Pharmacology of Pain Management

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Questions and Answers

What is the primary function of dantrolene?

It increases muscle contraction in striated muscle.

It promotes the uptake of Ca2+ ions in muscle cells.

It blocks the release of Ca2+ ions from the sarcoplasmic reticulum. (correct)

It enhances the release of Ca2+ ions from the sarcoplasmic reticulum.

In what condition is dantrolene primarily used for treatment?

Muscle spasms in dogs

Hypertension in horses

Rhabdomyolysis in humans

Malignant hyperthermia (correct)

Which type of drug would block the production of inflammatory mediators?

TRPV1 agonists

Afferent pathway inhibitors

Non-steroidal anti-inflammatory drugs (NSAIDs) (correct)

Local anaesthetics

How do anti-NGF monoclonal antibodies function in pain management?

They prevent the firing of nociceptors. Signup and view all the answers

What mechanism is primarily affected when local anaesthetics are used?

They block the transmission of pain signals. Signup and view all the answers

What are the potential side effects of chronic use of glucocorticoids?

Cushingoid signs Signup and view all the answers

What role do glucocorticoids have in the arachidonic acid cascade?

They inhibit phospholipase A2 Signup and view all the answers

What distinguishes COX-1 from COX-2?

COX-1 is constitutively expressed while COX-2 is induced during inflammation Signup and view all the answers

Which condition can be exacerbated by the use of glucocorticoids?

Laminitis Signup and view all the answers

What is the purpose of selective COX-2 inhibitors?

To reduce adverse effects associated with pain relief Signup and view all the answers

Which statement about NSAIDs is correct?

They can lead to gastrointestinal irritation. Signup and view all the answers

Which of the following statements about phospholipase A2 is true?

It is involved in the arachidonic acid cascade. Signup and view all the answers

What effect does COX-1 have on platelet aggregation?

It promotes platelet aggregation. Signup and view all the answers

Which class of medication is known for acting as a selective EP4 receptor antagonist?

Grapiprant Signup and view all the answers

What role do inflammatory mediators play in pain perception?

They trigger nociceptors. Signup and view all the answers

Which of the following medications is classified as a GABA agonist?

Gabapentin Signup and view all the answers

Which medication is NOT classified as a local anaesthetic?

Tramadol Signup and view all the answers

Which of the following is an example of a nutraceutical?

Glucosamine Signup and view all the answers

What is the action mechanism of NMDA receptor antagonists in pain management?

Blocking excitatory neurotransmission Signup and view all the answers

Which of the following statements about NSAIDs is incorrect?

They are used as anti-NGF monoclonal antibodies. Signup and view all the answers

Which pain management strategy primarily interrupts pain signal transmission along afferent axons?

Local anaesthetics Signup and view all the answers

What class of drugs do benzodiazepines belong to and how are they used in pre-operative protocols?

Muscle relaxants, aiding in neuromuscular function Signup and view all the answers

What is the main action of amantadine as an NMDA receptor antagonist?

Blocks excitatory signals in the CNS Signup and view all the answers

What is a significant risk associated with the combination of amantadine and tramadol?

Heightened risk of seizures Signup and view all the answers

Which of the following drugs cannot be reversed once administered?

Suxamethonium Signup and view all the answers

What role do glucocorticosteroids serve in musculoskeletal conditions?

Suppress the inflammatory response Signup and view all the answers

Which class of drugs includes non-steroidal anti-inflammatory drugs (NSAIDs) typically used for pain relief?

Analgesics Signup and view all the answers

Which of the following statements is true regarding neuromuscular blocking agents (NMBAs)?

Non-depolarizing agents can be reversed using anticholinesterases Signup and view all the answers

What is a common side effect of amantadine in humans?

Hallucinations Signup and view all the answers

What is a key feature of COX-2 selective NSAIDs?

They significantly reduce gastrointestinal side effects. Signup and view all the answers

Which of the following is a potential adverse effect of NSAIDs?

Nausea and vomiting Signup and view all the answers

What is the main risk associated with NSAID use in dehydrated patients?

Reversible renal insufficiency Signup and view all the answers

In which situation should NSAIDs be monitored closely for adverse effects?

In patients on potentially nephrotoxic drugs Signup and view all the answers

What role does the EP4 receptor play regarding Grapiprant’s function?

It mediates pain and inflammation. Signup and view all the answers

What is the primary function of COX-2 selective NSAIDs?

Block the production of mediators of inflammation, pain, and fever Signup and view all the answers

Which statement is true regarding paracetamol?

It is an NSAID with analgesic and antipyretic properties. Signup and view all the answers

What class of drug is Grapiprant?

Non-steroidal, non-cyclooxygenase inhibiting anti-inflammatory Signup and view all the answers

Which drug is indicated for the treatment of mild to moderate acute pain?

Tramadol Signup and view all the answers

What mechanism of action (MoA) is associated with Gabapentin?

Unknown, but it is an analogue of GABA Signup and view all the answers

What is a common characteristic of nutraceuticals used to treat arthritis?

They have variable and incomplete evidence for efficacy. Signup and view all the answers

Which medication is indicated for use in both dog and cat osteoarthritis?

Bedinvetmab Signup and view all the answers

Which of the following drugs should be avoided in dehydrated patients?

NSAIDs Signup and view all the answers

Study Notes

Therapeutics for the musculoskeletal system

This presentation outlines various therapeutic approaches for musculoskeletal conditions in veterinary medicine.
Learning outcomes include identifying functional issues from musculoskeletal diseases, understanding drugs modifying neuromuscular function (peripherally vs centrally), and recognizing uses for these in common animal diseases.
The presentation delves into drugs used to alter neuromuscular function (e.g., benzodiazepines, neuromuscular blocking agents [NMBAs]).
Benzodiazepines like diazepam and midazolam are pre-anesthetics/sedatives, relaxing muscles for balanced anesthesia, via central action on GABA receptors.
Neuromuscular blocking agents (NMBAs) are used for inducing paralysis (non-depolarizing, e.g., atracurium, vecuronium; depolarizing, e.g., suxamethonium).
These agents affect acetylcholine (ACh) receptors and can be reversed (non-depolarizing) or not (depolarizing).

Drugs to alter neuromuscular function

Benzodiazepines (e.g., diazepam) are used as pre-anesthetics/sedatives to relax muscles (during balanced anesthesia).
These also have sedative and anxiolytic effects and reduce muscle tone by centrally acting on GABA-A receptors in the spinal cord.
Muscle relaxation is weak and without noticeable coordination loss.
Neuromuscular blocking agents (NMBAs) are used to induce paralysis (e.g., atracurium, vecuronium, suxamethonium).
Non-depolarizing NMBAs (eg., atracurium/vecuronium) are ACh antagonists. These can be reversed with acetylcholinesterase agents (e.g., neostigmine).
Depolarizing NMBAs (e.g. suxamethonium) are ACh receptor agonists and cannot be reversed.
Ryanodine receptor (RYR1) antagonists (e.g., dantrolene) are used to treat recurrent exertional rhabdomyolysis in horses and in the past, malignant hyperthermia where there is runaway muscle contraction.
This is often due to complications of older volatile anesthetics.

Peripherally and centrally acting drugs to treat neuromuscular disorders

Glucocorticoids, such as methylprednisolone and triamcinolone, are intra-articular glucocorticoids used to treat inflammatory musculoskeletal conditions.
Non-steroidal anti-inflammatory drugs (NSAIDs) like meloxicam, carprofen, and firocoxib are commonly used, as they inhibit cyclooxygenase enzymes, reducing inflammation, pain, and fever.
Certain NSAIDs (e.g., aspirin) affect renal blood flow, so usage is not recommended in dehydrated or renal impaired individuals.
Paracetamol may also be used as an NSAID with analgesic and antipyretic properties, but with weak anti-inflammatory action.
Caution is advised with its use and it's not recommended for use in cats.

Pain and inflammation

Tissue injury triggers a series of events involving inflammatory mediators.
Drugs like glucocorticoids or NSAIDs are used to treat inflammatory responses.
Anti-NGF monoclonal antibodies effectively target NGF function.
Various treatments for pain include local anesthetics (e.g., bupivacaine, lidocaine, mepivacaine).
Other options include opioids (e.g., tramadol), GABA agonists (e.g., gabapentin), and NMDA receptor antagonists (e.g., ketamine, amantadine).
These drugs modulate pain signals at different stages.

Intra-articular glucocorticoids

Intra-articular glucocorticoids (e.g., methylprednisolone, triamcinolone) are used to treat inflammatory musculoskeletal conditions, especially in horses, via aseptic techniques.
Single doses are well-tolerated, but chronic use can lead to side effects like Cushingoid signs and may exacerbate laminitis.

Arachidonic Acid Cascade and Inflammation

The arachidonic acid cascade is involved in inflammation, prostaglandin production, and inflammatory mediators
Glucocorticoids and NSAIDs interfere with prostaglandin synthesis in this cascade.

Cyclo-oxygenase COX1 and COX2

Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are enzymes and play roles in inflammation and homeostasis.
COX-2 is generally responsible for inflammation in the body.

COX-2 vs COX-1 selectivity

COX-2 selective NSAIDs are favored due to lesser GI side effects compared to non-selective ones
Older NSAIDS are non-selective while newer NSAIDs are usually COX-2 selective.

NSAIDs

NSAIDs (e.g., aspirin, phenylbutazone) have actions as anti-inflammatory, analgesic, and antipyretic agents
Possible adverse effects of NSAIDs include GI issues, reversible renal insufficiency, and cardiac failure in predisposed animals.
NSAID 'failure' can occur in a smaller percentage of dogs and alternative NSAIDs should be considered if needed.

Grapiprant

Grapiprant is a non-steroidal, non-cyclooxygenase inhibiting anti-inflammatory drug
Grapiprant specifically blocks the EP4 receptor, an important mediator of prostaglandin E2-induced inflammation and pain.
Minor GI problems (soft faeces/diarrhoea, or vomiting) tend to be temporary.

Pentosan polysulfate Sodium

Pentosan polysulfate sodium (NaPPS) is used to treat lameness and pain from degenerative joint disease (OA) in dogs via a course of weekly subcutaneous injections
Response can be variable and some dogs might need multiple courses.
Concurrent use with steroids and NSAIDs is avoided due to bleeding risk.

Nutraceuticals

Nutraceuticals such as chondroitin sulfate, glucosamine, antioxidants, and EFAs, are nutritional supplements used in arthritis treatment.
Evidence for their effectiveness is variable and often incomplete.

Bedinvetmab / frunevetmab

Nerve growth factor (NGF) increases inflammatory mediators and stimulates nociceptors.
Bedinvetmab and frunevetmab are anti-NGF monoclonal antibodies to manage OA pain (but not acute pain), targeting long-term management.
Usage should be avoided in young or pregnant animals to avoid possible teratogenic effects.

Paracetamol

Paracetamol is a first-line pharmaceutical treatment for OA in humans.
The mechanism is not fully understood but it affects CNS COX3 and reduces ion conduction in pain sensory neurons.
Paracetamol is used in dogs, but specific veterinary products are not licensed, and it should not be used in cats.

Tramadol

Tramadol is a centrally acting analgesic, acting on opioid, norepinephrine, and serotonin receptors. In contrast to morphine, tramadol has less effect on respiration and GI motility.
It's helpful for mild-to-moderate acute pain and as adjunct for chronic pain.
Potential effects include sedation at high doses and other potential dysphoria issues especially in cats.

Gabapentin

Gabapentin is an analogue of GABA, often used as an antiepileptic but also for neuropathic pain.
The mechanism for analgesia is uncertain, low starting doses are needed and slow increased dosages. It can sometimes cause mild sedation and ataxia.
Withdrawal has potential for rebound pain, so it needs tapering off gradually.

Amantadine

Amantadine is an NMDA receptor antagonist, acting similarly to ketamine but blocking excitatory signals in the CNS.
It's used for treating moderate-severe OA and osteosarcomas pain in animals.
Potential side effects include potential anxiety, confusion, depression, hallucinations, headaches, altered mood, movement issues, sleep disorder, and problems with vision.
Its use may increase the risk of seizures when used along with tramadol.

Multimodal management of osteoarthritis

Managing osteoarthritis (OA) often uses multimodal approaches involving physical therapy, hydrotherapy, and joint repair surgery.
Medical management typically includes NSAIDs, and protection/supplementation of cartilage with nutraceuticals like Cosequin.
Further care should include appropriate exercises, weight control and Omega-3 fatty acid rich diets.

Key Points - summary

LO - Identify drugs for modifying neuromuscular function: various drugs, including benzodiazepines (e.g., diazepam) and neuromuscular blocking agents (NMBAs) are used to modify neuromuscular function.
LO - Identify peripherally vs centrally active drugs: glucocorticoids, NSAIDs, and various other analgesics have varying action in managing inflammatory conditions and pain.

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Description

This quiz covers key concepts in pharmacology related to pain management, including the functions of various drugs such as dantrolene, glucocorticoids, and NSAIDs. It also explores mechanisms involved in pain perception and the role of inflammatory mediators. Test your knowledge on drug classifications and their effects on pain conditions.