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• Module 1 focuses on Pharmacokinetics (PK), Pharmacodynamics (PD), and Pharmacogenomics (PG).

Definitions

• Pharmacokinetics (PK) involves studying the body's effect on a drug, encompassing Absorption, Distribution, Metabolism, and Excretion (ADME).
• Pharmacodynamics (PD) involves the study of the drug's effect on the body, including mechanisms of action and dose-response relationships.
• Pharmacogenomics (PG) involves the study of how genetic variations affect drug response and metabolism.

Factors Influencing Drug Response

• Genetic enzyme activity differences, like CYP450 variations, affect drug response.
• Age-related changes in metabolism and elimination create variability.
• The presence of liver or kidney diseases influences drug response.
• Drug-drug interactions can alter metabolism or excretion.
• Food intake affects drug absorption.

Key Parameters

• Bioavailability refers to the proportion of a drug that reaches systemic circulation.
• Half-life (t1/2) is the time it takes for plasma drug concentration to reduce by half.
• Volume of Distribution (Vd) is the extent of drug distribution in the body.
• Clearance (CL) defines the rate at which a drug is eliminated from circulation.
• Therapeutic Index (TI) is the margin between effective and toxic doses.

Therapeutic Drug Monitoring

• Patients on drugs with a narrow therapeutic index, like digoxin and lithium, are candidates for TDM.
• Patients with altered metabolism, such as those with liver/kidney impairment are TDM candidates.
• Candidates for TDM include those experiencing toxicity or poor therapy response.

Pharmacogenomics Role in Clinical Practice

• Currently, PG helps identify genetic polymorphisms affecting drug metabolism, such as CYP2D6 variations for antidepressants and opioids.
• In the future, PG may facilitate personalized drug regimens to optimize benefit and minimize adverse effects.
• Adjustments to drug doses should be based on a patient's metabolism.
• Slow CYP2D6 metabolizers may need lower opioid doses.
• Plasma drug levels of high-risk drugs, like phenytoin, should be monitored.
• Genetic testing can help determine optimal anticoagulant therapy.

Key Medications and Their Effects

• Warfarin's pharmacodynamics involve inhibiting Vitamin K-dependent clotting factors (II, VII, IX, X).
• Warfarin is metabolized by CYP2C9, CYP1A2, and CYP3A4.
• Adverse effects include bleeding, bruising, and warfarin skin necrosis.
• CYP2C9 polymorphisms affect warfarin dosing considerations.
• Phenytoin prolongs sodium (Na+) channel inactivation, stabilizing neurons.
• Phenytoin is highly protein-bound with nonlinear kinetics and is metabolized by CYP2C9 and CYP2C19.
• Adverse effects of Phenytoin include gingival hyperplasia, hepatotoxicity, ataxia, nystagmus, and teratogenicity.
• Therapeutic range for Phenytoin is 10-20 mcg/mL (total) or 1-2 mcg/mL (free).
• Carbamazepine blocks Na+ channels, reducing neuron excitability and auto-induces CYP3A4, decreasing its levels over time.
• Adverse effects of Carbamazepine include aplastic anemia, hepatotoxicity, and rash, particularly in those with the HLA-B*1502 allele.
• Therapeutic range for Carbamazepine is 4-12 mcg/mL.
• Omeprazole is a proton pump inhibitor (PPI) that reduces gastric acid secretion.
• Omeprazole metabolized by CYP2C19 and affects clopidogrel activation.
• Adverse effects of Omeprazole are osteoporosis, hypomagnesemia, and increased risk of C. difficile infection and should avoided with clopidogrel use.

Module 2: Pain Management

• Focuses on differences in pain types, analgesic medications and migraine treatments.

Difference Between Nociceptive and Neuropathic Pain

• Nociceptive pain is caused by tissue damage and detected by nociceptors.
• Somatic nociceptive pain is localized in muscles, bones, or joints (e.g., arthritis, laceration).
• Visceral nociceptive pain involves internal organs, often cramping or squeezing (e.g., appendicitis, kidney stones).
• Treatments for nociceptive pain: NSAIDs, acetaminophen, and/or opioids.
• Neuropathic pain is caused by nerve damage or dysfunction (e.g., diabetic neuropathy, postherpetic neuralgia).
• Neuropathic pain is characterized by hyperalgesia, which is an increased pain response and allodynia which is pain from normally non-painful stimuli.
• Neuropathic pain treatments: anticonvulsants (gabapentin, pregabalin), antidepressants (amitriptyline, duloxetine), and/or topical agents (lidocaine, capsaicin).

Analgesic Medications

• Non-Opioid Analgesics:
• Acetaminophen reduces pain and fever but lacks anti-inflammatory effects, and carries a risk of hepatotoxicity.
• NSAIDs inhibit COX enzymes to reduce inflammation, examples are ibuprofen and naproxen. NSAIDs carry a risk of GI bleeding and renal impairment.
• Opioids:
• Opioids are used for severe pain, binding to opioid receptors to inhibit pain perception.
• Examples include morphine, oxycodone, fentanyl, and hydromorphone.
• Risks: Respiratory depression, addiction, and tolerance.
• Adjuvant Analgesics: adjuvant analgesics are for neuropathic pain or multimodal pain management examples include:
  • Gabapentin (anticonvulsant),
  • Duloxetine (SNRI),
  • Lidocaine patches (local anesthetic).

Migraine Prophylaxis

• Migraine Prophylaxis Indications:
• Used of frequent migraines, that occur more than 5 per month.
• Use if there are 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) constrict blood vessels via 5-HT1 agonism and are used for acute migraine relief
• Combining NSAIDs plus triptans are used for severe pain caused by Migraines
• Avoid opioids because they are ineffective and carry risk of dependence.

Non-Opioid Analgesics in Pain Management

• Use as first-line analgesics for mild to moderate pain which is preferred over opioids.
• Use alone or with adjuncts to reduce opioid use.
• Using non-opioids pose a lower risk of dependence, overdose, and respiratory depression.
• Examples:
  • Acetaminophen for osteoarthritis.
  • NSAIDs for inflammatory pain (e.g., arthritis, musculoskeletal pain).

Opioid Classes and 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).

Equianalgesic Opioid Dose Conversion

• Morphine to oxycodone conversion: 30 mg morphine = 20 mg oxycodone.
• To convert Morphine 90 mg/day to oxycodone use this equation: (90 mg morphine ÷ 30 mg) × 20 mg = 60 mg oxycodone/day.
• Use caution with 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.

Exam Key Points for Pain Management

• Treat nociceptive pain with NSAIDs/opioids, and neuropathic pain with adjuvants like gabapentin or antidepressants.
• Acetaminophen is safer than NSAIDs but lacks anti-inflammatory effects. NSAIDs reduce inflammation but risk GI/renal toxicity.
• Reserve opioids for severe pain due to addiction and respiratory depression risks.
• Triptans and CGRP antagonists are first-line for migraines, and opioids avoided.
• Use equianalgesic opioid conversions accounts for cross-tolerance in order to prevent overdose.

Non-Opioid Analgesics

• Acetaminophen (Tylenol®)

• PD: Reduces pain and fever by prostaglandin synthesis inhibition in CNS. It is analgesic and antipyretic, acting as a weak COX-1 & COX-2 inhibitor, with no anti-inflammatory action.

• PK: Undergoes hepatic metabolism via glucuronidation/sulfation and toxic accumulation can lead NAPQI accumulation.

• Adverse Effects: Hepatotoxicity, especially with alcohol use, combined with rash, and anaphylaxis.

• Max Dose: 4g/day (adults); 2g/day (cirrhosis).

• NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)

  • Ibuprofen (Advil®, Motrin®), Naproxen (Aleve®), Celecoxib (Celebrex®)

  • PD: Inhibit COX-1 and COX-2, reducing prostaglandin synthesis for anti-inflammatory, analgesic, and antipyretic (anti-fever) effects.

  • PK: Elimination is renal with ibuprofen having a half-life of 2-4h and naproxen is 12-17h.

  • Adverse Effects: GI ulcers/bleeding, renal impairment and cardiovascular risk and particularly with COX-2 inhibitors.

Opioid Analgesics

• Morphine

  • PD: mu-opioid receptor agonist, inhibiting pain transmission.
  • PK: Metabolism hepatic (via glucuronidation) releasing clear and active metabolites (morphine-6-glucuronide).
  • Adverse Effects: Respiratory depression, constipation, hypotension, pruritus.
  • Conversion: 10 mg IV = 30 mg PO.

• Oxycodone (OxyContin®, Percocet®)

  • PD: µ-opioid receptor agonist.
  • PK: Metabolized by CYP3A4 and CYP2D6.
    • Adverse Effects: High addiction risk, similar to morphine, also carries a highter risk of CYP interactions
  • Often combined with acetaminophen.

• Fentanyl (Duragesic®, Actiq®)

  • PD: Highly potent µ-opioid receptor agonist.
  • PK: Hepatic metabolism (CYP3A4) takes place with a rapid onset (~1 min IV) , and is lipophilic.
  • Adverse Effects: Possible chest wall rigidity (high-dose IV), can also cause profound respiratory depression.
  • 100 mcg IV = 10 mg morphine IV.

Module 3: Controlled Substances & Prescribing Regulations

• Focuses on regulations for prescribing controlled substances

Reviewing State and Federal Regulations for Controlled Substance Prescribing

• Controlled substances have been categorized into Schedules I–V based on abuse potential and acceptable medical use.

• Schedule I Drugs: High abuse potential and have no accepted medical use, examples are like heroin.

• Schedule II Drugs: High abuse potential, also have accepted medical uses, examples include oxycodone.

• Schedule III-V Drugs: Have lower abuse potential, examples are cough syrups with codeine

• Prescribing laws:

• Schedule II: Requires a new prescription with no refills for each needed dose.

• 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 , also must be dated the day they is written.

• State laws many introduce regulations that are more strict than federall aws.

Components of a Controlled Substance Prescription

• A valid prescription must include:
• Name and Address of the patient
• Name, address, and DEA number of the prescriber
• Complete details of the medication like drug name, strength, dosage form, quantity, and directions for use.
• Schedule III–V must have refills , max of 5 in 6 months from the issuance.
• Signtaure must be manually signed by the prescribing professional
• The following Schedule II requirements mus be stated: No refills are allowed, only written scripts allowed with exceptions for any emergency.

State Prescription Monitoring Program

• The state maintains their own electronic PMP databases to track all controlled substance prescriptions.
  • Goal: Detect misuse and doctor shopping/ excessive abuse, prevent any potential diversion of drug compounds.
  • Mandatory review: Physicians in some regions are mandated to cross check the PMP system to see if any of their current or new patients that have filled a high risk or opioid script in the past. This also includes any current ongoing medication treatments that may need to be monitored.

Ethical and Legal Standards for Prescribing Controlled Substances

• Medications must be prescribed for a legitimate medical need, and also within the scope of a prescribing professional's medical practice.

  • For example, dentists cannot prescribe ADHD medications.

  • Both prescriber and pharmacists bear partial accountability in ensuring correctness and validity of prescription orders.

  • Signing prescription blanks is not allowed and it shoudl be written by the prescribing professional.

  • Accepted Methods for Correct Prescribing of Medications

  • Prescription pads that meet a certain resistance and tamper standard.

  • Word form or written form to confirm quantity, for example: 30 (thirty) to eliminate confusion on exact quantity of medication and reduce illegal alterations.

  • Report any concerning activity to the DEA.

Substances of Abuse and Treatments

• Opioids: This drug class has high risk of dependency and or overdose , below are some treatment options.

• Medication Assisted Treatment (MAT): Methadone, which requires DEA registration.

• Buprenorphine, which requires DEA waiver to issue out opioid prescriptions

• Naltrexone, opioid antagonist. Which can reduce opioid effects, but does not reverse it.

• Naloxone treats opioid overdose.

• Withdrawal requires benzodiazepines ( e.g. lorazepam, dizepam)

• Alcohol: Treatment options exist -Naltrexone reduces cravings.

  • Acamprosate promotes abstinence from alcohol cravings.
  • Disulfiram creates an adverse reaction to alcohol.

• Benzos are addictive.

• Nicotine treatment options:

  • Nicotine replacement therapy (patches, gum, lozenges).
  • Varenicline can block nicotine receptors.
  • Bupropion : Helps by supplementing dopamine levels to help dopamine and norepinephrine activity.
  • Schedule II drugs require written prescriptions, no refills, and strict monitoring.
  • Every prescription must have patient info.

Module 4: CNS Agents & Psychotropics

• Focuses on commonly used CNS Agents .

• Antidepressants:

  • SSRIs: Sertraline and fuoxetime are commonly prescribed to increase serotonin levels, typically used as a first line treatment for anxiety and deprsesion.
    • Bu proprion ( atpyical version from SSRIs) Helps with dopamine and neropinephrine levels, used for deprsesion with a small risk of triggering a seizure, also helps with smoking cessation.
  • Mirtazapine can helps serotonin and norepinephrine levels, but many patients report weight gain in the process.

• TCAS: Amitripyline are an older form used w significant anticholinergic effects.

• Anti pyschotics:

  • Haloperidol is known to be known as first gen version.

  • Quetiapine is a 2nd gen version that effects serotonin and dopamine.

  • Lithium requires consistent hydration and can cause confusion or tremmors if used -Benxodiazepines are known to be dependednt on -Stimunlants should be taken in the AM to maintain balance

Benzodiazepines (Schedule IV Controlled Substances)

• alprazolam PD: Enhances central nervous system activity, slowing down neural activity, it's heavily effected by CYP34A during metabolism. Adverse: Sedation dependence, respiratoiry
  • Dizapram is is known to take a longer time to effect the body Effects : Sedation, anxiety

Module 5: Anticonvulsants & Seizures

Focuses on appropriate anti convulsant Regimens

• Partial Seizures:
  • First-line: Levetiracetam (500–3000 mg daily, divided).
  • Altenative: Lamotrigine (slow titration )
  • Benzodiazepines (first-line for acute seizures)
• Step 2: Longer-acting anticonvulsants to prevent seizure recurrence
  • Phenytoin, Fosphenytoin, or Valproic Acid
    • Step 3: escalate to .Lacosemide

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

Treatment Considerations for Epilepsy in Pregnancy

• Key Risks: -Levetiracetam and Lamotrigine reduce pregnancy complications of epilepsy .
  • Consider Withdrawal: Seizure-free for 2–5 years, abnormal EEG

Common Anti convulsants

Valproic Acid (Depakote®)Modulation

• highly protein and can be affected in the liver.
• Steven syndrome can happen requires slow titration.

Module 6: Asthma, COPD, Allergic Rhinitis

• 1. Identify Risk Factors for Asthma, COPD,*
• 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
  • Allergic triggers : pollution , exposure to allergen

Medications Used for Asthma etc.

• Asthma: rescue medications with long lasting maintenance therapy for those w extreme eosiniphilic phenotypes
  • COPD and chronic bronchitis: Anti-inflammatory: Fluticasone and Budesonide are used where eisoniphilic levels are high
• Combination Inhalers:LABA + LAMA:,LABA & more.

Pharmacologic Regimens for Asthma, COPD, and Allergic Rhinitis

• Asthma Regimens:*
• Mild Intermittent, Mild Persistent, high use doses for extreme phenotype.
• Albuterol (Ventolin®, ProAir®)*
• is a relaxer or muscle spasms and also commonly inasthma
• COPD Medications
• Long -acting is preferred for COPD patients
• Combination Therapies*
• *Fluticasone,, Almeterol = maintenance not for quick relief Fluticasone, Budesonide are 1st line asthma relief but not CPOP

Module 7: Hypertension & Dyslipidemia

• General population & low-risk patients: Severe hypertension: ≥ 180/120 mmHg (hypertensive crisis)*
• LDL-C: Very high-risk*
• Moderate_Risk : 100 mg * Statins (HMG-CoA Reductase Inhibitors): Atorvastatin, Lowers LDL levels
• General Hypertension: ACEi* Dyslipidemia First-Line Therapy Diabetes (40-75 years old): Moderate-Intensity

1. ACE Inhibitors -Angiotensin I to angiotensin II, lowering the tension. -Once daily to help liver

Atorvastatin (Lipitor®)

• Helps liver and LDL levels reduce and increase the ability to express those.
• High potency Statin