Analgesics and Local Anaesthetic Drugs

What is PAIN?

Gate Theory of Pain

1) Sometimes pain is not linked to detectable tissue damage​

2) Sometimes tissue damage is not (very) painful​

Melzack and Wall 1965 theory:​

1) C fibres (afferent) let pain through​

2) A-beta fibres (afferent) stimulate inhibitory neurones​

3) Descending pathways prevent central passage​

• I.e. deliberate decisions to not feel pain​

Pain Assessment

WHO - Pain Ladder

What are OPIODS?

What are the different OPIOID RECEPTORS?

What are the different types of Opioids?

What is NALOXONE?

What are the SIDE EFFECTS fo Opioids?

What is BUPRENORPHINE?

What is the Mechanism of Action of Buprenorphine?

Other Analgesics: NSAIDS

What are the SIDE EFFECTS of NSAIDS?

What is ASPIRIN (ACETYLSALICYLIC ACID)?

Irreversible COX 1 and 2 inhibitor

Aspirin Side Effect - SALICYLATE TOXICITY

Aspirin Side Effect - REYE’S SYNDROME

What is PARACETAMOL (ACETAMINOPHEN)?

1) Centrally acting COX-1 and 2 inhibitor, but also has active metabolite (AM404) with endocannabinoid and TRPV1 receptor interactions

2) Does not significantly reduce inflammation

3) No significant antiplatelet action

4) Excellent analgesic and anti-pyretic

Paracetamol - MECHANISM OF ACTION

Mechanism of action – Paracetamol produces analgesic and antipyretic effects predominantly within the central nervous system, probably involving inhibition of prostaglandin synthesis, although its precise mechanism remains incompletely understood.

Paracetamol - SIDE EFFECTS

Side effects – At therapeutic doses, paracetamol is generally well tolerated and, unlike NSAIDs, has little effect on gastric mucosa or platelet function.

What happens when there is PARACETAMOL OVERDOSE?

1) Overdose: hepatotoxicity/glutathione depletion – In overdose, more paracetamol is converted to the toxic metabolite NAPQI (N-acetyl-p-benzoquinone imine); glutathione becomes depleted, allowing NAPQI to damage hepatocytes and potentially cause acute liver failure.

2) Glutathione (GSH) is a plentiful endogenous molecule that protects cells from damage caused by normal oxidative metabolism (ie the everyday activities of the cell can cause it damage, and GSH prevents some of this). GSH helps neutralise reactive oxygen species and other potentially damaging reactive molecules before they can damage important cellular components. GSH is particularly important in the liver, where it helps detoxify reactive metabolites produced during the metabolism of drugs, foodstuffs, and metabolites throughout the body that end up in the bloodstream.

How is Paracetamol Overdose REVERSED?

N-acetylcysteine (NAC) – N-acetylcysteine is the antidote for paracetamol poisoning and principally works by restoring glutathione availability, allowing toxic NAPQI to be detoxified.

What is KETAMINE?

Why is Ketamine used over other drugs?

Ketamine - SIDE EFFECTS

What are SEDATIVES?

A medically induced state of reduced conscious level, awareness, anxiety or responsiveness

Continuum Level of Sedation

1) Sedation is a continuum

2) 4 distinct classifications

• Minimal (light)

• Moderate (conscious)

• Deep

• General anaesthesia

What are BENZODIAZEPINES?

What are the RISKS of Benzodiazepines?

Benzodiazepines - SIDE EFFECTS

Benzodiazepines - MANAGEMENT

ABC – If excessive sedation occurs, management begins with Airway, Breathing and Circulation (ABC), with airway support and ventilation taking priority over antidote administration.

How can Benzodiazepine Overdose be REVERSED?

What are ‘Z-DRUGS’?

What are LOCAL ANAESTHETICS?

Local Anaesthetics - MECHANISM OF ACTION

Local Anaesthetics - AMINO ESTERS

Local Anaesthetics - AMINO AMIDES

What is COCAINE?

1) In addition to voltage gated sodium channel blockade, cocaine also inhibits noradrenaline, dopamine and serotonin reuptake in nerve endings

2) Sympathomimetic properties

3) Used in ENT surgery as part of Moffett’s solution to reduce bleeding by causing vasoconstriction

Cocaine - MECHANISM OF ACTION

1) This prevents noradrenaline from being removed from the synaptic cleft, increasing sympathetic stimulation and causing vasoconstriction.

2) In contrast, most other local anaesthetics cause vasodilation, increasing local blood flow and drug absorption.

3) Cocaine’s vasoconstrictive properties reduce bleeding and slow systemic absorption, making it useful in certain ENT procedures.

Cocaine - SIDE EFFECTS

1) Cocaine can cause serious cardiovascular effects, including:

• hypertension

• tachycardia

• arrhythmias due to excessive sympathetic stimulation.

Where is Local Anaesthetics USED?

What is LOCAL ANAESTHETIC SYSTEMIC TOXICITY (LAST)?

1) Voltage-gated sodium channels are not just found in nerves

2) They are particularly abundant in heart and brain

Local Anaesthetic Systemic Toxicity - MECHANISM OF ACTION

1) Toxicity follows a predictable dose-response relationship

2) Initially, patients may experience oral or tongue numbness and a metallic taste.

3) Early neurological symptoms can include dizziness, tinnitus and agitation. As toxicity progresses, CNS excitation causes seizures, followed by CNS depression, reduced consciousness and respiratory arrest.

4) Cardiovascular toxicity may develop, causing hypertension and tachycardia initially, followed by hypotension, bradycardia, conduction abnormalities and ventricular arrhythmias.

5) Ultimately, severe cardiovascular depression can lead to cardiac arrest.

Local Anaesthetic Systemic Toxicity - INTRALIPID TREATMENT

Intralipids - AAGBI Safety Guidlines