NURS 472A - Block 1

Define drug

Any chemical that can affect living processes

Define pharmacology

Study of drugs and their interactions with living systems

Define clinical pharmacology

Study of drugs in humans

Define therapeutics

The use of drugs to diagnose, prevent, or treat disease or to prevent pregnancy

List the three most important properties of an ideal drug

Effectiveness, safety, selectivity

What is effectiveness?

Drug elicits expected response

What is safety?

Drug cannot produce harmful effects

What is selectivity?

Drug elicits only the response for which it is given

List the other important properties of an ideal drug

Reversible action, predictability, ease of administration, freedom from drug interactions, low cost, chemical stability, simple generic name

Explain why no drug has the traits of an ideal drug

All drugs have the potential to produce side effects. Drug responses may be difficult to predict and may be altered by drug interactions. Drugs may be expensive, unstable, and hard to administer

What is the therapeutic objective?

To provide maximum benefit while causing minimal harm

What is maximum benefit with minimum harm?

Treatment with a drug must result in more good than harm

Identify factors in determining the intensity of drug responses

Administration, pharmacokinetics, pharmacodynamics, sources of individual variation

What is pharmacokinetics?

How the drug moves through the body to the site of action, impact of the body on drugs

What five landmark drug legislation are of note?

Controlled Substances Act, Best Pharmaceuticals for Children Act, Pediatric Research Equity Act, Family Smoking Prevention and Tobacco Control Act, Comprehensive Addiction and Recovery Act

When was the Controlled Substances Act signed into law?

1970

When was the Comprehensive Addiction and Recovery Act signed into law?

2016

What is the aim of the Controlled Substances Act?

Set rules for manufacture/distribution of drugs that could have the potential for abuse, defines five schedules (categories) of drugs, abuse potential lessens as you move from schedule I to schedule V

What are schedule I drugs?

Have no accepted medical use, highest potential for abuse, ex. heroin

What is the aim of the Comprehensive Addiction and Recovery Act?

Provide resources to combat the opioid epidemic

What is the chemical name of a drug?

Description of a drug based on chemistry nomenclature

What is the generic name of a drug?

Name assigned by the United States Adopted Names Council, each drug has only one generic name

What is the proprietary name of drugs?

Trade/brand name, used for marketing, created by drug companies, must be approved by the FDA

Explain the benefits, if any, of generic drugs over brand-name drugs

In most cases the generic drug is equivalent to the brand-name drug, one drug can have multiple brand-names so it is confusing, generic drugs are also less expensive

What are the four main processes that make up pharmacokinetics?

Absorption, distribution, metabolism, excretion

What is absorption?

Movement of a drug from its site of administration into the blood

What is the rate of absorption?

How fast a drug is absorbed, which determines how soon effects will begin

What is the impact of the amount of drug absorbed?

Determines how intense the effects will be

What factors impact drug absorption?

Rate of dissolution, surface area, blood flow, lipid solubility, pH partitioning

What is rate of dissolution?

The rate at which a drug dissolves, faster dissolution means faster onset of action

How does surface area impact drug absorption?

Larger surface area has faster absorption

How does blood flow impact drug absorption?

Drugs are absorbed more rapidly from sites where blood flow is high, drugs get carried away by the blood which creates a large concentration gradient outside/inside the blood, large conc. gradient has faster absorption

How does lipid solubility impact drug absorption?

High lipid soluble drugs are absorbed more rapidly because they move readily across cell membranes

How does pH partitioning impact drug absorption?

A drug will accumulate on the side of a cell membrane where the pH most favors its ionization, thus acidic drugs will move to the basic side and vice versa, absorption is enhanced when a drug can move down its pH gradient

What must drugs cross throughout the body?

Cytoplasmic membranes around cells made of phospholipids and large proteins

What are the three ways drugs cross the cell membrane?

Channels/pores, transport systems, direct penetration of the membrane

How do drugs move through channels/pores?

Very few drugs cross through channels or pores, channels are extremely small and specific

How do drugs move through transport systems?

Most drugs lack transport systems, transport systems are carriers, selective, ex. P-Glycoprotein (PGP)

What is PGP?

P-Glycoprotein, multidrug transporter protein that transports a wide variety of drugs out of cells

Where are PGPs present?

Liver, kidney, placenta, intestines, brain capillaries

How do drugs move through direct penetration of the membrane?

Most common way for drugs to pass through cells, lipophilic substances can pass through the membrane

What are water-soluble drugs?

Polar substances that are hydrophilic and can dissolve in water

What characteristics inhibit movement of a drug?

A drug being polar or being an ion

What is distribution?

Movement of drugs from blood to tissues and cells

What three factors impact drug distribution?

Blood flow to tissues, exiting the vascular system, entering cells

Describe blood flow to tissues

Drugs are carried by the blood to tissues and organs of the body, blood flow determine the rate of delivery

Describe the ability of a drug to exit the vascular system

Most drugs effect systems outside of the blood, the ability of a drug to leave the vasculature determines its action/metabolism/excretion, drugs leave the vasculature at capillary beds through pores which typically offer no resistance

What are the three exceptions of drugs exiting the vascular system?

The blood-brain barrier (BBB), the placental drug transfer, protein binding

How do drugs exit the vasculature differently at the BBB?

Tight junctions between cells in the CNS prevent drug passage, only lipid-soluble drugs, or drugs with a transport system (PGP) can cross the BBB

How do drugs exit the vasculature differently at the placenta?

Drugs must cross the membranes of the maternal and the fetal vasculature, lipid-soluble drugs can readily cross these membranes and enter fetal blood, ions/polar molecules are prevented from entering the fetal blood

How do drugs exit the vasculature differently with protein binding?

Reversible bonds are formed with large blood proteins like albumin, these proteins are too large to fit through capillary pores and no transport systems exist for them, a drug that is bound to albumin cannot leave the blood

Describe the ability of a drug to enter cells

Some drugs must enter cells to reach the site of action, most drugs must enter cells to undergo metabolism and excretion, many drugs produce their effects by binding with receptors on the external surface of the cell membrane

What is metabolism?

Also known as biotransformation, altering the drug structure through enzymatic reactions

Where does most metabolism occur?

Liver

What is the P450 system?

Hepatic microsomal enzyme system, a group of 12 closely related enzyme families, 3 of these enzyme families metabolize drugs

What 3 enzyme families metabolize drugs in the P450 system?

CYP1, CYP2, CYP3

What does the term P450 refer to?

Cytochrome (CYP) P450, a key component of the P450 system

What does metabolism usual result in for drugs?

Breakdown of drugs into smaller molecules

What are the six therapeutic consequences of drug metabolism?

Accelerated renal drug excretion, drug inactivation, increased therapeutic action, activation of prodrugs, increased toxicity, decreased toxicity

What is accelerated renal drug excretion via metabolism?

Metabolism of lipid-soluble drugs to convert them into more hydrophilic forms to allow excretion via the kidneys

What is drug inactivation via metabolism?

Metabolism converts active drugs into inactive compounds

What is another term for inactive drug compounds?

Metabolites

What is increased therapeutic action via metabolism?

Metabolism can increase the effectiveness of some drugs by converting a less effective drug into a more effective form

What is a prodrug?

A compound that is inactive when administered and then undergoes activation via metabolism

What is increased toxicity due to metabolism?

Metabolism may increase the potential for harm by converting relatively safe compounds into toxic ones

What is decreased toxicity due to metabolism?

By converting drugs to inactive forms, metabolism can decrease toxicity

What are some special considerations in drug metabolism?

Age, induction/inhibition of drug-metabolizing enzymes, first-pass effect, nutritional status, competition among drugs

How does age impact drug metabolism?

Infants have an immature liver, older adults have decreased liver function

How does induction/inhibition of drug-metabolizing enzymes impact drug metabolism?

Drugs may be P450 substrates, P450 enzyme inducers, P450 enzyme inhibitors, the rate of metabolism depends on if P450 enzyme inducers/inhibitors are present

How does the first-pass effect impact drug metabolism?

Rapid inactivation of certain oral drugs by liver due to the drug traveling through hepatic portal vein and being metabolized quickly, inactivated before influencing the body

How does nutritional status impact drug metabolism?

Certain cofactors necessary for the P450 system may be deficient in a malnourished patient

How does competition among drugs impact drug metabolism?

If two drugs are metabolized by the same P450 enzyme, they may compete for metabolism

What is excretion?

Movement of a drug and its metabolites out of the body

What is the most important organ in drug excretion?

Kidneys

What impacts the duration of many drug actions?

Renal excretion

What three processes result in urinary excretion?

Glomerular filtration, passive tubular reabsorption, active tubular secretion

What is the impact of glomerular filtration on drugs?

Moves drugs from the bloodstream into the tubular urine, drugs bound to albumin are not filtered and remain in circulation

What is the impact of passive tubular reabsorption on drugs?

When drug concentrations in the blood are lower than drug concentrations in the tubule a conc. gradient is created, moving lipid soluble drugs back into the bloodstream, ions/polar drugs remain in the tubule

What is the impact of active tubular secretion on drugs?

Movement of drugs from the bloodstream to the tubule via a system of active transport pumps for organic acids/bases

What factors modify renal drug excretion?

pH-dependent ionization, competition for active tubular transport, age/kidney function

What are non-renal routes of drug excretion?

Breast milk, bile, lungs, sweat/saliva

What can occur if drugs are excreted through breast milk?

They may affect a breastfeeding baby

What can occur if drugs are excreted through bile?

Bile enters the intestines and the drug can be reabsorbed through the hepatic portal vein leading to enterohepatic recirculation, this can prolong the drug's effect on the body

What is the primary route of excretion of volatile anesthetics?

Lungs

What can impact the time course of drug responses?

Plasma drug levels, single-dose time course, half-life, repeated doses

What is the minimum effective concentration?

The plasma drug level below which therapeutic effects will not occur

What is the toxic concentration?

The plasma drug level at which toxic effects begin, drug doses must be kept small enough not to reach the toxic concentration

What is the therapeutic range?

The range between the minimum effective concentration and the toxic concentration

What does a narrow therapeutic range mean about a drug?

The drug is less safe

What is the half-life of a drug?

Time required for the amount of drug in the body to decrease by 50%

What determines the dosing interval?

Drug half-life

What does a long half-life mean about a drug?

The drug will leave the body slowly

What is the effect of repeated drug doses?

Allows a drug to build up in the body until plateau drug levels are achieved

What is a plateau drug level?

When the amount of drug eliminated equals the amount of drug administered between each dose

When will plateau drug level be reached?

Approximately in 4 half-lives

What are peaks and troughs?

Highest and lowest conc. fluctuations of plasma drug levels between doses

Why does a nurse have to pay attention to peak concentration?

These must be kept below toxic concentration

Why does a nurse have to pay attention to trough concentration?

These must be kept above the minimum effective concentration

What is a loading dose?

A large initial dose that can be administered when plateau must be reached quickly

What is a maintenance dose?

Smaller doses used to maintain plateau after a loading dose