Chapter 2

conjugation

(glucuronidation, glycination, sulfation, methylation, alkylation) in combination w/ another substance ( glucronide, glycine, sulfate, methyl groups, and alkyl groups) - result is forms a less toxic product w/ less activity

transdermal

(subtype of topical) provides relatively constant rate of drug absorption; one patch can last 1-7 days, depending on drug; avoids first-pass metabolism - rate of absorption can be affected by excessive perspiration and body temp; patch may peel off; high cost; used patches must be disposed safely - must be placed on alternating sites and on clean, nonhairy, nonirritated area, and only after the previously applied patch has been removed and that area is cleansed and dried; single-dose, adhesive backed drug application system

Glucose-6-phosphate dehydrogenase deficiency

A hereditary condition in which red blood cells break down when the body is exposed to certain drugs.

topical dosage forms

Aerosols, ointments, creams, pastes, powders, solutions, foams, gels, transdermal patches, inhalers, rectal and vaginal suppositories - can be transdermal or inhaled *•Skin (including transdermal patches)•Eyes•Ears•Nose•Lungs (inhalation)•Rectum•Vagina*

chemical name

Describes the drug's chemical composition and molecular structure

parenteral dosage forms

Injectable forms, solutions, suspensions, emulsions, powders for reconstitution *•Intravenous (fastest delivery into the blood circulation)•Intramuscular•Subcutaneous•Intradermal•Intraarterial•Intrathecal•Intraarticular* - fastest route for absorption, followed by enteral and topical routes - intramuscular junction and subcutaneous injection are absorbed more slowly than IV over hours, days, weeks, or months - advantage of bypassing the first-pass effect of liver but still must be absorbed into cells and tissues before exerting pharmacologic effects

drug interaction

alteration of the action of one drug by another

toxic effects

an extension of drug's therapeutic action

metabolite

another ingredient in a drug formulation as a dangerous foreign substance

drug

any chemical that affects the physiologic processes of a living organism; have at least three different names: chemical name; generic name; rade name

contraindication

any patient condition, especially a disease state, that makes the use of the given medication dangerous for the patient

adverse drug reaction

any unexpected, unintended, undesired, or excessive response to a medication given at therapeutic dosages (as opposed to overdose)

therapeutic equivalence

b/c drug cost is high, many institutions have implemented programs where one drug in a class of several drugs is chosen as the preferred agent even if it does not have the same active ingredients - must be approved before selling by having the same effects

empiric therapy

based on clinical probabilities; involves drug administration when a certain pathologic condition has an uncertain but high likelihood of occurrence based on patient's initial presenting symptoms

adverse drug event

broad term for any undesirable occurrence related to administering or failing to administer a prescribed medication

receptor

can be defined as a reactive site on the surface or inside of a cell; critical when mechanism of action of a drug involves a receptor interaction, then the molecular structure of the drug is critical - interaction with drug are agonist, partial agonist, antagonist, competitive antagonist, noncompetitive antagonist

combination dosage

contains multiple drugs in one dose

tolerance

decreasing response to repeated drug doses

drug dissolution

dissolving of solid dosage forms and their absorption, e.g. from GI tract; affected by dosage form and particle size - oral forms are solid (tablet, capsule, or powder), or liquid (solution/suspension) which are already dissolved and absorbed more quickly

short bowel syndrome

drug absorption may be altered in pateitns who have had portions of the small intestine removed because of this and can result in gastric dumping

agonist

drug binds to the receptor, there is a response

antagonist

drug binds to the receptor, there's no repsonse. Drug prevents binding of agonists

partial agonist

drug binds to the receptor; the response is diminshed compared w/ that elicited by an agonist

noncompetitive antagonist

drug combines w/ different parts of the receptor and inactivates; agonist then has no effect

competitive antagonist

drug competes w/ the agonist for binding to the receptor. If bind, there's no response

bioequivalent

drug that has the same strength and action of another drug - if two drug products have the same bioavailability and same concentration of active ingredient

prophylactic therapy

drug therapy provided to prevent illness or other undesirable outcome during planned events

drug classification

drugs are grouped together based on similar properties; can be classified by structure or by therapeutic use - drugs are categorized into pharmacologic classes according to their physiologic functions and primary disease states treated - each class may have subclasses

drug-induced teratogenesis

drugs capable of crossing the placenta causing anomalies or defects in the developing fetus caused by toxic effects of the drug

nonselective interactions

drugs physically interfere with or chemically alter cellular structures or processes

excretion

elimination of drugs from body •RENAL excretion (urine) •Bowel excretion (bile) •Exhalation

Cytochrome P450

enzymes involved in hepatic metabolism that control a variety of reactions that aid a variety of reactions that aid in the metabolism of medications - common types are 1A2, 2C9, 2C19, 2D6, 2E1, 3A4

pharmacoeconomics

focuses on the economic aspects of drug therapy - Study of the economic factors influencing the cost of drug therapy - Cost-benefit analysis

gastric dumping

from short bowel syndrome, bariatric weight loss surgery reduces size of stomach and absorption can be altered b/c stomach contents are delivered to intestines mroe rapidly than usual

allergic reaction

involves the patient's immune system/hypersensitivity - an immunologic hypersensitivity reaction resulting from the unusual sensitivity of a patient to a particular medication; type of adverse drug event

patent life

length of time from patent approval until patent expiration; typically 17 years where 10 is research process and remaining 7 is sales profits to fund the research - after expiration: manufacturers may legally begin to manufacture generic drugs with same active ingredient and the price decreases substantially

duration of action

length of time the drug concentration is sufficient (w/o more doses) to elicit a therapeutic response

monitoring

looking for therapeutic index, drug concentration, patient's condition, tolerance and dependence, interactions, adverse drug events, other drug effects

supportive therapy

maintains the integrity of body functions while the patient is recovering from illness or trauma

medication use process

medication errors during the prescribing, dispensing, administering, or monitoring of drug therapy

biosimilars

new category of generic drug market; a copy version of an already authorized biological product

generic name

nonproprietary name; often much shorter and simpler than the chemical name; used in most official drug compendiums to list drugs - given by the US Adopted Names council - shorter and simpler than chemical name and not protected by trademark

idiosyncratic reaction

not the result of a known pharmacologic property of a drug or of a patient allergy, but instead occurs unexpectedly in a particular patient

antagonistic effects

occur when the combination of two drugs results in drug effects that are less than the sum of the effects (1+1 equals less than 2); caused by an antagonizing (blocking or reducing) effect of one drug on another)

acute therapy

often involves more intensive drug treatment and is implemented in the acutely ill (those with rapid onset of illness) or the critically ill.

patent owner

owner of the patent for the drug

dependence

physiologic or psychological need for a drug

drug effects

physiological reactions of the body to a drug; onset peak, duration, and trough are the effects - peak (highest) and trough (trough) are also used to describe drug concentrations

trade name

proprietary name; drug's registered trademark, and indicates that its commercial use is restricted to the owner of the patent for the drug; usually created by the manufacturer

rectal

prvodies relatively rapid absorption; good alternative when oral route not feasible; useful for local or systemic drug delivery; usually leads to mixed first pass and non-first pass metabolism - possible discomfort and embarrassment to patient; often higher cost than oral - absorption is erratic and unpredictable but provides safe alternative when nausea and vomiting prevents oral dosing of drugs; pt must be placed on left side so normal anatomy of colon allows safe insertion; suppositories are inserted using a gloved hand/gloved index finger and water-soluble lubricant; must be administered as ordered

therapeutic index

ratio of a drug's toxic level to the level that provides therapeutic benefits

steady state

refers to physiological state in which the amount of drug removed via elimination is equal to amount of drug absorbed with each dose

FDA

regulates the approval and clinical use of all drugs in the US including requirement of an expiration date on all drugs

immediate-release dosage form

release all active ingredient immediately upon dissolution in GI tract

extended-release tablets and capsules

release drug molcules in the pt's GI tract over a prolonged period: prolongs drug absorption as well as duration of action - normally easily identified by various capital letter abbreviations attached to their names - must not be crushed b/c could cause accelerated release of drug from dosage form and possible toxicity and disrupt coating to protect lining of stomach

drug actions

some drug mechanisms of action are more clearly understood than others - the process involved in the interaction b/w a drug and body cells; mechanisms

toxicology

study of adverse effects of drugs and other chemicals on living systems - frequently involves overlapping principles of both pharmacotherapy and toxicology

pharmaceutics

study of how various dosage forms influence the way in which the drug affects the body

pharmacognosy

study of natural (vs. synthetic) drug sources i.e. plants, animals, minerals

pharmacogenomics

study of traits that are revealed by drug administration

pharmacokinetics

study of what the body does to the drug; involves the process of what the body does to the drug; involves the process of absorption, distribution, metabolism, and excretion - half-life, therapeutic drug monitoring, therapeutic window •Goal: How much of a drug is needed to reach its target in the body? •Absorption •Distribution •Metabolism •Excretion

pharmacodynamics

study of what the drug does to the body; involves drug-receptor relationships •How well do the target cells respond to the drug?•Mechanism of action, through: •Receptors •Enzymes •Ion Channels •Immune System •Nonselective Interactions •Or... we have no idea how it works

phramacology

study or science of drugs and how it affects humans - encompasses a variety of topics i.e. absorption, biochemical effects, biotransformation (metabolism), distribution, drug history, drug origin, excretion, mechanisms of action, physical and chemical properties, physical effects, drug receptor mechanisms, therapeutic effects, toxic effects - has a variety of subspecialties: pharmaceutics, pharmacokinetics, pharmacodynamics, pharmacogenomics, pharmaeconomics, pharmacotherapeutics, pharamcognosy, and toxicology - has 3 areas: pharmaceutics, pharmacokinetics, and pharmacodynamics: describe the relationship b/w dose of drug and activity treating the disorder

enzymes

substances that catalyze nearly every biochemicalr eaction in a cell

supplemental therapy

supplies the body with a substance needed to maintain normal function

Enteral dosage forms

tablets, capsules, oral soluble wafers, pills, timed-release capsules, timed-release tablets, elixirs, suspensions, syrups, emulsions, solutions, lozenges, or troches, rectal suppositories, sublinguial or buccal tablets - drug is absorbed into systemic circulation through mucosa of the stomach/small/large intetines - orally administered are absorbed from the intestinal lumen in blood system and transported to the liver where enzymes metabolize it and remaining active ingredients are passed through general circulation - absorption affected by acidity of stomach, absorption changes of intestine, and presence/absence of food - *oral rectal, sublinguinal, or buccal administered*

substrate

target for enzyme

bioavailability

term used to express the extent of drug absorption - ex: if a large proportion of a drug is chemically changed into inactive metabolites in the liver, then a much smaller amount of drug will pass into the circulation (be bioavailable and high first-pass effect) - less than 100% with drugs administered by mouth and IV route are 100%

parent drug

the chemical form of a drug that is administered before it is metabolized by the body into its active or inactive metabolites - active have pharmacologic activity of their own even if parent drug is inactive - inactive lack pharmacologic activity and are siply drug waste products awaiting excretion from the body

absorption

the movement of a drug from its site of administration into the blood for distribution to the tissues •How does a drug enter the bloodstream? •Bioavailability: the extent of drug absorption •First pass effect - affected by route of administration •Enteral •Sublingual buccal •Parenteral: Skips the absorption process •Topical •Transdermal •Inhaled

volume of distribuion

theoretical volume; used to describe the various areas in which drugs may be distributed (compartments)

peak effect

time required for drug to reach its maximum therapeutic response -> corresponds with drug concentration - if level too high = toxicity - too low trough level = not therapeutic

half-life

time required for one-half of given drug to be removed from body; measure of rate at which drug is eliminated from the body - used to see when steady state will be reached

onset of action

time required for the drug to elicit a therapeutic response

oxidation-reduction hydrolysis

type of biotransformation that produces chemical reactions - result is increase of polarity of chemical, making it more water-soluble and more easily excreted -> often results in loss of pharmacologic activity

incompatibility

used to describe parenteral drugs; when two parenteral drugs/solutions are mixed together and the result is a chemical deterioration of one or both the drugs or formation of a physical precipitate

drug-drug interaction

when an individual is taking two medications that are highly protein bound, medications may compete for binding sites on the albumin molecule -> free and unbound drug -> unpredictable drug response - when presence of one drug decreases or increases action of another drug administered

synergistic effects

when two drugs administered together interact in such a way that their combined effects are greater than the sum of the effects for each drug given alone

intraarticular

within a joint

intraathecal

within a sheath

intraarterial

within an artery

pharmacotherapeutics

(therapeutics) focuses on the clinical use of drugs to prevent and treat diseases; defines the principles of drug actions •What is the end goal of the drug therapy? *•Acute:* Vasopressors to maintain BP *•Maintenance:* oral contraceptives for birth control *•Supplemental:* Insulin to diabetics, Iron to anemics *•Palliative:* High dose opioid analgesics for end-stage Ca *•Supportive:* Giving blood during surgery *•Prophylactic:* Preventative vaccinations *•Monitoring:* Therapeutic Index, Drug Concentrations, Patient's Condition, Tolerance and Dependence, Interactions, Adverse effects, Toxic effects •Tolerance: decreasing response to repeated drug doses •Dependence: physiologic or psychological need for a drug •Physical dependence: physiologic need for a drug to avoid physical withdrawal symptoms •Psychological dependence: also known as addiction and is the obsessive desire for the euphoric effects of a drug •Interactions •Additive effects 1+1=2 •Synergistic effects 1+1= >2 •Antagonistic effects 1+1= <2•Incompatibility: IV drugs or NG/GT drugs •Adverse drug event •Adverse drug withdrawal event •Medication error •Adverse drug reaction: AT THERAPUTIC DOSAGES •pharmacologic, hypersensitivity, idiosyncratic, & drug interaction •Toxic effects: ABOVE THERAPEUTIC LEVELS •Other drug effects • Teratogenic, mutagenic, carcinogenic

sublinguinal, buccal

- absorbed more rapidly from oral mucosa and leads to more rapid onset of action; avoids breakdown of drug by stomach acid; avoids first-pass absorption is bypassed - pt's may swallow pill instead of keeping under tongue until dissolved; pills often smaller to handle - drugs given are to be placed under tongue and then swallowed; nonirritating, w/o flavor and water-soluble

topical

- delivers medication directly to affected area; decreases likelihood of systemic drug effects - sometimes awkward to self-administer; can be messy; higher cost than oral route - mostly given in form of solution, ointment, spray, or drops; maximal absorption is enhanced w/ skin that's clean and free of debris; wear gloves and perform sterile techniques

additive effects

- drug interactions in which the effect of two or more drugs with similar actions is equivalent to the sum of the individual effects of the same drugs given alone (1+1 = 2)

intramuscular and subcutaneous

- good for poorly soluble drugs which are often given in 'depot' preparation form and are then absorbed over a prolonged period; onsets of action differ depending on route - discomfort of injection; inconvenience; bruising; slower onset of action compared to IV but quicker than oral mostly - using landmarks to indentify correct sites is always required and at 90 degree angle

biotransformation

- one or more biochemical reactions involving a parent drug; occurs mainly in the liver and produces a metabolite that is either inactive or active; metabolism - next step after absorption - types are oxidation reduction hydrolysis, and conjugation

inhalational

- provides rapid absorption; drug delivered directly to lung tissues where most of these drugs exert their actions - rate of absorption can be too rapid, increasing risk for exaggerated drug effects; requires pt education for self-administration - to be used exactly as prescribed w/ clean equipment

intravenous

- provides rapid onset (drug delivered immediately to bloodstream); allows more direct control of drug level in blood; gives option of larger fluid volume -> diluting irritating drugs; avoids first-pass metabolism - high cost; not self-administered; irreversibility of drug action and inability to retrieve medication; risk of fluid overload; greater likelihood of infection; possibility of embolism - continuous requires frequent monitoring to be sure correct volume and amount are administered and drug reaches safe, therapeutic blood levels; must be checked for compatabilities; monitored for complications, must be flushed with saline

therapeutic drug monitoring

- used to help maintain drug levels within the therapeutic window Peak and Trough levels are measured to verify adequate drug exposure, maximize therapeutic effects , and minimize drug toxcicity - done by a clinical pharmacist

oral

- usually easier, more convenient, and less expensive; safer than injection, dosing more likely to be reversible in cases of accidental ingestion (emesis) - variable absorption; inactivation of some drugs by stomach acid/pH, problems with first-pass effect or presystemic metabolism; greater dependence of drug action on pt variables - involve a variety of dosage forms; some medications are to be taken with food while others aren't; taken with fluid i.e. water, prior tube placement if needed

maintenance therapy

Does not eradicate pre-existing problems the patient may have, but will prevent progression of a disease or condition.

enteric-coated tablets

Have a special coating that allows them to pass through the stomach (acidic) & dissolve in the small intestine (alkaline)

blood-brain barrier

The barrier system that restricts the passage of various chemicals and microscopic entities (e.g., bacteria, viruses) between the bloodstream and the central nervous system. It still allows for the passage of essential substances such as oxygen.

palliative therapy

The goal of palliative therapy is to make the patient as comfortable as possible. It is typically used in the end stages of an illness when all attempts at curative therapy have failed. ex. use of high dose opioid analgesics to relieve pain in final stage cancer patients

first-pass effect

The initial metabolism in the liver of a drug absorbed from the gastrointestinal tract before the drug reaches systemic circulation through the bloodstream. Reduces the bioavailability of the drug to less than 100%

dosage form

The physical manifestation of the drug or how the drug is supplied. - variety exists to provide accurate and convenient delivery systems: enteral, parenteral, topical