final 07-2019 noma 2019 4pm pain medicine...

PAIN MEDICINE PHARMACOLOGICAL

REVIEW

John M. DiMuro, DO, MBAAnesthesiology & Pain MedicineDiMuro Pain Management

Reno & Las Vegas

NOMA 2019 Las Vegas

PAIN MEDICINE PHARMACOLOGICAL

REVIEW

AGENDA

▪Most common classes of pain medications

▪What each class is best treating▪Common side effects

▪Relevant details▪On the horizon…

PAIN MEDICINE PHARMACOLOGICAL REVIEW

CLASSES OF PAIN MEDICATIONS

1) NSAIDs

Best to treat for: Acute painMost notable side effects: Vascular complications, GI distress, bleeding

PAIN MEDICINE PHARMACOLOGICAL

REVIEW

CLASSES OF PAIN MEDICATIONS

1) NSAIDsAspirin, Celebrex, Diclofenac, Ibuprofen

• Prostaglandins promote inflammation that isnecessary for healing, but also results in painand fever. Prostaglandins are produced withinthe body's cells by the enzyme cyclooxygenase(COX). There are two COX enzymes, COX-1and COX-2. However, only COX-1 producesprostaglandins that support platelets andprotect the stomach.

• Nonsteroidal anti-inflammatory drugs block theCOX enzymes and reduce prostaglandinsthroughout the body. As a consequence,ongoing inflammation, pain, and fever arereduced. Since the prostaglandins that protectthe stomach and support platelets and bloodclotting also are reduced, NSAIDs can causeulcers in the stomach and promote bleeding.

PAIN MEDICINE PHARMACOLOGICAL REVIEW

CLASSES OF PAIN MEDICATIONS 1) NSAIDs

Can be used for both acute and chronic pain BUTIncreased risk for long-term administration and

especially in the perioperative period.

NSAIDsCOX selectivity

ANALGESIC MEDICATIONS

NSAIDsNonsteroidal anti-inflammatory drugs block the COX enzymes and reduce the release of prostaglandins throughout the body. As a consequence, ongoing inflammation, pain, and fever are reduced.

1SAIDsActually interfere with the synthesis of COX as they suppress the immune system.Best treatment for: Chronic diseaseCommon side effects: ….

2

STEROIDSAre not benign!

STEROIDS

Bone loss

Reduces sex hormone levels

Hypercalciuria

Myopathy

Avascular necrosis

Increase serum lipids

Hyperglycemia

HTN

Psychiatric effects

Gastritis

ANALGESIC MEDICATIONS

Muscle Relaxants

Best for: Myalgias, insomniaSide effects: Somnolence

NSAIDs

SAIDs

MUSCLE RELAXANTS▪Flexeril: CNS at brain stem

▪Baclofen: Stimulation of Gabaβ

▪Zanaflex: α-2 agonistSkelaxin: ?

ANALGESIC MEDICATIONS

NSAIDS SAIDS MUSCLE RELAXANTS

ANTI-NEUROPATHIC AGENTS

Gabapentin: ?Lyrica: ? α-2 delta subunitTopamax: ? But thought to be blockage of Na channels, augment GABA, block AMPA, inhibit carbonic anhydrase

Best: Peripheral neuropathySide Effects: Somnolence, weight gain (not Topamax)

ANALGESIC MEDICATIONS

NSAIDs SAIDs Muscle relaxants

Anti-neuropathic

agents

ANTI-DEPRESSANTS

TCAs•Amitriptyline: ? but

inhibits NE and S•Nortriptyline: ? but

inhibits H, S, Ach

•Best for: Peripheral and spinal neuritis

•Side effects: Somnolence, weight gain

ANALGESIC MEDICATIONS• NSAIDs

• SAIDs

• Muscle relaxants• Anti-neuropathic agents

• Anti-depressants

MY FAVORITES:

• 6) Alpha agonistsClonidine: reduced CNS outflowTizanidine: increases inhibition of pre-synaptic

motor neurons

ANALGESIC MEDICATIONS

MY FAVORITES:

• 6) Alpha agonistsClonidine: reduced CNS outflowTizanidine: increases inhibition of pre-synaptic

motor neurons

Best for: Hypersensitivity, diffuse painSide effects: CV, somnolence

MY FAVORITES

6) Alpha agonists 7) NMDA blockersKetamineMethadoneNamendaMagnesiumDextromethorphan

Best for: Severe and refractory pain, nociceptive & neuropathic pain

Side effects: Sedation

Routes of Administration

Sublingual

Implanted

Mucosal

Inhalation

TOPICAL

PR

IM

IV

PO

Intraspinal

ANALGESIC MEDICATIONS

BENZODIAZEPINES

• Best used for: Muscle relaxation, insomnia,

anxiety

• Side effects: Sedation, addiction

ANALGESIC MEDICATIONS

NSAIDs

SAIDs

Muscle relaxantsAnti-

Neuropathic agents

Anti-depressants

Alpha agonists NMDA blockers

Benzodiazepines

TRAMADOL

What is TRAMADOL?

• Synthetic OPIOID analgesic (direct from package insert)

• Indicated for moderate to moderate severe pain

• Binds mu receptor• Weak inhibitor of NE and S reuptake

• Partially antagonized by naloxone• Peak plasma in 2-3 hours

• 30% excreted unchanged in urine

• 60% excreted as metabolites

TRAMADOL

CONCERNS• Increased risk of seizures with concomitant use of multiple drugs including anti-depressants

• SEROTONIN SYNDROME

SEROTONIN SYNDROMEFig. 1: Mechanisms of serotonin syndrome. (1) Increased doses of L-tryptophan will proportionally increase 5-hydroxytryptamine (5-HT or serotonin) formation. (2) Amphetamines and other drugs increase the release of stored serotonin. (3) Inhibition of serotonin metabolism by monoamine oxidase (MAO) inhibitors will increase presynaptic 5-HT concentration. (4) Impairment of 5-HT transport into the presynaptic neuron by uptake blockers (e.g., selective serotonin reuptake inhibitors, tricyclic antidepressants) increases synaptic 5-HT concentration. (5) Direct serotonin agonists can stimulate postsynaptic 5-HT receptors. (6) Lithium increases postsynaptic receptor responses. From Elsevier Science (Critical Care Clinics 1997;13[4]:763-83). Photo: Chesley Sheppard

SEROTONIN SYNDROME

• Common presentation: The most common presenting symptoms and signs are confusion, agitation, diaphoresis, tachycardia, myoclonus, and hyperreflexia.

OPIOIDSWhat to do about opioid prescribing?

OPIOIDSOpioid drugs bind to opioid receptors centrally and peripherally

• GOOD• Provide excellent analgesia

• Can obtain better analgesia with higher doses

• CV stable

HELP!• BAD• Provides such great analgesia they

can be addicting

• Dose-dependent effects can lead to overdose and death

• Decrease respiratory rate

MOST COMMONLY PRESCRIBED OPIOIDS

• Short-acting• Hydrocodone• Oxycodone• Morphine• Tramadol• Hydromorphone• Oxymorphone

• Long-acting• Zohydro, Hysingla• Oxycontin, Xtampza• MS Contin, Arymo• Methadone• Exalgo, Palladone• Opana ER

OPIOIDS

• Best for acute pain

• Well-tolerated with chronic pain but patient needs to have routine follow-up

• Tool in the toolbox• Don’t be scared!

• Use the PDMP• Follow the opioid law –

AB474

On the horizon ….

• NKTR – 181 (Loxicodegol)• Selective mu opioid

agonist• Less euphoria• Reduction in CNS side

effects• Reduced rate of entry

into the brain

On the horizon …

• TANEZUMAB• Monoclonal antibody

against nerve growth factor

Take Home Points

▪There are multiple medical classes to choose from when treating pain▪There are multiple routes of administration for analgesics▪Be careful with polypharmacy regiments

▪Make sure you have an evidence-based diagnosis▪Use the PDMP▪Understand Nevada AB474-Opioid Law▪Understand how these drugs work▪Don’t be afraid to refer out to a specialist early in the case▪Don’t be afraid to ask for help!▪Like everything else, moderation is the key

Questions?John DiMuro, DO

DiMuro Pain ManagementDiMuroPainManagement@gmail.com