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289 Cards in this Set
- Front
- Back
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What is a drug?
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A chemical compound capable of producing a biological effect
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What is pharmacology?
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biomedical science concerned w/ the interaction of chemical substances with living cells, tissues, and organisms
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What is the first phase of drug use?
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superstition
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What is superstition?
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driving out spirits with noxious substance
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What does pharmakon mean?
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magic charm
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What is the second phase of drug use?
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empircism
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What is empiricism?
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"watch and learn", "trial and error"--not a controlled experiment, just observational
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What is the third phase of drug use?
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rational or scientific use of therapeutics
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What is done in the third phase that sets it way apart from the rest?
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safety and efficacy are studied prior to general use and mechanisms of drug action are studied
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Who was the first scientific pharmacologist?
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Schmiedeberg (used mushrooms--muscarine)
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Who was the first to start "pharmacology"?
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John Jacob Abel (discovered how to crystallize insulin)
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Who was Paul Erlich?
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father of receptor pharmacology
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What is the possible fourth stage of drug use that may be emerging?
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genetic and proteomic pharmacology
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What is pharmacokinetics?
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What the body does with the drug, concerned w/ the processes that determine the concentration of drugs in body fluids and tissues over time (ADME)
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What 4 processes do drugs go through in the body?
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absorption, distribution, metabolism, and excretion
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What is pharmacodynamics?
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what the drug does to the body, study of the actions of drugs on target organs (biochemical mech and dose-response relationships)
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What can the drug possibly effect?
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biochemistry, receptor activation, changes in cell activity, changes in organ function, and behavioral changes
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What is toxicology?
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study of poisons
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What are the harmful effects of drugs?
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pathology, disease, death
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What is therapeutics?
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treating disease with drugs
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What do clinical trials determine?
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safety, efficacy, improvement over standard therapies
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What is pharmacy?
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preparation, dispensing, and use of drugs
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What is pharmacognosy?
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drug extraction from natural products (ex. algae)
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What is medicinal chemistry?
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synthesis of drugs
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What is pharmaceutics?
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formulation of durgs
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What does alkaloid mean?
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comes from a plant
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What is a hormone that we get from animals to help human disease?
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insulin from pigs
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What are some examples of minerals used for drugs?
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lithium, calcium, and arsenic
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Are there many true synthetic drugs?
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No, most are modified natural drugs
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Is accurate dosing possible with herbal supplements?
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Not if they are truly natural b/c nothing has been extracted to measure and put back in
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What does purification of active constituents allow for?
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compounding and accurate dosing
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What are the 4 types of inert ingredients in a tablet or capsule?
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fillers (cornstarch), lubricants (talc), adhesives, and disintegrants
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What are gastric acid resistant polymers known as?
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Enteric Coatings
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What is aspirin isolated from?
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bark of a willow tree
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How do osmotic pump tablets work?
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water enters the capsule and displaces the drug and is an example of controlled diffusion sustained-release
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What is a transdermal patch an example of?
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controlled diffusion sustained-release
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What type of tablet breaks down at controlled rates?
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sustained release tablets
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What contains pellets that dissolve at various rates due to varying sizes?
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sustained-release capsules or "tiny time pills"
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What is used in treatments of skin conditions?
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topical ointments and creams
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How are nitrates and opioids usually administered?
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sublingually
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Suppositories can be local or systemic and are preferred when?
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with PO difficulties: unconscious, nausea and vomiting, and kids
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What is the benefit of aerosols?
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localizes effect to where it's needed (parenterally would go throughout entire body) and it has IV-like kinetics
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What are 3 types of solutions and suspensions?
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syrups (sweet), elixirs, and sterile (for IV)
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When do you use elixirs?
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for the drugs that are not water-soluble, alcohol is used to dissolve those lipophilic compounds
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What are the 4 enteral routes of administration?
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oral, rectal, buccal, and sublingual
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What is Latin for "by mouth" and its abbreviation?
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per os (PO)
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What are the advantages of PO admin?
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convenient, safe, and economical
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What are the disadvantages of PO admin?
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first pass metabolism (liver portal system), inactivation by gastric acid (enteric coated tablet), GI upset, variable absorption
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What are the 5 types of parenteral admin?
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intravenous (IV), intramuscular (IM), subcutaneous (SC), intrathecal, and intra-articular
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What is intrathecal?
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injection in the spine
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What is intra-articular?
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injection in the joints
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What are the advantages of IV admin?
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bypasses absorption, avoids first pass metabolism, and allows response titration
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What are the disadvantages of IV admin?
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dangerous (once you inject it, you can't take it back), sometimes inconvenient
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What are the advantages of IM and SC admin?
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allows depot admin (bubble of med under skin), appropriate for suspensions
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What are the disadvantages of IM and SC admin?
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may be painful, limited volume of admin, and can't be sued for irritants
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What are the chemical names of drugs based on?
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structure, standard nomenclature
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Why are chemical names not used for drugs?
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it is elaborate for large molecules
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Who determines the generic name of drugs?
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United States Adopted Names (USAN) Council (should be used by us)
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What name of drugs is used by manufacturers, encountered clinically, and may be confusing?
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proprietary, trade, or brand name
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How are most drugs excreted?
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in the urine
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Which drugs can cross a membrane...ionized or unionized?
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unionized
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A weak acid protonated form is _____________.
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unionized
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A weak base protonated form is ______________.
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ionized
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pKa is the pH at which ______ amounts of drug are ______ and __________.
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equal, charged, and uncharged
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Are weak acids or bases better to take by mouth?
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weak acids b/c they will be able to get out of the stomach b/c they are uncharged
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Will weak acids be absorbed when taken by mouth?
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yes
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What is the best way to take a weak base?
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injection or inhalation because the charged ions would not be able to exit the stomach
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Why is the 2-compartment model hard to measure acurately?
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b/c you can't directly measure distribution
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What is volume of distribution (Vd)?
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the volume of a dose of drug would need to be dissolved in to produce the concentration measured from a blood sample
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What does a low value Vd mean?
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the drug is mainly restricted to the blood
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What does a high value Vd mean?
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the drug is distributed throughout the body
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In a Vd graph, what is the slope of the line equal to?
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the rate of excretion
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What is drug biotransformation?
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the enzymatic metabolism of drugs
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Where does drug biotransformation occur?
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mostly in the liver, some in the kidney, gut, brain, lungs, and skin
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Why does drug biotransformation occur?
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to terminate effect of xenobiotics and to activate prodrugs
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When does drug biotransformation occur and you don't want it to?
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first pass liver metabolism
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What has 100% bioavailability?
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Drugs admin IV
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What occurs in phase I of biotransformation?
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oxidation, hydrolysis or reduction
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What does phase I of biotransformation accomplish?
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oxidation in the liver makes drug more polar and unmasks functional groups and usually prepares xenobiotic for phase II modifications
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What is phase II of biotransformation?
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conjugation
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What does phase II of biotransformation accomplish?
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makes xenobiotic more polar for easier renal or biliary excretion
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What is the most common phase I reaction and what does it require?
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microsomal cytochrome P450 monooxygenase system, requires O2 and NADPH
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What is the most common phase II reaction?
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glucuronidation and is catalyzed by glucuronosyltransferases
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What are some other phase II reactions?
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acetylation, sulfation, glycine conjugation, and O-, S-, and N-methylation
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What can influence biotransformation?
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genetics, age, pathology, and other drugs
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What is the first step of excretion?
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glomerular filtration
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Where are small molecules filtered?
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in the renal tubule
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What drugs are not filtered?
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those that are bound to large molecules such as proteins
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What is the selective process and step 2 of excretion?
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active tubular secretion
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What are some qualities of active tubular secretion?
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selective, competitive (potential drug interactions), and it requires energy
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What is the third step of excretion?
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tubular re-absorption
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Is tubular re-absorption active or passive?
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passive, most water has been absorbed back into blood and gradient favors re-absorption
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What does tubular re-absorption depend on?
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lipids and unchanged molecules (filtrate pH is important)
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What will be reabsorbed at a low filtrate pH?
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acids
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What will be reabsorbed at a high filtrate pH?
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bases
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When can you alter urine pH in a drug overdose effectively?
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when the drug has not been extensively metabolized prior to renal excretion and if the drug is a weak acid
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What will increase urine pH?
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sodium bicarbonate
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What does increasing the urine pH do?
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it reduces re-absorption and mitigates metabolic acidosis
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What is first order elimination kinetics?
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where a fraction of drug is removed per unit time, elimination depends on drug concentration
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What is zero order elimination kinetics?
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where a set of mass drug is removed per unit time, elimination depends on the mechanistic rate
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What is a good example of zero order elimination kinetics?
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elimination of alcohol
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Which order is initially fast and slows over time?
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first order
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Which order elimination would you want in case of OD?
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depends--whichever one yields a less toxic dose first
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What is clearance?
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fraction of Vd from which drug is eliminated at t1/2 ckearabce = 1/2 Vd
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How do you compare bioavailabilty of PO to IV?
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it = area under the curve oral / area under the curve IV
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How do you achieve continuous infusion kinetics?
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accumulation through a first order process of IV
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Why is oral admin not preferred over IV?
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b/c it does not achieve a steady state--too many peaks and valleys
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Will a longer or shorter 1/2 life remove less drug per unit time?
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longer
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How do most drugs produce their effects?
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by binding to macromolecular receptors
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What are antibiotics isolated from?
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microorganisms
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What is the most common type of durg obtained from animals?
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hormones
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What are two methods used to extend the release of a drug?
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controlled diffusion and controlled dissolution
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What are hard capsules used to enclose?
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powdered drugs
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What do soft capsules enclose?
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drugs in solution
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Are sublingual and buccal admin affected by first-pass metabolism?
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no b/c they have rapid absorption
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What does parenteral admin mean?
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refers to drug admin w/ a needle and syringe or w/ an IV infusion device
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What provides the greatest control and reliability over the dose of the drug reaching general circulation?
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IV
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The development of pharmacology was made possible by important advances in chem and phys that enabled scientists to isolate and synthesize pure chemical compounds (drugs) and to design methods for ________ and ________ the physiologic actions of the compounds.
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identifying and quantifying
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What is concerned with the mechanisms of drug action and the dose-response relationship?
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pharmacodynamics
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What is concerned with the relationship b/t the drug dose and the plasma drug concentration over time?
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pharmacokinetics
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The sources of drugs are ______ products and ______ synthesis.
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natural and chemical
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Drugs can exist as ______ drug preparations, _____ drug compounds, or _______ preparations used to administer a specific dose to a patient.
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crude, pure, pharmaceutical
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What are the primary routes of administration?
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enteral, parenteral, transdermal, inhalational, and topical
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Most routes of administration produce __________ effects.
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systemic
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______ admin produces a localized effect at the site of admin.
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topical
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All drugs have a _______ name and a _______ name.
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proprietary and chemical
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Drugs are absorbed into the _______ compartment (blood), distributed from the ______ compartment to the _______ comp (tissues), and eliminated from the ________ comp.
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central, central, peripheral, central
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How are most drugs absorbed across a biologic barrier and into the circulation?
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by passive diffusion
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What is a process in which the drug dissolves in the lipid components of the cell membrane?
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lipid diffusion
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What is aqueous diffusion?
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passage through the aqueous pores in cell membrane
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If the pH is _____ than the pKa, the protonated form predominates.
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less
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What is the only form of a drug that can readily penetrate cell membranes?
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nonionized form
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Where are weak bases more readily absorbed than in the stomach?
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intestines
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Where are drugs rapidly distributed to?
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highly perfused tissues
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When do drug molecules dissociate from albumin to maintain the equilibrium between free drug and bound drug?
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as the free (unbound) drug diffuses into interstitial fluid and cells
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What type of molecules does the blood-brain barrier restrict penetration of?
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polar and ionized
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What is drug metabolism?
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enzyme-catalyzed conversion of drugs to their metabolites
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Are drug metabolites more or less water soluble than the parent molecule?
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more (makes them more readily excreted by the kidneys)
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T/F Most conjugated drug metabolites are inactive.
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true
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What are admin as inactive compounds and, subsequently, are biotransformed to active metabolites?
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prodrugs
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_______ acetylation is an autosomal recessive trait.
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slow
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The amount of drug excreted is the sum of the amounts of ______ and _______ minus the amount ________.
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filtered, secreted, reabsorbed
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Is active tubular secretion affected by plasma protein binding?
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no
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What does the extent to which a drug undergoes passive reabsorption across renal tubular cells and into the circulation depend on?
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lipid solubility of the drug
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What affects the proportion of ionized and nonionized drugs?
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renal tubular pH
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What is a drug's rate of elimination equal to?
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the plasma drug concentration multiplied by the drug clearance
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What is clearance?
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the volume of body fluid (blood) from which a drug is removed per unit time
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What can accelerate the excretion of a weak acid?
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alkalinizing the urine (acidifying for a weak base)
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How do you calculate the renal clearance?
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renal excretion rate/plasma drug concentration
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What is teh time required to eliminate half of the amount of a drug in the body or to reduce the plasma drug concentration by 50%?
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elimination half-life
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After a single dose of drug is admin, the plasma concentration _______ as the drug is absorbed, reaches a peak as absorption is completed, and then _______ as the drug is eliminated.
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increases, declines
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What is bioavailability?
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the fraction of the administered dose of a drug that reaches the systemic circulation in an active form
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When is a steady-state condition achieved?
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when the rate of drug elimination equals the rate of drug administration
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What is the time required to reach the steady state independent of?
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drug dose and the rate or frequency of drug admin
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What does the steady-state drug concentration depend on?
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drug dose admin per unit time and on the 1/2 life of the drug
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What is given to rapidly establish a therapeutic plasma drug concentration?
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priming or loading dose
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What is given to establish or maintain a desired steady-state plasma drug concentration?
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maintenance dose
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What form of weak acids and bases is the only form lipid soluble?
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nonionized
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What influences the distribution of a drug?
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organ blood flow and by the plasma protein binding, molecular size, and lipid solubility of the drug
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How is Vd calculated?
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by dividing the drug dose by the plasma drug concentration at time zero
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What are the most important oxidative biotransformation enzymes and where are they located?
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cytochrome P450 enzymes in the endoplasmic reticulum of liver cells
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When does a drug exhibit zero order elimination kintetics?
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when drug elimination mechanisms become saturated
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What is constant in first-order kinetics as long as physiologic elimination processes are constant?
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drug's half-life and clearance
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What are some factors that reduce bioavailability?
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incomplete tablet disintegration and first-pass and gastric inactivation of a drug
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How many drug half-lives does it take to achieve the steady-state condition?
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about 4-5
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The ______ dose can be calculated by multiplying the _____ by the desired plasma drug concentration.
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loading, Vd
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Why do you admin a loading dose?
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to rapidly establish a therapeutic plasma drug concentration
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Calculate loading dose...
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Vd x Cp
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What do you need to know to calculate the maintenance dose?
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clearance
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What is clearance?
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Vd that has drug removed per unit time
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Calculate maintenance dose...
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desired Cp x clearance per hour x dosage interval
(desired Cp X clearance is hourly elimination rate) |
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What is a receptor?
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a protein
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A receptor-ligand interaction is usually ____________ and reversible.
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non-covalent
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What does binding to a receptor always cause?
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a confirmational change
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Does a drug dissociate faster or slower with a low affinity for a receptor?
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faster
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G-protein coupled receptors open _____ channels.
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K+
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Ligand-gated ion channels open _____ channels.
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Na+
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What are transcription factors?
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proteins that bind DNA and alter transcription of other genes (steroid hormones)
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What do kinases do?
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phosphorylation
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What is the phosphorylation cascade of receptor tyrosine kinases?
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bind growth factor, dimerize, autophosphorylate, and phosphorylate other cellular proteins
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What does the job in cytokine receptors since there is no intrinsic kinase?
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JAK--Janus kinase
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Are drugs ever really specific?
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no, they're just selective
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If you drive up the dose of a drug, what will happen?
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it will start interacting w/ other receptors that have a lower affinity--results in problems
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What occurs as ligand concentration increases?
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a maximal amount of binding is attained
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At equilibrium, the drug concentration that occupies ____ of receptors defines ___.
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1/2, Kd
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What is Kd a measure of?
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affinity
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Will an increased affinity take more or less drug?
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less b/c they bind and don't dissociate as readily
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What is EC50 defined as?
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a measure of potency
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Are efficacy and affinity indirectly or directly related?
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indirectly
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What is efficacy?
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the ability of a drug to produce an effect
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What are drugs that are only capable of producing partial efficacies?
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partial agonists
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What is an agonist?
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a drug that BINDS a receptor, ACTIVATES a receptor, and produces and EFFECT
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What is an antagonist?
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a drug that binds a receptor, does NOT activate receptor, and may or may not produce an effect
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What has a maximal intrinsic activity and is capable of producing max responses?
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full agonists
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What has less than max intrinsic activity, are not capable of producing a full response, and may antagonize effects of full agonists?
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partial agonists
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What have NO intrinsic activity, may antagonize effects of agonists, and may prevent an agonist from having an effect?
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antagonists
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Competitive anatgonists "compete" for ____________ binding sites.
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agonist (can be overcome by adding more agonist)
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What do irreversible antagonists do?
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covalently modify receptors, don't dissociate, and effects CANNOT be overcome by adding more agonist
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What binds to a distinct site, prevents receptor activation, and has effects that CANNOT be overcome by adding more agonist?
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noncompetitive antagonists
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When do both competitive and noncompetitive antagonists decrease apparent agonist potency?
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when there are spare receptors and full efficacy can be achieved
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When there are no spare receptors ___________ antagonists will ALSO reduce efficacy.
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noncompetitive
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What is the graded dose response?
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the relationship b/t drug dosage and percentage of the max drug effect
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What is quantal dose response?
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the relationship b/t drug dosage and percentage of responders
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Do you want a higher or lower therapeutic index and certain safety factor?
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higher b/c that means that you need a lot more drug to be toxic and very little to be efficacious
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Is TI or CSF more useful?
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CSF
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Why does drug development cost so much?
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high failure rate, drugs must be evaluated in humans, and liability
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What is step 1 in drug development?
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identify a novel compound or formulation
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What is step 2 in drug development?
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preclinical animal studies (at least 2 species) and pharmacologic characterization of new drug
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What is step 3 in drug development?
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File "Investigational New Drug Application" (IND) w/ FDA (it notifies FDA that you want to try it out on people)
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What is step 4 in drug development?
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Phase 1 clinical trials (uses healthy volunteers for prelim toxicity assessment)
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What is step 5 in drug development?
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phase 2 clinical trials (uses small # of patients w/ targeted condition for toxicity assessment)
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What do phase 1 clinical trials determine?
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pharmacokinetics in humans
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What do phase 2 clinical trials determine?
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dose-response evaluation
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What is step 6 in drug development?
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phase 3 clinical trials (thousands of patients)
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How are phase 3 clinical trials conducted?
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on a large-scale with placebo-controlled usually double-blind studies
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What do phase 3 clinical trials determine?
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safety, efficacy, and advantages over standard therapy
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What is step 7 in drug development?
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file a "New Drug Application" (NDA) w/ FDA
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What is step 8 in drug development?
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market drug
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What is step 9 in drug development?
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post-marketing safety surveillance (rare and delayed toxicities)
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What are excessive pharmacological effects?
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excessive dosage and selectivity problems
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What are hypersensitivity reactions?
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immune responses (immune system becomes more sensitive to xenobiotics)
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What are some examples of organ system toxicity?
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hematopoetic, hepatic, renal, pulmonary, and skin rashes
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What is chemical incompatibility?
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drug-drug interactoin that forms insoluble precipitate
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What are pharmacodynamic interactions?
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additive, synergistic, and antagonistic drug effects
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What are pharmacokinetic interactions?
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absorption, distribution, biotransformation, and excretion
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What is the largest family of receptors?
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G-protein coupled receptors, called GPCR
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What is a ligand that binds to the same active, catalytic site as the endogenous substrate?
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competitive inhibitor
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What are ligands that bind at a different site on the enzyme and alter the shape of the molecule, thereby reducing its catalytic activity?
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noncompetitive inhibitors
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What are some other macromolecules that serve as receptors?
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lipids and phospholipids that make up the membrane
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How are drug receptors classified?
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according to drug specificity, tissue location, and by their molecular structure
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What are receptor-like proteins predicted from gene sequencing for which an endogenous ligand is not identified?
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orphan receptors
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What is affinity?
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the tendency of a drug to combine with its receptor which is a measure of the strength of the drug receptor bonding
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What is Kd?
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it represents the drug concentration required to saturate 50% of the receptors
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Agonists have both receptor ________What __ and __________.
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affinity and efficacy
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Drugs that have receptor affinity but lack efficacy are called __________.
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antagonists
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What decreases the rate of signal transduction?
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inverse agonists
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What can continuous or repeated exposure to agonists do to receptors?
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desensitize
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Short term agonist exposure is called _______ or ______ while longer term is called ______.
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desensitization or tachyphylaxis and down-regulation
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What does supersensitivity result from?
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continuous exposure to antagonists
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What is usually responsible for pharmacodynamic tolerance
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receptor down-regulation
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What usually causes pharmacokinetic tolerance?
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accelerated drug elimination (usually an up-regulation of the enzymes that metabolize the drug)
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How is the response elicited in graded dose-response relationships described?
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in terms of percentage of max response and is plotted against the log dose of the drug
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How is potency expressed?
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in terms of the median effective dose (ED50) which is the dose that produces 50% of the max response
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How is the response elicited with each dose of a drug described in quantal dose-response relationships?
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all-or-none effect plotted against the log dose of the drug
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Most drugs form ________, ___________ bonds with macromolecular receptors located in target cells.
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reversible, stereospecific
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Are affinity and potency directly or indirectly related?
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directly
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A competitive antagonist and a noncompetitive antagonist will both cause a __________ shift in the dose-response curve of an agonist.
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rightward
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What is the only antagonist that will reduce the max response of the agonist?
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noncompetitive antagonist
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What is the therapeutic index?
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the ratio of the median lethal dose to the median effective dose
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Studies are designed to study the risk of ______, ________, and _______ toxicity as well as teh risk of _______, __________, and _________.
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acute, subacute, and chronic, teratogenesis, mutagenesis, and carcinogenesis
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Phase 2 clinical studies are the first to establish a ______ _______.
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dosage range
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What is a cross-over study?
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one in which the pt receives one medication or placebo for a period of tiem and then is switched, after a washout period, to the other medication or placebo
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How long does a statistically significant therapeutic effect have to be demonstrated for the placebo to begin receiving the treatment or else it is unethical?
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6 months
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What was the first federal legislation concerning drug product safety and efficacy in the U.S.?
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the Pure Food and Drug Act of 1906
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What does the Food, Drug, and Cosmetic Act prohibit?
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the distribution of drug products that are adulterated, misbranded, or that do not have an approved New Drug Application
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What amendment created a legal distinction b/t nonprescription and prescription drugs?
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Durham-Humphrey Amendment in 1952
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When was accelerated drug approval authorized for new drugs to treat life-threatening conditions?
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1992
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What are Schedule I drugs?
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drugs that have a high abuse potential and no legitimate medical use
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What are Schedule II drugs?
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drugs that have a high abuse potential but a legitimate medical use
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What are Schedule III, IV, and V drugs?
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drugs that have lower abuse potential and fewer restrictions on distribution
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Hypersensitivity reactions are better known as...
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drug allergies
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What are Type I hypersensitivity reactions?
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immediate that are mediated by immunoglobulin E antibodies
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What are Type II drug allergies?
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cytolytic reactions that involve complement and are mediated by immmunoglobulins G and M
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What are Type III drug allergies?
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mediated by immune complexes
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What are Type IV hypersensitivity reactions?
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mediated by sensitized lymphocytes
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What is the most serious form of hematopoietic toxicity?
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aplastic anemia
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Is cardiotoxicity common?
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no
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What are pharmaceutical interactions due to?
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chemical reaction between drugs prior to their administration or absorption
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What is an additive effect?
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equal to the sum of the individual drug effects
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What is a synergistic effect?
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greater than the sum of the individual drug effects
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Are drugs more rapidly absorbed in the intestines or the stomach?
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intestines
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As the free drug concentration increases, the drug's rate of elimination _______, and any change in the drug's effect on target tissue is usually short-lived.
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increases
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Drug interactions are more likely to occur if the affected drug as a _____ therapeutic index or is being used to treat a critically ill patient.
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low
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In what ages is the capacity to metabolize and excrete drugs often greatly reduced?
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elderly, neonates and especially premature infants
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Hepatic and renal disease may reduce the capacity of the liver and kidneys to ______ and _____ drugs.
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biotransform and excrete
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What are drug-induced developmental abnormalities called?
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teratogenic effects
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When is the risk of teratogenic effects the greatest?
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during the period of organogenesis from the 4th week to the 10th week of gestation
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What has the greatest risk of developmental abnormalities after the 10th week of gestation?
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the brain and spinal cord
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What are Category A drugs?
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drugs that have been shown in clinical studies to pose no risk to the fetus
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What are Category B drugs?
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drugs that may have shown risk in animal studies but not in human studies
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What are Category C drugs?
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drugs in which adverse effects on the fetus have been demonstrated in animals but there is insuffcient data in pregnant women, so risk to the fetus can't be ruled out
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What are Category D drugs?
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drugs that show positive evidence of risk to the fetus
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What are Category X drugs?
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drugs that are contraindicated in pregnancy
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When should breast feeding be avoided?
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if a drug taken by the mother would cause the infant's plasma drug concentration to be greater than 50% of the mother's plasma concentration
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What act classifies potentially abused drugs in five categories, requires registration of legitimate drug distributors and health care professionals, and limits the prescription and distribution of controlled substances?
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The Comprehensive Drug Abuse Prevention and Control Act also called the Controlled Substances Act (CSA)
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When do drug interactions occur?
|
when one drug alters the pharmacologic properties of another drug (usually due to pharmacokinetic effects)
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What are factors that must be considered in drug selection and dosage?
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age, disease, pregnancy, and lactation
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The very young and very old tend to have an __________ sensitivity to therapeutic agents, usually b/c of a reduced capacity to eliminate drugs.
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increased
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What is step 8 in drug development?
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market drug
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