Basic Concepts Flashcards
Drug nomenclature
chemical name
generic name
brand name
Chemical name refers to:
the compound’s structure
- not typically used
ex: 2-acetoxybenzoic acid
Generic name
non-proprietary- not owned or trademarked
may be less well recognized
appropriate to use in medical literature
similarities across drug classes
ex: acetylsalicylic acid
Brand name
proprietary name- privately owned
in case presentations must include generic name, brand name optional
ex: aspirin is a registered trademark owned by Bayer
over the counter medication
no prescription required
can be purchased directly to the consumer
deemed to be safe without direct medical supervision
some of these drugs move to OTC status after rx
OTC drugs can still be involved in significant drug interactions
prescription medication
requires prescription from licensed health care provider (HCP)
what is the purpose of controlled substance scheduling?
drugs are scheduled I-V primarily for the purpose of prosecution
regulates the amount
who is prescribing and how much of certain substances? (Dr.s have DEA #s)
schedule I controlled substances
highest potential for abuse
no accepted medical use in the US or lacks accepted safety for use in the treatment in the US
ex: heroine (legal in some other countries), marijuana
schedule II controlled substances
2nd highest potential for abuse
has a currently accepted medical use in the US
abuse of substance may lead to severe psychological or physical dependence
ex: opiates in pure form (oxy cotin, morphine; excludes codine. also, adderall and ritalin: drugs prescribed for 1 reason but used for others)
schedule III controlled substances
abuse potential less than scheduled I or II substances
currently accepted medical use in the US
abuse may lead to moderate or low physical dependence or high psychological dependence
ex: vicodin, percocet, certain codine products
schedule IV controlled substances
abuse potential less than schedule III substances
currently accepted medical use in the US
abuse may lead to limited physical or psychological dependence relative to schedule III
ex: benzodiazepines
schedule V controlled substances
low potential for abuse relative to schedule IV
currently accepted medical use in the US
some schedule V products may be sold in limited amounts w/out a prescription at the discretion of a pharmacist
ex: low dose condone (often in syrup form)- based on the dose
where should you look for drug information
E facts and comparisons clinical pharmacology Lexi-comp MICROMEDEX product package insert national guidelines primary literature Ehealth
new drug approval process (7 steps)
once a compound is “discovered” it must be rigorously evaluated in both animal and human trials
1- compound discovery & “bench” testing/evaluation
2- animal phase of testing
3- human phase I (primarily looking at dosing)
4- human phase II (efficacy becomes more critical)
5- human phase III (typically larger population, placebo enrolled, mix of 1 &2)
6- FDA approval w/ patent
7- human phase IV - post marketing phase (no defined end point- determining if there is anything missed)
off label usage=
drugs prescribed for reasons other than what they were approved for
why are mice/rats used for drug testing?
have a fast reproduction rate
small, cheaper
much similarity between mice and humans
condensed life span- able to look at a life in a relatively short amount of time
pharmaceutical=
drug dose administration
disintegration of drug formulation
pharmacokinetics=
what the body does to the drug absorption distribution metabolism excretion
pharmacodynamics=
drug/receptor interaction
what the drug does the body
study of biochemical and physiological effects of drugs and their mechanism of action
pharmacotherapeutics=
drug effect or response
therapeutic use of the drug (why wold you use it?)
what are the different types of preparations of drugs?
aqueous alcohol solid or semi-solid powder tablets lozenge capsule delayed-release (time release) enteric coated products suppositories ointments transdermal
what are the routes of administration?
1: oral or PO (per os/ per oral)
2: enteral: directly passes through GI
3: Parenteral: bipasses the GI: injections of all sorts, transdermal patches, sprays, inhalers, topical cream
what is ADME?
absorption: stomach & SI
distribution: bloodstream
metabolism: liver
excretion: kidney & LI
drug absorption refers to:
the entrance of a drug into the bloodstream
occurs in the stomach and/or small intestine
what drug factors effect the speed of drug absorption?
1- dosage form
2- drug water solubility
3- drug lipid solubility
4- drug particle size
5- drug configuration
**properties of the drug
***properties of the environment the drug is entering
what are physiologic factors affecting drug absorption?
1- biologic membranes act as barriers- protective
2- body is separated into various “compartments”
3- drug may need to cross several membrane barriers to reach target tissue
4- cell membrane- phospholipid bilayer (impermeable to water)
*small Uncharged ions are able to cross lipid bilayer but large uncharged or small charged ions are denied
what is bioavailability?
the percentage of the administered dose that is absorbed into systemic circulation
what are some factors that influence bioavailability?
1- physical properties of the drug
2-lipid solubility
3- affinity
4- drug protein complex
after a drug gains access to the bloodstream it is distributed to ?
the organ/tissues of the body
what factors effect the amount of drug penetrating specific tissue?
1- physical properties of the drug
2-lipid solubility
3- affinity
4- drug protein complex
what are 4 special anatomical barriers?
1- blood brain barrier (BBB)
2- plasma protein binding
3- blood flow
4- fetal-placental barrier
what is the blood brain barrier?
an additional lipid barrier that protects the brain by restricting the passage of electrolytes and similar water soluble substances into the brain
drugs must have a certain degree of lipid solubility to penetrate the BBB
general body capillaries allow drug molecules to pass freely into the surrounding tissue– brain capillaries have a dense-walled structure and are surrounded by glial cells (lipid). This prevents many drug molecules from entering the surrounding tissue.
tight junctions prevent flow of ionized substances and large particles. (small, unionized, lipophilic are most likely to permeate BBB)
what has high brain bioavailability?
small, ionized, lipophilic ions- most likely to permeate BBB
what is plasma protein binding?
plasma proteins assist in the transport of hormones and vitamins through the body. Many drugs are also able to attach to plasma proteins, specifically albumin
only the unbound portion of the drug is able to exert its pharmacologic activity. the remainder of the bound drug will continue to circulate in the bloodstream
what parts of the body receive the largest blood supply?
the liver, kidneys and brain
therefore they are exposed to the largest amount of the drug
Vd=
volume of distribution (volume in which the drug appears to distribute)
Vd is not a physical volume; it is simply the size of the compatment necessary to account for total amount of drug in the body if it were present throughout in the same concentration found in plasma
Vd= (amount of drug administered) / (plasma concentration of drug)
what is drug metabolism?
1- conversion of a drug to a form easily excreted
2- usually converted to an inactive form
3- some drugs are activated (pro-drugs)
*metabolism occurs in the liver
what is biotransformation?
chemical alteration of drugs and foreign compounds in the body
what is the most critical organ involved in drug metabolism?
the liver
are other organs capable of drug metabolism?
yes!
kidney, lung, GI, skin, etc
what are the phases of metabolism?
can be metabolized by either one or both
phase I- biochemical reactions
phase II- conjugation reactions
what are biochemical reactions?
phase I of metabolism
```
forms of metabolism in the liver:
hydrolysis
oxidation
reductions
DMMS/hepatic microsomal enzyme system
~~~
what it the main function of the DMMS?
to take lipid-soluble drugs and prepare them for excretion via the renal system
what is drug metabolism?
1- conversion of a drug to a form easily excreted
2- usually converted to an inactive form
3- some drugs are activated (pro-drugs)
*metabolism occurs in the liver
what is biotransformation?
chemical alteration of drugs and foreign compounds in the body
what is the most critical organ involved in drug metabolism?
the liver
are other organs capable of drug metabolism?
yes!
kidney, lung, GI, skin, etc
what are the phases of metabolism?
can be metabolized by either one or both
phase I- biochemical reactions
phase II- conjugation reactions
what are biochemical reactions?
forms of metabolism in the liver
hydrolysis
oxidation
reductions
DMMS/hepatic microsomal enzyme system
what is drug excretion?
clearance (CL)
the ability of the body to remove drug from the blood or plasma
expressed as volume per unit time (mL/min)
the amount of drug removed depends on plasma concentration as well as clearance
what are conjugation reactions?
phase II of metabolism
adds charge to the drug in order to make it inactive (ionized)
what is first-pass effect?
drugs taken orally are absorbed through the GI tract into portal circulation. This transports the drug to the liver BEFORE they are distributed through the body. Many drugs administered orally are INACTIVATED by the liver..
if a drug is metabolized significantly before reaching general circulation this can reduce the amount of active drug that reaches general circulation
what are some alternative routes of administration that by-pass first-pass effect?
up the dosage
alter the route of administration- parenteral
what is enzyme induction?
when used repetitively, some drugs may increase enzyme activity. This may lead to FASTER METABOLISM of the drug and SHORTER DURATION of drug action
metabolic tolerance/ drug disposition
what is enzyme inhibition?
some drugs may cause enzyme inhibition- will SLOW METABOLISM of all other drugs metabolized by the enzyme system and will INCREASE DURATION and INTENSITY of the drug
what are the common pathways of drug excretion?
kidney/renal
liver/hepatic
lungs/pulmonary
what is drug excretion?
clearance (CL)
the ability of the body to remove drug from the blood or plasma
expressed as volume per unit time (mL/min)
the amount of drug removed depends on plasma concentration as well as clearance
what is entero-hepatic recirculation?
drug is secreted into bile- may go to feces OR
some drugs are reabsorbed, and the process may be repeated
what are drug levels in the bloodstream?
the plasma level of a drug is always changing
once a drug is administered the plasma level increases as absorption and distribution occur
later, the plasma level will fall as drug metabolism and excretion occur
periodic measurements of a drug can help establish the correct therapeutic range for the given drug
dosing concepts
minimum effective concentration- where the drug becomes active
therapeutic range- b/t min effective concentration and toxic concentration
toxic concentration
loading dose- trying to get into therapeutic range quickly
maintenance dose-
potency- strength
efficacy- effect, how it works
what is plasma half-life (t1/2)?
the half life of a drug= the time required for the plasma concentration of a given drug to fall to half of its original level
what does plasma half life depend on?
CL= clearance
Vd= volume of distribution
why is establishing a half life important?
to determine dose frequency (maintain consistency or effective dose)
median effective dose (ED50)=
the dose required to produce a specific therapeutic response in 50% of a group of patients
median lethal dose (LD50)=
the dose that causes lethality in 50% of a group of animals
therapeutic index (T1) =
(median lethal dose) / median effective dose
receptors=
specific molecules in the body that control the action of cells and tissues
many drugs act though interaction with specific molecules in the body
drug receptor interactions & drugs as agonists
lock and key mechanism: agonist binds perfectly to the receptor and the agonist-receptor interaction facilitates the receptors normal function
drug receptor interactions & drugs as antagonists
the antagonist binds to the receptor and blocks binding of an agonist- therefore the antagonist-receptor complex prevents the receptors normal function
ex: anti-psychotic drugs - D2 (dopamine)
psychotic patient- getting too much dopamine, antagonist drug blocks D2-dopamine receptor so no more can reach
competitive antagonists
compete for the binding site
reversible:
irreversible:
non-competitive antagonists
bind elsewhere in the receptor (channel blockers)
what are some of the factors that influence drug response? (physiological & psychological)
age weight gender percent body fat genetics emotional state placebo effect presence of disease patient compliance
what are teratogens?
certain drugs taken by the mother that can be harmful to the developing fetus
the placenta is NOT a drug barrier
what is passive exposure?
drugs can be passed from the breast milk to the infant, termed passive exposure, possibly causing harm
why are there PK and PD differences between pediatric and adult patients?
infants and young children have:
thinner skin less skeletal muscle higher percentage of body water lower body fat higher percentage of unbound drug due to reduced plasma protein levels
physiology of aging…
due to the physiologic changes of age, the elderly process drugs differently than young/middle aged adults:
CO decreases at an average of 1%/year after age 30
BF decreases due to CO reduction
reduced gastric acid secretion, motility and intestinal absorption
lean body mass and total body water decrease with age while percent body fat increases
the rate of drug metabolism decreases with age
many enzyme systems have decreased production w/age: the enzyme system that appears to be most affected is the mixed function oxidase system
renal BF decreases with age
bioavailability of oral drugs may increase w/ age
**these factors lead to an expected reduced rate of drug metabolism and an increase in duration of drug action
special populations?
patients taking numerous meds
acute or chronic illness
patients in drug/alcohol recovery
known of suspected alterations in drug metabolism (genetic or other)
