Pharmacology Exam Review

**Module 1: Pharmacokinetics (PK), Pharmacodynamics (PD), and Pharmacogenomics (PG)** **1. Define Pharmacokinetics (PK), Pharmacodynamics (PD), and Pharmacogenomics (PG).** - **Pharmacokinetics (PK):** The study of what the body does to a drug, including Absorption, Distribution, Metabolism,...

**Module 1: Pharmacokinetics (PK), Pharmacodynamics (PD), and Pharmacogenomics (PG)** **1. Define Pharmacokinetics (PK), Pharmacodynamics (PD), and Pharmacogenomics (PG).** - **Pharmacokinetics (PK):** The study of what the body does to a drug, including Absorption, Distribution, Metabolism, and Excretion (ADME)​. - **Pharmacodynamics (PD):** The study of what a drug does to the body, including mechanisms of action and dose-response relationships. - **Pharmacogenomics (PG):** The study of how genetic variations affect drug response and metabolism​. **2. Identify factors responsible for interpatient variability in drug response.** - Genetic differences in enzyme activity (e.g., CYP450 variations). - Age-related changes in metabolism and elimination. - Presence of diseases (e.g., liver or kidney disease). - Drug-drug interactions affecting metabolism or excretion. - Food intake affecting drug absorption​. **3. Interpret key PK and PD parameters.** - **Bioavailability:** The proportion of the drug reaching systemic circulation. - **Half-life (t½):** The time it takes for plasma drug concentration to reduce by half. - **Volume of Distribution (Vd):** The extent of drug distribution in the body. - **Clearance (CL):** The rate at which a drug is eliminated from circulation. - **Therapeutic Index (TI):** The margin between effective and toxic doses​. **4. Select appropriate candidates for therapeutic drug monitoring (TDM).** - Patients on drugs with a narrow therapeutic index (e.g., digoxin, lithium). - Patients with altered metabolism (e.g., liver/kidney impairment). - Patients experiencing toxicity or poor response to therapy​. **5. Describe current and possible future roles of PG in clinical practice.** - **Current:** Identifying genetic polymorphisms affecting drug metabolism (e.g., CYP2D6 variations for antidepressants and opioids). - **Future:** Personalized drug regimens to optimize treatment and minimize adverse effects​. **6. Apply knowledge of PK, PD, and PG principles to individual patient scenarios, including the use of TDM.** - Adjust drug doses based on a patient's metabolism (e.g., slow CYP2D6 metabolizers need lower opioid doses). - Monitor plasma drug levels in high-risk drugs like phenytoin. - Use genetic testing to determine optimal anticoagulant therapy​. **Key Medications Affecting PK and PD** **CYP450 System and Drug Metabolism** 1. **Warfarin** - **PD:** Inhibits vitamin K-dependent clotting factors (II, VII, IX, X). - **PK:** Metabolized by **CYP2C9**, **CYP1A2**, and **CYP3A4**. - **Adverse Effects:** Bleeding, bruising, warfarin skin necrosis. - **Considerations:** CYP2C9 polymorphisms affect dosing. 2. **Phenytoin (Dilantin®)** - **PD:** Prolongs inactivation of sodium (Na+) channels, stabilizing neurons. - **PK:** **Highly protein-bound**, nonlinear kinetics. Metabolized by **CYP2C9**, **CYP2C19**. - **Adverse Effects:** Gingival hyperplasia, hepatotoxicity, ataxia, nystagmus, teratogenicity. - **Monitoring:** Therapeutic range **10-20 mcg/mL** (total), **1-2 mcg/mL** (free). 3. **Carbamazepine (Tegretol®)** - **PD:** Blocks Na+ channels, reducing neuron excitability. - **PK:** **Auto-induces CYP3A4**, decreasing its own levels over time. - **Adverse Effects:** **Aplastic anemia**, hepatotoxicity, rash (esp. Steve Johnson Syndrome in **HLA-B\*1502** allele). - **Monitoring:** Therapeutic range **4-12 mcg/mL**. 4. **Omeprazole (Prilosec®)** - **PD:** Proton pump inhibitor (PPI), reduces gastric acid secretion. - **PK:** Metabolized by **CYP2C19**, affects clopidogrel activation. - **Adverse Effects:** Osteoporosis, hypomagnesemia, increased risk of C. difficile infection. Avoid with **clopidogrel** due to interaction. **Module 2: Pain Management** #### **1. Explain the Differences Between Nociceptive and Neuropathic Pain** - **Nociceptive Pain:** - **Caused by tissue damage**, detected by nociceptors. - **Subtypes:** - **Somatic:** Localized pain from muscles, bones, or joints (e.g., arthritis, laceration). - **Visceral:** Internal organ pain, often cramping or squeezing (e.g., appendicitis, kidney stones). - **Treatment:** NSAIDs, acetaminophen, opioids​. - **Neuropathic Pain:** - **Caused by nerve damage** or dysfunction (e.g., diabetic neuropathy, postherpetic neuralgia). - **Characterized by:** - **Hyperalgesia:** Increased pain response. - **Allodynia:** Pain from normally non-painful stimuli. - **Treatment:** Anticonvulsants (gabapentin, pregabalin), antidepressants (amitriptyline, duloxetine), topical agents (lidocaine, capsaicin)​. #### **2. Compare and Contrast Classes of Analgesic Medications** - **Non-Opioid Analgesics:** - **Acetaminophen:** Reduces pain and fever but **lacks anti-inflammatory effects**; **risk of hepatotoxicity**. - **NSAIDs:** Inhibit COX enzymes to reduce inflammation (e.g., ibuprofen, naproxen); **risk of GI bleeding and renal impairment**​. - **Opioids:** - **Used for severe pain**, bind to opioid receptors to inhibit pain perception. - **Examples:** Morphine, oxycodone, fentanyl, hydromorphone. - **Risks:** Respiratory depression, addiction, tolerance​. - **Adjuvant Analgesics:** - **Primarily for neuropathic pain or multimodal pain management.** - **Examples:** Gabapentin (anticonvulsant), duloxetine (SNRI), lidocaine patches (local anesthetic)​. #### **3. Select an Appropriate Candidate for Migraine Prophylaxis and Create an Analgesic Regimen** - **Migraine Prophylaxis Indications:** - Frequent migraines (\>5 per month). - Contraindications to acute therapies or risk of medication overuse. - **Regimen:** - **Prophylaxis:** - **First-line:** Beta-blockers (propranolol), CGRP antagonists (erenumab), anticonvulsants (topiramate). - **Acute Migraine Relief:** - **Triptans (sumatriptan, rizatriptan):** 5-HT1 agonists that **cause vasoconstriction**. - **NSAIDs + triptans for severe pain**. - **Avoid opioids** (ineffective, risk of dependence)​. #### **4. Identify the Role of Non-Opioid Analgesics in the Management of Pain** - **First-line for mild to moderate pain** (preferred over opioids). - **Used alone or as adjuncts** to reduce opioid use. - **Lower risk of dependence, overdose, and respiratory depression**. - **Examples:** - **Acetaminophen for osteoarthritis**. - **NSAIDs for inflammatory pain** (e.g., arthritis, musculoskeletal pain)​. #### **5. Review the Various Opioid Classes and Specific Opioid Medications** - **Opioid Structural Classes:** - **Phenanthrenes:** Morphine, codeine, oxycodone, hydromorphone. - **Phenylpiperidines:** Fentanyl, meperidine. - **Phenylheptanes:** Methadone​. - **Functional Classes:** - **Full agonists:** Morphine, oxycodone, fentanyl. - **Partial agonists:** Buprenorphine. - **Antagonists:** Naloxone, naltrexone (opioid reversal agents). #### **6. Calculate an Equianalgesic Dose of an Opioid Regimen When Converting to Another Regimen** - **Conversion Example:** Morphine 90 mg/day to oxycodone - **Morphine to oxycodone ratio:** 30 mg morphine = 20 mg oxycodone. - **Total oxycodone dose:** (90 mg morphine ÷ 30 mg) × 20 mg = **60 mg oxycodone/day**. - **Adjust for cross-tolerance (\~25% reduction):** 60 mg × 0.75 = **45 mg/day oxycodone**. - **Dosing recommendation:** Oxycodone ER 20 mg BID + Oxycodone IR 5 mg Q6H PRN​. ### **Key Takeaways for Exam** - Nociceptive pain is treated with NSAIDs/opioids, while neuropathic pain requires adjuvants (gabapentin, antidepressants). - Acetaminophen is safer but lacks anti-inflammatory effects; NSAIDs reduce inflammation but risk GI/renal toxicity. - Opioids are reserved for severe pain, with high risks of addiction and respiratory depression. - Triptans and CGRP antagonists are first-line for migraines, while opioids are avoided. - Equianalgesic opioid conversion accounts for cross-tolerance to prevent overdose. **Non-Opioid Analgesics** **1. Acetaminophen (Tylenol®)** - **PD:** Inhibits prostaglandin synthesis in CNS, analgesic and antipyretic; weak COX-1 & COX-2 inhibitor. NO ANTI-INFLAMMATORY. - **PK:** **Hepatic metabolism** via glucuronidation/sulfation; toxic dose leads to **NAPQI accumulation**. - **Adverse Effects:** Hepatotoxicity (especially with alcohol use), rash, anaphylaxis. - **Max Dose:** 4g/day (adults), 2g/day (cirrhosis). **2. NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)** **Ibuprofen (Advil®, Motrin®), Naproxen (Aleve®), Celecoxib (Celebrex®)** - **PD:** Inhibit **COX-1** and **COX-2**, reducing prostaglandin synthesis (anti-inflammatory, analgesic, antipyretic). - **PK:** **Renal elimination**, half-life varies (ibuprofen: **2-4h**, naproxen: **12-17h**). - **Adverse Effects:** GI ulcers/bleeding, renal impairment, cardiovascular risk (esp. with COX-2 inhibitors). **Opioid Analgesics** **1. Morphine** - **PD:** μ-opioid receptor agonist, inhibits pain transmission. - **PK:** **Hepatic metabolism** (via glucuronidation); renally cleared **active metabolites** (**morphine-6-glucuronide**). - **Adverse Effects:** Respiratory depression, constipation, hypotension, pruritus. - **Conversion:** 10 mg IV = 30 mg PO. **2. Oxycodone (OxyContin®, Percocet®)** - **PD:** μ-opioid receptor agonist. - **PK:** Metabolized by **CYP3A4** and **CYP2D6**. - **Adverse Effects:** Similar to morphine; higher risk of **CYP interactions**. High addiction risk. - **Note:** Often combined with **acetaminophen.** **3. Fentanyl (Duragesic®, Actiq®)** - **PD:** Highly **potent μ-opioid receptor agonist**. - **PK:** **Hepatic metabolism (CYP3A4), rapid onset (\~1 min IV), lipophilic**. - **Adverse Effects:** **Chest wall rigidity** (high-dose IV), profound respiratory depression. - **Notes:** 100 mcg IV = 10 mg morphine IV. **Module 3: Controlled Substances & Prescribing Regulations** #### **1. Review State and Federal Regulations Pertaining to the Prescribing of Controlled Substances** - **Controlled substances are classified into Schedules I--V based on abuse potential and medical use**. - **Schedule I:** No accepted medical use, high abuse potential (e.g., heroin, LSD, ecstasy, marijuana at the federal level). - **Schedule II:** High abuse potential but accepted medical use (e.g., oxycodone, fentanyl, methadone, hydrocodone, morphine, cocaine). - **Schedule III--V:** Lower abuse potential (e.g., ketamine, benzodiazepines, cough syrups with codeine). - **Prescribing laws:** - **Schedule II:** No refills, requires a new prescription each time. - **Schedule III--V:** Can have up to five refills within six months​. - **DEA Requirements:** - Prescribers must have a **DEA registration number**. - Schedule II prescriptions must be **hand-signed and dated the day they are written**. - State laws may impose stricter regulations than federal laws​. #### **2. Identify the Necessary Components of a Controlled Substance Prescription** A valid prescription must include: - **Patient information:** Full name and address. - **Prescriber information:** Name, address, DEA number. - **Medication details:** Drug name, strength, dosage form, quantity, directions for use. - **Refills:** Allowed only for Schedule III--V (maximum five refills in six months). - **Signature:** Must be **manually signed by the prescriber**. - **Additional requirements for Schedule II:** **No refills allowed, written prescriptions only (except in emergencies)**​. #### **3. Describe Your State's Prescription Monitoring Program (PMP)** - **PMPS are state-run electronic databases tracking controlled substance prescriptions**. - **Purpose:** Detect misuse, doctor shopping, and potential diversion of controlled substances. - **Mandatory Checking:** Some states require prescribers to check the PMP before issuing prescriptions for opioids or other high-risk drugs​. #### **4. Discuss Ethical and Legal Standards of Prescribing Controlled Substances** - **Prescriptions must be for a legitimate medical purpose and within the prescriber's scope of practice**. - Example: Dentists should not prescribe ADHD medications. - **Prescribers and pharmacists share responsibility** in ensuring prescriptions are valid. - **Pre-signing prescription blanks is prohibited**. - **Best practices include:** - Using **tamper-resistant prescription pads**. - Writing out the quantity in both **numerical and word form** (e.g., "30 (thirty)"). - Reporting **suspicious prescription activity to the DEA**​. #### **5. Discuss Substances of Abuse and the Appropriate Treatment** - **Opioids:** High risk of dependence and overdose. Treatment includes: - **Medication-Assisted Treatment (MAT):** - **Methadone (Schedule II):** Requires DEA registration for addiction treatment. - **Buprenorphine (Schedule III):** Requires DEA waiver to prescribe for opioid use disorder. - **Naltrexone:** Opioid antagonist, blocks opioid effects. - **Naloxone (Narcan®):** Opioid reversal agent, available IV, IM, or intranasally​. - **Alcohol:** - **Treatment options:** - **Naltrexone:** Reduces cravings. - **Acamprosate:** Helps maintain abstinence. - **Disulfiram:** Causes aversive reaction to alcohol. - **Withdrawal requires benzodiazepines** (e.g., diazepam, lorazepam)​. - **Benzodiazepines:** Used for anxiety and insomnia but **can be addictive**. - **Tapering required to avoid withdrawal symptoms** (e.g., seizures, agitation, insomnia). - **Nicotine:** - **Treatment options:** - **Nicotine replacement therapy (patches, gum, lozenges).** - **Varenicline (Chantix®):** Blocks nicotine receptors. - **Bupropion (Zyban®):** Aids smoking cessation by increasing dopamine and norepinephrine​. ### **Key Takeaways for Exam** - Schedule II drugs require written prescriptions, no refills, and strict monitoring**.** - A valid controlled substance prescription must include patient info, drug details, DEA number, and manual signature**.** - State PMPs are essential tools to track opioid prescribing and prevent abuse**.** - Ethical prescribing ensures medications are used for legitimate medical purposes within a provider's scope of practice**.** - Substance use disorders require individualized treatment, including MAT for opioids and behavioral therapy for all addictions**.** **Benzodiazepines (Schedule IV Controlled Substances)** **1. Alprazolam (Xanax®)** - **PD:** **Enhances GABA-A receptor activity**, leading to CNS depression. - **PK:** **Metabolized by CYP3A4**, **short half-life (\~6-12h)**. - **Adverse Effects:** Sedation, dependence, respiratory depression (esp. with opioids). - **Notes:** Avoid in elderly (fall risk). **2. Diazepam (Valium®)** - **PK:** **Long half-life (\~30-60h), active metabolites prolong effects**. - **PD**: GABAergic inhibition. - **Indications:** Anxiety, muscle spasms, alcohol withdrawal. - **Adverse Effects:** Sedation, confusion, - **Notes:** Used for **alcohol withdrawal**. **Module 4: CNS Agents & Psychotropics** #### **1. Review Commonly Used CNS Agents** - **Antidepressants:** - **SSRIs:** Fluoxetine, Sertraline (**increase serotonin levels, first-line for depression and anxiety**). - **SNRIs:** Venlafaxine, Duloxetine (**increase serotonin & norepinephrine, used for depression and neuropathic pain**). - **Atypical Antidepressants:** Bupropion (**dopamine & norepinephrine effects, used for depression and smoking cessation; avoid in seizure risk**), Mirtazapine (**enhances serotonin & norepinephrine, causes sedation and weight gain**). - **TCAs:** Amitriptyline, Nortriptyline (**older, significant anticholinergic effects, sedating**). - **MAOIs:** Phenelzine, Tranylcypromine (**reserved for treatment-resistant cases, requires dietary restrictions to avoid hypertensive crisis**)​. - **Antipsychotics:** - **Typical (First-Generation, FGAs):** Haloperidol (**dopamine receptor blockade, high risk of extrapyramidal symptoms (EPS)**). - **Atypical (Second-Generation, SGAs):** Quetiapine, Aripiprazole (**dopamine & serotonin receptor blockade, lower EPS risk but higher metabolic side effects**)​. - **Mood Stabilizers:** - **Lithium:** **Gold standard for bipolar disorder, requires serum monitoring due to narrow therapeutic index**. - **Anticonvulsants for mood stabilization:** Valproate, Lamotrigine (**used in bipolar disorder**)​. - **Anxiolytics:** - **Benzodiazepines:** Lorazepam, Diazepam (**enhance GABA, used for acute anxiety, risk of dependence**). - **Buspirone:** **Non-sedating, takes weeks to show effects, used for long-term anxiety management**​. - **Stimulants:** - **Methylphenidate, Amphetamines:** **Increase dopamine and norepinephrine, used for ADHD**​. #### **2. Important Counseling Points for CNS Agents** - **Antidepressants:** - May take **4--6 weeks** for full effect. - Risk of **increased suicidal ideation in young adults (18--24 years)**. - Avoid **abrupt discontinuation** to prevent withdrawal symptoms​. - **Antipsychotics:** - **Adherence is critical** to avoid relapse. - **Monitor for metabolic syndrome** (SGAs: weight gain, dyslipidemia, diabetes risk). - **EPS risk is higher with FGAs** (dystonia, tardive dyskinesia)​. - **Mood Stabilizers:** - **Lithium:** Maintain **consistent hydration and sodium intake**. Watch for **toxicity signs (tremors, confusion, nausea)**. - **Monitor weight, thyroid, and renal function regularly**​. - **Anxiolytics:** - **Benzodiazepines:** Risk of **dependence**, limit use to **short-term**. - **Buspirone:** Takes **weeks for effect**, **not sedating**​. - **Stimulants:** - **Take in the morning** to avoid insomnia. - **Monitor appetite and growth in children**​. #### **3. Developing an Optimal Psychotropic Regimen** - **Patient-Specific Factors:** - **Age:** Lower doses in older adults due to metabolic changes. - **Comorbidities:** Avoid bupropion in seizure history, use caution with lithium in kidney disease. - **Medication History:** Prior response to specific agents is critical​. - **Medication-Specific Factors:** - **Pharmacokinetics:** Half-life, metabolism (e.g., CYP450 interactions). - **Adverse Effects:** Tailor treatment to minimize side effects (e.g., avoiding weight gain in obese patients). - **Cost & Accessibility:** Consider **insurance coverage and affordability**​. #### **4. Drug Interactions, Monitoring, and Contraindications** - **Clinically Significant Drug Interactions:** - **SSRIs + MAOIs:** Risk of **serotonin syndrome** (agitation, tachycardia, fever, clonus). - **Lithium + NSAIDs/Diuretics:** Increased **lithium levels → toxicity risk**. - **Benzodiazepines + CNS Depressants (alcohol, opioids):** **Additive sedation, respiratory depression**​. - **Key Monitoring Parameters:** - **Antidepressants:** Mood changes, weight, QTc interval (citalopram). - **Antipsychotics:** Lipids, glucose, weight (SGAs), EPS monitoring (FGAs). - **Lithium:** Serum levels (therapeutic range: **0.6--1.2 mEq/L**), thyroid, renal function. - **Stimulants:** Blood pressure, heart rate, growth in children​. - **Contraindications:** - **Bupropion:** Seizure or eating disorder history. - **Clozapine:** **Risk of agranulocytosis, requires frequent CBC monitoring**. - **Lithium:** Avoid in **significant renal impairment**​. ### **Key Takeaways for Exam** - **SSRIs are first-line for depression/anxiety** but take **4--6 weeks for full effect**. - **FGAs have higher EPS risk, while SGAs have higher metabolic risk**. - **Lithium requires serum monitoring and hydration balance to prevent toxicity**. - **Avoid benzodiazepines long-term due to dependence risk**; consider **buspirone** for anxiety instead. - **Monitor weight, glucose, and lipids with SGAs to prevent metabolic syndrome**. - **Check lithium, thyroid, and renal function periodically in bipolar treatment**. **Antidepressants** **1. Selective Serotonin Reuptake Inhibitors (SSRIs)** - **Fluoxetine (Prozac®), Sertraline (Zoloft®), Escitalopram (Lexapro®)** - **PD:** Block presynaptic serotonin reuptake (↑ 5-HT). - **PK:** **Hepatic metabolism (CYP2D6, CYP3A4)**, **long half-life (fluoxetine: \~7-9 days)**. - **Adverse Effects:** Sexual dysfunction, GI upset, serotonin syndrome. - **Notes:** 4 to 6 weeks for full effect. **2. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)** - **Duloxetine (Cymbalta®), Venlafaxine (Effexor®)** - **PD:** Increases serotonin & norepinephrine. - **PK:** Venlafaxine increases BP; Duloxetine is hepatotoxic. - **Adverse Effects:** Hypertension (venlafaxine), hepatotoxicity (duloxetine). - **Notes:** Venlafaxine used for neuropathic pain. **Module 5: Anticonvulsants & Seizures** #### **1. Review Common Anticonvulsant Medications** Anticonvulsants are divided into **classic** and **modern** agents. - **Classic Anticonvulsants:** - **Phenytoin, Carbamazepine, Phenobarbital** - Require **therapeutic drug monitoring**. - Strong CYP3A4 inducers, leading to multiple drug interactions. - Highly **protein-bound**, meaning small dose changes can result in large serum fluctuations​. - **Modern Anticonvulsants:** - **Levetiracetam, Lamotrigine, Topiramate** - **Minimal need for drug level monitoring**. - Fewer drug-drug interactions. - Broad-spectrum efficacy across multiple seizure types​. #### **2. Propose an Appropriate Anticonvulsant Regimen in a Given Patient Case** - **Partial Seizures:** - **First-line:** Levetiracetam (500--3000 mg daily, divided). - **Alternative:** Lamotrigine (requires **slow titration** to prevent rash). - **Generalized Tonic-Clonic Seizures:** - **First-line:** Valproic Acid (**monitor LFTs due to hepatotoxicity risk**). - **Alternative:** Lamotrigine or Topiramate​. - **Absence Seizures:** - **Ethosuximide or Valproic Acid** are most effective. - **Avoid Phenytoin and Phenobarbital** as they can worsen absence seizures​. #### **3. Emergency Management of Seizures** A **seizure lasting \>5 minutes** or multiple seizures without recovery is considered **status epilepticus**, requiring **urgent intervention**. - **Step 1:** **Benzodiazepines (first-line for acute seizures)** - **Lorazepam 4 mg IV push** - **Midazolam 10 mg IM** - **Diazepam 10--20 mg PR** - **Step 2:** Longer-acting anticonvulsants to prevent seizure recurrence - **Phenytoin, Fosphenytoin, or Valproic Acid** - **Step 3:** If seizures persist, escalate to - **Phenobarbital, Levetiracetam, Lacosamide, or Propofol/Ketamine infusion**​. **Non-Pharmacologic Emergency Measures:** - **Position patient on their side** to prevent aspiration. - **Remove dangerous objects** from the surroundings. - **DO NOT place objects in the mouth**. - **Call 911 if seizure lasts \>5 minutes**​. #### **4. Treatment Considerations for Epilepsy in Pregnancy** - **Key Risks:** - **25--30% of pregnant patients** experience **increased seizure frequency** due to changing drug metabolism. - Seizures can cause **miscarriage, trauma, fetal hypoxia, and acidosis**​. - **Preferred Medications:** - **Levetiracetam and Lamotrigine** (lower teratogenic risk). - **Avoid Valproic Acid, Phenytoin, and Phenobarbital** due to **high teratogenic risk**. - **Drug Clearance Changes in Pregnancy:** - **Increased clearance:** Phenytoin, Carbamazepine, Lamotrigine. - **Decreased clearance:** Levetiracetam, Oxcarbazepine. - **Monitor drug levels frequently** and adjust doses accordingly​. - **Supplementation:** - **Folic Acid (≥4 mg daily)** 3 months before conception to prevent neural tube defects. - **Vitamin K (before birth)** if taking Phenytoin, Carbamazepine, Phenobarbital (reduces neonatal bleeding risk)​. #### **5. Strategies for Withdrawing Anticonvulsant Medications** - **Consider Withdrawal If:** - **Seizure-free for 2--5 years**. - **No abnormal EEG** and low relapse risk. - **Tapering Recommendations:** - **Gradual dose reduction over several months** to prevent withdrawal seizures. - **Monitor for recurrence**, as **60% of patients relapse after stopping** treatment​. - **Risk of Relapse Higher If:** - **Generalized tonic-clonic or partial seizures** were present. - **Longer disease duration and abnormal EEG** findings exist​. ### **Key Takeaways for Exam** - Anticonvulsants are classified as \"classic\" (e.g., Phenytoin, Carbamazepine) or \"modern\" (e.g., Levetiracetam, Lamotrigine). - Status Epilepticus requires urgent treatment with Benzodiazepines, followed by long-acting anticonvulsants. - Pregnancy considerations: Avoid Valproic Acid, use Levetiracetam/Lamotrigine instead. - Withdrawal of therapy should be gradual, with high relapse risk in certain seizure types. **Common Anticonvulsants** **1. Valproic Acid (Depakote®)** - **PD:** Inhibits GABA degradation, Na+ channel modulation. - **PK:** **Highly protein-bound**, metabolized in liver. - **Adverse Effects:** Hepatotoxicity, pancreatitis, teratogenicity. - **Notes:** Contraindicated in pregnancy. **2. Lamotrigine (Lamictal®)** - **PD:** Inhibits Na+ channels, stabilizing neuronal membranes. - **PK:** Hepatic metabolism, slow titration required, - **Adverse Effects:** **Steven-Johnson syndrome (SJS)** risk---**requires slow titration**. - **Notes:** Must titrate slowly to avoid rash. **Module 6: Asthma, COPD, Allergic Rhinitis** #### **1. Identify Risk Factors for Asthma, COPD, and Allergic Rhinitis** - **Asthma:** - **Environmental:** Allergens (dust mites, pollen, mold, pet dander), air pollution, occupational exposures. - **Genetic:** Family history of asthma or atopy. - **Lifestyle:** Smoking, obesity, sedentary behavior. - **Other:** Respiratory infections, exposure to cold air or exercise​. - **COPD:** - **Smoking:** Leading cause; includes secondhand smoke exposure. - **Environmental:** Air pollution, occupational exposure to dust and chemicals. - **Genetic:** Alpha-1 antitrypsin deficiency. - **Other:** History of childhood respiratory infections​. - **Allergic Rhinitis:** - **Environmental:** Exposure to allergens like pollen, mold, dust mites, and pet dander. - **Genetic:** Family history of atopy (allergic rhinitis, asthma, eczema). - **Seasonal Factors:** Spring and fall when pollen counts are high. - **Other:** Urban living, pollution exposure​. #### **2. Medications Used for Asthma, COPD, and Allergic Rhinitis** - **Asthma:** - **Rescue Medications:** Short-acting beta-2 agonists (SABA) like Albuterol. - **Maintenance Therapy:** - **Inhaled corticosteroids (ICS):** Fluticasone, Budesonide. - **Long-acting beta-2 agonists (LABA):** Salmeterol, Formoterol (**always combined with ICS**). - **Leukotriene receptor antagonists:** Montelukast. - **Biologics:** Omalizumab (for severe asthma with allergic or eosinophilic phenotypes)​. - **COPD:** - **Bronchodilators:** - **Short-acting muscarinic antagonists (SAMA):** Ipratropium. - **Long-acting muscarinic antagonists (LAMA):** Tiotropium, Umeclidinium. - **LABA:** Indacaterol, Salmeterol. - **Anti-inflammatory:** - **ICS:** Fluticasone, Budesonide (**used selectively for frequent exacerbations and high eosinophil counts**). - **Combination Inhalers:** - **LABA + LAMA:** Formoterol/Glycopyrronium. - **LABA + ICS:** Salmeterol/Fluticasone. - **Triple therapy:** LABA + LAMA + ICS (Trelegy®). - **Adjuncts:** Roflumilast (PDE-4 inhibitor), Azithromycin (for former smokers)​. - **Allergic Rhinitis:** - **First-Line Therapy:** Intranasal corticosteroids (Fluticasone, Budesonide). - **Antihistamines:** - **Oral:** Loratadine, Cetirizine (second-generation, less sedating). - **Intranasal:** Azelastine (more effective than oral antihistamines). - **Decongestants:** Oxymetazoline (**limit to 3 days to avoid rebound congestion**). - **Adjuncts:** Montelukast (useful for patients with both allergic rhinitis and asthma)​. #### **3. Pharmacologic Regimens for Asthma, COPD, and Allergic Rhinitis** - **Asthma Regimens:** - **Mild Intermittent:** SABA PRN. - **Mild Persistent:** Low-dose ICS + SABA PRN. - **Moderate Persistent:** Low-dose ICS + LABA, or medium-dose ICS. - **Severe Persistent:** High-dose ICS + LABA ± biologic (e.g., Omalizumab for allergic asthma). - **Considerations:** Monitor adherence, inhaler technique, and adjust therapy based on symptom control​. - **COPD Regimens (GOLD Guidelines):** - **Mild Symptoms (GOLD A):** SABA or SAMA PRN. - **Moderate Symptoms (GOLD B):** LABA or LAMA. - **Frequent Exacerbations (GOLD C):** LAMA. - **Severe Symptoms/Exacerbations (GOLD D):** LABA + LAMA ± ICS or triple therapy. - **Considerations:** Include Roflumilast for FEV1 \< 50% with chronic bronchitis and Azithromycin for former smokers​. - **Allergic Rhinitis Regimens:** - **Mild Symptoms:** Oral antihistamine (e.g., Loratadine). - **Moderate-Severe Symptoms:** Intranasal corticosteroids (e.g., Fluticasone). - **Persistent Congestion:** Add intranasal antihistamine or Montelukast for concurrent asthma. - **Considerations:** Address patient adherence and educate on proper nasal spray technique​. #### **4. Patient Education for Medications** - **Asthma and COPD:** - **Inhaler Use:** - Demonstrate proper technique for MDIs, DPIs, or nebulizers. - Use spacers with MDIs for patients with coordination issues. - **Adherence:** - Reinforce daily ICS use for asthma control. - Avoid overuse of rescue inhalers (SABAs). - **Side Effects:** - Rinse mouth after ICS use to prevent thrush. - Monitor for beta-agonist effects (tachycardia, tremors). - **COPD-Specific Education:** - **Smoking Cessation:** Essential for slowing disease progression. - **Vaccinations:** Annual influenza and pneumococcal vaccines to reduce exacerbations. - **Pulmonary Rehabilitation:** Improves quality of life in moderate to severe COPD​. - **Allergic Rhinitis:** - **Intranasal Corticosteroids:** Correct spray technique to avoid epistaxis. - **Antihistamines:** Second-generation preferred to reduce sedation. - **Decongestants:** Limit oxymetazoline use to avoid rebound congestion​. ### **Key Takeaways for Exam** - **Asthma:** - **ICS is the foundation of therapy**; LABAs **must** be combined with ICS. - **Montelukast has an FDA Boxed Warning for neuropsychiatric effects**. - **Biologics (Omalizumab, Mepolizumab) are reserved for severe eosinophilic or allergic asthma**. - **COPD:** - **GOLD guidelines classify COPD severity and guide therapy selection**. - **LABAs and LAMAs are preferred for maintenance**; ICS is **used selectively** in frequent exacerbators. - **Roflumilast and Azithromycin are adjuncts for specific COPD subtypes**. - **Allergic Rhinitis:** - **Intranasal corticosteroids (Fluticasone, Budesonide) are first-line**. - **Second-generation antihistamines (Cetirizine, Loratadine) are preferred for systemic relief**. - **Montelukast is an option for patients with concurrent asthma**. **Module 6: Asthma & COPD Medications** **1. Short-Acting Beta Agonists (SABAs)** SABAs are **rescue medications** for acute bronchospasm. **a) Albuterol (Ventolin®, ProAir®)** - **PD: β2 agonist**---Relaxes bronchial smooth muscle. - **PK:** Inhaled, rapid onset. Onset: 5 min; Duration: 4-6 hours. - **Adverse Effects:** Tachycardia, tremors, hypokalemia. - **Notes:** First-line rescue inhaler for asthma attacks. **b) Levalbuterol (Xopenex®)** - **PD:** Selective **β2 agonist**, smooth muscle relaxation - **PK:** Inhaled, rapid onset. Onset: 5-10 min; Duration: 5-8 hrs. - **Adverse Effects:** Less tachycardia than albuterol, tremors. - **Notes:** **Preferred in patients with cardiac disease.** **c) Terbutaline (Brethine®)** - **PD: β2 agonist**, bronchodilation. - **PK:** Oral and subcutaneous forms available - **Adverse Effects:** Hypotension, tachycardia, hyperglycemia. - **Notes:** **Rarely used due to systemic effects.** ### **2. Long-Acting Beta-Agonists (LABAs)** LABAs are **bronchodilators** used for **long-term asthma control**, but must be used **with ICS** in asthma to prevent increased mortality risk. **a) Salmeterol (Serevent®)** - **PD: β2 agonist**---Relaxes bronchial smooth muscle. - **PK:** Onset: 15-30 min; Duration: \~12 hours. - **Adverse Effects:** Tachycardia, tremors, headache. - **Notes:** BBW: NEVER use as monotherapy in asthma (↑ mortality risk). **b) Formoterol (Foradil®)** - **PD: β2 agonist**, bronchodilation via cAMP activation - **PK:** Onset: \~5 min, Duration: \~12 hours. - **Adverse Effects:** QT prolongation, palpitations, hypokalemia. - **Notes:** Often combined with ICS (e.g., Symbicort® = budesonide + formoterol). **c) Vilanterol (Breo Ellipta®)** - **PD: Ultra-LABA**, smooth muscle relaxation. - **PK:** Onset: \~5 min, Duration: \~24 hours. - **Adverse Effects:** Increased HR, headache, tremor. - **Notes:** Once-daily dosing; combined with fluticasone. **3. Inhaled Corticosteroids (ICS)** ICS are **first-line therapy** for long-term asthma control due to their **anti-inflammatory** effects. **a) Fluticasone (Flovent®)** - **PD:** Inhibits inflammatory mediators, reduces airway hyperreactivity. - **PK**: **Liver metabolism (CYP3A4);** minimal systemic absorption. - **Adverse Effects:** **Oral candidiasis (thrush),** hoarseness, cough. - **Notes**: **Rinse mouth after use** to prevent thrush. **b) Budesonide (Pulmicort®)** - **PD:** Decreases airway inflammation, **suppresses cytokines.** - **PK**: Rapid lung absorption, **hepatic metabolism (CYP3A4)** - **Adverse Effects:** Dysphonia, Oral candidiasis (thrush), cough. - **Notes**: **Preferred in pregnancy** for asthma control. **Rinse mouth after use** to prevent thrush. **c) Beclomethasone (QVAR®)** - **PD:** Suppresses inflammatory cells in airways. - **PK**: Hepatic metabolism, minimal systemic absorption - **Adverse Effects:** Sore throat, hoarseness, oral candidiasis. - **Notes**: Used for maintenance therapy. **d) Mometasone (Asmanex®)** - **PD:** Reduces airway inflammation and bronchial hyperresponsiveness. - **PK**: Liver metabolism, low systemic bioavailability. - **Adverse Effects:** Oral candidiasis (thrush), dysphonia, cough. - **Notes**: High potency; used once daily. **COPD Medications** ==================== LABAs and **anticholinergics** (LAMA) are first-line for COPD **maintenance therapy**. ### **1. Long-Acting Beta-Agonists (LABAs) in COPD** **a) Indacaterol (Arcapta Neohaler®)** - **PD: β2 agonist**, long-acting bronchodilator - **PK**: Onset: 5 min, Duration: \~24 hours. - **Adverse Effects:** Tachycardia, palpitations, tremors. - **Notes**: Once-daily dosing, COPD only (not for asthma). **b) Olodaterol (Striverdi Respimat®)** - **PD: β2 agonist**, smooth muscle relaxation. - **PK**: Onset: 5 min, Duration: \~24 hours. - **Adverse Effects:** Tachycardia, QT prolongation. - **Notes**: Used in COPD, often combined with LAMAs. ### **2. Long-Acting Muscarinic Antagonists (LAMA) / Anticholinergics** LAMAs are **first-line therapy for COPD**, reducing **bronchoconstriction** by **blocking acetylcholine**. **a) Tiotropium (Spiriva®)** - **PD: Blocks M3 receptors**, reducing bronchoconstriction. - **PK**: Long-acting, once-daily dosing. - **Adverse Effects:** Dry mouth, urinary retention, glaucoma risk. - **Notes**: Preferred for COPD maintenance. **b) Aclidinium (Tudorza Pressair®)** - **PD: M3 receptor antagonist**, long-acting bronchodilation. - **PK**: Onset: 5 min, Duration: \~12 hours. - **Adverse Effects:** Blurred vision, dry mouth, cough - **Notes**: Twice-daily dosing. **c) Umeclidinium (Incruse Ellipta®)** - **PD: M3 receptor antagonist**, inhibits bronchoconstriction. - **PK**: Onset: 10 min, Duration: \~24 hours. - **Adverse Effects:** Dry mouth, constipation. - **Notes**: Once-daily inhaler. **d) Glycopyrrolate (Seebri Neohaler®)** - **PD: Blocks M3 receptors**, smooth muscle relaxation. - **PK**: Onset: 5 min, Duration: \~12 hours. - **Adverse Effects:** Urinary retention, blurred vision. - **Notes**: Used in combination with LABAs. ### **3. Short-Acting Muscarinic Antagonists (SAMA) / Anticholinergics** SAMAs are used for **acute COPD exacerbations**. **a) Ipratropium (Atrovent®)** - **PD: M3 receptor antagonist**, inhibits bronchoconstriction. - **PK**: Onset: 15 min, Duration: 4 to 6 hours. - **Adverse Effects:** Dry mouth, headache, blurred vision. - **Notes**: Used as PRN for COPD; less effective in asthma. **4. Combination Therapies (ICS + LABA or LAMA + LABA)** The following are combination therapies that include **inhaled corticosteroids (ICS) + long-acting beta-agonists (LABA)** or **long-acting muscarinic antagonists (LAMA) + LABA**: 1. **Advair Diskus®** contains **fluticasone + salmeterol** and is used for **asthma and COPD**. 2. **Symbicort®** contains **budesonide + formoterol** and is used for **asthma and COPD**. 3. **Breo Ellipta®** contains **fluticasone + vilanterol** and is used for **asthma and COPD**, with the advantage of **once-daily dosing**. 4. **Anoro Ellipta®** contains **umeclidinium + vilanterol** and is indicated for **COPD only** as a **LAMA + LABA** combination. 5. **Stiolto Respimat®** contains **tiotropium + olodaterol** and is used for **COPD only** as a **LAMA + LABA** combination. ### **Key Takeaways** - **ICS (e.g., Fluticasone, Budesonide)** = First-line for asthma **but** not COPD monotherapy**.** - **LABAs (e.g., Salmeterol, Formoterol)** = Must be combined with ICS in asthma **but** used alone in COPD**.** - **LAMAs (e.g., Tiotropium, Umeclidinium)** **=** First-line for COPD maintenance**.** - **SABAs (e.g., Albuterol, Levalbuterol)** = Rescue therapy for asthma and COPD**.** **Module 7: Hypertension & Dyslipidemia** ### **1. Define Hypertension and Goal Blood Pressure** - **Hypertension** is defined as **systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg** based on repeated measurements. - **Goal Blood Pressure (BP):** - **General population & low-risk patients:** \