Pharmacology

Pharmacology

DRUG ABSORPTION → concepts you don’t understand: Hepatic Clearance (slide 34,35)

1. Define pharmacology, pharmacodynamics, pharmacokinetics, drugs, receptors, and the nature of drugs. (Level 1)

   1. Pharmacology: study of the effect of drugs

   2. Pharmacodynamics: body’s biological response to drugs

   3. Pharmacokinetics: movement of drugs through the body

   4. Drugs: change the physiology of your body

   5. Receptors: activate or inactivate different processes in the body

   6. Nature of Drugs:

2. Explain the phenomenon of drug absorption and how it affects bioavailability, bioequivalence, speed of drug onset and site of action. (Level 2)

3. Illustrate first-pass process and its effect on drug concentration. (Level 2)

   1. When drugs are taken orally or rectally, they must go through digestion. First, they must go through the GI tract and then the liver before they get absorbed into the body and travel through the blood. Undergoes BIOTRANSFORMATION - METABOLISM

4. Analyze factors that affect drug absorption. (Level 4)

   1. Food, concentration of drug

5. Summarize the importance of lipid solubility in the transfer of drugs across biologic membranes. (Level 2)

6. Identify the effect of pH and pKa in the transfer of drugs across biologic membranes (concept of Henderson-Hasselbalch equation). (Level 2)

7. Illustrate the role of transporters in determining drug access to the target site. (Level 2)

8. Compare common routes of drug administration. (Level 2)

   1. Rapid Absorption: Drugs that are Intravenous, intramuscular, Sublingual, and through the skin bypass the GI tract and enter systemic circulation rapidly. Less drugs are needed to have higher concentrations.

9. Compare the advantages and disadvantages associated with the various routes of administration of drugs. (Level 2)

10. Explain the difference between sublingual and oral administration. (Level 2)

    1. Oral administration goes through the first-pass process, which metabolizes it by the GI Tract, whereas sublingual directly go through systemic circulation (blood).

11. Summarize advantages and disadvantages of intravenous administration. (Level 2)

12. Describe the process of transdermal absorption. (Level 2)

Passive Transfer - no energy required - low to high concentration

1. Aqueous diffusion (filtration) - Pores where H2O, ions, and small molecules can pass

   1. Filtration decreases as molecular weight increases - BULKY MOLECULES

2. Lipid diffusion (Simple) - Lipid Soluble substances are transferred after penetration of mostly lipid cell membrane

   1. Transfer proportional to:

      1. The concentration gradient of the non-ionized frm (lipid soluble)

      2. The LW partition coefficient of non-ionized form - the ratio of lipid:water

   2. Drugs can have similar pKa and still have DIFFERENT ABSORPTION RATES

      1. The factor of absorption is based on the lipid solubility of the non-ionized form compared to a ratio of non-ionized to ionized form

   3. Ion trapping: at equilibrium, the non-ionized concentration will be equal on both sides, BUT the total drug (I + Non-I) concentration will be on the side where the ionization degree is larger

3. Carrier-facilitated - Substance forms a complex with carrier molecule (protein) which is contained within the biological membrane; travels from one side of membrane to other

   1. Limited by: number of binding sites on carrier molecule

   2. Concentration gradient - only PASSIVE SO low to high concentration

Active Transfer - energy required - high to low concentrations

CAN BE REDUCED BY: non-competitive inhibition (POISON) and competitive inhibition

1. Endocytosis - transfers huge molecules

   1. molecules engulfed with membrane: transported inside; REQUIRES ENERGY

Effect of pH → nonionized to ionized fraction depends on pKa of drug and body fluid pH

pK = pH at which molecule is 50% ionized and 50% NON-ionized

pH = 1 (acid) | pH = 12 (base)

2 pH away from maximum change

BIOAVAILABILITY: rate (speed) and extent (amount) of absorption of unchanged drug from its dosage form into blood

Oral administration: Dosage form → Disintegration → Dissolution → Absorption

Dissolution: rate it dissolves

Equivalence →

Chemical equivalence → amount of active ingredient is the same

Pharmaceutical equivalence → same amount of active ingredient and inactive ingredient

Biological equivalence → bioavalibility of active ingredient is the same

Theraupeutic Equivalence → effectiveness of treatment is the same in target disorder, which shouln’t differ if the bioavailability is the same

DRUG DISTRIBUTION -

1. Examine determinants of drug distribution, including organ blood flow, barriers, adipose tissue, tissue protein binding, and plasma protein binding. (Level 4)

   1. Too much free drug → Toxicity because of overdose.

   2. Too much bound drug → Ineffective because not enough free drug is available.

   3. Sudden release of bound drug → Toxicity even without taking more drug!

2. Identify importance of plasma protein-binding of drugs. (Level 3)

3. Explain effect of the blood-brain-barrier and the placental barrier on drug distribution. (Level 2)

4. Describe effect of lipid solubility on drug distribution. (Level 2)

5. Identify clinical significance of redistribution of drugs. (Level 3)

   1. High L/W Coefficient → highly lipid-soluble accumulate in adipose tisue

   2. Fast redistribution → Shorter drug effect (e.g., anesthetics like thiopental).

   3. Slow redistribution → Prolonged drug action (e.g., diazepam, bisphosphonates).

   4. Affects dosing schedules & toxicity risk (especially in obesity & elderly patients).

6. Explain how drug distribution affects its site of action, elimination, and half-life. (Level 2)

DRUG BIOTRANSFORMATION (Metabolism) → don’t understand Antipyrine Test - know its to test hepatic function levels

1. Explain importance of elimination half-life in duration of drug action. (Level 2)

2. Analyze difference between zero- and first-order reactions. (Level 4)

3. Explain four possible consequences of drug metabolism. (Level 2)

4. Summarize phase I and phase II drug metabolism reactions. (Level 2)

5. Explain importance of cytochrome P450 isoforms in drug metabolism. (Level 2)

6. Identify effect of genetic polymorphisms on drug metabolism. (Level 2)

7. Examine effects of induction and inhibition of cytochrome P450 isoforms on drug metabolism and drug interactions. (Level 4)

DRUG ELIMINATION →

1. Analyze characteristics of various routes of drug elimination (kidneys, bile, intestines, lungs, sweat glands, and mammary glands. (Level 4)

2. Analyze drug characteristics that influence renal elimination. (Level 4)

3. Summarize impact of renal system on duration of drug action. (Level 2)

4. Explain difference between glomerular filtration and tubular secretion regarding removal of a drug from the circulatory system. (Level 2)

5. Explain why a urine drug level cannot be used to determine impairment. (Level 2)

6. Summarize clinical significance of enterohepatic circulation. (Level 2)