Chapter 2: Basic Concepts and Processes

Define Drugs

Substances that can stimulate or inhibit cellular activities.

What must occur for a drug to induce a systemic effect?

* Drug must enter body and be circulated (i.e. Enter the bloodstream) to target cells
* Adequate concentrations of the drug must be present in the bloodstream

What are the two substances that can alter receptors?

1. Endogenous Substances
2. Exogenous Drugs

What are the different drug transport pathways?

1. Lipid-Soluble Drugs
2. Protein Channels
3. Carrier Proteins

Describe the Lipid-Soluble Drug transport pathway

A pathway where lipid-soluble drugs directly penetrate the cell membrane due to the membrane being composed of lipids. Most systemic drugs are lipid-soluble. Only drugs that are lipid-soluble can cross the blood-brain barrier.

Describe the Protein Channel transport pathway

Majority of drugs do not utilize this pathway as the drugs are too large. Small ions use this pathway, but it is regulated by a gating mechanism.

Describe the Carrier Protein transport pathway

A selective carrier protein moves a specific drug from one side of the membrane to another.

What are the three drug transport mechanisms?

1. Passive diffusion
2. Facilitated diffusion
3. Active transport

Describe Passive Diffusion

A drug transport mechanism where a drug moves from an area of higher concentration to an area of lower concentration until equilibrium is reached. This is the most common drug transport mechanism.

Describe Facilitated Diffusion

A drug transport mechanism that is similar to passive diffusion, but the drug must first find to a carrier.

Describe Active Transport

A drug transport mechanism where a drug moves from an area of lower concentration to an area of higher concentration. Thus mechanism requires both energy and a carrier.

Define Pharmacokinetics

Movement of drugs throughout the body

Define Drug Onset

Amount of time for a drug to show therapeutic effects. Determined by rate of absorption.

Define Peak

Point in time where drug is at highest level in body

Define Trough

Point in time where drug is at lowest level in body 

Define Duration of Action

Amount of time it takes for therapeutic effects to last without additional doses

List the Processes of Pharmacokinetics

1. Absorption
2. Distribution
3. Metabolism/Biotransformation
4. Excretion

Describe Absorption

The first process of pharmacokinetics where a drug enters the body and is absorbed into the bloodstream. Absorption rate determines onset of of action and, thus, the following factors affect drug absorption:

• Dose, form, and route of administration

• Blood flow of administration site

• G.I. functioning

• Presence of food or other drugs

Describe Bioavailability

The amount of a dose that reaches systemic circulation and can act on cells. Heavily influenced by drug form.

Describe Distribution

The second process of pharmacokinetics referring to the transportation of drugs throughout the body via the bloodstream. The better the perfusion of an area, the better a drug will be able to reach that area.

Therefore, distribution affects the following:

• Ability of drugs to reach target tissues

• Ability of drugs to be metabolized

• Ability of drugs to be excreted

In addition, distribution isn affected by the following:

• Protein binding

• Blood-Brain Barrier (BBB)

• Pregnancy

• Lactation

Describe the role of albumin in drug transportation

Albumin is a plasma protein that drugs bind to, causing albumin to act as a drug carrier. Albumin also acts as a reservoir, releasing drugs when unbound serum drug levels fall.

Drugs bound to albumin are active. T/F

False

For a drug to reach target tissues, the drug has to exit the bloodstream via small openings in capillary walls. When drugs are bound to albumin, the resulting compound is too big to exit the bloodstream and does no reach the target tissues. Thus, drugs bound to albumin are INACTIVE while drugs not bound to albumin are ACTIVE.

Describe Metabolism/Biotransformation

The second pharmacokinetic process concerned with the changing of the chemical structure of a drug. Usually, drugs are metabolized from an active form to inactive metabolites. However, some drugs (Prodrugs) are metabolized from inactive forms to active metabolites.

Enzymes that metabolize drugs are located in the following areas:

• Kidneys

• Liver

• Erythrocytes

• Plasma

• Lungs

• G.I. Mucosa

The following affects drug metabolism:

• Enzyme induction

• Enzyme inhibition

Describe Hepatic Drug Metabolism

Hepatic drug metabolism converts lipid-soluble drugs (Majority of drugs) to water-soluble metabolites so they can be excreted by the kidneys.

Describe the Cytochrome P-450 (CYP) System

The CYO-450 System is the system of liver enzymes that metabolizes majority of drugs and endogenous substances.

What is enzyme induction?

Enzyme induction refers to the stimulation of increased enzyme production. This occurs in some drugs over time which leads to rapid metabolism of the drug.

Rapid metabolism leads to the following:

• Need for larger doses

• Increased production of toxic metabolites in certain drugs

• Increased rate of endogenous steroidal hormone metabolism

What is enzyme inhibition?

Inhibition of enzymatic activity as a result of a specific substance. Usually results from two or more drugs competing for the same metabolizing enzyme. One drug is then metabolized faster than the other. Enzyme inhibition usually results in the need for smaller doses of the slowly metabolized drug and decreased drug metabolism. Enzyme inhibition usually occurs quicker than enzyme induction.

Describe the First-Past Effect/Presystemic Metabolism

A phenomenon to be aware of when administering oral medication. Following absorption in the G.I. tract, drugs will enter portal circulation before total systemic circulation. This leads to a metabolization of a large amount of the administered drug, leaving little to reach systemic circulation.

Describe excretion

The final pharmacokinetic process in which drugs are eliminated from the body either in urine (Majority of cases), feces (Via bile), or enterohepatic recirculating (Excreted in bile, reabsorbed in small intestine, returned to liver, metabolized, then excreted in urine). Elimination requires adequate functioning of the following:

• Circulatory system

• Kidneys

• Bowel

• Lungs

• Skin

What are serum drug levels and what do they reflect?

Serum drug levels are lab measurements of the amount of drug in blood at a specific time.

It reflects the following:

• Absorption

• Dosage

• Bioavailability

• Elimination half-life

• Rate of elimination

• Rate of metabolism

Serum drug levels are important for the following reasons:

• Monitoring for dosage reaching toxic levels

• Documenting serum drug levels associated with specific doses and effects

• Monitor unexpected responses to a dose

• Confirm suspected drug overdose

Define Minimum Effective Concentration (MEC)

The drug serum level at which drug action begins. Drug onset refers to when MEC is reached.

Define Therapeutic Range

Serum drug level at which the drug is beneficial, but not toxic. Peak drug action occurs when therapeutic range is at its highest. Reaching and maintaining therapeutic range is the goal of drug therapy.

What does toxic concentration mean?

An excessive amount of medication in the bloodstream. Toxic concentrations are caused by the following:

1. Single large dose

2. Multiple smaller doses

3. Slow metabolism and/or excretion

How do drugs induce effects?

1. A specific drug will form a drug-receptor complex with a specific receptor
2. This complex stimulate or inhibits cellular functions via specific reactions which includes:


1. Activation, inactivation, or other alteration to intracellular enzymes
2. Changing permeability of membranes to certain ions
3. Modification of synthesis, release, or inactivation of neurohormones

Define Agonistic Drugs

Drug activates a receptor.

Describe Receptor Desensitization/Down-Regulation

Prolonged agonist use decreases number or sensitivity of receptors. The cell becomes less receptive to agonistic drugs.

Describe Antagonistic Drugs

Drugs that occupy a receptor and inhibited its effects.

What are the two types of antagonistic drugs?

1. Competitive Antagonists
2. Non competitive Antagonists

Describe Competitive Antagonists

Antagonistic drug competes with agonists for receptor sites.

Describe Noncompetitive Antagonists

Antagonistic drugs that prevents agonistic action without competing for binding site.

Describe Receptor Up-Regulation

Prolonged use of antagonistic drugs makes the cell more receptive to agonists.

What is a loading dose?

An initial dose given at initiation of drug therapy to quickly achieve therapeutic serum levels. Usually larger than maintenance dose.

Describe maintenance doses

Doses given to maintain therapeutic serum levels after such levels have been reached.

How does route affect pharmacokinetics?

Different routes have different absorption and distribution rates.

In young children, why must you be very careful in drug administration?

Young children have immature body systems and are at different developmental stages. Thus, drug dosage usually must be reduced and is based on weight.

In geriatric patients, why must you be careful when administering medications?

The organ systems of geriatric patients have a decreased efficiency. At the same time, advanced age increases the likelihood of polypharmacy. Thus, drug dosage must usually be decreased.

Describe why the cardiovascular system affects geriatric pharmacokinetic

Decreased cardiac output makes distribution slower.

Describe why the liver affects geriatric pharmacokinetics

Decreased blood flow and enzymes means drugs are metabolized slower, has a longer action, and are more likely to accumulate

Describe why the kidneys affect geriatric pharmacokinetics

Decreased blood flow, glomerular filtration rate, and tubular secretion decreases rate of excretion

What is pharmacogenomics/pharmacogenetics

Study of how individual genetic variations affect drug response.

How would sex and ethnic characteristics affect drug response?

Majority of drug trials have been done on caucasian males. Thus, the effects of those drugs on people who are not caucasian males has not been as well documented.

What are the believed reasons on why women are more likely to experience adverse drug effects?

1. Lower volume of distribution
2. Lower glomerular filtration rate
3. Lower hepatic enzyme activity

How do cardiovascular disorders affect pharmacokinetics?

Decreases blood flow, thus affecting all pharmacokinetic processes.

How do G.I. disorders affect pharmacokinetics?

Inhibition of oral drug absorption

How do hepatic disorders affect pharmacokinetics?

Inhibits drug metabolism.

How do renal disorders affect pharmacokinetics?

Interferes with excretion.

How do thyroid disorders affects pharmacokinetics?

* Hypothyroidism slows metabolism, prolonging action and slowing elimination
* Hyperthyroidism accelerates metabolism, shortening action and accelerating elimination

What types of drug interactions increases therapeutic and/or adverse effects of drugs?

• Additive effects

• Synergism

• Interference

• Displacement

What are additive effects?

Two drugs with similar effects are taken. The effect you get is equal to the effects of the two drugs combined.

What are synergistic effects?

Two drugs are taken. The effect you get is greater than the effects of the two drugs combined.

What is drug interference?

One drug interferes with the metabolism of a second drug. The serum blood levels of the second drug is increased.

Describe displacement

One drug has a higher affinity for a plasma protein than a second drug. The unbound, active, level of the second drug is increased.

What types of drug interactions can decrease drug effects?

• Antidote medication

• Decreased intestinal absorption of drugs

• Increased metabolism rate of drugs

What is an antidote?

A drug given to antagonize the toxic effects of another drug

How would one drug/substance decrease intestinal absorption of another drug/substance?

The two drugs/substances combine to form a non-absorbable compound.

Describe enzyme inducing drugs

Drugs that activate the CYP-450 System, increasing metabolizing rate of drugs metabolized by this system.

What are adverse effects?

Unintended effects of a drug that occurs at therapeutic doses. Effects range from inconvenient to life-threatening and any system can be affected. Any drug can trigger adverse effects.

Adverse effects are more likely to occur in the following scenarios:

• High dosing

• Specific drugs

• Geriatric patients due to polypharmacy

Describe CNS adverse effects

* CNS Stimulation (Ex. Hallucination)
* CNS Depression (Ex. Decreased LOC)

Describe G.I. adverse effects

* Nausea and vomiting
* Diarrhea
* Bleeding/Ulceration
* Colitis

Describe Hematologic Adverse Effects

* Excessive bleeding
* Thrombosis (Clot formation)
* Bone marrow depression

Describe Hepatic Adverse Effects

Usually, hepatic adverse effects are seen in abnormal liver function values before manifestation of clinical signs

Describe renal adverse effects

Includes nephrotoxicity which interferes with excretion

Describe Hypersensitivity (Allergies)

An adverse effect that can range from mild to serious and usually occurs in those who have been previously exposed to the drug.

Describe drug fever

An adverse effect in which a drug causes fever via different mechanisms. Resolution of the fever is dependent upon excretion of the drug.

Describe idiosyncrasy

Unexpected reaction to a drug occurring the first time it is given.

What is carcinogenicity?

Ability to cause cancer

What is teratogenicity?

Ability to cause abnormal fetal development in pregnant women

Pregnancy category A

Risk to fetus not seen in studies

Pregnancy category B

Risk to fetus not seen in animal studies, no human studies available

Pregnancy category C

Category B, but potential benefits may outweigh potential risks

Pregnancy category D

Evidence of risk to fetus, but benefits may outweigh risk in life-threatening situations

Category X

Contraindicated in those who are pregnant or who may become pregnant. Studies indicate fetal abnormality and/or risk

Describe overdoses and overdose management

Overdoses occur when a heavily excessive amount of the drug is present leading to increase chance of tissue damage. Overdoes are considered an emergency regardless of location.

The goals of overdose management includes the following:

• Beginning treatment ASAP

• Supporting and stabilizing vitals and LOC (First priority)

• Preventing further damage by reducing absorption and/or increasing elimination

• If able to, administer an antidote

What is the universal antidote in orally ingested drugs?

Activated charcoal due to its ability to absorb drugs and minimal risks of complications. Adverse effects includes pulmonary aspiration and bowel obstruction.

Due to minimal effectiveness and potential complications, what procedures are no longer routinely performed for oral drug overdose?

Ipecac-induced vomiting and gastric lavage