Module 1: General Principles of Pharmacology

Question 1

Factors Influencing Drug Response

Answer 1

Med. prescription process:

1. Diagnosis
2. Therapeutic goal established
3. Drug prescribed
4. Drug admin.
5. Concentration at site of action
6. Response
7. Monitor and/or adjust dose

Influencing factors:
1. Admin. issues — Drug source, med. errors, adherence

2. Pharmacokinetics (PK) — Absorption, distribution, metabolism, excretion (individual variation)
3. Pharmacodynamics (PD) — Drug-receptor, pt’s functional state, placebo effects (individual variation)

Question 2

Pharmacokinetics

Answer 2

Four basic PK processes:
1. ABSORPTION — the process by which drugs enter the body and bloodstream

2. DISTRIBUTION — drug goes from the blood to the interstitial and intercellular tissue
3. METABOLISM — enzymatic-mediated alteration of a drug structure (most drugs are metabolized by the liver)
4. EXCRETION — most drugs are eliminated via urine (also eliminated via bile by the livers)

Question 3

PK Process #1: Absorption

Answer 3

Major routes (rate and extent of absorption varies by route) — Oral, IV, SQ, and IM (permits use of long-acting depot preparations)

Factors affecting absorption:
1. Rate of dissolution

2. Rate of absorption — surface area, lipid solubility, blood flow, pH partitioning
3. Completeness of absorption — changes in anatomy, drug, or food interaction

Question 4

Bioavailability

Answer 4

Amount of active drug that reaches systemic circulation from its site of admin.

BIOEQUIVALENCE: the absence of a significant difference in the rate and extent of absorption of the active ingredient that reaches systemic circulation

Generic drugs must be bioequivalent to the brand name drug, and can usually be readily changed; Bioequivalence studies must be within +/- 20% (minimal) drug response variation

Question 5

PK Process #2: Distribution

Answer 5

Factors affecting distribution:
1. Blood flow to tissues

2. Ability of drug to exit the vascular system (brain, fat, lung, eye, etc.)
3. Ability of the drug to enter cells

Question 6

Blood-Brain Barrier (BBB)

Answer 6

Factors affecting drug movement across the BBB:
1. Lipid-soluble (non-polar) drugs: dissolve right through the lipid membrane of the BBB (i.e. drugs that treat pain or CNS disorders)

2. Water-soluble (ionized or polar) drugs: CANNOT pass through the BBB; must become lipid-soluble or enter via some sort of transport system

Question 7

Protein Binding

Answer 7

Albumin is the most prevalent protein in plasma and the most important of the proteins to which drugs bind

Only unbound (free) drug molecules can leave the vascular system; bound molecules are too large to fit through the pores in the capillary wall

i.e. A pt with hypoalbuminemia will have more free, unbound drug in their vasculature

Question 8

PK Process #3: Metabolism

Answer 8

Types of hepatic metabolism:
1. Phase I (Non-synthetic, “P450 system”) — responsible for a larger amount of drug metabolism via oxidation, reduction, demethylation, and hydrolysis; Concerns: age, nutrition, and DDIs

2. Phase II (Synthetic) — conjugation

Both metabolic processes will convert the drug into a more water-soluble (polar) compound for excretion via bodily fluids (urine or bile)

PRODRUG: a biologically inactive compound which can be metabolized in the body to produce a drug

Question 9

First Pass Effect

Answer 9

Occurs when a drug is admin. orally, and enters the liver where it suffers extensive biotransformation to such an extent that the bioavailability is drastically reduced, thus showing subtherapeutic effects

Sublingual (SL), nasal, and parenteral routes avoid first-pass effect, thus require lower doses than oral route admin.

Question 10

PK Process #4: Excretion

Answer 10

Drugs (i.e. anesthetics) must be water-soluble (polar) to be eliminated in urine, bile, breast milk, or expired air; lipid-soluble drugs can be reabsorbed through passive reabsorption

Drugs that are eliminated slowly require lower doses

Normal serum creatinine (0.5-1.5 mg/dl) does not necessarily mean ideal renal function and excretion; Creatinine clearance is a much better indicator of renal impairment

P glycoprotein: active transporter found in the kidneys that move compounds into the urine

Causes of impaired excretion:
1. Poor organ function (i.e. age-related)

2. DDIs
3. Genetic predisposition

Question 11

Half Life

Answer 11

Time for the concentration of a particular drug to drop by one-half in a particular pt

A regular, established admin. schedule allows for drug accumulation until steady state (therapeutic range) is achieved

~5 half lives are required to reach steady state (97% concentration)

Question 12

Pharmacodynamics

Answer 12

Dose-response relationship (the dose is compared to the intensity of the response produced)

Efficacy & potency:
1. Maximal efficacy: the maximum achievable effect of a particular drug

2. Relative potency: the amount of drug necessary to attain a given effect

Question 13

Drug Receptors Theory

Answer 13

Types of drugs:
1. Agonists: activate receptors (i.e. NE)

2. Partial agonists: activate receptors less than full agonists
3. Antagonists: prevent receptor activation by endogenous molecules or other drugs

Question 14

Non-Receptor Mediated

Answer 14

Simple physical or chemical reactions in the body caused by drugs that do not require receptor activation/inhibition

i.e. Antacids, saline laxatives (retain water in the intestines by osmosis), chelation therapy (form complexes with metals for excretion), and antiseptics (precipitate proteins and bacteria)