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Definition
| any chemical that can affect living processes |
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Definition
| study of drugs and their interactions with living systems |
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| the use of drugs to diagnose, prevent, or treat disease or to prevent pregnancy |
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| 3 Most Important Properties of an “Ideal Drug” |
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Definition
| effectiveness, safety, selectivity |
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Definition
| right drug, dose, time, route, patient, documentation |
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| a drug’s route of administration affects the rate and extent of absorption of the drug (enteral, parenteral, and topical) |
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Definition
| determining how much of an administered dose gets to its sites of action; consisting of absorption, distribution, metabolism, and excretion; it can be thought of as the impact of the body on drugs |
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Definition
the impact of drugs on the body
- binding of drug to its receptor, sequence of events → response
-patient's functional state (tolerance, etc. – individual variation)
-placebo effects |
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Definition
| age, gender, weight, pathologic variables such as diminished functioning of kidneys and liver, and genetic variables that can alter the metabolism of drugs and predispose a patient to unique interactions |
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| Seven Aspects of Drug Administration |
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Definition
| preadministration assessment, dosage and administration, evaluating and promoting therapeutic effects, minimizing adverse effects, minimizing adverse interactions, making PRN decisions, managing toxicity |
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| Preadministration Assessment |
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Definition
- collecting baseline data to evaluate therapeutic/adverse responses
- identifying high-risk patients such as those with liver and kidney impairment, genetic factors, drug allergies, pregnancy, elderly and pediatrics |
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| Dosage and Administration |
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Definition
| drugs with different indications, dependent on dosage, different routes, IV extravasation |
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| Evaluating and Promoting Therapeutic Effects |
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Definition
-evaluating therapeutic responses and knowing rationale for drug (why they are taking it, how long it takes to work)
- promoting patient adherence
- implementing nondrug measures (music, massage, etc) |
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| Minimizing Adverse Interactions |
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Definition
| thorough drug history – even OTC drugs, food, and herbals |
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Definition
| know the reason for drug use and be able to assess the patient’s medication needs |
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| early identification and signs, know procedure for toxicity management |
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| Landmark Drug Legislation |
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Definition
- start of regulation = 1906 Federal Pure Food and Drug Act - required that drugs be free of adulterants (nothing about safety or effectiveness)
- 2003 = PREA (pediatric research equity Act) FDA allows limited clinical trials on children
- 2007 = (FDA Amendments Act) FDA also includes limited drug trials on pregnant women |
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| Randomized Control Trial (RCT) |
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Definition
| use of control, randomization, and blinding |
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| Stages of New Development |
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Definition
- preclinical testing (animals), clinical testing
- phase I - healthy volunteers (look at kidney and liver)
- phases II and III - mild to severe form of disease volunteers
- phase IV - postmarketing surveillance |
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Definition
| the study of drug movement throughout the body including drug metabolism and excretion |
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| Site of Most Common Excretion |
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Definition
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| Site of Most Common Metabolism |
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Definition
| liver - detect size of liver through palpitation; hepatomegaly indicates poor liver function |
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| 3 Ways to Cross the Cell Membrane |
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Definition
| channels and pores, transport systems, direct penetration of membrane |
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Definition
| very few drugs can pass through this, only the smallest compounds can pass and it has to be the correct channel (small ions such as Na and K) |
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Definition
- carriers that move drugs from one side of the cell membrane to the other (some require energy, some don’t); all systems are selective
-p-glycoprotein - transports drugs out of cells! Unique system to bind and be brought out after they have affected their therapeutic response (kidneys, liver, placenta, intestine and capillaries of brain) |
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| Direct Penetration of Membrane |
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Definition
| most common; the drug must be lipo-philic (lipid soluble) |
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Definition
| the rate at which a drug leaves it site of administration, and the extent to which absorption occurs |
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Term
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Definition
| first-pass effect reduces bioavailability of the drug < 100%. If first-pass is very high there is low bioavailability |
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Definition
| route, foods or fluids administered with drug, absorptive surface, rate of blood flow, acidity of stomach, GI motility |
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Definition
- acidic drugs - will ionize in basic media and accumulate on the alkaline side of a pH gradient
- basic drugs - will ionize in acidic media and accumulate on the acidic side of a pH gradient |
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Definition
| Ex = aspirin. Aspirin ingested and disintegrated in stomach. Since Aspirin is acidic, it will be nonionized in stomach and therefore lipid soluble and able to cross the membrane into the bloodstream. Once into the plasma (which is slightly alkaline) the Aspirin becomes ionized and can’t move back into the stomach. |
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Definition
| metabolism of a drug and its passage from the liver into the circulation, only have this with enteral drugs - doesn’t happen when given IV |
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Definition
transport of a drug in the body by the bloodstream to its site of action
- blood flow to tissues, exiting the vascular system, protein binding, entering cells |
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Definition
| rate at which drugs are delivered to a particular tissue depends on blood flow to that tissue (abscesses and tumors can affect blood flow and perfusion) |
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| Exiting the Vascular System |
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Definition
- in typical capillary beds, drugs pass between capillary cells rather than through them
- BBB - tight junctions between the cells that compose the walls of most capillaries in the CNS so only drugs that are lipid soluble or have a transport system can cross the BBB to a significant degree |
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Definition
- drugs can form reversible bonds with various proteins. Plasma albumin is the most abundant and important. Drugs that are protein bound are not free to exact action (only free drugs can have therapeutic effects)
- once a drug is protein bound, it remains bound until either receptor on protein down regulates and releases the molecule or is inactivated, or some other drug with a higher affinity for that protein molecule knocks it off (competitive) |
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Definition
| some drugs must enter cells to reach site of action, most drugs must enter cells to undergo metabolism and excretion, but many drugs produce their effects by binding with receptors on the external surface of the cell membrane |
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Definition
- the biologic transformation of a drug into an inactive metabolite, a more soluble compound, or a more potent metabolite (also known as biotransformation)
- transforms drug into nonactive form to be excreted
- pro-drugs - need to be broken down and metabolized before affecting its response
- only free drug (not protein bound) can affect a response
- delayed drug metabolism results in accumulation of drugs and prolonged action of the drugs
- stimulating drug metabolism causes diminished pharmacologic effects
- the most important consequence of drug metabolism is accelerated renal excretion (changing the drug from lipo to hydrophilic) |
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| Factors That Decrease Metabolism |
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Definition
| CV dysfunction, renal insufficiency, starvation, obstructive jaundice, slow aceytlator, erythromycin or ketaconazole |
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Definition
| no blood flow to the liver, have decreases/changes in metabolism |
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Definition
| need kidneys to excrete drug after it’s metabolized |
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Definition
| more acidic environment in stomach, decreases protein in blood therefore starving the liver of nutrients and micronutrients which upsets metabolism |
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Definition
| unable to metabolize drugs and substances normally |
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Definition
| genetic component metabolizing slower than normal leading to toxicity |
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Term
| Erythromycin or Ketaconazole |
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Definition
| inhibits the P450 enzymatic system |
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Term
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Definition
- hepatic microsomal enzyme system. P450 refers to cytochrom P450, a key component of the system. P450 = CYP. 3 CYP families metabolize drugs – CYP1, CYP2, and CYP3 which all metabolize drugs are also composed of multiple forms, each of which metabolizes only certain drugs
- metabolism doesn’t always result in a smaller molecule
- mono-oxygenase - tranform lipophilic drugs into hydrophilic so they can be excreted |
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Definition
the elimination of drugs from the body (main organ – kidney)
SEE NEPHRON |
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Term
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Definition
| blood moves through afferent arteriole, filtered through the glomerulus, and the remaining blood goes into the efferent arteriole. The filtrate however moves on through the proximal tubule. If the drug molecules are not biotransformed (metabolized) into a hydrophilic substance, it will be reabsorbed from the PT back into the bloodstream and won’t be excreted |
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Definition
| the time it takes for the drug to elicit a therapeutic response |
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| the time it takes for a drug to reach its maximum therapeutic response |
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| the time a drug concentration is sufficient to elicit a therapeutic response |
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| study of the biochemical and physiologic effects of drugs and the molecular mechanisms by which those effects are produced – basically the study of what drugs do to the body and how they do it |
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- indicated by highest dose-response curve
- higher efficacy = smaller dose with best response
- lower efficacy = large dose with mediocre response |
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Definition
| relates to how many mg needed to get a certain dose response |
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Definition
| any functional macromolecule in a cell to which a drug binds to produce its effects |
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| Non-competitive Antagonists |
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Definition
bind irreversibly to receptors and reduce the maximal response that an agonist can elicit because of fewer available receptors
Ex = narcan knocking off an opiod to reverse toxicity by blocking opiods from binding with opiod receptors |
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Definition
| compete with agonists for receptor binding; bind reversibly to receptors, the receptor will be occupied by whichever agent has the higher affinity for that receptor – if there is equal affinity the molecule present in the highest concentration will bind |
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| Regulation of Receptor Sensitivity |
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Definition
- number of receptors on the cell surface and sensitivity to agonists can change in response to continuous activation or continuous inhibition
- receptors on cell surface are either recycled or down regulated
- when the receptors of a cell are continually exposed to an agonist, the cell usually becomes less responsive – desensitized, refractory, or down regulated
- continuous exposure to antagonists cause the cell to become hypersensitive (supersensitive) from the synthesis of more receptors |
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| Drug Responses that DO NOT Involve Receptors |
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Definition
| simple physical or chemical interactions with other small molecules including: antacids, antiseptics, saline laxative, chelating agents (which are drugs that bind to other drugs such as activated charcoal to reduce toxicity) and eye drops (saline eye drops only!) |
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| 3 Possible Drug-Drug Interactions |
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Definition
- one drug may intensify the effects of the other (potentiative) - Ex = morphine and diazepam are both CNS depressants, if given together they will both increase the others CNS depression
- one drug may reduce the effects of the other (inhibitory) - Ex = HCTZ and spironolactone are opposite diuretics, one is potassium wasting one is potassium sparing
- the combination may produce a new response not seen with either drug alone |
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| Pharmacokinetic Drug-Drug Interactions |
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Definition
| altered absorption, altered distribution, altered renal excretion, altered metabolism, interactions that involve P-Glycoprotein |
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Definition
| antacids elevating gastric pH, laxatives, drugs that depress peristalsis, drug induced vomiting, adsorbent drugs |
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Definition
| competitive drugs, alteration of extracellular pH |
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| Interactions That Involve P-Glycoprotein |
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Definition
| transport drugs out of cells which results in reduced absorption, reduced fetal drug exposure, reduced brain exposure, increased drug elimination |
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Definition
- can result in increased or decreased absorption
- grapefruit juice effect |
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Definition
food can affect rate and extent of absorption
Ex = milk and tetracycline/digoxin and fiber can result in therapeutic failure |
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Definition
| high calorie meals and saquinavir (if not taken with a meal it will reduce the absorption) |
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Definition
| inhibits the metabolism of certain drugs and raises the drug’s blood levels |
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Term
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Definition
| St. John's Wart is the big one |
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Definition
| any noxious, unintended, and undesired effect that occurs at normal drug doses – excludes excessive dosages |
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| a nearly unavoidable secondary drug effect produced at therapeutic doses; it may develop soon after a drug is initiated or not until the drug has been taken for weeks or months |
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Definition
| adverse drugs reaction caused by excessive dosing (but may even occur with normal dosing depending on the patient’s genetics or for example neutropenia which leads to risk for infection when being treated with anti-cancer medication) |
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Definition
| an immune response with prior sensitization. When re-exposure occurs, the drug can trigger an allergic response; the intensity of allergic reactions is largely independent of dosage |
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Definition
| an uncommon drug response resulting from a genetic predisposition |
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Definition
| disease produced by drugs – the drug may not cause an actually disease but will produce the signs and symptoms that come along with that disease (once off the drug the signs and symptoms will cease) |
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Definition
- hepatotoxicity - some damage to the liver or cellular structure of the liver (a lot of these!)
- nephrotoxicity - damage to the kidneys
- ototoxicity - damage to the inner cilliary or inner ear resulting in hearing loss |
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Term
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Definition
| the amount of time it takes for your ventricles to repolarize in between each contraction; when the QT interval is prolonged, patients can develop a dysrhytmia known as torsades de pointes, which can progress to potentially fatal ventricular fibrillation |
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| Individual Variation in Drug Responses |
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Definition
| body weight and composition, age, kidney disease, live disease, acid-base imbalance, altered electrolyte status |
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| Body Weight and Composition |
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Definition
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- infants --> organ immaturity
- elderly --> organ degeneration |
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Definition
| reduced excretion and increased toxicity |
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Definition
| reduced metabolism and increased toxicity |
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Definition
| pH changes that alter absorption, distribution, metabolism, and excretion of drugs |
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| Altered Electrolyte Status |
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Definition
| rare for electrolyte changes to have significant impact on drug responses |
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Definition
- decreased responsiveness to a drug as a result of repeated drug administration
- pharmacodynamic tolerance, metabolic tolerance, tachyphylaxis, placebo effect |
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| Pharmacodynamic Tolerance |
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Definition
| MEC of a drug is abnormally high |
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Definition
| accelerated drug metabolism |
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Definition
| reduction in drug responsiveness brought on by repeated dosing over a short time (not common) |
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Definition
| drug response caused by psychologic factors and not by biochemical or physiologic properties of a drug |
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Definition
- ability of the drug to reach the systemic circulation from its site of administration (PO preps, not parenteral) such as tablet disintegration time, enteric coatings, sustained release formulations
- variable absorption may also be caused by changes in gastric pH, diarrhea, constipation, or food in the stomach |
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Definition
| study of genotypes people have that impact absorption, metabolism, distribution, and excretion of drugs – ability to give targeted drugs and dosages without ADRs |
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Definition
- fast - so rapid that the drug may be excreted before affecting therapeutic responses
- slow - increased risk of causing toxicity |
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Definition
- first-trimester is the period of greatest danger for drug-induced developmental defects; during the third trimester, drugs are eliminated much quicker because blood flow through the kidneys is doubled
- essentially all drugs can cross the placenta – some cross more readily than others |
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Definition
| Drug that causes birth-defects |
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| FDA Pregnancy Risk Categories |
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Definition
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Definition
| relatively safe drug to give to a pregnant mom |
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Definition
| slightly more risk, animal studies show no fetal risk |
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Definition
| greater risk, animal studies show fetal risk of harm but no human studies done, but risk to mom may be higher than risk to fetus where giving the drug is acceptable |
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Definition
| proven risk to fetus – weigh benefits to mom vs. risk to fetus |
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Definition
| never give this drug to a pregnant woman (exception in diagnosed with cancer while pregnant – in this situation a decision needs to be made) |
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Definition
| breast-fed infants are at risk for exposure to drugs consumed by the mother |
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| Pediatric Absorption Considerations |
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Definition
| gastric pH less acidic than in adults, gastric emptying is slowed, first-pass elimination by liver is reduced because of immature liver function (however may still have first-pass effect but may affect bioavailability), topical absorption faster through the skin, IM absorption faster and irregular because muscles are smaller than in adults but irregular because each child (even at same age) has different sizes of muscles and blood flow to that area |
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| Pediatric Distribution Considerations |
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Definition
| TBW greater than in adults, Greater TBW = Lower fat content, decreased level of protein binding so more free drug available, immature BBB |
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| Pediatric Metabolism Considerations |
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Definition
| immature liver that doesn’t produce enough microsomal enzymes which can result in toxicity, older children may have increase metabolism requiring higher doses |
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| Pediatric Excretion Considerations |
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Definition
| kidney immaturity affects GFR and tubular secretion (if kidneys can’t secrete a drug they won’t be able to excrete it → accumulation) and decreased perfusion rate of the kidneys |
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| Methods of Dosage Calculation |
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Definition
| mg/kg… to calculate BSA you need height in cm, weight in kg. |
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Term
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Definition
- 65 y.o. and older
- these patients have altered pharmacokinetics with more sensitivity to drugs and wider variation of reactions from multiple pathologies, polypharmacy, and organ degeneration
- change in adipose tissue, TBW, and lean muscle mass lead to risk of addiction |
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| Physiologic Changes in the Geriatric Patient |
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Definition
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Definition
- decreased CO = decreased absorption and decreased distribution
- decreased blood flow = decreased absorption and decreased distribution |
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Definition
- increased pH = decreased or increased absorption depending on acidity of drug
- decreased peristalsis = delayed gastric emptying |
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Definition
- decreased enzyme production = decreased metabolism
- decreased blood flow = decreased metabolism |
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Definition
- decreased blood flow = decreased excretion
- decreased renal function = decreased excretion
- decreased GFR = decreased excretion |
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| Geriatric Distribution Considerations |
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Definition
| increased percent of body fat, storage of lipid soluble drugs, decreased TBW distribution in smaller volumes so concentration is increased and effects are more intense, increased level of free drug from reduced protein binding |
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| Geriatric Metabolism Considerations |
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Definition
| liver produces less microsomal enzymes, affecting drug metabolism and reduced blood flow to the liver |
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