Pharmacology Midterm Exam Revision

• Formative Midterm Exam Revision

Material Included

• Material from Week 1 to Week 3 is included
• All sessions are included, except Journal Clubs
• Practicals will be included, ask Myrtani for guidance at [email protected]

Revision Suggestions

• Random topic selection avoided
• Basic principles of Pharmacology understood
  • Pharmacokinetics
  • Pharmacodynamics
• Critical thinking used when applying the knowledge

Key Points

• Key drugs along with their characteristics like mode of action, clinical use/indications, important side effects & contraindications memorized
• Classic and distinguishing toxicities of the major drugs studied
• Prototype drugs in each class focused on
  • Obscure derivatives not memorized
• Specific drug dosages or trade names are not testable
  • Generic names are testable
• Summary tables prepared to aid revision

Drug Classification

• Prototypes of each drug class known, for example, atropine is anti-muscarinic
• Drugs discussed in class/cases/TBL/CBL or heavily emphasized remembered
• Drugs recognized
  • Propranolol is a beta-blocker
  • Albuterol is a beta2-agonist

Clinical Trials - Drug Development Stages

• Preclinical stage exists
• Phase I exists
• Phase II exists
• Phase III exists
• Phase V exists

General Principles - Potency

• The concentration or dose needed to produce a 50% maximal response
• Indicated by the proximity of the respective curves to the y-axis, which is known as EC50 or ED50

General Principles - Efficacy

• The maximal response that a drug can produce
• Efficacy measures how well a drug generates a response
• Efficacy shown by the maximal height reached by the curve known as Emax

Agonist vs Antagonist

• Agonist: Binding of a drug to a receptor results in a response
  • Types of agonists: full, partial, inverse
• Antagonist: Binding of a drug to the receptor is not associated with a response
  • Types of antagonists: pharmacologic (same receptor), physiologic (different receptor), chemical

Pharmacokinetics - Movement of Drugs

• Drugs can diffuse directly through the lipid
• Aqueous diffusion is influenced by the concentration gradient
• Drugs can diffuse through aqueous pores (aquaporins)
• Combination with a solute carrier (SLC) occurs

Pharmacokinetics - Ion Trapping and pH

• Urinary acidification with ammonium chloride accelerates excretion of weak bases like amphetamines, and retards excretion of weak acids
• Urinary alkalinization with bicarbonate reduces excretion of weak bases and increases excretion of weak acids like aspirin or acetylsalicylic acid

Pharmacokinetics - Absorption and Bioavailability

• Drug Absorption defined as the passage of a drug from its administration site into the plasma or systemic circulation
• Bioavailability indicates the fraction (F) of an orally administered dose that reaches the systemic circulation as an intact drug
• For an IV dose, F = 100% versus Orally: F typically < 100% because of incomplete absorption and first-pass metabolism

Pharmacokinetics - First Pass Effect

• With oral administration, some drugs are efficiently extracted by the liver via portal circulation, or by the gut wall
  • The amount reaching systemic circulation is considerably less than the amount administered

Pharmacokinetics - Routes of Administration

• Enteral - absorbed via the GI tract
  • Oral (PO)
  • Buccal, sublingual (SL)
  • Rectal (R or PR)
• Parenteral - bypasses the GI tract
  • Injection
    • Intramuscular (IM)
    • Subcutaneous (SC)
    • Intravenous (IV)
    • Intradermal (ID)
    • Injected into other body cavity
  • Topical
    • Offers local action (or systemic effect)
    • Examples: Inhalers, creams/ointments/patches/drops

Pharmacokinetcs - Distribution

• Distribution is the process where a drug moves from systemic circulation to organs and tissues
• Important for the drug to reach its pharmacological target
• The apparent volume of distribution, Vd, is defined as the volume of fluid containing total drug amount in the body Q, at the same concentration as in the plasma Cp:
• Va= Q/Cp

Pharmacokinetcs - Volume of Distribution

• Vd may be influenced by:
  • Age: increase in fat results in increased Vd for lipophilic drugs
  • Sex
  • Weight
  • Disease: edema leading to increased body water will increase Vd for hydrophilic drugs

Pharmacokinetics - Drug Metabolism

• Drug metabolism makes drugs more water-soluble for excretion

• Paracetamol metabolism is a good example of metabolic reaction types

Pharmacokinetics - Elimination Half Life

• The time taken to eliminate 50% of a given amount of a drug is called the elimination half-life (t1/2)
• Steady state designates an average plasma concentration and the range of fluctuations
• The time required to reach steady state is equal to 4-5 half-lives

Pharmacokinetics - Dosage Calculations

• Loading dose - Required initially when the therapeutic drug concentration in plasma must be achieved rapidly
• Maintenance dose - Required per unit time to maintain a desired steady-state level in the plasma to achieve a therapeutic effect

Fluid Homeostasis

• Terminology understood:
  • Osmolarity
    • Osmolality
    • Osmosis
    • Hypertonic
    • Hypotonic
    • Isotonic solutions
• Differences between ECF and ICF understood including their ionic composition
• Importance of understanding the hydrostatic vs oncotic pressure and how that balance effects normal blood flow understood, as well as;
• Dehydration understood with treatments

Fluid Homeostasis - Effect of Adding Saline Solution to the Extracellular Fluid

• In the case of an isotonic saline solution added to the extracellular fluid compartment
  • Extracellular fluid osmolarity does not change, preventing osmosis
  • The only effect being an increase in extracellular fluid volume
  • Sodium and chloride remain in the extracellular fluid as the cell membrane behaves as though virtually impermeable to sodium

Fluid Homeostasis - Effect of Adding Hypertonic Solution to the Extracellular Fluid

• In the case of a hypertonic solution added to the extracellular fluid
  • Extracellular osmolarity increases thus causing osmosis
  • Causing the cells to release water into the extracellular compartment
  • Sodium chloride remains in the extracellular compartment
  • Fluid diffuses from the cells into the extracellular space
• Overall effect is an increase in the extracellular volume with a reduction in the intracellular volume also results in a rise in osmolarity in both compartments

Fluid Homeostasis - Effect of Adding Hypotonic Solution to the Extracellular Fluid

• In the case of a hypotonic solution added to the extracellular fluid
  • Extracellular fluid osmolarity decreases with extracellular water diffusing into the cells
• Overall both intracellular and extracellular volumes increases
  • Intracellular volume increases to a greater extent

Action Potentials

• Mechanism of action potentials understood
• Channels involved in action potentials understood
• Resting potential and how to effect depolarization and hyperpolarization understood