Module 3 Study Guide: Part 1.docx

**[Local Anesthetics]** **MOA of local anesthetics:** Local anesthetics work by blocking sodium channels in the neuronal cell membrane, preventing the initiation and conduction of nerve impulses. The anesthetic must diffuse from its site of administration to the sites of action within the axon. **...

**[Local Anesthetics]** **MOA of local anesthetics:** Local anesthetics work by blocking sodium channels in the neuronal cell membrane, preventing the initiation and conduction of nerve impulses. The anesthetic must diffuse from its site of administration to the sites of action within the axon. **Properties determining the ability to penetrate axon membrane:** 1. Lipid solubility 2. Molecular size 3. Degree of ionization at tissue pH(pKa) - **Lidocaine** - Effects are extended when given with epinephrine (see below). - Can be used for cardiac dysrhythmias suppresses cardiac excitability secondary to blocking Na **Reason for using vasoconstrictors with local anesthetics:** Vasoconstrictors reduce local blood flow, which prolongs the duration of anesthesia and reduces systemic absorption and toxicity. **Blood dyscrasia from benzocaine:** Methemoglobinemia **Application guidelines for topical anesthetics to prevent systemic reactions:** - Use the smallest effective amount - Apply to the smallest surface area - Avoid application to broken or irritated skin - Avoid strenuous exercise - Avoid heating the site accelerate absorption - Do not use under occlusive dressings unless prescribed **[Opioids] NOT THAT MANY QUESTIONS ON TEST (addictive, respiratory depression)** **Three main classes of opioid receptors:** 1. Mu (μ) receptors: response to activation analgesia, respiratory dep, euphoria, sedation, and physical dependence. Opioids primarily act on this one! 2. Kappa (κ) receptors: response to activation analgesia, sedation. May underlie psychomimetic effects. 3. Delta (δ) receptors do not interact with opioids **Three classifications of drugs acting as opioid receptors:** 1. Pure opioid agonists (e.g., morphine, fentanyl): activate Mu and Kappa receptors. 2. Opioid agonist-antagonists (e.g., pentazocine, nalbuphine, butorphanol, buprenorphine): when administered alone produce analgesia. If administered w/ pure opioid agonist, they can antagonize the analgesia caused by the pure agonist. 3. Pure opioid antagonists (e.g., naloxone, naltrexone): reverse respiratory and cns depression caused by opioid agonist. They work at the Mu and Kappa receptors. **Opioid medications and details:** **Active ingredient** **Indications** **Brand** ------------------------------- -------------------------------------------------- -------------------------------------------------- **Morphine** Severe acute pain Avinza ext-release capsand Morphine sulfate tabs **Hydromorphone** Break through pain or around the clock dosing Dilaudid tabs **Oxycodone** Mod to severe persistent pain OiyIR caps and Oxycontin controlled -rel tabs **Oxymorphone HCL** Mod to severe acute and persistent pain Opana immediate rel tabs and opana ext-rel tabs **Fentanyl** Persistent pain Druagesic transdermal system **Hydrocodone/acetaminophen** Acute, recurrent, and episodic breakthrough pain Lortab and Vicodin tabs **Hydrocodone/ibuprofen** Short term acute pain Vicoprofen tabs **Oxycodone/acetaminphen** Moderate to severe pain Percocet tabs **Oxycodone/salicylate** Moerate to severe pain Percocet tabs **Morphine: Pro-agonist** - **Therapeutic uses:** Severe pain relief by mimicking action of being endogenous opioid peptides, primarily at Mu receptors - **Side effects:** euphoria, drowsiness, mental clouding anxiety reduction, RESPIRATORY DEPRESSION, constipation, cough suppression, biliary colic, tolerance, physical dependence and histamine relief, emesis, miosis - **Black Box Warning:** Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome - **Tolerance:** Reduced response to the drug over time - **Cross-tolerance:** Tolerance to other opioids when tolerant to one opioid - **Dependence:** Physical adaptation to the drug, causing withdrawal symptoms upon cessation - **Medications for opioid-induced constipation (OIC):** Methylnaltrexone, naloxegol, lubiprostone - **Reversal drug:** Naloxone - **Drug to discourage abuse:** Naltrexone **Moderate to strong opioid agonists:** - Codeine (Class II alone, III with acetaminophen, V as cough suppressant) - 10% converts to morphine in the liver. 30 mg produces same effect as 325mg of acetaminophen. - Oxycodone - High abuse potential crush and snort, inject. OP formulation prevents this. Can come in immediate release or controlled release, which is OxyContin. O - Hydrocodone - Used for pain and cough. Usually combined with aspirin, acetaminophen, or ibuprophen - Tapentadol - Less constipation **Opioid agonist-antagonists:** Can induce withdrawal in patients physically dependent on a pure opioid. - Pentazocine - Mild to mod pain. Much less effective than morphine. - PO: pentazocine naloxone 50mg/0.5mg one tablet Q3-4 hrs. can increase to two tablets for daily max of 12 tablets or 600 mg - Nalbuphine - Butorphanol - Buprenorphine (prolongs QT) **Dosing guidelines:** - **Physical dependence:** Adaptation causing withdrawal symptoms upon cessation - **Abuse:** Misuse of medication for non-medical purposes - **Addiction:** Chronic, relapsing disorder characterized by compulsive drug seeking **Patients at risk screening tools:** Various screening tools like ORT (Opioid Risk Tool) and SOAPP (Screener and Opioid Assessment for Patients with Pain) **Prescription Drug Monitoring Program (PDMP):** A state-run program that tracks prescriptions for controlled substances to prevent misuse. **Risk Evaluation and Mitigation Strategies (REMS):** FDA program to manage known or potential serious risks associated with drugs. **Opioid antagonists:** - **Naloxone:** Onset of SubQ injection/IM: 2-5 minutes, T1/2 life: 2hrs. Elimination is by hepatic metabolism. Cannot be used orally due to rapid first pass inactivation - **Naltrexone:** Used for alcohol and opioid abuse. Prevents euphoria if the abuser takes an opioid. Candidates for Tx must be rendered opioid-free before starting. Does not prevent cravings. - **Methylnaltrexone, lubiprostone, naloxegol:** Used for OIC. Blocks Mu receptors in the GI tract - **Alvimopan:** Used to accelerate GI recovery post-surgery. Peripherally acting Mu opioid antagonist. Does not reduced opioid mediated analgesia **[Nonopioid Centrally Acting Analgesics]** **Tramadol:** - **Suicide risk:** Increased in patients with depression or suicidal tendencies - **Seizure risk:** Increased risk, especially with a history of seizures or taking medications that lower the seizure threshold **Clonidine:** Used for hypertension and severe cancer pain (off-label) **Ziconotide:** Used for severe chronic pain via intrathecal route **Dexmedetomidine:** Used for sedation of patients on mechanical ventilation **[Cyclooxygenase Inhibitors (Anti-Inflammatories)]** - **Differentiate Cox 1 and Cox 2 drugs:** - **Cox-1 inhibitors** (e.g., aspirin, ibuprofen, naproxen) affect protective gastric mucosa, platelet aggregation, supports renal function - **Benefits:** protection against MI and stroke - **Cons:** GI ulcer, bleeding, and renal impairment - **Cox-2 inhibitors** (e.g., celecoxib) produced at sites of tissue injury: target inflammatory pathways, less GI side effects but increased cardiovascular risk. - **Benefits:** suppression of inflammation, alleviation of pain, protection against colorectal cancer - **Cons:** GI ulceration, bleeding, renal impairment, increased risk for MI/stroke **NSAIDs and Acetaminophen:** **-First-generation NSAIDs: inhibit COX 1&2** - **Indications:** Tx inflammatory disorders: RA, OA, bursitis. Mild-mod pain, suppress fever, and relieve dysmenorrhea (menstrual cramps) - **Examples:** Aspirin, Ibuprofen, Naproxen **Safety alert:** Increased risk of GI bleeding/ulceration, renal impairment with all first-generation NSAIDs **-Second-generation NSAIDs: ONLY inhibits COX2** - **Indications:** suppress inflammation causing GI fewer adverse effects BUT less safe than first gen because of increased risk for MI/STROKE! - **Examples:** Celecoxib - **Drug interactions:** increased anticoagulant effect (warfarin), decrease diuretic effect (furosemide), decrease antihypertensive effect (ACE inhibitors), increase lithium levels, celecoxib levels may increase with fluconazole. - **Celecoxib:** - Cardiovascular risk: HTN, edema, increased risk of MI/Stroke no COX1 inhibition! - A/E: MI/Stroke, sulfonamide allergy - Cannot be used during pregnancy. **-ASA: non-selective inhibitor** - **Uses**: analgesic, anti-pyretic, and anti-inflammatory, suppression of plt aggregation, protection in thrombotic disorders, cancer prevention, and prevention of Alzheimer's. Decreases risk for colorectal cancer at low dosage. - **Drug interactions:** Increased bleeding risk with anticoagulants, corticosteroids, and alcohol - **Side effects:** GI bleeding, renal impairment, Reye's syndrome in children - **GI effects caused by:** - Increased secretion of acid and pepsin - Decreased production of cytoprotective mucus and bicarb - Decreased mucosal blood flow - Direct irritant action of asn on gastric mucosa - Increased RF: advanced age, hx of PUD, prev intolerance to asn or other nsaids, cigarette smoking, and alcohol abuse. **Acetaminophen: WITHOUT anti-inflammatory properties** Not associated with Reye syndrome so can be given to children - **MOA**: inhibits prostaglandin synthesis in CNS - **A/E:** SJS, exanthematous pustulosis, toxic epidermal necolysis, and hepatotoxicity with overdose - **Drug interactions:** alcohol, warfarin, vaccines - **Vaccines:** Can reduce immune response to some vaccines - **Treatment for overdose:** N-acetylcysteine (NAC) - **\*\*\*** careful with patients taking hydrocodone too much acetaminophen. No more than 3g/24 hrs due to liver toxicity **[Commonly Used NSAIDs]** +-----------------------+-----------------------+-----------------------+ | **Drug (generic and | **Dosage/How | **Comments** | | trade name)** | Supplied** | | +=======================+=======================+=======================+ | **Celecoxib/Celebrex* | Adult: 200 mg po | -Cox 2 selective | | * | daily or 100 mg po | | | | BID | -Avoid if allergic to | | | | sulfa | | | Caps: 50 mg, 100 mg, | | | | and 200 mg | -Reduce dosage by 50 | | | | % with hepatic | | | | impairment | | | | | | | | See pregnancy | | | | recommendations | +-----------------------+-----------------------+-----------------------+ | **Dicolfenac/Voltaren | Total daily dose of | -See pregnancy | | ** | 100-150 mg PO in 2-3 | recommendations | | | divided doses | | | | | Causes contractions | | | Tabs: 25 mg, 50 mg, | in late pregnancy | | | 75 mg | | +-----------------------+-----------------------+-----------------------+ | **Diclofenac | Gel: Apply 4 g QID; | See pregnancy | | gel/Voltaren | Max: 16/g/joint/day | recommendations | | gel/Pennsaid** | up to 32 g/day total | | | | | -Avoid if history of | | | Solution: Apply 2 | asthma or ASA allergy | | | sprays 2% solution | | | | per knee BID or apply | \- Creatnine at | | | 40 gtt 1.5% solution | baseline | | | per knee QID | | | | | CBC and chemistries | | | Gel: 1% | if long term use | | | | | | | Solution: 1.5%, 2% | -Do not use prior or | | | | after CABG | +-----------------------+-----------------------+-----------------------+ Top of Form **[Glucocorticoids]** **MOA:** inhibit synthesis of chemical mediators **Therapeutic uses:** - Anti-inflammatory and immunosuppressive effects for conditions like asthma, OA/RA, lupus, tendonitis, synovitis, gouty arthritis, and disorders of the eye. **Metabolic effects:** - Hyperglycemia, increased fat deposition, muscle wasting, thinning of skin, growth retardation in children, cataracts/glaucoma Cushing's syndrome **Adverse effects:** - Osteoporosis, adrenal suppression, increased infection risk, GI ulceration, mood changes - **Drug interactions:** Interact with NSAIDs, antidiabetic drugs, vaccines - **Contraindicated:** pts with systemic/fungal infections, live virus vaccines, caution use with peds, pregnant/breastfeeding **Tapering:** - Gradual reduction in dose to prevent adrenal insufficiency. Tapered over 7 days. - Bottom of Form - Switch from multiple doses to single doses - Taper dosage by 50% of physiologic values - Monitor for signs of insufficiency