Pharmacology Ch. 20 - Drugs Used for Pain Management

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naloxone (Narcan)

- A opiate antagonists that has no effect of its own other than its ability to reverse the CNS depressant effects of opiate agonist, opiate partial agonists, and propoxyphene - When administered to patients who have not recently received opiates, there is no respiratory depression, psychomimetic effect, circulatory changes, or other pharmacologic activity - If administered to a person addicted to opiate agonists or opiate partidal agonists, withdrawal symptoms may be precipitated. - It's a drug choice for treatment of respiratory depression when escessive doses of opiate agonists, opiate partial agonists, or propoxyphene have been administered.

Nonsteroidal Anti-inflammatory drug (NSAID)

- Aspirin like drugs, unrelated to salicylates, but are prostaglandin inhibitors and share many of the same therapeutic actions and adverse effects. - Block cyclooxygenase. - Varying degrees of analgesic, antipyretic, and anti-inflammatory activity.

Uses of salicylates

- Drug of choice for symptomatic relief of discomfort, pain, inflammation, or fever associated with bacterial and viral infections, headache, muscle aches, and rheumatoid arthritis. - It's not recommended for children because of the associated risk of Reye's syndrome - Aspirin, because of its antiplatelet activity, is indicated for reducing the risk of recurrent transient ischemic attacks (TIAs) or stroke, also reduce the risk of MI in patients with previous MI or unstable angina pectoris

Kappa receptors

- Found in greatest concentration in the cerebral cortex and in the substantia gelatinosa of the dorsal horn of the spinal cord. - They are responsible for analgesia at the levels of the spinal cord and brain - Produces sedation and dysphoria

Common adverse effects of salicylates

- Gastric irritation: if occurs, administer medication with food, milk or antacids (1 hour later), or with large amounts of water. Serious Adverse Effect: - Gastrointestinal bleeding - Salicylism (salicylate intoxication) - Tinnitus (ring in the ears), impaired hearing, dimming of vision, sweating, fever, lethargy, dizziness, mental confusion, nausea, and vomiting. Massive overdose may lead to respiratory depression and coma

Common adverse effects of NSAIDs

- If gastric irritation occurs, administer medication with food, milk, antacids, or large amounts of water Serious adverse effect include gastrointestinal bleeding, hepatotoxicity, hives, pruritus, rash, facial swelling, nephrotoxicity, blood dyscrasias

Sigma receptors

- Located in the limbic area of the brain and in the spinal cord and may play a role in the euphoria produced by selected opiates - Are thought to produce the autonomic stimulation and psychotomimetic (eg, hallucinations) and dysphoric effects of some opiate agonists and partial agonists.

Mu receptors

- Located in the pain-modulating centers of the CNS and induce central analgesia, euphoria, physical dependence, miosis, and respiratory depression

naltrexone (Revia)

- Opiate antagonist. Its differ from naloxone (Narcan) in that it is active after oral administration and has a considerably longer duration of action. It blocks the effects of opioids by competitive binding at opioid receptors. - Can be a treatment of alcoholism

Uses of NSAID

- Reduce pain,fever, inflammation of rheumatoid arthritis, osteorthritis, ankylosing spondylistis, and gout - Certain agents are also approved for use to control the discomfort of primary dysmenorrhea. - Ibprofen, naproxen, and ketoprofen are available OTC to be used for the temporary relief of minor aches and pain associated with the common cold, headache, toothache, muscle aches, backaches, arthritis, and menstrual cramps, as well as to reduce fever

acetaminophen (Tylenol)

- Synthetic nonopiate analgesic that works by prostaglandin inhibition in the central nervous system and blocks generation of pain impulses in the peripheral tissue - Use for discomfort associated with bacterial and viral infections, headache, and musculoskeletal pain.

salicylates

-Three primary pharmacologic effects: analgesic, antipyretic, anti-inflammatory agents - It inhibition of of prostaglandins that sensitize pain receptors to stimulation causing pain (analgesia), they inhibit the prostaglandins that produce the signs and symptoms of inflammation, and they inhibit the synthesis and release of prostaglandins in the brain that cause the elevation of body temperature. - Aspirin has unique property of inhibiting platelet aggregation and enhancement of bleeding time.

Therapeutic Outcome for naltrexone

1. Improved adherence with a substance abuse program because of reduced craving of opioids. 2. Improved adherence with an alcohol treatment program by diminishing craving for alcohol.

Transduction

1. Noxious stimuli causes cell damage with the release of sensitizing chemicals; prostaglandins, bradykinin, serotonin, substance P, histamine 2. These substances activate nociceptors and lead to generation of action potential

Premedication assessment for salicylates

1. Perform baseline neurologic assessment 2. Monitor vital signs 3. Check laboratory values for hepatotoxicity and renal impairment and clotting time. 4. Monitor for GI symptoms before and during therapy; conduct stool guaiac test if GI tract bleeding is suspected. 5. Check for concurrent use of anticoagulant agents 6. If on oral hypoglycemics, review baseline serum glucose level 7. When used as analgesic, perform pain assessment before administering salicylates and at appropriate intervals during therapy.

Premedication assessment for NSAIDs

1. Perform baseline neurologic assessment 2. Monitor vital signs 3. Check laboratory values for hepatotoxicity, nephrotoxicity, bleeding time, and blood dyscrasias 4. Monitor for GI symptoms before and during therapy; conduct stook guaiac test if GI tract bleeding is suspected 5. Check bowel sounds and note stool consistency 6. Check for concurrent use of anticoagulant agents 7. When used as an analgesic, perform pain assessment before administering NSAIDs.

Premedication assessment for naltrexone

1. Perform baseline neurologic assessment 2. Monitor vital signs 3. Check laboratory values for hepatotoxicity; urine screen for opiate use 4. Monitor for GI symptoms before and during therapy 5. The manufacturer recommends that baseline determinations of liver function should be performed before initiation of therapy and repeated monthly for the 6 months 6. The manufacturer recommends a minimum of 7 to 10 days of abstinence from all opiates, a urinalysis to confirm the absence of opiates, and the use of a naloxone challenge test to ensure that the patient will not develop withdrawal symptoms.

Premedication assessment for naloxone

1. Perform baseline neurologic assessment 2. Monitor vital signs 3. Check prior use or dependence on opiate agonists or opiate partial agonists. 4. Have supportive equipment available in immediate area to maintain respiration 5. Check bowel sounds. Review voiding pattern and urine output

Premedication assessment for opiate agonists and opiate partial agonists

1. Perform baseline neurologic assessment 2. Take vital signs: hold medication if respirations are below 12/min, or according to age related respiratory parameters and consult with health care provider. 3. Check bowel sounds and note consistency of stools. Review the voiding pattern and urine output. 4. Check prior use of analgesics 5. Perform pain assessment before administration

Therapeutic Outcomes for Opiate agonist and for opiate partial agonist therapy

1. Relief of pain intensity and duration of pain complaint 2. Prevention of the conversion of persistent pain to chronic pain 3. Prevention of suffering and disability associated with pain 4. Prevention of psychological and socioeconomic consequences associated with inadequate pain management 5. Control of adverse effects associated with pain management 6. Optimization of the ability to perform ADLs

Premedication assessment for acetaminophen

1. Take vital signs 2. Check laboratory values for hepatotoxicity or nephrotoxicity 3. Monitor for GI symptoms before and during therapy 4. Check bowel sounds and review voiding pattern and urine output. 5. When used as an analgesic, perform pain assessment before administering acetaminophen and at appropriate intervals during therapy. 6. When used as an antipyretic, take baseline temperature and continue monitoring temperature at appropriate intervals.

1. Transduction 2. Transmission 3. Perception 4. Modulation

4 Steps in Nociception:

Leukotrienes

A group of chemical mediators that initiate the inflammatory response:

Serotonin

A neurotransmitter that affects hunger,sleep,arousal,and mood. appears in lower than normal levels in depressed persons

Substance P

A neurotransmitter that is involved in the transmission of pain messages to the brain.

Somatostain, Cholecystokinin, Substance P

A series of neurotransmitters play roles in the transmission of nerve impulses from the site of damage to the spinal cord

Transmission

Action potential continues from - Site of injury to spinal cord - Spinal cord to brainstem and thalamus - Thalamus to cortex for processing

- Addiction may develop after 3 to 6 weeks of continual use of the opiate agonists if used for recreational purposes. - Early signs of withdrawal are restlessness, perspiration, gooseflesh, lacrimation, runny nose, and mydriasis. Over the next 24 hours, these symmptoms intensify, and the patient develops muscular spasms; severe aches in the back, abdomen, and legs; abdominal and muscle cramps; not and cold flashes, insomnia; nausea, vomiting, and diarrhea; sever sneezing; and increase in body temperature, blood pressure, and respiratory and heart rates. These symptoms reach a peak at 36 to 72 hours after discontinuation of the medication and disappear over the next 5 to 14 days

Actions of Opiate Agonists

Brandykinins

Acts on mast cells to increase vascular permeability:

Opiate Agoinsts interaction with Selective Serotonin Reuptake Inhibitors, Monoamine Oxidase Inhibitors

All these agents increase serotonin levels, potentially causing serotonin syndrome when taken by a person receiving tramadol. These medicines should be used only under the supervision of the prescriber

Pain Experience

An unpleasant sensation that us part of a larger situation

The American Pain Foundation develop the Pain Care Bill of Rights

As a Person with Pain, You Have the Right to: - Have your report of pain taken seriously and to be treated with dignity and respect by doctors, nurses, pharmacists, and other health care professionals. - Have your pain thoroughly assessed and promptly treated. - Be informed by your doctor about what may be causing your pain, possible treatments, and the benefits, risks, and costs of each. - Participate actively in decisions about how to manage your pain. - Have your pain reassessed regularly and your treatment adjusted if your pain has not been eased. - Be referred to a pain specialist if your pain persists. - Get clear and prompt answers to your questions, take time to make decisions, and refuse a particular type of treatment if you choose.

McGill-Melzack Pain Questionnaire

Assist the patient in describing subjective pain experience. It is useful for individuals who have chronic pain:

Side Effect of Opiate Partial Agonists

CNS: clamminess, dizzines, sedation, sweating GI: nausea, vomiting, dry mouth, constipatiion Serious Adverse Effects: NEUROLOGIC: confusion, disorientation, hallucination RESP: respiratory depression PSYCHOLOGICAL: excessive use or abuse

Side Effects of Opiate Agonists

CNS: lightheadedness, dizziness, sedation, sweating, confusion, disorientation CARDIO: orthostatic hypotension GI: nausea, vomiting, Constipation Serious Adverse Effect: RESP: respiratory depression GUI: urinary retention PSY: excessive use or abuse

Opiate Agonists intereaction with Carbamazepine

Carbamazepine may enhance the metabolism of tramadol (Ultram), reducing its analgesic effect. If used concurrently, the dose of tramadol may need to be increased.

Prostaglandins

Chemicals released from cells that cause smooth muscle contraction and pain:

Naltrexone drug interactions with Clonidine

Clonidine may be administered in patients to reduce the severity of withdrawal symptoms precipitated or exacerbating by naltrexone.

Perception

Conscious experience of pain

Analgesics

Drugs that relieve pain without producing loss of consciousness or reflex activity:

Somatostain

Found in stomach, inhibits secretion of gastric and pancreatic juice and emptying of stomach and gall bladder

Common adverse effects of acetaminophen

Gastric irritation, hepatotoxicity

Opiate Agonists intereaction with CNS Depressants

General anesthetics, phenothiazines, tranquilizers, sedative-hypnotics, tricyclic antidepressants, antihisamines, and alcohol. Respiratory depression, hypotension, and profound sedation or coma may result from this interaction unless the dosage of the opiate agonist has been reduced appropriately, usually by one third to one half the normal dose

Chronic Pain

Has slower onset and lasts longer than 3 months beyond healing process and does not relate to an injury or provide physiologic value.

Cholecystokinin

Hormone the small intestine secretes to stimulate release of pancreatic juice from pancreas and bile from gallbladder

Ceiling effect

Increasing the dosage does not significantly increase the analgesia but definitely increases the incidence of adverse effects.

Pain Tolerance

Individual's ability to endure pain:

Pain Perception

Individual's awareness of the feeling or sensation of pain, also known as Nociception:

Uses of Opiate Partial Agonists

May be used for the short-term relief (up to 3 weeks) of moderate to severe pain associated with cancer, burns, renal colic, preoperative analgesia, and obstetric and surgical analgesia.

Modulation

Neurons originating in the brainstem descend to the spinal cord and release substances (eg, endogenous opioids) that inhibit nociceptive impulses.

Phantom Limb Pain

Neuropathic pain experienced by amputees in a body part that is no longer there is known as:

Thermal, chemical, and mechanical-thermal

Nociceptors are classified as:

Idiopathic pain

Nonspecific pain of unknown origin. Anxiety, depression, and stress are often associated with this type of pain. Common area associated with this type of pain are the pelvis, neck, shoulders, abdomen, and head:

Nalbuphine

Opiate Partial Agonists. Has minimal addiction liability and is not a controlled substance. Because it has a ceiling effect for analgesia and respiratory depression, it is often used as an analgesic for obstetrics.

Analgesics relieve pain; can be classified according to neurologic mechanisms:

Opiate agonists - for severe acute pain Opiate partial agonists - for unrelieved or moderate acute pain Opiate antagonists - reverse adverse effects of opiate agonist Salicylates - for mild acute pain Nonsteroidal antiinflammatory drugs - for mild acute pain Miscellaneous analgesic agents

1. Morphine-like derivatives, 2. Meperidine-like derivatives, 3. Methadone-like derivatives and 4. "other" category

Opiate agonists can be subdivided into four groups:

Opiate partial agonists interaction with opiate agonists

Opiate partial agonists have weak antagoinst activity. When administered to patients who have been receiving opiate agonists such as morphine or meperidine on a regular basis, it may precipitate withdrawal symptoms.

Visceral Pain

Originates from the abdominal and thoracic organs:

MOPS- Modified Objective Pain Score

Pain assessment tool for children 1 to 4 years of age after ear, nose, and throat surgery:

POPS- Postoperative Pain Score

Pain assessment tool for infants having surgical procedures:

NIPS- Neonatal Infant Pain Scale

Pain assessment tool for pain in preterm and full-term neonates used to monitor pain before, during, and after a painful procedure

TPPPS- Toddler-Preschooler Postoperative Pain Scale

Pain assessment tool for smaller children during and following medical or surgical procedures:

Somatic Pain

Pain originates from the skin, bones, joints, muscles, or connective tissue (eg, arthritis pain):

POCIS- Pain Observation Scale for Young Children

Pain scale for children 1 to 4 years of age:

FLACC- Face, Legs, Activity, Cry, Consolability.

Pain scale use in nonverbal patients:

Nociceptive Pain

Pain that's usually dull and aching:

Opiate Agonists interaction with Phenytoin

Phenytoin is an enzyme-inducing agent that may enhance the metabolism of meperidine to normeperidine. Those dose of meperidine may have to be increased if used concurrently with phenytoin

Pain Threshold

Point at which an individual first acknowledges or interprets a sensation of being painful:

Opiate receptors

Receptors activated by opioid narcotic drugs such as heroin and morphine. And are subdivided into four types: mu, delta, kappa, and epsilon receptors. Sigma is another receptor type that reacts to opioid agonists and partial agonists. The receptors are located in different are

Neuropathic Pain

Results from injury to the peripheral or central nervous system--CNS; eg, trigeminal neuralgia. Patient describe pain as stabbing and burning:

Opiate Antagonists

Reverse adverse effects of opiate agonists, Naloxone (Narcan) and Naltrexone (Revia)

Placebo therapy

Should never be used with pain management. It is implies a lack of belief in the patient's description, and can seriously damage the patient-provider relationship. The American Pain Society has declared that the use of placebos is unethical and should be avoided

Nociceptors

The first step leading to the sensation of pain is the stimulatiom of receptors known as:

Common Adverse Effects of naloxone (Narcan)

The following adverse effect have been reported very rarely when extremely high doses have been used: mental depression, apathy, inability to concentrate, sleepiness, irritability, anorexia, nausea, and vomiting. These adverse effects usually occurred in the first few days of treatment and dissipated rapidly with continued therapy. Serious adverse effects are hepatotoxicity.

Opiate parital agonists interaction with CNS Depressant

The following drugs may enhance the depressant effect of the opiate partial agonists: General anesthetics, phenothiazines, tranquilizers, sedativehypnotics, tricyclic antidepressants, antihistamines, and alcohol Respiratory depression, hypotension, and profound sedation or coma may resultfrom this interaction unless the dosage of theopiate partialagonist has been reduced appropriately (usually by one third to one half the normal dose)

Opiate Agonists interaction with Warfarin

The oral anticoagulat effect of warfarin may be increased by tramadol (Ultram). Carefully monitor coagulation values and adjust the dose as needed when tramadol is initiated or discontinued

Acute pain

The sympathetic nervous system is activated, resulting in an increase in the heart rate, pulse, respirations, and blood pressure. This sympathetic nervous stimulation also causes nausea, diaphoresis, dilated pupils, and an elevated glucose level.

Pain Perception, Pain Threshold, Pain Tolerance

Three terms used in relationship to the pain experience are:

Wong-Baker scale

Use for those 3 years of age and older and is particularly useful for adults who have language barriers or who do not read, because they can select the face that best describes their pain:

Opiate Partial agonists

Used for short term relieve of moderate to severe pain associated with cancer, burns, renal colic, preop, OB, and surgical analgesia e.g. butorphanol- Stadol, nalbuphine- nubain, pentazocine- Talwin

Opiate agonists

Used to relieve mild to severe acute pain or as a preoperative medication e.g. morphine-like derivatives--codeine; meperidine-like derivatives--fentanyl; methadone-like derivatives--methadone. - Group of naturally occurring semisynthetic and synthetic drugs that have the capability to relieve severe pain without the loss of consciousness.

Morphine Sulfate

Usually the drug of choice for the treatment of severe chronic pain

NSAIDs drug interaction

Warfarin - increase bleeding risk through platelet inhibition Phenytoin - phenytoin toxicity Valproic Acid - aspirin inhibits valproic acid metabolism Oral hypoglycemic agents - monitor for hypoglycemia Furosemide, Thiazide Diuretics - inhibit the diuretic activity of these agents Probenecid - inhibits the excretion of NSAIDs Lithium - may induce lithium toxicity Aspirin - COX-1 may reduce the platelet-inhibiting effects of aspirin when administered at about the same time Cholestyramine - inhibiting absorption

Actions of Opiate Partial Agonists

When used without prior administration of opiate agonists, the opiate partial agonists are effective analgesics. If an opiate partial agonist is administered to a patient addicted to an opiate agonist such as morphine or meperidine, the opiate partial agonist will induce withdrawal symptoms from the opiate agonist. If the patient is not addicted to the opiate agonist, there is no interaction and the patient will be relieved of pain.

Histamine

chemical released by activated mast cells that increases the flow of blood and fluids to the surrounding area; inflammatory response


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