Drugs for Pain Management

Analgesics not recommended for routine dosing

1.) Meperidine (t1/2 of 3 hours) has a principle metabolite normeperidine (t1/2 of 15-20 hours) that produces significant adverse effects when it accumulates: tremulousness, dysphoria, myoclonus, and seizures. 2.) Agonist-antagonists (due to ceiling effect) 3.) Pentazocine and Butorphanol: cause psychotomimetic effects in patients that are already fearful and anxious.

3 Step Model Guide to the treatment of cancer pain (WHO)

1.) Non-opiod +or- adjuvent 2.) Opioid for mild to moderate pain, +/- non-pioid, +/- Adjuvant. 3.) Opiod for moderate to severe pain +/- Non-opioid +/- Adjuvant *Adjuvents used to manage adverse effects and/or augment analgesia. Mild Pain (1-3/10): Begin on step 1 Moderate Pain (4-6/10): Begin on step 2 Sever pain (7-10/10): Begin on step 3

Clinical Presentation of Pain

Acute Pain - usually nociceptive but can be neuropathic. - occurs as a result of injury or surgery - usually self-limited, subsiding when injury heals. Chronic Pain - Some acute pain lasts for months or years, leading to chronic pain. - Chronic pain may be nociceptive, inflammatory, neuropathic, or functional. Chronic Malignant Pain - Associated with progressive diseases like cancer or AIDS. Chronic non-malignant Pain Pain lasting longer than 6 months beyond the healing period and not associated with any life-threatening disease.

Opioid Administration PCA What opioids are delivered via PCA?

Administered via a variety of routes! Oral (tablet and liquid), sublingual, rectal, transdermal, transmucosal, intravenous, subcutaneous, intraspinal. PCA: Patient controlled administration. Gold-standard for management of acute post-operative pain (for opioid administration). MORPHINE, HYDROMORPHINE, FENTANYL, and METHADONE.

TCA's Most Common Side Effects Other Side Effects Warnings/Precautions/Contraindications Patients to avoid giving TCA's to

Adverse Effects TCA's: Most common: constipation, dry mouth, blurred vision, cognitive changes, tachycardia, urinary hesitation. (associated with anti-cholinergic activity). Other: Orthostatic Hypotension, falls, weight gain, sedation. Secondary Amines (better for elderly) produce less adverse effects- Desipiramine, Nortriptyline. Tertiary Amines- Amitriptyline, Imipramine. Warnings/Precautions/Contraindications: Angle-closure glaucoma BPH Urinary Retention Constipation CV Disease Impaired Liver Function AVOID TCA's in patients with: 2nd or 3rd degree Heart Block Arrhythmias Prolonged QT Interval Severe Liver Disease Recent Acute MI

Gabapentin and Pregabalin MOA Adveres Effects

Anticonvulsants used to treat pain MOA: Bock voltage-gated Ca channels. Decreased influx of Ca --> decrease release glutamate, NE, and substance P. Adverse Effects: Dizziness, Somnolence, Peripheral Edema.

Other Drugs Used in Pain Management

Clonidine Hydroxyzine Lidocaine Capsaicin Caffeine

Opioids for Moderate Pain

Codeine Hydrocodone Oxycodone Meperidine Tramadol

Glucocorticoids Drugs of choice MOA Uses ST Adverse Effects LT Adverse Effects

Commonly used in advanced illness. DOC= Dexamethasone. (Prednisone and methylprednisolone can also be used). MOA: Relieve pain via modulating inflammatory responses. Suppress several inflammatory pathways. Inhibit PG synthesis through 3 independent mechanisms- 1.) inhibition of PLA2 2.) Induction of MAPK phosphatase 1 3.) Reduction of expression of COX-2 Uses: Acute Nerve Compression Increased ICP Bone Pain Visceral Pain Anorexia Nausea Depressed Mood Short-term Adverse Effects: Hypertension Hyperglycemia Immunosuppression Psychotic Reactions Cognitive Impairment Long-term Adverse Effects: Myopathy Cushing's Syndrome Osteoporosis

Carbamazepine

DOC trigeminal neuralgia. MOA: blocks voltage-gated Na channels in sensory neurons (play a crucial role in neuropathic pain). Adverse Effects: Drowsiness, dizziness, nausea and vomiting Carbamazepine-induced leukopenia is not uncommon, but is usually benign. Aplastic anemia is a rare side-effect.

Analgesic Adjunctive Agents (Coanalgesics)

Drugs useful in the management of pain but that are not primarily classified as analgesics. Can be used as monotherapy or in combination with non-opioids and opioids. Antidepressants Anticonvulsants Glucocorticoids Other Drugs

Dosing of Analgesics

During initial Stages of severe pain: analgesics given by the clock, ie at fixed intervals of time. Gradually increase the dose until the patient is comfortable. Give the next dose before the previous has fully worn off. As pain subsides: "as needed" schedule may be appropriate.

Antidepressants and anticonvulsants

Mainstay treatment for several neuropathic pain syndromes.

Opioid Analgesics

Management of moderate to severe acute and chronic pain. Wide variety of potencies available.

Non-opiod Analgesics

Mild-Moderate Pain Acetaminophen and NSAIDS Non-opioids do not cause physical dependance or tolerance. Have a CEILING EFFECT (a maximum dose past which no further analgesia can be achieved). Reach maximum analgesia at low-moderate doses. Often, non-opiod analgesics are prescribed at doses in excess of their effective maximal analgesic dose.

Opioids for Moderate-Severe Pain

Morphine Hydromorphone Oxymorphone Levorphanol Fentanyl Sufentanil Methadone

Antidepressants and Pain

Most effective for pain are those that enhance BOTH the serotonergic and norandrenergic transmission. TCA's and the SNRI's (Seratonin and NE reuptake inhibitors): Serotonin and NE mediate descending inhibition of ascending pain. *Selective Serotonin reuptake inhibitors (SSRI's) are less effective. Adverse Effects TCA's: Most common: constipation, dry mouth, blurred vision, cognitive changes, tachycardia, urinary hesitation. (associated with anti-cholinergic activity). Other: Orthostatic Hypotension, falls, weight gain, sedation. Secondary Amines (better for elderly) produce less adverse effects- Desipiramine, Nortriptyline. Tertiary Amines- Amitriptyline, Imipramine. Warnings/Precautions/Contraindications: Angle-closure glaucoma BPH Urinary Retention Constipation CV Disease Impaired Liver Function AVOID TCA's in patients with: 2nd or 3rd degree Heart Block Arrhythmias Prolonged QT Interval Severe Liver Disease Recent Acute MI

Most common opioid side-effects and there antidotes

Nausea/Vomiting: Usually disappears in a couple days (tolerance). Treat with Hydroxyzine, metoclopromide or prochlorperazine. Sedation: Usually disappears over a few days as tolerance develops. Treat with methylphenidate or modafinil. Itching (pruritis): due to histamine release from mast cells. Manage with Hydroxyzine or diphenhydramine. Constipation: almost universal! Tolerance may develop gradually or not at all. We need to prescribe a laxative, usually a Stimulant Laxative is prescribed or combo stimulant/softener. (Not bulk-forming agents b/c these require alot of fluid intake- not good for those with advanced disease or poor mobility).

What is Pain?

Net result of a complex interaction between the ascending and descending nervous systems. UNPLEASANT, SUBJECTIVE experience Most common symptom prompting patients to seek medical attention.

Types of Pain

Nociceptive- Pain in response to a noxious stimulus.Can be somatic or visceral= defense system. Inflammatory- when tissue damage occurs despite nociceptive defense system. Neuropathic- results from damage to or dysfunction of the peripheral or central nervous system, rather than stimulation of pain receptors. Functional- pain sensitivity due to an abnormal processing or function of the central nervous system in response to to normal stimuli.

Acetaminophen First line for- Adverse Effects-

Often selected as the first-line for mild-moderate pain. First-line: Low back pain and Osteoarthritis Adverse Effects: Hepatotoxicity reported with excessive use and overdose.

Combination Therapy

Opiod and Non-opiod analgesics together generally produce a superior analgesic effect than either one alone.

Respiratory Depression Antidote?

Pharmacological tolerance to respiratory depression develops quickly. Naloxone can be given if respirations are compromised.

Pain Assessment

Rating scales provide a simple way to classify the intensity of pain.

SNRI's Uses Adverse Effects

Serotonin and NE Reuptake Inhibitors VENLAFAXINE AND DULOXETINE Uses: Effective for several types of neuropathic pain. Lack the antihistamine, a-andrenergic blocking, and anti-cholinergic effects of TCA's! Adverse Effects: Nausea Sexual Dysfunction Somnolence * better tolerated than TCA's

Analgesic Ceiling Effect

The dose beyond which there is no additional analgesic effect. Higher doses do not provide a benefit but can increase the likelihood for adverse side effects. NSAIDS have an analgesic ceiling. Pure opioid agonists do not have an analgesic ceiling. If combining a non-opioid and an opioid, the analgesic ceiling of the non-opioid should be the dose-limiting factor. Mixed agonist-antagonists do have a ceiling effect (pentazocine, butorphanol, nalbuphine, and buprenorphine) and are poor choices for patients with severe pain.

NSAIDS

Treatment of mild-moderate pain Especially for inflammatory pain- ARTHRITIS AND GOUT

Anticonvulsants and pain

Useful in treating neuropathic pain Gabapentin, Pregabalin, Carbamazepine

Breakthrough Pain

When a patient with chronic pain on an adequate opioid analgesic regimen experiences transitory acute pain. Treatment: "Rescue doses" of opioids. Typically we use a short-acting supplemental opioid. Typical dose= 5-15% of the basal daily requirement. -or- Transmucosal Fentanyl Formulation (6 types): 1.) Oral Mucosal Lozenge 2.) Immediate-release transmucosal tablet 3.) Effervescent buccal tablet 4.) Buccal soluble film 5.) Nasal Spray 6.) Sublingual Spray

Mixed Opioid agonist-antagonists (pentazocine, butorphanol and nalbuphine) given to a patient on a pure opioid agonist can cause:

Withdrawal reaction (due to competition for receptors).