Intro to pharmacology of analgesic agents - Pharmacology Flashcards
Define pain
An unpleasant sensory and emotional experience which we primarily associate with tissue damage or describe in terms of tissue damage or both (IASP definition).
List the sources of pain
Injury
Disease
What is the sensory pathway?
Transduction Transmission - sensory fibres (touch, pain) Transmission - spinal cord Perception/learning - limbic Transmission - thalamus Perception - somatosensory cortex
How is pain modulated?
Emotion and attention profoundly modulate nociception
Amount of pain experience does not relate to severity of tissue damage
Anxiety increases pain transmission
Examples of dental pain?
Infec - acute inflam
Exposed nerve endings - neurogenic pain
Swelling in confined space - pressure effects
Fear and anxiety
How to treat pain?
Reduce tissue damage; - Non steroidal anti-inflam drugs - Steroids - Cooling Nerve block - LA Spinal cord - opioids CNS - Opioids, psychological factors
What does the world health organisation do?
Believe the pt History of symptoms Assess severity Physical exam Pain management
What are the WHO steps?
Step 1 - mild pain
- ‘Non-opioids’
Step 2 - mod pain
- Weak opioids and ‘’
Step 3 - severe pain
- Strong opioids and ‘’
What is the placebo effect?
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.
Features of paracetamol?
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
NSAID features?
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
Effects of NSAIDS on the body?
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
Features of COX2?
Less bleeding as GIT and platelets have mainly COX1
Newer COX2 inhibitors: Parecoxib celecoxib
Not less nephrotic
How are COX2 and cardiovascular disease related?
COX2 and CV disease:
- Absence of antiplatelet effects
- Slightly pro thrombotic
- Increased risk MI and stroke
Contraindicated in CV disease
When elective surgery is required, how are NSAIDs involved?
Stop NSAIDs consumption at least 5 days before elective surgery
Bleeding at operation: platelet transfusion
Consider platelets if emergency surgery
What opioids should be used for moderate to severe pain?
Codeine
Di-hydrocodeine
= Weak opioids
Both metabolised to morphine
What effect do opioids have on the CV system, resp and GI tract?
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
CNS opioid effects?
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
How to reverse opioid effects?
• 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
What occurs with chronic opioid use?
Reduced effect as CNS becomes more tolerant - dose increase
When opioid dependency is reached, what occurs with acute withdrawal?
Hypertension, tachycardia,
tachypnoea, diarrhoea, sweating, anxiety, hallucinations.
What do chronic opioid medications cause?
Withdrawal reactions if stopped suddenly
Give examples of newer oral opioids, features?
Tramadol and nefopam
= as effective as codeine, less variability and constipation
List the usual opioid effects?
Sedation, dizziness, nausea, occasional flushing/sweating with tramadol
Adverse effects of tramadol?
Overdose = resp depression Dependency = difficult to withdraw New legislation: controlled drug (class 3) = prescription only and must be signed for
Give examples of weak opioids
Co-codamol, co-proxamol
Group cautions when prescribing opioids?
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
What do WHO suggest to use with severe pain?
Morphine, diamorphine, fentanyl patch
Oral dose= 3x the iv dose
Post operative analgesia?
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
Routes of opioids administration?
- Oral
- i.v.
- s.c. and i.m.
- Rectal
- Intrathecal
- Epidural
- Buccal
- Trans dermal
How to treat severe/chronic pain?
Oral morphine syrup or tablets • Morphine s.c. infusion • Diamorphine s.c. infusion • Fentanyl transdermal patch lasts 5 days • Buprenorphine patch
What are Gabapentin and pregabalin?
Effective for chronic neurogenic pain
Reduce central transmission and pain projection
Aderse effect: sedation, dizziness, nausea, occasionally hypotension
Examples of antidepressant drugs?
Uses?
Adverse effects?
Amitryptiline
Duloxetine & Citalopram
Useful adjuvant effects in neurogenic pain
Adverse effects - GI and CVS
How to manage pain?
Assess severity on daily living and functioning
Amount of analgesia required to stop the pain = correct dose
