Clin Pharm Exam 5

Activation of descending serotonergic inhibitory pathways in the CNS; inhibition of the hypothalamic heat-regulating system

What is the MOA of acetaminophen?

Mild to moderate pain, fever, and adjunct with opioids for moderate-to-severe pain

What are the clinical uses of acetaminophen?

Hepatotoxicity, skin erythema/blistering/rash, hearing loss

What are the major side effects of acetaminophen?

Alcohol

What is the major drug interaction with acetaminophen?

Limit total daily dose from all formulations; use cautiously in hepatic impairment because glutathione depletion can cause fatal liver necrosis

What are the major warnings for acetaminophen?

Preferred analgesic for migraine during pregnancy/lactation; available PO, IV, and PR

What are important notes about acetaminophen?

Irreversible inhibition of COX-1 and COX-2 with inhibition of platelet aggregation via thromboxane A2 blockade

What is the MOA of aspirin?

Headache, migraine, musculoskeletal pain, osteoarthritis, rheumatoid arthritis, MI/TIA/DVT prevention, Kawasaki disease

What are the clinical uses of aspirin?

GI bleeding, nausea/vomiting/diarrhea, anemia, thrombocytopenia, tinnitus, gout exacerbation

What are the major side effects of aspirin?

Anticoagulants, NSAIDs, methotrexate, diuretics, ACE inhibitors

What are the major drug interactions with aspirin?

Avoid in children <12 years (Reye syndrome); contraindicated in the third trimester of pregnancy and active GI ulcer disease

What are the major warnings for aspirin?

Tinnitus and metabolic acidosis are classic signs of aspirin overdose

What are important notes about aspirin?

Reversible inhibition of COX-1 and COX-2 decreasing prostaglandin synthesis

What is the MOA of ibuprofen?

Inflammation, fever, and pain

What are the clinical uses of ibuprofen?

Edema, hypertension, decreased hemoglobin, GI irritation

What are the major side effects of ibuprofen?

ACE inhibitors, ARBs, loop diuretics (Triple Whammy), lithium, aspirin

What are the major drug interactions with ibuprofen?

Black box warning for GI bleeding/ulcer and increased CV thrombotic events; avoid in CHF and pregnancy

What are the major warnings for ibuprofen?

Mu-opioid receptor agonist

What is the MOA of morphine?

Acute pain, cancer pain, standard comparison for opioid potency (MME)

What are the clinical uses of morphine?

Constipation, sedation, respiratory depression, pruritus, myoclonus

What are the major side effects of morphine?

Benzodiazepines, naloxone, olopatadine

What are the major drug interactions with morphine?

Contraindicated in head trauma; monitor closely for fatal respiratory depression, especially in opioid-naive and elderly patients

What are the major warnings for morphine?

Tolerance develops to all effects except constipation; Schedule II

What are important notes about morphine?

Potent mu-opioid receptor agonist

What is the MOA of hydromorphone?

Severe pain

What are the clinical uses of hydromorphone?

Constipation, sedation, respiratory depression

What are the major side effects of hydromorphone?

Benzodiazepines and other CNS depressants

What are the major drug interactions with hydromorphone?

High potency increases accidental overdose risk; contraindicated in head trauma

What are the major warnings for hydromorphone?

Approximately 4 times more potent than oral morphine; Schedule II

What are important notes about hydromorphone?

Mu-opioid receptor agonist

What is the MOA of meperidine?

Limited use for acute pain; not recommended for cancer pain

What are the clinical uses of meperidine?

Seizures, tremors, agitation, myoclonus

What are the major side effects of meperidine?

MAO inhibitors (serotonin syndrome risk)

What are the major drug interactions with meperidine?

Avoid in CKD/renal failure due to accumulation of toxic normeperidine metabolite

What are the major warnings for meperidine?

Higher adverse effect risk than morphine; Schedule II

What are important notes about meperidine?

Mu-opioid receptor agonist

What is the MOA of oxycodone?

Moderate to severe acute or chronic pain

What are the clinical uses of oxycodone?

Constipation, sedation, pruritus, dizziness

What are the major side effects of oxycodone?

Benzodiazepines and CYP3A4 inhibitors/inducers

What are the major drug interactions with oxycodone?

Contraindicated in respiratory depression, ileus, or GI obstruction

What are the major warnings for oxycodone?

Often combined with acetaminophen (Percocet); does not lower seizure threshold; Schedule II

What are important notes about oxycodone?

Binds CNS opioid receptors and inhibits ascending pain pathways

What is the MOA of fentanyl?

IV for acute pain; transdermal patch for chronic stable severe pain

What are the clinical uses of fentanyl?

Respiratory depression and severe constipation

What are the major side effects of fentanyl?

CYP3A4 inhibitors, diuretics, naltrexone

What are the major drug interactions with fentanyl?

Avoid patches in opioid-naive patients, asthma, acute pain, or postoperative pain

What are the major warnings for fentanyl?

50-100 times more potent than morphine; drug of choice for chronic pain in renal/liver failure; Schedule II

What are important notes about fentanyl?

Weak mu-opioid receptor agonist with inhibition of norepinephrine and serotonin reuptake

What is the MOA of tramadol?

Moderate to severe pain; may benefit neuropathic pain

What are the clinical uses of tramadol?

Nausea, dizziness, constipation, euphoria, seizures

What are the major side effects of tramadol?

SSRIs, TCAs, and MAO inhibitors (serotonin syndrome risk)

What are the major drug interactions with tramadol?

Contraindicated in children <12 years and after tonsillectomy/adenoidectomy in patients <18 years; use cautiously in seizure disorders

What are the major warnings for tramadol?

Schedule IV; lower abuse potential than Schedule II opioids

What are important notes about tramadol?

Mu-opioid receptor agonist plus NMDA receptor antagonism

What is the MOA of methadone?

Chronic pain and opioid use disorder

What are the clinical uses of methadone?

QT prolongation, respiratory depression, constipation

What are the major side effects of methadone?

CYP3A4 inhibitors/inducers and other QT-prolonging drugs

What are the major drug interactions with methadone?

Requires ECG monitoring due to torsades risk; difficult dose titration because of long half-life

What are the major warnings for methadone?

Long half-life with variable duration; inexpensive option for opioid use disorder; Schedule II

What are important notes about methadone?

Inhibit serotonin and norepinephrine reuptake

What is the MOA of SNRIs?

Depression, anxiety, neuropathic pain, fibromyalgia

What are the clinical uses of SNRIs?

Nausea, hypertension, insomnia, sweating, sexual dysfunction

What are the major side effects of SNRIs?

MAO inhibitors and other serotonergic drugs

What are the major drug interactions with SNRIs?

Monitor for serotonin syndrome and increased suicidal ideation

What are the major warnings for SNRIs?

Duloxetine is FDA-approved for diabetic neuropathy

What are important notes about SNRIs?

Selectively inhibit serotonin reuptake

What is the MOA of SSRIs?

Depression, anxiety disorders, OCD, PTSD

What are the clinical uses of SSRIs?

GI upset, sexual dysfunction, insomnia, serotonin syndrome

What are the major side effects of SSRIs?

MAO inhibitors, tramadol, linezolid, and other serotonergic drugs

What are the major drug interactions with SSRIs?

Black box warning for suicidal ideation in young patients; avoid with MAO inhibitors

What are the major warnings for SSRIs?

First-line treatment for many anxiety and depressive disorders

What are important notes about SSRIs?

Inhibit serotonin and norepinephrine reuptake while also blocking muscarinic, histamine, and alpha-1 receptors

What is the MOA of TCAs?

Depression, neuropathic pain, migraine prevention

What are the clinical uses of TCAs?

Anticholinergic effects, sedation, orthostatic hypotension, QT prolongation

What are the major side effects of TCAs?

MAO inhibitors and other QT-prolonging drugs

What are the major drug interactions with TCAs?

Avoid in patients with long QT syndrome and use caution in overdose due to cardiotoxicity

What are the major warnings for TCAs?

First-line option for neuropathic pain but often limited by adverse effects

What are important notes about TCAs

Chemical mediators activate and sensitize nociceptors, increasing neuronal excitability

What is the primary role of chemical mediators in pain?

Substance P, prostaglandins, bradykinin, histamine, glutamate, and aspartate

Which chemical mediators increase pain transmission?

Serotonin, endorphins, and enkephalins

Which endogenous mediators decrease pain transmission and produce analgesia?

Sharp, localized pain with identifiable tissue injury plus tachycardia, diaphoresis, increased BP, and increased respiratory rate

What are the classic features of acute pain?

Pain persisting beyond the normal healing time of the original injury

How is chronic pain defined?

No structural or nerve damage; neuroplastic changes causing peripheral and central sensitization

What characterizes chronic primary pain?

Underlying disease with a verifiable source of pain

What characterizes chronic secondary pain?

Improve pain perception and improve functional status

What are the two primary goals of pain management?

Sleep hygiene, cognitive behavioral therapy, exercise, and environmental modifications

What nonpharmacologic therapies should be incorporated into pain management?

Nonopioid therapies are preferred first-line for subacute and chronic pain

What is the CDC recommendation for initial treatment of subacute and chronic pain?

Immediate-release opioids at the lowest effective dose

According to CDC guidelines, how should opioids be initiated?

Greater than 50 MME/day offers little additional pain benefit for most non-cancer pain while increasing overdose risk

What is the clinical significance of exceeding 50 MME/day?

Avoid abrupt discontinuation; taper slowly (about 10% per month or slower for long-term therapy)

What is the recommended approach to opioid tapering?

Concurrent benzodiazepine use

What medication combination should be avoided with opioids because of increased overdose risk?

Offer naloxone and evaluate overdose risk

What harm-reduction strategy should be considered for patients receiving opioid therapy?

Less than 300 mg/day = antiplatelet; 300-2400 mg/day = analgesic/antipyretic; greater than 2400 mg/day = anti-inflammatory

How do aspirin's clinical effects change with increasing dose?

Prophylactic stimulant laxative or polyethylene glycol (PEG/Miralax)

What should routinely be prescribed with chronic opioid therapy to prevent constipation?

Increasing dietary fiber alone (e.g., psyllium)

What commonly worsens opioid-induced constipation by adding bulk without improving transit time?

Reduce the calculated equianalgesic dose to 50-75% (25-50% reduction) because of incomplete cross-tolerance

What dosing principle should be followed when rotating from one opioid to another?

Methadone and transdermal fentanyl

Which opioid conversions require extra caution because of overdose risk and complex conversion principles?

Pain persisting beyond the normal time to treat the original condition or injury.

What is the defining time duration for pain to be classified as 'Chronic'?