Drugs Affecting Neurological System

Pain

• Definition: an unpleasant, uncomfortable sensation that usually indicates tissue damage.

• Most common symptom prompting one to seek health care.

• Ineffective pain management may greatly impair quality of life and ability to perform activities of daily living.

Etiology of Pain

• Causes of pain

  • nerve damage

  • actual tissue injury

  • cancer

  • surgery

• Classified according to duration, origin in body structure (Box 49.1) or cause

• Cause of tissue damage may be

  • Physical- heat, cold, pressure, stretch, spasm, ischemia

  • Chemical- substances released into extracellular fluid around nerve fibers (release of inflammatory substances)

Physiology of Pain

• Tissue damage activates nociceptors, which transmit signals to brain by two types of nerve cells.

• a-delta fibers (myelinated) sharp pain

• c fibers (unmyelinated) dull pain

• Dorsal horn of spinal cord is a relay station for information from fibers

• Thalamus is relay station in brain → pain perceived

Endogenous Analgesia

• CNS has own system for relieving pain.

  • Suppresses pain signal from peripheral nerves.

  • Opioid (morphine-like) peptides interact with opioid receptors to inhibit perception and transmission of pain signals.

    • Endorphins, enkephalins, dynorphins

Pain Clinical Manifestations

• Pain is subjective

  • Self-reporting is gold standard of assessment measurement

• Affected by:

  • Mood, sleep disturbances, fatigue, medications

  • Culture, gender, age, other psychosocial factors

• Measurement tools include

  • Visual analog scales

  • Verbal or numerical rating scales

  • Picture scales

  • SOCRATES

Opioid analgesics

• Moderate to severe pain

  • Inhibit adenylate cyclase

    • Reduce the perception of pain sensations in the brain

    • Decrease emotional upset

• Inhibit production of pain and inflammation

• Tolerance develops

Nonopioid analgesics

• Acute and chronic pain

• Neuropathic or bone pain

Drug Selection

• Wide choice of medications to use in pain management.

• Several factors should influence medication choice.

  • Type of pain

• Combinations of medications may be more effective in pain management.

• GOAL: Use the least potent pain medication that is effective.

General Characteristics: Opioid Analgesics

• Relieve moderate to severe pain by inhibiting pain signal transmission from periphery to brain

• Well-absorbed via PO, IM, sub-Q, IV administration

• Metabolized in the liver, metabolites excreted in urine

• Liver or renal impairment can interfere with excretion

• Exert widespread pharmacologic effects, especially in CNS and GI

  • CNS effects: analgesia, CNS depression, respiratory depression

  • GI effects: slow motility, constipation, bowel and biliary spasm

Opioid BBW

• Present with all opioid analgesics because of potentially fatal adverse effects and risk of drug abuse

• Analgesics with warnings include

  • Fentanyl, hydromorphone, methadone, oxycodone, and oxymorphone

• Highest potential for abuse (opioid crisis)

• Highest risk of fatal overdoses because of respiratory depression

Opioids (morphine)- Schedule II drug Pharmacodynamics/Action

• Bind to opioid receptors including mu, kappa and delta (closing the gate)

  • Brain

  • Spinal cord

  • Peripheral tissues

• activate the endogenous analgesia system

Opioids (morphine)- Schedule II drug Uses/Indications

• Primary use: prevent or relieve acute or chronic pain

• Used in specific conditions: Biliary or renal colic, Burns, other traumatic injuries, Postoperative states, Cancer

Opioids (morphine)- Schedule II drug contraindications

• Existing respiratory depression

• Chronic lung disease

• Liver or kidney disease

• Prostatic hypertrophy

• Increased intracranial pressure, Sz disorders

• Hypersensitivity to opioids

• Pregnancy

Opioids (morphine)- Schedule II drug adverse rxn

• CNS depression

• Respiratory depression

• Nausea, vomiting, Constipation

• Pupil constriction

Other Opioid Analgesics

• Codeine

• Fentanyl

• Duragesic

• Hydrocodone

• Hydromorphone

• Meperidine

• Methadone

• Oxycodone, oxymorphone, tramadol

Opioid Dosing Guidelines

• Small to moderate doses relieve constant, dull pain.

• Moderate to large doses relieve intermittent, sharp pain.

  • Trauma, visceral pain

• Opioid doses should be reduced for patients already receiving CNS depressants.

  • Antianxiety, antidepressant, antihistamine, antipsychotic medications

• Dosages often differ according to the route of administration.

• Dosages change when opioids are changed.

• May be given routinely or PRN.

Opioid Use in Special Populations

• Opioid-tolerant patients

  • Larger-than-usual doses are required to treat pain.

  • Signs/symptoms of withdrawal occur if adequate dosage is not maintained.

• Older adults

  • Cautious use because of potential for respiratory depression, excessive sedation, confusion, etc.

Fentanyl

• potent opioid agonist and Schedule II–controlled substance that is widely used for preanesthetic medication, postoperative analgesia, and chronic pain that requires an opioid analgesic. Because of the high risk of respiratory depression, the drug is contraindicated in the use of acute pain.

• Routes of administration include IV and IM injection, transdermal application, sublingual tablets and spray, lozenges, and nasal spray.

• These formulations are not interchangeable on a microgram-per-microgram basis, and current dosages must be exchanged appropriately using a conversion table.

Hydrocodone (Hysingla)

• schedule II drug, like codeine in its analgesic and antitussive effects.

• Available only in oral combination products for cough and with acetaminophen or ibuprofen for pain. Its half-life is about 4 hours, and its duration of action is 4 to 6 hours.

Hydromorphone (Dilaudid)

• schedule II, semisynthetic derivative of morphine that has the same actions, uses, contraindications, and adverse effects as morphine.

• more potent on a milligram-to-milligram basis and more effective orally than morphine. Effects occur in 15 to 30 minutes, peak in 30 to 90 minutes, and last 4 to 5 hours.

Meperidine (Demerol)

• a synthetic drug like morphine in action and adverse effects. After injection, analgesia occurs in 10 to 20 minutes, peaks in 1 hour, and lasts 2 to 4 hours.

• Prescribers order it infrequently for therapeutic purposes, mainly because it produces a neurotoxic metabolite (normeperidine).

• Normeperidine accumulates with chronic use, large doses, or renal failure and produces CNS stimulation characterized by agitation, hallucinations, and seizures

Methadone (Dolophine)

• a synthetic drug like morphine but with a longer duration of action. It is usually given orally, and onset and peak of action occur in 30 to 60 minutes. Effects last 4 to 6 hours initially and longer with repeated use.

• Prescribers order it for severe pain and in the detoxification and maintenance treatment of opiate addicts.

• the FDA issued an alert about serious adverse effects (e.g., death, overdose, and serious cardiac dysrhythmias) reported in patients taking it.

Oxycodone (OxyContin, Xtampza ER)

• a derivative of codeine used to relieve moderate pain; its pharmacologic actions are like those of other opioid analgesics.

• is a Schedule II drug of abuse. With oral administration, action starts in 15 to 30 minutes, peaks in 60 minutes, and lasts 4 to 6 hours.

• is a popular drug of abuse and is associated with many deaths and much criminal activity. Most deaths have resulted from inappropriate use through diversion either (1) by chewing, crushing, and snorting through the nose or (2) crushing and injecting the drug. Chewing or crushing destroys the long-acting feature and constitutes an overdose.

Tramadol (Ultram, ConZip)

is an oral, synthetic, Schedule IV opioid that acts at the central opioid receptors for moderate to severe pain. It is effective and well tolerated in older adults and in people with acute or chronic pain, back pain, fibromyalgia, osteoarthritis, and neuropathic pain.

Opioid Agonist/Antagonists (Butorphanol)- Schedule IV Pharmacodynamics/Action

• Agonist of kappa opiate receptors and a partial agonist of mu opiate receptors (same pain receptors in the CNS as morphine and other opiates)

  • Interfere with pain transmission and/or pain sensation

Opioid Agonist/Antagonists (Butorphanol)- Schedule IV Uses/Indications

• Moderate to severe pain not adequately managed with alternative treatments

• Preoperative medication and a supplement to multimodal anesthesia

• Pain management during labor with a fetus greater than 37 weeks of gestation and in no signs of respiratory distress

Opioid Agonist/Antagonists (Butorphanol)- Schedule IV contraindications

• Use with caution in patients with asthma- histamine release

• Patients with respiratory depression

Opioid Agonist/Antagonists (Butorphanol)- Schedule IV Adverse Effects

• Headache, dizziness, drowsiness, vertigo, constipation, nausea and/or vomiting, dizziness, hallucinations, and euphoria

• Effects with the nasal spray include nasal congestion, cough, dyspnea, and rhinitis.

• Ceiling effect on respiratory depressant action

Opioid Antagonist (Naloxone) Pharmacodynamics/Action

Competes with opioids for receptor sites in the brain; prevents binding with receptors or displaces opioids already occupying receptor sites.

Opioid Antagonist (Naloxone) Uses/Indications

• Primary use to relieve opioid-induced CNS and respiratory depression

• ANTIDOTE for opioid overdoses

Opioid Antagonist (Naloxone) Contraindications

• Known hypersensitivity to the drug, presence of methadone use, and pregnancy.

• The drug may precipitate withdrawal, producing tachycardia, hypertension, and violent behavior.

Opioid Antagonist (Naloxone) Adverse Effects

tremors, drowsiness, sweating, decreased respirations, hypertension, and nausea and vomiting

Opioid Antagonists Naloxone therapeutic effects occur

• Therapeutic effects occur rapidly:

  • IV: about 2 minutes

  • IM: 2 to 5 minutes

  • Subcutaneous: 2 to 5 minutes

  • Intranasal administration: 8 to 13 minutes

• Must be readily available in all health care settings in which opioids are given

Pain Management Assessment

• Location

• Intensity or severity

• In relation to time, activities, and other signs and symptoms

• Use a consistent method for assessing pain

• Assess on a regular schedule

• Prevent when possible

• Manage pain to provide relief and prevent recurrence

Local Anesthesia

• Used to produce loss of sensation and motor activity

• Prevent cells from responding to pain impulses and sensory stimulation

Local anesthetic systemic toxicity (LAST)

• Severe and life threatening

• May progress to seizure activity and then lead to symptoms of CNS depression, including coma, respiratory arrest, and cardiovascular depression

Local Anesthesia Methods of Administration

• Topical- ointment

• Field block- tooth extraction

• Nerve block- group of nerves

• Neuraxial block

  • Epidural

  • Spinal

  • Caudal

• Peripheral nerve block- single nerve or group

Topical Anesthesia

• Application of a local anesthetic to skin and mucous membranes

• Used to relieve pain and itching of dermatoses, sunburn, minor skin wounds, hemorrhoids, sore throat, and other conditions

Epidural Anesthesia

• Injection of the anesthetic into the epidural space

• Used most often in obstetrics during labor and delivery

• Used for patients with postoperative or other pain

Spinal Anesthesia

• Injection of the anesthetic agent into the cerebrospinal fluid, usually in the lumbar spine

• Useful for surgery involving the lower abdomen and legs

Amides (Lidocaine) Pharmacodynamics/Action

• Decrease permeability of nerve cell membrane to ions (sodium)

• Stop the nerve from depolarizing

• Stop nerve cells from conducting

Amides (Lidocaine) Uses/Indications

• Relieve pain from postherpetic neuralgia

• in preparation for painful procedure including: IV, CVC, Spinal, Epidural or minor surgery procedure

Amides (Lidocaine) Contraindications

• Known hypersensitivity

• Severe trauma, sepsis, blood dyscrasias (disorders or abnormalities affecting the blood cells ex: anemia), and cardiac abnormalities (heart block)

• Use with caution in Infants are of particular risk for systemic absorption

• Anbesol

Amides (Lidocaine) Adverse Effects

• Redness, hives, rash

• Bronchospasm

• Local anesthetic systemic toxicity (LAST)

  • Severe and life threatening

  • May progress to seizure activity and then lead to symptoms of CNS depression, including coma, respiratory arrest, and cardiovascular depression

Other Amide Drugs (same class as lidocaine)

• Bupivacaine

• Dibucaine

• Mepivacaine

General Anesthesia

• is a medication-induced reversible unconsciousness with loss of protective reflexes.

• Balanced anesthesia works collectively to produce a superior outcomes:

  • Amnesia or memory loss (limited duration)

  • Analgesia or a reduction or absence of pain

  • Hypnosis or unconsciousness

  • Muscle relaxation or immobility

General Anesthesia administration

• a complex task that requires the expertise of certified registered nurse anesthetist (CRNA), anesthesiologist (physician), or both.

• The nurse must recognize adverse consequences and intervene to avoid detrimental outcomes.

General Anesthesia administration phases

• Induction is rendering the patient unconscious by using inhalation anesthetics, IV anesthetics, or both.

• Maintenance is administering a continuous level of inhalation and/or intravenous anesthetics until the procedure is complete.

• Emergence is when the procedure ends, the general anesthetic medications are stopped, and the patient is permitted to wake up.

Inhaled Anesthetics (Isoflurane) Pharmacodynamics/Action

• Produces amnesia, skeletal muscle relaxation and hypnosis

• Blocks perception of pain

Inhaled Anesthetics (Isoflurane) Uses/Indications

General anesthesia for surgical procedures

Inhaled Anesthetics (Isoflurane) contraindications

• Avoidance of inhalation anesthetics may be necessary.

• it may substitute with a technique called total intravenous anesthesia (TIVA)

Inhaled Anesthetics (Isoflurane) Adverse Effects

• Cardiovascular (hypotension) and respiratory depression

• Airway irritation

• Spasms in susceptible patients

• Nausea and Vomiting

• Rare possibility of immune-mediated hepatotoxicity

• Shivering

Isoflurane Administration

• Requires use of an anesthesia machine.

• a mixture of agents is delivered through a plastic breathing circuit that connects to a mask, endotracheal tube, or a supraglottic airway device.

Other Drugs in the Class Inhaled Anesthetics

• Suprane

• Ultane

• Enflurane

• Sevoflurane

Intravenous Anesthetics (Propofol) Pharmacodynamics/Action

• Amplifies inhibitory neurotransmitter GABA

• Modulates excitatory NMDA receptors, glycine receptors, and the endocannabinoid system

  • NMDA receptors: These receptors play a crucial role in synaptic plasticity, learning, and memory. Modulating them can affect cognitive functions and neuronal communication.

  • Glycine receptors: Glycine is an inhibitory neurotransmitter in the central nervous system. Its receptors regulate neuronal excitability. Modulating these receptors can impact processes like motor control and sensory perception.

  • Endocannabinoid system: This system regulates various physiological processes, including mood, memory, appetite, and pain sensation. Modulating it can have effects on pain perception, mood regulation, and appetite control.

• Produces amnesia, euphoria, and hypnosis

• Blocks the perception of pain

Intravenous Anesthetics (Propofol) Uses/Indications

• Most widely used intravenous anesthetic

• Used extensively for ambulatory surgery and diagnostic procedures

• Induction and maintenance of general anesthesia

• Monitored Anesthesia Care (MAC)

• sedate patients on mechanical ventilation

Intravenous Anesthetics (Propofol) Contraindications

• Use with caution in patients with disorders of lipid metabolism or pancreatitis

• Patients allergic to eggs or soy

• Patients with history of reactive airway disease or an allergy to sulfites (preservative)

Intravenous Anesthetics (Propofol) Adverse Effects

Pain, burning or stinging at IV site

Propofol Administration

• by an anesthesia provider

• by a nurse who is skilled in the care of critically ill patients and educated in advanced life support to include airway management

• Injected manually or attached to an electronic pump

• Aseptic technique

Intravenous Anesthetics Other Drugs

• Etomidate

  • Amplifies GABA but Maintains hemodynamics, not for use in adrenal insufficiency

• Ketamine

  • Dissociative hypnotic, noncompetitive NMDA receptor antagonist, sympathomimetic, multiple administration routes, Black Box- emergence delirium

• Fospropofol

• Brevital- ultra short acting barbituate

• Pentothal

Neuromuscular Blocking Agents

• Depolarizing and non-depolarizing

• Binds to nicotinic receptors

• Neuromuscular blocking agent

• Temporarily suspends nerve impulse at the neuromuscular junction

• Can be titrated to produce weakness through complete paralysis

• Use in special populations

Non-depolarizing Neuromuscular Blockade (Vecuronium) Pharmacodynamics/Action

• Competitively binds to nicotinic acetylcholine receptors

• Temporarily prevents transmission of nerve impulses

Non-depolarizing Neuromuscular Blockade (Vecuronium) Uses/Indications

• No movement during surgery

• For intubation

• Some Post-surgical patients

Non-depolarizing Neuromuscular Blockade (Vecuronium) Contraindications

Known hypersensitivity or allergy

Non-depolarizing Neuromuscular Blockade (Vecuronium) Adverse Effects

allergic reactions during anesthesia such as anaphylaxis or mild dermatologic conditions such as urticaria or erythema

Assessing for Therapeutic Effects of Neuromuscular Blockade

• Train of Four (TOF) - a medical test used to assess the level of muscle relaxation in patients under anesthesia

• Neuromuscular Blocking Agents (NMBAs) have no anesthetic or analgesic properties, medication-induced hypnosis and amnesia must be provided to ensure patient comfort.

Adjuvant Medications - surgery

• Administered during preoperative, intraoperative, and postoperative phase in support of balanced anesthesia

• Benzodiazepines (CH 54)

  • Midazolam (prototype)

• Opioid analgesics

  • Fentanyl (prototype)

• Alpha-2 Adrenergic Agonist

  • Dexmedetomidine (prototype)

Types of Headaches

• cluster

• tension

• migraines

• menstrual migraine

Cluster headaches

• Recurrent, severe headaches

• Associated with histamine reactions

Tension headaches

• Most common- intermittent, mild

• Contraction of scalp muscles

Migraines

Severe, disabling, unilateral, subjective aura

Menstrual migraine

drop in estrogen 2-3 before cycle

Treatment of cluster headaches

subcutaneous sumatriptan and oxygen.

Acute therapy for tension headaches

• Nonpharmacological methods such as rest, relaxation, or stress reduction strategies.

• Pharmacological treatment of tension headaches includes acetaminophen, aspirin, and NSAIDS.

Drug Therapy of Migraine

• Therapy guided by several factors:

  • Severity of the attacks

  • Presence of associated symptoms, such as nausea and vomiting

  • Type of treatment setting (outpatient or inpatient)

  • Patient-specific factors

• Abortive therapy

  • Treatment of existing migraine headaches

• Preventive therapy

  • Treatment to prevent development of migraine

NSAIDS (Naproxen Sodium) Pharmacodynamics/Action

nonselective inhibitor of cyclooxygenase resulting in the inhibition of prostaglandin synthesis of COX-1 and COX-2.

NSAIDS (Naproxen Sodium) Uses/Indications

reduce the pain resulting from an acute migraine

NSAIDS (Naproxen Sodium) contraindications

• known allergy to aspirin or other nonsteroidal anti-inflammatory drugs

• pregnancy and lactation

• Use with caution in patients with asthma, cardiovascular dysfunction, hypertension, GI bleeding, and peptic ulcer

NSAIDS (Naproxen Sodium) Adverse Effects

• bronchospasm and anaphylaxis

• Gastrointestinal (GI) adverse effects include GI bleeding, nausea, dyspepsia (discomfort or pain in the upper abdomen, often occurring after eating), and GI pain

• Black box warning stating that it may put patients at increased risk for cardiovascular events and GI bleeding

Acetaminophen, Aspirin, and Caffeine (Excedrin)

• Used to reduce pain related to migraine or tension headaches

• Each component has adverse effects and contraindications

• Patient teaching regarding each medication

Ergot Alkaloids (Ergotamine tartrate) Pharmacodynamics/Action

• Alpha-adrenergic antagonist

• Produces stimulation of the cranial and peripheral vascular smooth muscles while depressing the effects of the central vasomotor centers

  • stimulates the muscles in blood vessels in both the head and body, causing them to contract. At the same time, it reduces the activity of the central vasomotor centers in the brain, which regulate blood vessel dilation and constriction. This combination of effects can lead to changes in blood pressure and blood flow throughout the body.

Ergot Alkaloids (Ergotamine tartrate) Uses/Indications

• Abortive Therapy for migraine headaches

• May use individually or in combination with caffeine

Ergot Alkaloids (Ergotamine tartrate) Contraindications

• known hypersensitivity reaction to the drug or its components

• existence of peripheral vascular disease, hepatic and renal disease, coronary artery disease, hypertension, and sepsis

Ergot Alkaloids (Ergotamine tartrate) Adverse Effects

• absence of pulse, bradycardia, cardiac valvular fibrosis (thickening and scarring of heart valves), cyanosis, edema, heart rhythm changes, gangrene (body tissue dies due to a lack of blood supply), hypertension, ischemia, precordial distress (discomfort or pain in the chest area around precordium overlying the heart), chest pain, tachycardia, and vasospasm (sudden constriction of blood vessels, leading to reduced blood flow to tissues).

• muscle pain, numbness, paresthesia, and weakness.

• vertigo, nausea, vomiting, itching, pulmonary fibrosis, and genitourinary retroperitoneal fibrosis (abnormal growth of fibrous tissue in the retroperitoneal space, which is the area behind the abdominal cavity.)

Triptans (Sumatriptan) Pharmacodynamics/Action

Binds to the serotonin receptors 5-HT1D, producing vascular constriction of the cranial blood vessels

Triptans (Sumatriptan) Uses/Indications

• relieves the pain of a migraine headache

• relieves the nausea, vomiting, photophobia, and phonophobia that accompany the migraine headache

Triptans (Sumatriptan) Contraindications

• history of hypersensitivity reactions to the drug.

• existing cerebrovascular or peripheral vascular syndromes

Triptans (Sumatriptan) Adverse Effects

• dizziness, vertigo, headache, anxiety, malaise, myalgia, and fatigue.

• alterations in blood pressure and chest pain as well as the most severe cardiovascular adverse effect, shock

Triptan Administration

• at the onset of migraine symptoms

• With the administration of all preparations, it is necessary to monitor the blood pressure for hypertension.

• Patient teaching – important to administer at the start of symptoms

• Black box warnings – increased risk of adverse thrombotic events, including MI and stroke

Estrogen (Estradiol) Pharmacodynamics/Action

• minimizes the premenstrual decline in estrogen that precipitates the development of the migraine headache.

• increases the estrogen levels in the late luteal phase of the menstrual cycle that contribute to the development of menstrual migraine headaches

Estrogen (Estradiol) Uses/Indications

Migraine headaches associated with menstrual cycle

Estrogen (Estradiol) Contraindications

• incomplete bone growth

• neoplasms, breast cancer, thromboembolic disorders, fibroids, endometriosis, thyroid disease, and pregnancy

Estrogen (Estradiol) Adverse Effects

• thromboembolic disorders

• Menstrual irregularities

Preventive Therapy for Migraine Headaches

• Carboxylic acid derivative

  • Valproic acid

• Gamma-aminobutyric acid

  • Gabapentin

• Sulfamate-substituted monosaccharide

  • Topiramate

• Beta-adrenergic blocking agents

  • Propranolol

• Calcium channel blockers

  • Verapamil

• Angiotensin-converting enzyme inhibitors

  • Enalapril maleate; lisinopril

• Angiotensin II receptor blockers

  • Candesartan; olmesartan

• Tricyclic antidepressants

  • Imipramine; amitriptyline

• Herbal supplements

  • Feverfew; butterbur

• Vitamins

  • Magnesium; riboflavin

Adjuvant Medications - Migraine

• Antiemetics

  • to control symptoms of nausea and vomiting related to migraine, tension-type, and cluster headaches

  • Chlorpromazine hydrochloride

  • Metoclopramide

  • Prochlorperazine

• Opioid analgesics

  • Controversial – so NO