Anxiety Disorders Management

Here are the study notes:

Sedative-Hypnotic Drugs and Anxiety

• Sedative-hypnotic drugs, including benzodiazepines (e.g., Ativan, Xanax, Valium, Klonopin) and "z-drugs" (e.g., Ambien, Lunesta), are widely prescribed for insomnia and anxiety.
• Long-term use of these drugs by older people has caused concern among researchers due to potential risks.

Risks Associated with Sedative-Hypnotic Drugs

• Higher rates of falls and fractures
• Increased auto accidents
• Cognitive problems
• Increased emergency room visits and hospital admissions

American Geriatrics Society's Choosing Wisely List

• Sedative-hypnotic drugs are included in the list of treatments that doctors and patients should question.

Study on Benzodiazepine Use and Alzheimer's Disease

• Researchers from France and Canada conducted a study on the link between benzodiazepine use and Alzheimer's disease.
• The study reviewed medical records of almost 1,800 older people diagnosed with Alzheimer's and compared them with nearly 7,200 control subjects.
• Results:
  • Benzodiazepine users had a 51% increase in the odds of a subsequent Alzheimer's diagnosis.
  • The association strengthened with greater exposure to the drugs (i.e., longer duration of use).
  • Short-term use (≤ 90 days) did not increase the risk of Alzheimer's disease.

Conclusion

• Long-term use of benzodiazepines is linked to a higher risk of Alzheimer's disease, particularly with prolonged exposure.### Benzodiazepines and Alzheimer's Disease
• Taking benzodiazepines for a longer period increases the risk of developing Alzheimer's disease
  • 32% increased risk for patients who took daily doses for 91-180 days
  • 84% increased risk for patients who took daily doses for more than 180 days
• The association between benzodiazepines and Alzheimer's disease persists despite controlling for health and demographic factors
• The link is stronger for longer-acting forms of benzodiazepines, such as Valium, compared to formulations that leave the body more quickly, such as Ativan and Xanax

Opioids and Pain Relief

• Analgesics are drugs that relieve pain without causing loss of consciousness
• Opioids are the most effective pain relievers available
• Endogenous opioid peptides, such as enkephalins, endorphins, and dynorphins, are naturally produced by the body
• Opioid receptors, including mu, kappa, and delta receptors, are responsible for the effects of opioids

Morphine

• Morphine is a strong opioid agonist that activates mu and kappa receptors
• It is used to relieve pain, particularly in cancer patients, and has a range of effects, including:
  • Analgesia
  • Drowsiness
  • Mental clouding
  • Anxiety reduction
  • Sense of well-being
  • Respiratory depression
  • Constipation
  • Urinary retention
  • Orthostatic hypotension
  • Emesis
  • Miosis
  • Cough suppression
  • Biliary colic
• Tolerance to morphine can develop, leading to the need for higher doses
• Physical dependence on morphine can occur, leading to withdrawal symptoms when the drug is discontinued

Other Opioid Agonists

• Fentanyl is a strong opioid agonist that is 100 times more potent than morphine
• It is available in various formulations, including patches, lozenges, and buccal tablets
• Other strong opioid agonists include alfentanil, sufentanil, remifentanil, meperidine, and methadone
• Each of these drugs has its own unique characteristics, benefits, and risks

Important Considerations

• Opioid agonists should be used with caution and under close medical supervision
• They can be habit-forming and may lead to physical dependence and addiction
• Patients should be monitored for signs of respiratory depression, and dosage should be adjusted accordingly
• Opioid agonists should not be used in combination with other CNS depressants, as this can increase the risk of respiratory depression and death### Moderate to Strong Opioid Agonists
• Similar to morphine in most respects
• Produce analgesia, sedation, and euphoria
• Can cause:
  • Respiratory depression
  • Constipation
  • Urinary retention
  • Cough suppression
  • Miosis
• Can be reversed with naloxone
• Different from morphine:
  • Produce less analgesia and respiratory depression
  • Somewhat lower potential for abuse

Codeine

• Actions and uses:
  • 10% converts to morphine in liver
  • Pain and cough suppression
• Preparations, dosage, and administration:
  • Usually oral (formulated alone or with aspirin or acetaminophen)
  • 30 mg produces same effect as 325 mg of acetaminophen

Oxycodone

• Analgesic actions equivalent to those of codeine
• Long-acting analgesics:
  • Immediate-release
  • Controlled-release (OxyContin)
  • Abuse: Crushes and snorts or injects medication
  • 2010 OP formulation much harder to crush and does not dissolve into an injectable solution to decrease risk of abuse

Hydrocodone

• Most widely prescribed drug in the United States
• Combined with aspirin, acetaminophen, or ibuprofen

Tapentadol

• Analgesic effects equivalent to oxycodone
• Causes less constipation than traditional medications

Agonist-Antagonist Opioids

• Pentazocine
• Nalbuphine
• Butorphanol
• Buprenorphine
  • 7-day patch: Butrans
  • Sublingual film: Suboxone

Clinical Use of Opioids

• Pain assessment:
  • Essential component of management
  • Based on patient's description
  • Evaluate:
    • Pain location, characteristics, and duration
    • Things that improve or worsen pain
    • Status before taking drug and 1 hour after
• Dosing guidelines:
  • Assessment of pain
    • Pain status should be evaluated before opioid administration and about 1 hour after
  • Dosage determination
    • Opioid analgesics must be adjusted to accommodate individual variation
  • Dosing schedule
    • As a rule, opioids should be administered on a fixed schedule
  • Avoiding withdrawal
• Physical dependence:
  • State in which an abstinence syndrome will occur if the dependence-producing drug is abruptly withdrawn
  • NOT equated with addiction
• Abuse:
  • Drug use that is inconsistent with medical or social norms
• Addiction:
  • Behavior pattern characterized by continued use of a psychoactive substance despite physical, psychologic, or social harm

REMS

• Risk Evaluation and Mitigation Strategy (REMS)
• Developed by the U.S. Food and Drug Administration
• Designed to reduce opioid-related injuries and deaths

Opioid Antagonists

• Principal uses:
  • Treatment of opioid overdose and relief of opioid-induced constipation
  • Reversal of postoperative opioid effects
  • Reversal of neonatal respiratory depression
  • Management of opioid addiction

Pure Opioid Antagonists

• Naloxone (Narcan)
• Methylnaltrexone (Relistor)
• Alvimopan (Entereg)
• Naltrexone (ReVia, Vivitrol)

Naloxone

• Mechanism of action:
  • Competitive antagonist
• Pharmacologic effects:
  • Reversal of opioid effects
• Pharmacokinetics:
  • Distributed through the body
  • Eliminated through metabolism
• Therapeutic uses:
  • Reversal of opioid overdose
  • Reversal of postoperative opioid effects
  • Reversal of neonatal respiratory depression

Nonopioid Centrally Acting Analgesics

• Relieve pain by mechanisms largely or completely unrelated to opioid receptors
• Do not cause respiratory depression, physical dependence, or abuse
• Not regulated under the Controlled Substances Act

Tramadol

• Mechanism of action:
  • Combination of opioid and nonopioid mechanisms
• Therapeutic use:
  • Pain relief
• Adverse effects and interactions:
  • CNS depression
  • Seizure risk
• Drug interactions:
  • CNS depressants
• Abuse liability:
  • Suicide risk
• Preparations, dosage, and administration:
  • Immediate-release and extended-release

Clonidine

• Treatment of hypertension and relief of severe pain
• Mechanism of pain relief:
  • Alpha2-adrenergic agonist
• Analgesic use:
  • Used in combination with opioid analgesics
• Adverse effects:
  • Cardiovascular: Severe hypotension, rebound hypertension, and bradycardia
• Contraindications:
  • Pregnancy and lactation

Ziconotide

• Mechanism of action:
  • Selective antagonist at N-type voltage-sensitive calcium channels on neurons
  • Blocks calcium channels on primary nociceptive afferent neurons in dorsal horn of the spinal cord
• Pharmacokinetics:
  • Distributed through cerebrospinal fluid and then transported to systemic circulation
• Adverse effects:
  • CNS and muscle injury
• Drug interactions:
  • Formal studies not done
• Preparations, dosage, and administration:
  • Intrathecal administration

Dexmedetomidine

• Selective alpha2-adrenergic agonist
• Acts in the CNS to cause sedation and analgesia
• Uses:
  • Short-term sedation in critically ill patients who are initially intubated and undergoing mechanical ventilation
  • Sedation for nonintubated patients before or during surgical and other procedures
• Adverse effects:
  • Hypotension
  • Bradycardia
• Drug interactions:
  • No specific interactions
• Preparations, dosage, and administration:
  • IV administration

Pain Management in Patients with Cancer

• Barriers to treating cancer pain:
  • Patient concerns
  • Healthcare system
  • Healthcare professionals
  • Patients
• Pathophysiology of pain:
  • Neurophysiologic basis of painful sensations
  • Nociceptive pain versus neuropathic pain
• Assessment and ongoing evaluation:
  • Comprehensive initial assessment
  • Ongoing evaluation
  • Barriers to assessment
• Drug therapy:
  • Nonopioid analgesics
  • Opioid analgesics
  • Adjuvant analgesics
• Principles of drug therapy for cancer pain:
  • Comprehensive pretreatment assessment
  • Individualize the treatment plan
  • Use the World Health Organization analgesic ladder and the National Comprehensive Cancer Network guidelines
  • Avoid intramuscular injections
  • Provide a fixed schedule of around-the-clock treatment
  • Evaluate the patient frequently for pain relief and drug side effects