Cumulative Review Terms/Concepts

small molecule drugs

• small, organic compounds

• low molecular weight

• simple, well-defined structure

• able to diffuse across cell membranes to reach intracellular action sites

• majority of drugs on the market currently

• low immunogenicity

biologic drugs

• large, composed of proteins, sugars, nucleic acids, or living cells or tissues

• high molecular weight

• complex mixtures, not easily defined structures

• highly specific

• fastest growing area of drug development

• high immunogenicity

phase 1

• phase of clinical trials

• 10-100 healthy participants

• open label

• safety and tolerabillity

phase 2

• phase of clinical trials

• 50-500 diseased participants

• randomized & controlled

• efficacy & dose ranging

phase 3

• phase of clinical trials

• few hundred - few thousand diseased participants

• randomized & controlled or uncontrolled

• confirm efficacy in a larger population

phase 4

• phase of clinical trials

• post-marketing

• many thousands of participants in treatment with the approved drug

• open label

• adverse effects, compliance, drug-drug interactions

orphan drug

drug for diagnosis or treatment of a rare disease (affects less than 200,000 people in US); low clinical trial participant numbers

dosage form

physical state of the drug, in association with nondrug components, in which the drug is administered (ex: caplets, tablets, capsules, solutions, suspensions, emulsions, suppositories, ointments, creams, lotions, aerosols, gases, patches)

tablets/caplets

• compressed into a solid pill

• some can be cut in half

• enteric coatings

capsules

• dosage form

• hard shells enclose powdered drugs

• soft shells enclose drugs in solution

• can’t be chewed, crushed, or cut

• may be designed to be opened and sprinkled on food (not all)

solutions

• dosage form

• drug molecules dissolve completely in liquid

• don’t have to shake prior to usage

suspensions

• dosage form

• drug molecules insoluble in liquid, mixed with a suspending agent

• must be shaken well before each use to re-suspend drug molecules that settle

• can deliver more drug than a solution

ointments

• dosage form

• generally more oil than water

• form thick protective barrier that can help skin heal

• stay on skin longer, prolonged effect, but slower absorption

• greasy/shiny after use

creams

• dosage form

• generally equal oil & water

• easier absorption into skin

oral, sublingual, buccal, rectal

what are the 4 enteral routes of drug administration?

intravenous, intramuscular, intradermal, subcutaneous

what are the 4 parenteral routes of drug administration?

topical, inhalation, transdermal patches

what are the 3 “other” routes of drug administration?

oral (PO)

• route of drug administration

• enteral

• onset: variable

• convenient, easily self-administered

• safer, overdoses more easily overcome with antidotes

• cannot be used for drugs that are inactivated by gastric acid or that have a large first pass effect

• unsuitable if unconscious, vomiting, or cannot swallow

• can be affected by food & gastric motility

• most impacted by first pass effect

rectal

• route of drug administration

• enteral

• onset: erratic & variable

• ideal if pt has active vomiting, seizures, is an infant, or has a blockage that prevents the drug from moving through the GI system

• can irritate rectal mucosa

• not well accepted

• partial first pass effect

sublingual

• route of drug administration

• enteral

• drug placed under the tongue

• onset: some drugs rapidly, most are erratic & incomplete

• good for drugs that are inactivated by gastric acid or that have a large first pass effect

• useful in pt with nausea or swallowing difficulties

• can quickly terminate

• poor absorption

• can irritate oral mucosa

• limited to small doses

• cannot swallow

• no first pass effect

buccal

• route of drug administration

• enteral

• drug placed between the tongue and cheek

• onset: some drugs rapidly, most are erratic & incomplete

• good for drugs that are inactivated by gastric acid or that have a large first pass effect

• useful in pt with nausea or swallowing difficulties

• can quickly terminate

• poor absorption

• can irritate oral mucosa

• limited to small doses

• cannot swallow

• no first pass effect

intravenous

• route of drug administration

• rapid onset

• parenteral

• entire dose into circulation

• useful when a rapid, urgent, high or consistent dose is necessary

• can be given to unconscious patients

• requires trained personnel & equipment

• cannot be recalled once injected

• can cause pain/swelling/irritation at the injection site

• risk for infections & nerve injury

• 100% bioavailability

• no first pass effect

intramuscular

• route of drug administration

• parenteral

• rapid onset for solutions but slow & sustained for suspensions

• suitable for oily vehicles

• preferable to IV if pt must self administer

• pain/swelling/irritation at injection site

• no first pass effect

subcutaneous

• route of drug administration

• parenteral

• suitable for suspensions

• cannot be used for drugs that irritate cutaneous tissues

• can be self-administered

• only small volume can be given

• pain/swelling/irritation at injection site

• no first pass effect

intradermal

• route of drug administration

• parenteral

• slow/sustained onset

• cannot be used for drugs that irritate cutaneous tissues or that must be given in large volumes

• requires trained personnel/equipment

• pain/swelling/irritation at injection site

• no first pass effect

topical

• route of drug administration

• variable onset

• local effect

• mucous membranes can absorb

• convenient

• lower amount of the drug enters systemic circulation and result in less side effect risks

• no first pass effect

inhalation

• route of drug administration

• rapid onset

• can have systemic (general anesthesia) or local effect (aerosols to respiratory tract for lung problems) or both (unconscious overdose)

• lower amount of drug enters systemic circulation so there is less risk of side effects

• very minimal first pass effect

transdermal patch

• route of drug administration

• slow & sustained onset

• can cause skin reactions

• adhesiveness can be a limitation

• limited to small doses

• no first pass effect

bioavailability

amount of drug that reaches systemic circulation; amount available to be distributed to its intended action site; impacted by route of administration and dosage form

first pass effect

initial metabolism of a drug in the liver before the drug reaches systemic circulation; occurs when any drug is taken orally & can lead to a reduction in drug concentration reaching systemic circulation (lowers bioavailability)

pharmacognosy

study of drugs isolated from natural sources including plants, microbes, animal tissues, & minerals

pharmaceutics

study of formulating drugs into suitable products such as tablets, liquids, & aerosols

pharmacodynamics

how a drug binds to its molecular target (what the drug does to the body)

pharmacokinetics

how a drug gets into the bloodstream, moves around, is broken down & removed from the body (what the body does to the drug)

therapeutics

medical use of drugs in diagnosis & treatment of disease

pharmacy

science & profession concerned with preparation, storage, dispensing, & proper use of drug products

toxicology

study of poisons & organ toxicity

absorption, distribution, metabolism, excretion

what are the 4 phases of pharmacokinetics

absorption

phase 1 of pharmacokinetics: how the drug moves into systemic circulation

distribution

phase 2 of pharmacokinetics: where the drug moves/travels in the body

metabolism

phase 3 of pharmacokinetics: how the liver (mostly) chemically modifies the drug

excretion

phase 4 of pharmacokinetics: how the kidney (mostly) gets rid of the drug

small, lipophilic

most drugs are formulated to be ______ and _____ to passively diffuse through phospholipid membranes

passive

most drugs pass through phospholipid membranes via ________ diffusion

greater

the _____ the surface area of a membrane, the faster the rate of diffusion

greater

the _____ the concentration gradient across a membrane, the faster the rate of diffusion

thinner

the ______ the width of a membrane, the faster the rate of diffusion

Fick’s law

determines the rate of a drug passively diffusing through a membrane; = (surface area of the entire membrane x concentration gradient)/diffusion distance

weak acid, stomach

________ drugs are non-ionized in acidic pHs & more readily absorbed in the ______

weak base, intestines

_________ drugs are non-ionized in basic pHs & more readily absorbed in the _____

non-ionized form

form of a weak base/weak acid drug that is lipophilic/fat-soluble & can easily pass through membranes

no

do ionized forms of drugs pass through cell membranes?

prodrug

pharmacologically inactive compound that is converted to an active form by enzymes involved in metabolism

first order kinetics

most drug movement follows this; rate of drug movement is directly proportional to the concentration across a barrier

zero order kinetics

elimination rate of a drug is constant, independent of drug concentration; more dangerous

half life

time required to lower ½ of the total body load of a drug; estimates the frequency of dosing needed to maintain a therapeutic level

agonist (mimetics)

any drug that binds a receptor & activates its receptor; mimic normal body molecules

antagonist

any drug that binds a receptor but does not activate it, blocks/inhibits the action of agonists & normal body molecules from binding

affinity

measure of how tightly the drug binds to the receptor; stronger with stronger interactions

yes, yes

do agonists demonstrate affinity? do antagonists?

efficacy

a measure of the drug’s ability to activate the receptor and produce an effect/response when it is bound to a receptor; used to characterize the level of the max response of a drug

yes, no

do agonists show efficacy? do antagonists show efficacy?

potency

measure of the amount of drug that is required to achieve a desired effect

lower

a drug that requires a ______ dose to achieve the desired effect is considered to be more potent

therapeutic index

range of drug concentrations that allows a therapeutic response, without toxicity, estimate of drug safety

A

FDA pregnancy drug category: adequate & well-controlled studies have failed to demonstrate a risk to the fetus in the 1st trimester of pregnancy & there is no evidence of risk in later trimesters

B

FDA pregnancy drug category: animal reproduction studies have failed to demonstrate a risk to the fetus & there is no adequate & well controlled studies in pregnant women

C

FDA pregnancy drug category: animal reproduction studies have shown an adverse effect on the fetus & there are no adequate & well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks

D

FDA pregnancy drug category: there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks

X

FDA pregnancy drug category: studies in humans & animals have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, & the risks involved in use of the drug in pregnant women clearly outweigh potential benefits

pregnancy & lactation labeling rule

• new FDA labeling system

• applies to prescription drugs

• gives risk summaries, clinical considerations & data for pregnancy

• provides info about using a drug while breastfeeding

• gives the need for pregnancy testing, contraception recommendations, and info about fertility as it relates to the drug to females/males of reproductive potential

  • allows better patient-specific counseling & informed decision making for patients

teratogens

• drugs that can cause adverse effects in fetus or infant

• result in birth defects

• characteristic set of malformations selective for specific target organs

• exert their effect at a specific stage in fetal development

tachyphylaxis

rapid decrease in response to repeated doses; occurs quickly over a short time

tolerance

a decrease in response to a drug over time; larger doses of a drug are required to produce the same effect; occurs gradually

drug formulations

process of putting together active & inactive ingredients

active ingredients

the drug(s), using the generic/official name

inactive ingredients/excipients

preservatives, fillers, lubricants, adhesives, disintegrants, buffers, coatings, colors, flavors of drugs

preservatives

inactive ingredients in drugs that destroy or inhibit microorganisms introduced into product by accident

fillers

inactive ingredients in drugs that provide bulk

lubricants

inactive ingredients in drugs that prevent sticking during manufacturing

adhesives

inactive ingredients in drugs that maintain stability in the bottle

disintegrants

inactive ingredients in drugs that help solubility in GI fluids

buffers

inactive ingredients in drugs that adjust pH

coatings

inactive ingredients in drugs that help the body absorb the drug or time-release the active ingredients

toxic dose / effective dose

how do you calculate the therapeutic index of a drug?

wider, safer

the larger the therapeutic index value, the _____ the range b/t an effective dose & toxic dose & the ______ the drug

CYP450

citrus inhibits ______ which results in less drug break down & the drug stays in the system longer