Pharmacokinetics and Pharmacodynamics

Flashcards covering key pharmacology concepts including pharmacokinetics, pharmacodynamics, absorption, distribution, metabolism, excretion, half-life, and therapeutic drug monitoring based on lecture notes.

Pharmacokinetic Phase

The movement of medications or drugs into, within, and out of the body, summarized as what the body does to a drug. This movement is necessary to achieve a drug reaction.

Absorption

The movement of drugs into the bloodstream following administration. (How it gets into the blood stream)

Distribution

The process by which a drug becomes available to body fluids and body tissues. (Where does it go)

Metabolism

The process by which the body chemically changes drugs into a form that can be excreted. (How is it broken down to be used)

Excretion

How a medication leaves the body, primarily through the kidneys in urine.

Routes of Medication Administration

Methods of giving medication, including intramuscular (IM), subcutaneous (SQ/SC), oral (PO), topical, and intravenous (IV), which directly affect drug absorption and absorption rates.

Oral Administration Percentage

The proportion of medications taken orally or by mouth, which accounts for 80% of all administered drugs. These medications need to pass through the gastrointestinal (GI) system.

Villi of the Small Intestine

Projections covering the mucosal lining of the small intestine that increase surface area for drug absorption into the bloodstream, specifically from most oral drugs.

Pharmaceutic Phase

The phase in which a solid drug disintegrates into smaller particles and dissolves in a liquid to form a solution prior to absorption.

Excipients

Fillers and inert substances used in drug preparation to allow the drug to achieve optimal size and shape and enhance dissolution.

Disintegration

The process by which a solid drug or tablet breaks down into smaller particles to prepare for dissolution and absorption, apart of the pharmaceutic phases.

Dissolution

The last part of the pharmaceutic phases in which a solute dissolves in a solvent to form a homogeneous solution, essential for drug absorption.

Optimal Absorption Fluid

Drugs both disintegrate and are absorbed faster in fluids that are acidic rather than alkaline.

Gastric Disintegration Environment

An acidic fluid environment ($\text{pH } 1$ or $2$) in the stomach where most non-enteric coated medications disintegrate. However, many factors can affect the pH of the stomach and therefore affect disintegration (To eat or not to eat).

Enteric-Coated Medications

Medications coated with special polymers that resist disintegration in the gastric acid of the stomach and disintegrate later in the alkaline environment of the small intestine. Enteric coating can also be used for some meds that cause irritation of the stomach lining.

Enteric Coating Administration Rule

Enteric-coated medications should never be crushed, split, chewed, or dissolved prior to administration.

Examples of Enteric-Coated Medications

Erythromycin, Pancrelipase, and proton pump inhibitors (PPIs).

Passive Absorption

Drug movement across cell membranes occurring by diffusion from higher to lower concentration without requiring energy.

Active Absorption

Drug movement across cell membranes against a concentration gradient requiring cellular energy and a carrier enzyme or protein.

Pinocytosis

A process by which cells carry a drug across their membrane by engulfing the drug particles.

GI Membrane Composition

A cell membrane composed mostly of lipids and proteins that allows lipid-soluble drugs to pass through rapidly.

Lipid-Soluble and Nonionized Drugs

Drug forms that can affect absorption by passing rapidly through cell membranes and absorb faster than water-soluble and ionized drugs.

Water-Soluble Drugs

Drugs that require a carrier, such as an enzyme or protein, to pass across the lipid-rich cell membrane.

Intravenous (IV) Absorption Rate

The administration route with the fastest absorption rate because drugs are immediately available in the bloodstream.

Intramuscular (IM) Absorption Rate

Absorbed faster in muscles with more blood vessels (deltoid) than in those with fewer blood vessels (gluteal).

Subcutaneous (SC) Injection Absorption Rate

Absorption rate that is slower than IM or IV routes due to having fewer blood vessels in subcutaneous tissue.

Bioavailability

The percentage of an administered drug dose that reaches systemic circulation and is available for activity.

Oral Route Bioavailability

The percentage of bioavailability for oral administration, which is always less than $100\%$.

IV Route Bioavailability

The percentage of bioavailability for the IV route, which is usually $100\%$.

Oral to IV Dose Ratio

To obtain the desired drug effect, oral doses should be $3-5\,\text{times}$ larger than IV doses.

Factors Altering Bioavailability

Drug form, route, GI mucosa/motility, presence of food/drugs, and changes in liver metabolism or hepatic blood flow.

Hepatic Impairment and Bioavailability

Decreased liver function or hepatic blood flow increases bioavailability of liver-metabolized drugs because less drug is destroyed by hepatic metabolism in the presence of liver disorder.

Rapid Oral Absorption Risk

Fast absorption increases drug concentration and bioavailability, which can lead to drug toxicity.

Slow Oral Absorption Effect

Slow absorption limits drug bioavailability, causing a decrease in drug serum concentration.

First Pass Effect

The process in which oral drugs pass from the intestinal lumen to the liver via the portal vein before entering systemic circulation.

First Pass Metabolites

Some drugs in the liver may be metabolized to inactive forms for excretion, which reduce the amount of active drugs. Or other drugs metabolized to drug metabolites equally or more active than the original drug.

Drug Distribution

The process by which the drug becomes available to the body fluids and body tissues, influenced by blood flow, the drug's affinity to body tissues, and protein-binding effect. Drugs are classified by their % of protein binding.

Bound Drug Fraction

The portion of a drug bound to plasma proteins (such as albumin), which is inactive and unable to exert a pharmacological effect because it is not available to interact with tissue receptors.

Free Drug Fraction

The unbound portion of drug in plasma that is active and capable of producing a pharmacological response.

Protein Binding Equilibrium

As free drug concentration in circulation decreases, more bound drug is released from plasma protein to maintain the balance of free active drug.

Concurrent Protein-Bound Drug Interaction

When two highly protein-bound drugs (e.g., Warfarin and Ibuprofen) are given concurrently, they compete for protein binding sites, increasing free drug levels and toxicity risk.

Drug Toxicity

A condition occurring when drug levels in the body exceed the therapeutic range secondary to overdose or drug accumulation.

Hypoalbuminemia Impact

Low plasma protein levels decrease available binding sites, increasing free drug amount and leading to potential drug accumulation and toxicity.

Placental Transfer - First Trimester Risk

Drug passage across the placenta carries a primary risk of spontaneous abortion.

Placental Transfer - Second Trimester Risk

Drug passage carries risks of spontaneous abortion, teratogenesis, or subtler developmental defects.

Placental Transfer - Third Trimester Risk

Drug exposure can alter fetal growth and development.

Late Pregnancy NSAID Risk

Use of NSAIDs (such as Motrin or Advil) in the third trimester can lead to premature closure of the patent ductus arteriosus (PDA) in the womb.

Blood-Brain Barrier (BBB)

A special endothelial lining in brain blood vessels where cells are pressed tightly together to protect the brain from foreign substances.

BBB Permeability Characteristics

Drugs that are highly lipid-soluble and of low molecular weight cross the BBB via diffusion or transport proteins; water-soluble drugs do not cross.

Metabolism

Also known as biotransformation, it is the process by which the body chemically changes drugs into a form that can be excreted.

Primary Site of Drug Metabolism

The liver, where hepatic enzymes chemically convert drugs for elimination.

Cytochrome P450 (CYP450)

Liver enzymes that inactivate most drugs and convert them using hepatic enzymes into inactive metabolites or water-soluble substances for excretion.

Half-Life ($t_{1/2}$)

The time it takes for one half of the drug concentration to be eliminated from the body. Drug half life is also used to determine dosing interval.

Short Half-Life Dosing Frequency

Drugs with a short half-life need to be administered more frequently to maintain therapeutic action.

Adenosine Half-Life

An example of a drug with an extremely short half-life of less than 10 seconds ($t_{1/2} < 10\,\text{seconds}$).

Penicillin G Half-Life

An example of a drug with a short half-life of 2 hours ($t_{1/2} = 2\,\text{hours}$).

Long Half-Life Dosing Frequency

Drugs with a long half-life can be administered once per day.

Digoxin Half-Life

An example of a drug with a long half-life of 36 hours ($t_{1/2} = 36\,\text{hours}$).

Steady State

Occurs when the amount of drug being administered is equal to the amount of drug being eliminated, achieving optimal therapeutic benefit.

Time to Reach Steady State

It takes approximately 4 half-lives when all doses are equal to achieve steady state drug concentration.

Loading Dose

A large initial dose administered to achieve a rapid minimum effective concentration (MEC) in plasma for drugs with long half-lives where it isn’t acceptable to wait for steady state to be achieved.

Primary Route of Drug Excretion

The kidneys, which filter and eliminate drug substances through urine.

Secondary Routes of Drug Excretion

Bile, feces, lungs, saliva, sweat, and breast milk.

Renal Filtration Specifics

The kidneys filter free unbound drugs, water-soluble drugs, and unchanged drugs, but cannot filter protein-bound drugs.

Creatinine

A metabolic byproduct of muscle that is excreted by the kidneys.

Creatinine Clearance ($\text{CL}_{\text{cr}}$)

The most accurate test to determine renal function, comparing creatinine level in urine with creatinine level in blood. Medications will be adjusted according to levels.

Normal Creatinine Clearance Range

The normal standard range for creatinine clearance is $85-135\,\text{mL/min}$.

Creatinine Clearance Demographic Variations

Creatinine clearance varies with age and gender, with lower creatinine clearance values expected in older adults and females due to decreased muscle mass.

Renal GFR Relationship with Creatinine

A decrease in renal GFR results in an increase in serum creatinine level and a decrease in urine creatinine clearance.

Blood Urea Nitrogen (BUN)

An accurate blood test measuring a metabolic breakdown product of protein metabolism to evaluate renal function.

Pharmacodynamic Phase

The study of drug effects and mechanisms of action of medications, summarized as what the drug does to the body. Can cause a primary or secondary physiological effect or both.

Primary Physiological Effect

The intended or desired physiological effect of a drug.

Secondary Physiological Effect

Additional physiological effects of a drug, which can be desirable or undesirable.

Onset of Action ($T_0-T_1$ )

The time it takes after drug administration to reach the minimum effective concentration (MEC).

Peak Action

Occurs when the drug reaches its highest blood or plasma concentration ($T_0-T_2$).

Duration of Action

The length of time a drug exerts a therapeutic effect ($T_1-T_3$).

Dose-Response Relationship

The body’s physiologic response to changes in drug concentration at the site of action.

Drug Potency

The amount of drug needed to elicit a specific physiological response.

High Potency

Produces a significant therapeutic response at low concentrations (Example: fentanyl).

Low Potency

Produces minimal therapeutic responses at low concentrations (Example: codeine).

Therapeutic Range

The plasma drug concentration between the minimum effective concentration (MEC) for obtaining a desired drug action and the minimum toxic concentration (MTC).

Therapeutic Index (TI)

Estimates the margin of safety of a drug by calculating the difference between therapeutic index and the toxic effect. A TI ratio close to 1 (low) indicates a narrow margin of safety and high danger of toxicity requiring close monitoring. While a high TI indicates a wider margin of safety and less risk of toxicity.

Therapeutic Drug Monitoring

Measuring plasma drug concentration via peak and trough levels once steady state is achieved, requested for toxic drugs with narrow therapeutic indices.

Peak Drug Level

The highest concentration of a drug at a specific time, indicating the rate of absorption of the drug. For example, a blood sample should be drawn at the proposed peak time, according to the drug and route of administration.

Trough Drug Level

The lowest plasma concentration of a drug, and it measures the rate at which the drug is eliminated. Levels are drawn immediately before the next dose of drug is given, regardless of the route of administration.

Locations of Receptors

Most receptors are found on cell surface membranes or within the cell itself.

Receptor Theory

The concept that the binding of drugs produces responses by activating receptors, or it may inactivate a receptor by blocking a response. The better the drug fits a receptor site, the more active the drug is (lock and key).

Agonists

Drugs that activate receptors and produce a desired response.

Antagonists

Drugs that prevent receptor activation and block a response.

Side Effects of Drugs

Physiological effects not related to the desired drug effects. Even with the correct drug dosage, side effects occur because all drugs have side effects, some desirable and some undesirable. However, meds can also be used for their side effects for therapeutic effect.

Adverse Reactions

Adverse reactions are more severe than side effects and are always unintentional, unexpected reactions that occur with normal drug dosages. They are always undesirable and must be reported and documented because they are a variance from planned therapy. Effects may be mild to severe/toxic, for example, anaphylaxis (cardiovascular collapse).

Tolerance

Refers to decreased responsiveness over the course of therapy. An individual with drug tolerance requires higher dosage of drug to achieve the same therapeutic response.