Comp Pharm dịch

Potency vs. Efficacy

• Potency (Hiệu lực về liều)

  • Definition: The amount of drug needed to produce a specific effect.
    Tiếng Việt: Là lượng thuốc cần thiết để tạo ra một hiệu quả nhất định.

  • Example:

    • English: Ibuprofen (200 mg) vs Demerol (50 mg) — Demerol is more potent.

    • Tiếng Việt: Ibuprofen 200 mg so với Demerol 50 mg → Demerol mạnh hơn (cần liều thấp hơn để đạt cùng hiệu quả).

• Efficacy (Hiệu quả tối đa)

  • Definition: The maximum intensity of effect that can be achieved by a drug, regardless of dose.
    Tiếng Việt: Là mức độ hiệu quả tối đa mà thuốc có thể đạt được, không phụ thuộc liều.

  • Example:

    • English: A minor headache may require low-efficacy drugs, while severe pain (car accident) requires high-efficacy drugs.

    • Tiếng Việt: Đau đầu nhẹ cần thuốc hiệu quả thấp, nhưng đau nặng (tai nạn) cần thuốc hiệu quả cao.

Important Note

• Relation Between Potency and Efficacy

  • Potency and efficacy are NOT related.

  • Tiếng Việt: Hiệu lực (potency) và hiệu quả (efficacy) KHÔNG liên quan trực tiếp.

  • Explanation:

  • Potency = liều bao nhiêu? (how much drug)

  • Efficacy = mạnh tới mức nào? (how strong effect)

  • Understandable Example:

  • Drug A: Small dose produces effect → high potency

  • Drug B: Maximum effect is very strong → high efficacy

  • A drug can be:

  • Very potent but have low efficacy

  • Less potent but have high efficacy

Pharmacokinetics – ADME

1. Absorption (Hấp thu)

   • Definition: Transfer of the drug from the site of administration to the bloodstream.
     Tiếng Việt: Sự vận chuyển thuốc từ nơi đưa vào cơ thể vào máu.

   • Factors affecting absorption (Các yếu tố ảnh hưởng)

     1. Route of administration (Đường dùng)

     • IV → fastest (nhanh nhất)

     • Oral → slower (chậm hơn)

     1. Drug solubility (Độ tan)

     • Good solubility → rapid absorption (tan tốt → hấp thu nhanh)

     1. pH (Độ pH)

     • Infected tissues → acid → drug ionization → reduced absorption

     • Example: Local anesthesia in inflamed tissue → less effective

     1. Blood flow (Lưu lượng máu)

     • More blood flow → faster absorption (nhiều máu → hấp thu nhanh)

     1. Drug concentration (Nồng độ thuốc)

     • Higher concentration → more absorption (nồng độ cao → hấp thu nhiều hơn)

     1. Surface area (Diện tích hấp thu)

     • Small intestine → best absorption (ruột non → hấp thu tốt nhất)

2. Distribution (Phân bố)

   • Definition: Movement of drugs throughout the bloodstream into body tissues.
     Tiếng Việt: Sự phân bố thuốc từ máu đến các mô trong cơ thể.

   • Explanation:

     • Bound drug (gắn protein) → inactive → functions as a “storage depot” (không hoạt động ngay → giống “kho dự trữ”)

     • Free drug (tự do) → enters cells → produces effects (đi vào tế bào → gây tác dụng)

   • Example:

     • Albumin binds to drugs → gradually releases → prolongs effects (Albumin giữ thuốc → giải phóng từ từ → kéo dài tác dụng)

3. Metabolism (Chuyển hóa)

   • Definition: Chemical alteration of drugs to facilitate excretion.
     Tiếng Việt: Quá trình cơ thể biến đổi thuốc để dễ thải ra.

   • Explanation:

     • Creates polar (ionized) substances → easier to eliminate (tạo chất phân cực (ionized) → dễ đào thải)

     • Mainly occurs in the liver (Chủ yếu xảy ra ở gan)

Key Concepts: BBB & First Pass Effect

• Blood-Brain Barrier (Hàng rào máu não)

  • Definition: Only lipid-soluble drugs can cross.
    Tiếng Việt: Chỉ thuốc tan trong lipid (không ion hóa) mới qua được.

  • Example:

    • Anesthetic drugs → lipid-soluble → into the brain (Thuốc gây mê → tan trong lipid → vào não)

• First Pass Effect (Hiệu ứng chuyển hóa lần đầu)

  • Definition: Oral drugs are metabolized in the liver before reaching circulation.
    Tiếng Việt: Thuốc uống bị chuyển hóa tại gan trước khi vào máu → giảm tác dụng.

  • Example:

    • Some oral medications require higher doses because of "loss" in the liver (Một số thuốc uống phải dùng liều cao hơn vì bị “mất” ở gan)

1. Excretion (Thải trừ)

   • Definition: Removal of drug from the body (mainly kidneys).
     Tiếng Việt: Quá trình loại bỏ thuốc khỏi cơ thể (chủ yếu qua thận).

   • Half-life (Thời gian bán hủy)

     • Definition: Time for drug concentration to reduce by half.
       Tiếng Việt: Thời gian để nồng độ thuốc giảm còn 50%.

     • Example:

     • t½ = 5 days → requires ~10–12 days for complete elimination (t½ = 5 ngày → cần ~10–12 ngày để thải hết)

2. Kinetics (Động học)

   • First-order kinetics

     • Eliminated at a % rate (Thải theo tỷ lệ %)

     • Higher concentration → faster elimination (Nồng độ cao → thải nhanh hơn)

   • Zero-order kinetics

     • Fixed quantity eliminated (Thải lượng cố định)

     • Example: Alcohol (rượu)

Practice Question

• Multiple Choice Q1: Which statement is TRUE? A. Potency determines maximum effect B. Efficacy determines dose required C. Potency and efficacy are unrelated D. High potency = high efficacy

  • Answer: C

  • Explanation: Two concepts are independent (Hai khái niệm độc lập).

Drug Schedules & Abuse Potentials

• Overview of Drug Schedules

  • Drug schedules classify medications based on their potential for abuse and accepted medical use.
    Tiếng Việt: Hệ thống phân loại thuốc chia thuốc theo mức độ nguy cơ lạm dụng và giá trị sử dụng trong y học.

Detailed Schedules

• Schedule I (Cao nhất)

  • Abuse Potential: Highest (Nguy cơ lạm dụng: Cao nhất)

  • Examples: Heroin, LSD

  • Handling:

    • English: No accepted medical use; research only.

    • Tiếng Việt: Không có giá trị điều trị; chỉ dùng cho nghiên cứu.

• Schedule II

  • Abuse Potential: High (Nguy cơ lạm dụng: Cao)

  • Examples: Morphine, oxycodone, amphetamine

  • Handling:

    • Requires official prescription (written/typed)

    • No refills or phone prescriptions

  • Explanation:

    • Very powerful drugs (opioids, stimulants)

    • High addiction potential but have therapeutic value

• Schedule III

  • Abuse Potential: Moderate (Nguy cơ lạm dụng: Trung bình)

  • Examples: Codeine combinations (e.g., Tylenol 3)

  • Handling:

    • Can be prescribed over the phone

    • Maximum of 5 refills in 6 months

• Schedule IV

  • Abuse Potential: Less (Nguy cơ lạm dụng: Thấp hơn)

  • Examples: Diazepam (Valium), Tramadol (Ultram)

  • Handling:

    • Can be prescribed over the phone

    • Maximum of 5 refills in 6 months

  • Explanation:

    • Mainly sedatives, mild pain relief

    • Less addiction potential than Schedule II-III

• Schedule V (Thấp nhất)

  • Abuse Potential: Least (Nguy cơ lạm dụng: Thấp nhất)

  • Examples: Codeine cough syrup

  • Handling:

    • Some may be sold OTC (without prescription) in certain states

  • Explanation: Lower schedules (I → V): decrease in abuse potential, management regulations, and ease of access.

Summary Table for Schedules

Non-opioids vs Opioids

Non-opioid

• Mechanism: Inhibit prostaglandin synthesis (COX-1 & COX-2 enzymes).
  Tiếng Việt: Ức chế tổng hợp prostaglandin thông qua enzyme COX-1 và COX-2.

• Example: Acetaminophen has an unknown mechanism of action.
  Tiếng Việt: Acetaminophen có cơ chế chưa được hiểu hoàn toàn.

Opioid

• Mechanism: Depress the Central Nervous System (CNS).
  Tiếng Việt: Ức chế hệ thần kinh trung ương.

• Site of Action:

  • Non-opioids: Act at peripheral nerve endings.

  • Opioids: Act centrally (brain & spinal cord).

Pain Management (Quản lý đau)

• Non-opioids: Best for inflammatory pain (throbbing pain).
  Tiếng Việt: Hiệu quả nhất với đau do viêm (đau nhức, đau giật).

• Timing is important: Must be given before prostaglandin synthesis for best effect.
  Tiếng Việt: Nên dùng trước khi prostaglandin được tạo ra để đạt hiệu quả tối đa.

Prostaglandin Function

• Function:

  • Sensitize pain receptors

  • Lower pain threshold

  • Cause inflammation and edema

Explanation for Mechanisms

1. Non-opioids: Block COX → reduce prostaglandin → reduce inflammation & pain

   • Example:

   • Tooth extraction → inflammation → prostaglandin ↑ → pain

   • Use NSAIDs → decrease prostaglandin → reduce pain

2. Opioids: Do not affect inflammation; act on the brain to block pain perception.

   • Example:

     • Morphine → patient still has injury, but does not feel much pain

Comparison Summary

Practice Question

• Multiple Choice Q1: Non-opioid analgesics reduce pain by: A. Blocking CNS perception B. Increasing prostaglandin C. Inhibiting COX enzymes D. Stimulating pain receptors

  • Answer: C

  • Explanation: COX inhibition → reduce prostaglandin → alleviate pain.

True/False Q2

• Statement: "Opioids reduce inflammation at the site of injury." → False

  • Explanation: Opioids do not reduce inflammation; they only decrease pain perception in the brain.

Summary Table for Pain Management

Three Classes of Nonopioids (3 nhóm thuốc giảm đau không opioid)

1. Salicylates (Aspirin)

   • Mechanism: Analgesic, antipyretic, anti-inflammatory, and anti-platelet.

   • Explanation: Aspirin is versatile:

     • Analgesia

     • Antipyretic

     • Anti-inflammatory

     • Prevents clotting (used in heart disease, stroke)

   • Uricosuric Effect:

     • High dose: increases uric acid excretion → beneficial for gout

     • Low dose: may reduce the effectiveness of gout medication (e.g., probenecid)

   • Side Effects:

     1. GI irritation (stomach irritation) → nausea, ulcers → take after meals

     2. Bleeding → not to be used with anticoagulants (warfarin)

     3. Reye’s Syndrome → children + virus + aspirin → dangerous, may be fatal

     4. Hepatotoxicity + encephalopathy (liver + brain damage)

     5. Pregnancy: Not recommended

     6. Samter’s Triad: asthma + aspirin → severe reactions

     7. Salicylism (aspirin toxicity) → tinnitus, dizziness, nausea

2. NSAIDs (Nonsteroidal Anti-inflammatory Drugs)

   • Indications: Drug of choice for dental pain and nursing mothers.

   • Example: Ibuprofen is frequently used in dentistry (extractions, inflammation).

   • Effects:

     • Reduce pain

     • Decrease fever

     • Anti-inflammatory

     • Mildly decrease platelets

   • Mechanism: Inhibit prostaglandin (COX)

   • Side Effects:

     1. GI irritation (less than aspirin but still present)

     2. CNS: sedation, dizziness

     3. Cardiovascular & renal:

        • ↑ blood pressure

        • ↓ renal perfusion → renal failure

     4. Asthma: contraindicated

   • Important Note: Do not use aspirin + NSAIDs together (same mechanism → increases toxicity).

3. Acetaminophen

   • Characteristics: Analgesic & antipyretic, NO anti-inflammatory effects.

   • Advantages:

     • Fewer side effects

     • Does not cause gastric ulcers

     • No cardiovascular effects

   • Adverse Effects:

     1. Hepatotoxicity (liver toxicity) especially with high intake + alcohol

     2. Nephrotoxicity (kidney toxicity) with prolonged use

     3. Rare but serious skin reactions

   • Indications: Good choice for:

     • Aspirin allergy

     • Children

     • Patients on warfarin

     • Gastric ulcers

Allergy Symptoms (Triệu chứng dị ứng)

1. Non-opioids

   • Aspirin:

     • Wheezing (khò khè)

     • Rash (phát ban)

     • Edema (phù)

     • Anaphylaxis (sốc phản vệ)

   • NSAIDs:

     • Stevens-Johnson syndrome (very dangerous)

     • Angioedema (phù mạch)

   • Acetaminophen:

     • Severe skin reactions (rare but fatal)

2. Drug Reactions & Terms (Phản ứng thuốc & thuật ngữ)

Definitions

• Adverse Drug Reaction (ADR)

  • Definition: Undesirable drug response
    Tiếng Việt: Phản ứng có hại của thuốc

• Therapeutic Effect: Desired effect

• Adverse Effect: Undesired effect

  • Example:

    • Diphenhydramine → drowsiness

• Teratogenic Effect: Harmful to fetus

• Types of Reactions

  1. Toxic Reaction: Overdose → excessive effect

  2. Side Effect: Unwanted effect in another organ

     • Example: Ibuprofen → stomach pain

  3. Idiosyncratic: Unusual response due to genetics

  4. Drug Allergy: Immune response

     • Example: Anaphylaxis from penicillin

Pregnancy Categories (Old)

Practice Questions

• Multiple Choice Q1: Which drug has NO anti-inflammatory effect?
  A. Aspirin
  B. Ibuprofen
  C. Acetaminophen
  D. Naproxen

  • Answer: C

• True/False Q2: NSAIDs can be safely used in asthma patients. → False

  • Explanation: NSAIDs can cause bronchoconstriction.

Summary Table for Pregnancy Categories

Key Definitions

• Adverse Drug Reactions (ADR)

  • Definition: Undesirable reactions to a drug, can include toxic, side effects, idiosyncratic responses, and drug allergies.

  • Types:

  1. Toxic reactions – predictable, dose-related

  2. Side effects – predictable, secondary

  3. Idiosyncratic – unpredictable, rare

  4. Allergic reactions – immune-mediated

• Drug Tolerance

  • Definition: Condition from long-term drug use making dose ineffective, necessitating higher doses for similar therapeutic effects.

  • Explanation: Body adapts to the drug.

• Teratogenic

  • Definition: Substances causing malformations in embryos or fetuses, should be avoided in pregnancy.

Summary Table for Key Terms

Anti-infectives – Thuốc kháng nhiễm trùng

Key Definitions

• Anti-infective agents: Substances acting against or destroying infectious organisms.

• Antibacterials: Substances killing or inhibiting bacterial growth.

• Antibiotics: Chemical substances produced by microorganisms to inhibit or destroy other organisms.

• Antifungals: Substances targeting fungi.

Spectrum of Anti-infectives

• Narrow Spectrum: Effective against limited organisms.

  • Example: Penicillin G – mainly effective against gram-positive bacteria.

• Broad Spectrum: Effective against many organisms.

  • Example: Tetracycline – effective against both gram-positive & gram-negative.

• Suprainfection: Infection by different microbes than the original, often post-broad-spectrum antibiotic use.

• Sensitivity Testing: Determines antibiotic susceptibility of bacteria.

Key Anti-infective Concepts

• MIC (Minimum Inhibitory Concentration): Lowest concentration inhibiting visible growth.

• Synergism & Antagonism:

  • Synergism: Combined effect > individual effects (e.g., Ampicillin + Gentamicin)

  • Antagonism: Combined effect < individual effects (e.g., Penicillin + Tetracycline)

• Bactericidal vs. Bacteriostatic:

  • Bactericidal: Ability to kill bacteria (e.g., Penicillin)

  • Bacteriostatic: Inhibiting bacterial growth (e.g., Tetracycline)

Antibiotics Classification

Example Sentences for Anti-infectives

• Penicillin G: Kills Gram-positive bacteria → first-line for strep throat.

• Doxycycline: Inhibits protein synthesis → used for periodontal pockets.

• Metronidazole: Kills anaerobes → avoid alcohol to prevent reactions.

Practice Questions

• Multiple Choice Q1: Which antibiotic is bactericidal and inhibits cell wall synthesis? A. Tetracycline B. Penicillin C. Erythromycin D. Clindamycin

  • Answer: B – Penicillin

• Multiple Choice Q2: A patient develops C. Diff infection after taking antibiotics. This is an example of: A. Suprainfection B. Narrow-spectrum coverage C. Bactericidal effect D. MIC failure

  • Answer: A – Suprainfection

Summary Table for Antibiotics

Tuberculosis Drugs (Thuốc điều trị lao – TB)

Key Anti-TB Drugs

• Rifampin, Isoniazid, Pyrazinamide, Ethambutol are the main anti-TB drugs.

  • If a patient is taking rifampin or isoniazid, they will likely also receive antibiotics as preventive measures for latent TB treatment.

Drug Mechanism & Side Effects

• Rifampin

  • Mechanism: Inhibit bacterial RNA polymerase preventing RNA synthesis.

  • Use: Treats TB and prevent latent TB.

  • Side effects: Liver toxicity, gastrointestinal upset, red-orange urine.

• Isoniazid (INH)

  • Mechanism: Inhibit mycolic acid synthesis disrupting cell wall synthesis in TB.

  • Use: Treats TB and prevents latent TB.

  • Side effects: Liver toxicity, peripheral neuropathy (can prevent with vitamin B6).

• Pyrazinamide

  • Mechanism: Disrupts fatty acid metabolism killing bacteria in acid environments.

  • Use: Treats early phase TB.

  • Side effects: Liver toxicity, hyperuricemia (could lead to gout), and GI upset.

• Ethambutol

  • Mechanism: Inhibits cell wall synthesis → bacteriostatic.

  • Use: Combination therapy for TB.

  • Side effects: Optic neuritis, color blindness (green-red vision) requiring regular eye exams.

Important Note

• Rifampin & Isoniazid can be used alone for latent TB prevention.

• In active TB treatment, typically a combination of all four medications is required to avoid drug resistance.

Practice Questions

• Multiple Choice Q1: Which TB drug is associated with optic neuritis? A. Rifampin B. Ethambutol C. Isoniazid D. Pyrazinamide

  • Answer: B

  • Explanation: Ethambutol can cause vision issues.

• True/False Q2: Isoniazid can be used alone for latent TB prophylaxis. → True.

  • Explanation: Isoniazid is commonly used alone for 6–9 months to prevent latent TB.

HAART – Highly Active Antiretroviral Therapy

Definition

• A combination therapy typically involving three or more drugs to actively treat AIDS.

Drug Classes

• NRTIs (Nucleoside Reverse Transcriptase Inhibitors):

  • Mechanism: Inhibit viral reverse transcriptase → prevent viral DNA synthesis .

  • Example: Zidovudine, Lamivudine.

• NNRTIs (Non-nucleoside Reverse Transcriptase Inhibitors):

  • Mechanism: Bind directly to reverse transcriptase → inhibit viral replication..

  • Example: Efavirenz, Nevirapine.

• PIs (Protease Inhibitors):

  • Mechanism: Inhibit viral protease → prevent HIV virion maturation .

  • Example: Lopinavir, Ritonavir.

Patient Implications

• Multiple drugs prevent viral resistance.

• Requires monitoring for drug interactions and side effects.

Practice Questions

• Multiple Choice Q1: Which antifungal is primarily used for oral thrush and has both fungicidal and fungistatic effects? A. Fluconazole B. Nystatin C. Griseofulvin D. Ketoconazole

  • Answer: B – Nystatin.

• Multiple Choice Q2: HAART therapy usually includes: A. One antifungal and two antibiotics B. Three or more antiretroviral drugs C. Only protease inhibitors D. Nystatin + Ketoconazole

  • Answer: B – Three or more antiretroviral drugs.

Conclusion

• This study guide consolidates essential information on pharmacology, drug efficacy, pharmacokinetics, antibiotics, and drug interactions, offering a comprehensive understanding required for successful applications in medical settings, particularly in the context of treating infections and understanding drug classifications and their implications.