinal cord
Perception/learning - limbic
Transmission - thalamus
Perception - somatosensory cortex

Question 4

How is pain modulated?

Answer 4

Emotion and attention profoundly modulate nociception
Amount of pain experience does not relate to severity of tissue damage
Anxiety increases pain transmission

Question 5

Examples of dental pain?

Answer 5

Infec - acute inflam
Exposed nerve endings - neurogenic pain
Swelling in confined space - pressure effects
Fear and anxiety

Question 6

How to treat pain?

Answer 6

Reduce tissue damage;
- Non steroidal anti-inflam drugs
- Steroids
- Cooling
Nerve block - LA
Spinal cord - opioids
CNS - Opioids, psychological factors

Question 7

What does the world health organisation do?

Answer 7

Believe the pt
History of symptoms
Assess severity
Physical exam
Pain management

Question 8

What are the WHO steps?

Answer 8

Step 1 - mild pain
- ‘Non-opioids’

Step 2 - mod pain
- Weak opioids and ‘’

Step 3 - severe pain
- Strong opioids and ‘’

Question 9

What is the placebo effect?

Answer 9

Placebo is anything administered which is
pharmacologically and physiologically inert
• Placebo is not ineffective therapeutically. Can
have a measurable effect
• Reassurance and confidence in one’s therapy
may also have an effect.

Question 10

Features of paracetamol?

Answer 10

Inhibition of the synthesis of prostaglandins
Not much anti-inflam effect
Antipyretic
Analgesic
Oral, soluble potions, intravenous, rectal
1g 4-6 hourly adult does 4g in 24hrs
Adverse effects uncommon
Hepatotocitity if overdose - early treatment with N-acetyl-cysteine

Question 11

NSAID features?

Answer 11

Aspirin, ibuprofen, naproxen, indomethacin
Irreversile inhibitor of cyclooxygenase (COX1 or 2 enzyme)
COX generates inflam mediators: prostaglandins and theromboxanes
COX inhibitions are effective at reducing acute inflam
Adverse effects due to extension of therapeutic effects

Question 12

Effects of NSAIDS on the body?

Answer 12

GIT: Occult GI blood loss from minor breaches in mucosa, peptic ulceration, upset, indigestion

Renal function - reduction in intrarenal blood flow = renal failure

Platelets: COX inhibition, bleeding tendency

Cardiovascular: as a result of altered renal function, fluid retention can precipitate heart failure

Resp: Some aspirin sensitive asthmatics

Question 13

Features of COX2?

Answer 13

Less bleeding as GIT and platelets have mainly COX1
Newer COX2 inhibitors: Parecoxib celecoxib
Not less nephrotic

Question 14

How are COX2 and cardiovascular disease related?

Answer 14

COX2 and CV disease:

• Absence of antiplatelet effects
• Slightly pro thrombotic
• Increased risk MI and stroke

Contraindicated in CV disease

Question 15

When elective surgery is required, how are NSAIDs involved?

Answer 15

Stop NSAIDs consumption at least 5 days before elective surgery
Bleeding at operation: platelet transfusion
Consider platelets if emergency surgery

Question 16

What opioids should be used for moderate to severe pain?

Answer 16

Codeine
Di-hydrocodeine
= Weak opioids
Both metabolised to morphine

Question 17

What effect do opioids have on the CV system, resp and GI tract?

Answer 17

CV - reduced sympathetic outflow, increased vagal tone, bradycardia, hypotension, excitation

Resp - inhibit cough reflex, resp depression

GI tract - Reduced gastric motility, constipation, nausea and vomiting

Question 18

CNS opioid effects?

Answer 18

Sedation, euphoria, excitation
Analgesia:
- Spinal cord = reduced pain fibre transmission kappa opiod receptors
- Brainstem = reduced pain projection to higher centres - Mu opioid receptors

Resp depression, reduced brainstem response to hypoxia and hypercarbia

Question 19

How to reverse opioid effects?

Answer 19

• Naloxone 400 mcg i.v. dramatic reversal of mu receptor opioid effects.
• Far less effective on newer synthetic opioid like
substances as their effects in the CNS are less well
defined

Question 20

What occurs with chronic opioid use?

Answer 20

Reduced effect as CNS becomes more tolerant - dose increase

Question 21

When opioid dependency is reached, what occurs with acute withdrawal?

Answer 21

Hypertension, tachycardia,

tachypnoea, diarrhoea, sweating, anxiety, hallucinations.

Question 22

What do chronic opioid medications cause?

Answer 22

Withdrawal reactions if stopped suddenly

Question 23

Give examples of newer oral opioids, features?

Answer 23

Tramadol and nefopam

= as effective as codeine, less variability and constipation

Question 24

List the usual opioid effects?

Answer 24

Sedation, dizziness, nausea, occasional flushing/sweating with tramadol

Question 25

Adverse effects of tramadol?

Answer 25

Overdose = resp depression
Dependency = difficult to withdraw
New legislation: controlled drug (class 3) = prescription only and must be signed for

Question 26

Give examples of weak opioids

Answer 26

Co-codamol, co-proxamol

Question 27

Group cautions when prescribing opioids?

Answer 27

Dependent on hepatic metabolism and renal
excretion of metabolites. Some active metabolites

Prolonged effect in liver or renal impairment
Respiratory disease, sleep apnoea, increased
sensitivity
Aim for minimum duration of prescription

Question 28

What do WHO suggest to use with severe pain?

Answer 28

Morphine, diamorphine, fentanyl patch

Oral dose= 3x the iv dose

Question 29

Post operative analgesia?

Answer 29

If required i.v. in recovery 2mg increments every 3
minutes until comfortable (10 to 20mg) in a recovery
setting. Must be given by trained staff
Ward care: Morphine 10mg s.c. 3 hourly usually coprescribed antiemetic; Ondansetron or cycizine

Morphine Patient Controlled Analgesia:

• Syringe driver intermittent i.v. bolus delivery initiated by patient (push button)
• 1mg minimum frequency every FIVE minutes
• Multiple studies show: approximately 1/3 dose compared to nurse administered s.c. morphine

Question 30

Routes of opioids administration?

Answer 30

• Oral
• i.v.
• s.c. and i.m.
• Rectal
• Intrathecal
• Epidural
• Buccal
• Trans dermal

Question 31

How to treat severe/chronic pain?

Answer 31

Oral morphine syrup or tablets
• Morphine s.c. infusion
• Diamorphine s.c. infusion
• Fentanyl transdermal patch lasts 5 days
• Buprenorphine patch

Question 32

What are Gabapentin and pregabalin?

Answer 32

Effective for chronic neurogenic pain
Reduce central transmission and pain projection
Aderse effect: sedation, dizziness, nausea, occasionally hypotension

Question 33

Examples of antidepressant drugs?
Uses?
Adverse effects?

Answer 33

Amitryptiline
Duloxetine & Citalopram
Useful adjuvant effects in neurogenic pain
Adverse effects - GI and CVS

Question 34

How to manage pain?

Answer 34

Assess severity on daily living and functioning

Amount of analgesia required to stop the pain = correct dose