Analgesics Pharmacology

Analgesics

• Analgesics are medications that relieve pain without causing loss of consciousness.
• They are also known as painkillers.
• Analgesics include opioid and non-opioid agents.

What is Pain?

• Pain involves the actual sensation of pain from various nerve paths and the brain.
• Pain threshold is the level of stimulus needed to produce the sensation of pain.
• Pain perception is influenced genetically, with a μ (mu) opioid receptor gene influencing sensitivity. A higher number of μ receptors reduces pain sensitivity.
• Pain tolerance is subjective and varies widely among people, being influenced by age, sex, culture, previous experiences with pain, and anxiety levels.

Visual Pain Scale

• The Wong-Baker FACES Pain Rating Scale is a tool for assessing pain.
• It uses faces to represent different levels of pain, ranging from no hurt (0) to worst hurt (10).

Conditions that Alter Pain Threshold

• Lowered threshold: Conditions like anger, anxiety, depression, discomfort, fear, isolation, chronic pain, and sleeplessness and tiredness make pain more likely to be felt.
• Raised threshold: Conditions like diversion, empathy, rest, and medications such as analgesics, anti-anxiety agents, and antidepressants make pain less likely to be felt.

Pain Persistence

• Acute pain: Usually caused by obvious tissue damage, acts as a protective function, increases nervous system activity, and resolves upon healing.
• Chronic pain: Pain that persists beyond the expected healing period. Pain no longer serves a helpful function and changes in pain signalling and detection occur, degrading health and function.

Sources of Pain

• Somatic pain: Originates from skeletal muscles, ligaments, or joints, usually responds better to non-opioid medications (NSAIDs).
• Visceral pain: Originates from organs or smooth muscles, usually requires opioids for relief.

Nursing Mnemonics for Pain & Symptoms

• OLDCARTS: Onset, Location, Duration, Character, Alleviating & aggravating, Radiation, Time,Severity
• SOCRATES: Site, Onset, Character, Radiation, Associated symptoms, Time/duration, Exacerbating & relieving, Severity
• PQRST: Provoking, Quality, Region & radiation, Severity, Time

Undertreatment of Pain

• Up to 75% of patients experience unrelieved pain.
• Reasons for undertreatment include:
  • Sociocultural variables
  • Patient inability or unwillingness to describe their pain
  • Lack of regular assessment
  • Health care team attitudes
  • Inaccurate knowledge concerning addiction/tolerance
• Effects of unrelieved pain include increased heart rate, increased respiratory rate, increased blood pressure, increased stress response, urinary retention, and hyperglycemia.

WHO Ladder for Treatment of Pain

• A tiered approach for pain management, progressing from non-opioid to opioid medication as needed. The ladder stages increase opioid strength.

Non-opioid Analgesics

• Less potent than opioid analgesics.
• Used to treat mild to moderate pain.
• Effective for headaches, menstrual cramps, inflammation, minor injuries, and mild to moderate arthritis.
• Examples include aspirin, ibuprofen, and acetaminophen.

Acetaminophen

• Action: Inhibits prostaglandin synthesis.
• Uses: Relieves pain, discomfort and fever.
• Side effects: Rash, low incidence of GI distress.
• Toxic effects/overdose: Hepatotoxicity, thrombocytopenia.

Salicylates (aspirin)

• Action: Anti-inflammatory, antiplatelet, and antipyretic effects.
• Therapeutic serum salicylate level: 15-30 mg/dL
• Higher than 30 mg/dL: Toxic
• Interactions with drugs: Increased bleeding with anticoagulants, hypoglycemia with oral antidiabetics, and increased gastric ulcer risk with glucocorticoids.
• Labs: Increased Prothrombin Time (PT), bleeding time, INR. Also, decreased potassium, cholesterol, T3, and T4 levels.
• Foods containing salicylates: Prunes, raisins, licorice, certain spices.
• Caution: Do not take with other NSAIDs. Avoid during pregnancy. Do not give to children with flu or virus symptoms (Reye syndrome).

NSAIDS

• Action: Inhibition of cyclooxygenase (COX)
• 1st Generation NSAIDS: Aspirin, Ibuprofen, Naproxen, Ketorolac, Indomethacin, Diclofenac, Meloxicam. Inhibit COX-1 and COX-2. Inhibition of COX-1 causes kidney damage and decreased platelet aggregation.
• 2nd Generation NSAID: Celecoxib. Inhibits COX-2 only.
• Side effects and adverse reactions:
  • Headache
  • GI bleed
  • Constipation
  • Dyspepsia
  • Nausea
  • Vomiting
  • Steven-Johnson syndrome
  • Renal failure.

COX-1 and COX-2 Inhibitors

• COX-1: Protects stomach lining, decreases fever, and promotes blood clotting.
• COX-2: Triggers pain and inflammation.
• Medications can either block COX-1 or COX-2 or both.

Oxicams

• Piroxicam, Meloxicam
• Indicated for long-term arthritic conditions
• Can cause gastric problems, such as ulceration and epigastric distress
• Should not be taken with aspirin or other NSAIDS

Selective COX-2 Inhibitors

• Action: Selectively inhibits COX-2 enzyme without COX-1 inhibition.
• Use: Decreases inflammation and pain.
• Drug agents: Celecoxib
• Similar Agents: Nabumetone

Opioid Analgesics

• Opium obtained from the unripe seeds of the opium poppy, used for pain relief.

Common Opioid Analgesics

• A table listing common opioid analgesics, their trade names, routes of administration, and typical adult dosages.

Opioid Analgesics: Mechanisms of Action

• Opioids can be agonists, partial agonists, or antagonists.
• Agonists bind with receptors and cause a response.
• Partial agonists bind with receptors and cause only a limited response.
• Antagonists bind with receptors and cause no effect; they will complete for binding sites with agonists.

Opioid Analgesics: Therapeutic Uses

• Main use is to relieve moderate to severe pain.
• Many have affinity for the CNS, suppressing the medullary cough center.
• Often combined with other drugs for synergistic effect.

Opioid Analgesics: Therapeutic Uses (Continued)

• Strong opioid analgesics, such as fentanyl, sufentanil, and alfentanil, are commonly used with anesthetics during surgery, with the combination practice being known as balanced anesthesia.

Side Effects

• Central Nervous System: Sedation, disorientation, euphoria, lightheadedness, dysphoria, lowered seizure threshold, and tremors.
• Cardiovascular: Hypotension, palpitations, and flushing
• Respiratory: Respiratory depression, aggravation of asthma
• GI: Nausea, vomiting, constipation, and biliary tract spasm
• Other: Itching, rash, wheal formation, and urinary retention

Respiratory Depression

• One of the most serious side effects of opioids; strongly related to the degree of sedation.
• Careful titration may not prevent respiratory compromise. Assisted ventilation may be required.
• Opioid reversal agents, such as naloxone (Narcan), may be necessary to reverse respiratory depression. Opioid antagonists also reverse pain control.

Vital Signs Monitoring

• Monitor vital signs before, during, and after administration of opioid analgesics.
• Withhold medication if respirations are less than 12 breaths per minute or if there are any changes in consciousness.

Release of Histamine

• All opioids cause histamine release, more pronounced with natural opioids than synthetic ones.
• Believed to be responsible for many unwanted side effects: itching, rash, hemodynamic changes (BP, pulse), and flushing.
• Many patients misinterpret this as an allergic reaction, but true anaphylaxis is rare.

G.I. Side Effects

• Opioids irritate the gastrointestinal tract, causing nausea, vomiting, and constipation.

Psychological Dependence (addiction)

• A pattern of compulsive drug use characterized by continuous craving for an opioid and the need to take it for effects other than pain relief (e.g., euphoria).

Physical Dependence

• Body's physiologic adaptation to the effects of an opioid.
• Opioid tolerance: need for larger doses to achieve the same level of pain relief.
• Expected in patients on long-term opioid treatment. This is distinct from psychological dependence.

Opioid Abstinence Syndrome

• Physiologic response when an opioid agent is abruptly stopped or an opioid antagonist (such as naloxone) is administered.
• Manifestations: Anxiety, irritability, chills, hot flashes, joint pain, lacrimation, rhinorrhea, diaphoresis, nausea, vomiting, abdominal cramping, diarrhea.

Stages of Opiate Withdrawal Syndrome

• A series of stages (I-III) characterized by specific signs and symptoms, such as anxiety, drug craving, insomnia, GI disturbances, rhinorrhea (runny nose), mydriasis, diaphoresis (sweating), tachycardia, nausea/vomiting, hypertension, diarrhea, fever, chills, tremors, seizures, muscle spasms, and so on, typically presenting over a period of several hours to a few days after cessation of opioid use.

Opioid Interactions

• Additive effects, including an increased risk of respiratory depression, can occur when opioids are combined with alcohol, antihistamines, barbiturates, benzodiazepines, MAO inhibitors, phenothiazines, and other CNS depressants.

Opioid Agonists

• Morphine: C-II scheduled substance, used for severe pain, but is highly constipating. Usage should be done cautiously with head injury patients. Do not mistake with meperidine (Demerol).
• Codeine: C-II scheduled substance for mild-moderate pain; less effective than morphine. Sometimes used as a cough suppressant.

Hydromorphone

• Semi-synthetic opioid similar to morphine, six times more potent, with fewer hypnotic effects and less GI distress.

More Opioid Agonists

• Fentanyl: C-II scheduled, very potent, used for moderate to severe pain and as an adjunct to general anesthesia. Various routes, including transdermal. Respiratory depression may last longer than analgesic effects and is more concerning.
• Meperidine: C-II, synthetic opioid, used for moderate to severe pain, has risk of fatal reaction in patients receiving MAO inhibitors.

Fentanyl Overdoses

• Illicit fentanyl is a major driver of synthetic opioid deaths in recent years. Its potency is 50-100x greater than morphine. The amount of fentanyl in the US has increased drastically in recent years.

Partial Opioid Agonists

• Substances that bind to receptors and cause effects similar to pure agonists, but less pronounced.
• Includes buprenorphine, butorphanol, dezocine, nalbuphine, and pentazocine

Naloxone (Narcan)

• Pure opioid antagonist, no agonist properties.
• Drug of choice for complete or partial reversal of opioid-induced respiratory depression.
• Indicated for suspected acute opioid overdose and the diagnosis of opioid overdose.
• Can precipitate opioid withdrawal in physically dependent patients.

Opioid Antagonists (Continued)

• Side effects: Tremors, sweating, hypertension, tachycardia, excitement, nausea, vomiting, reversal of analgesia, dysrhythmias, and elevated PTT and bleeding.
• Nursing interventions: Continuous monitoring of vital signs and bleeding.

Combination Drugs

• Various opioid analgesics combined with other pain medications, such as NSAIDs and acetaminophen. Examples include hydrocodone and ibuprofen (Vicoprofen), hydrocodone and acetaminophen (Lortab, Vicodin), oxycodone and acetaminophen (Percocet), oxycodone and aspirin (Percodan), and acetaminophen and codeine (Tylenol #__) .

Transdermal Opioid Analgesics

• Provide continuous, around-the-clock pain control, particularly helpful for patients with chronic pain.
• Fentanyl (Duragesic): More potent than morphine; use caution with patients who weigh less than 110 pounds.

Analgesics in Special Populations

• Analgesic use varies among children, older adults, cognitively-impaired individuals, oncology patients, and individuals with a history of substance abuse.

Adjuvant Therapies

• Adjuvant therapy is often used along with non-opioid and opioid drugs.
• Includes anticonvulsants, antidepressants, corticosteroids, antidysrhythmics, and local anesthetics.