Term
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Definition
| the action of the body on a drug; Absorption, Distribution, Metabolism, and Elimination |
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Term
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Definition
| drug absorption from the site of administration permits entry of the therapeutic agent into plasma |
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Term
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Definition
| the drug may then reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids |
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Term
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Definition
| the drug may be metabolized by the liver, kidney, or other tissues |
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Term
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Definition
| the drug and its metabolites are removed from the body in urine, bile, or feces |
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Term
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Definition
| is the movement of drug molecules into and within the biologic environment |
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Term
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Definition
| Driven by the concentration across a membrane separating two body compartments—drug moves from a region of high concentration to one of lower concentration; No carrier involved; Is not saturable; Low structural specificity; Most drugs gain access to the body by this mechanism; Lipid-soluble drugs readily move across most biological membranes due to solubility in the membrane bilayers; Water-soluble drugs enter through aqueous channels or pores; Facilitated diffusion is an example |
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Term
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Definition
| Movement through transmembrane carrier proteins that undergo conformational changes to allow the passage of drugs or endogenous molecules; Movement from an area of high concentration to low concentration; Does not require energy, can be saturated, and may be inhibited |
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Term
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Definition
o Involves specific carrier proteins that span the membrane
Energy-dependent and driven by hydrolysis; Utilized by a few drugs that closely resemble the structure of naturally occurring metabolites; Can move drugs against a concentration gradient; Process shows saturation kinetics for the carrier |
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Term
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Definition
| engulfment of a large drug molecule by the cell membrane and transport into the cell by pinching off the drug-filled vesicle |
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Term
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Definition
| the reverse of endocytosis; used by cells to secrete many substances by a similar vesicle formation process |
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Term
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Definition
| drugs are subject to the first-pass effect, in which a significant amount of the agent is metabolized in the gut wall, portal circulation, and liver before it reaches the systemic circulation; decreased drug bioavailability |
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Term
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Definition
| drug has instantaneous and complete absorption |
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Term
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Definition
| absorption is often faster and more complete than with oral administration; First-pass metabolism is avoided; Anticoagulants cannot be given this way |
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Term
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Definition
| slower absorption than IM, first-pass metabolism is avoided, anticoagulants do not cause hematomas |
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Term
| Sublingual (buccal has same features) |
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Definition
| permits direct absorption into systemic venous circulation, bypassing hepatic portal circuit and first-pass metabolism; Formulation of the drug determines speed of absorption |
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Term
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Definition
| partial avoidance of first-pass (drug may migrate up and absorption from this location is partially into portal circulation) |
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Term
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Definition
| delivery closest to target tissue in the case of respiratory diseases; rapid absorption because of large and thin alveolar surface area available |
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Term
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Definition
| Application for a local effect; Rate of absorption varies with area of application and formulation of the drug, but usually slower |
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Term
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Definition
| application for a systemic effect; slow absorption (thickness of skin), avoids first-pass effect; disadvantage is varying rate of absorption based on skin condition at the site of application |
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Term
| pH--Blood flow to absorption site--Total surface area available for absorption--Contact time at absorption surface--Solubility--Concentration |
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Definition
| Factors that affect drug absorption |
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Term
| Uncharged drug passes through membrane more readily |
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Definition
| Effect of pH on drug absorption |
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Term
| Greater blood flow leads to higher rates of absorption |
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Definition
| Effect of blood flow to absorption site |
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Term
| Greater surface area = greater absorption |
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Definition
| Effect of surface area on absorption |
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Term
| Greater contact time = greater absorption |
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Definition
| Effect of contact time at absorption site |
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Term
| Drugs in aqueous solutions are best absorbed; solid forms and non-aqueous suspensions must be dissolved before absorption |
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Definition
| Effect of solubility on absorption |
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Term
| Higher drug concentration = more absorption |
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Definition
| Effect of drug concentration on absorption |
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Term
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Definition
| the fraction of administered drug that reaches the systemic circulation; expressed as the fraction of administered drug that gains access to the systemic circulation in a chemically unchanged form; determined by comparing plasma levels of a drug after a particular route of administration with plasma drug levels achieved by IV injection |
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Term
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Definition
| is the decline of drug concentration in the plasma from the arterial to the venous side of the kidney; the drug concentration at excretion from the kidney divided by the drug concentration at the point of entering the kidney |
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Term
Advantages: rapid onset of action without exposure to the harsh environment of the GI tract, can be utilized in unconscious patients
Disadvantages: overdoses cannot be readily treated, pain and fear are associated with administration, and there is a higher risk of introduction of infection |
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Definition
| General advantages and disadvantages of parenteral administration |
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Term
| infections through contamination at injection site (either systemic or local), hemolysis (especially with high concentrations), pain or injection site reaction |
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Definition
| Specific disadvantages of IV administration |
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Term
| still requires absorption from site of administration (smaller bioavailability than with IV) but avoids GI tract and 1st pass, drugs in aqueous solutions results in rapid absorption, depot formulations (drugs in non-aqueous suspensions) result in slow absorption and sustained release over a period of time |
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Definition
| Specific disadvantages of IM administration |
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Term
| requires absorption from site of administration, has slower action than IV, minimizes some of the risks associated with IV administration |
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Definition
| Specific disadvantages of subcutaneous administration |
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Term
Advantages: ease of administration (self-administer), minimizes risk of systemic infections (any microorganisms would be subjected to the GI tract environment), overdoses can be potentially treated by inducing emesis or use of activated charcoal
Disadvantages: complicated drug absorption pathways with 1st pass effect, harsh GI environment will destroy certain types of medications before absorption, absorption is influenced by food intake or other drugs |
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Definition
| Advantages and disadvantages of oral administration |
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Term
| Convenient administration with rapid absorption and low risk of infection, utilizes the GI system (mouth) but avoids the harsh GI environment and 1st pass effect |
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Definition
| Advantages of sublingual administration |
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Term
Advantages: prevents destruction of drugs by harsh GI environment, lower rates of biotransformation from the liver than PO, useful when patient is experiencing emesis, useful in patients that are unconscious or actively seizing
Disadvantages: discomfort with administration, drugs can often cause irritation or inflammation of the rectal mucosa, absorption can vary greatly |
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Definition
| Advantages and disadvantages of rectal administration |
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Term
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Definition
| process by which a drug reversibly leaves the blood stream and enters the interstitium (extracellular fluid) and/or the cells of the tissues; depends on blood flow, capillary permeability, blood-brain barrier, drug structure and properties/characteristics, protein binding, and route of administration |
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Term
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Definition
| the distribution of drug within the fluid compartments of the body is used to approximate the total amount of drug in the body compared to the amount of drug in the blood |
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Term
| A bound drug is inactive, while an unbound (free) drug is active |
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Definition
| Effect of drug binding to plasma proteins |
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Term
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Definition
| Given in doses less than the binding capacity of albumin, giving a low dose/capacity ratio; Binding sites are in excess of available drug (no saturation of protein binding sites); Bound-drug fraction is high; Protein bound drug is typically inactive; Most clinically useful agents are in this class |
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Term
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Definition
| Given in doses that greatly exceed the number of albumin binding sites; high dose/capacity ratio; Drug exceeds binding sites (saturation of protein binding sites); Relatively high proportion of the drug in the free state; Free drug is active |
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Term
| the drug may distribute out of the plasma; the overall concentration may not significantly change |
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Definition
| Effect of competition on a large Vd drug |
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Term
| the drug is displaced from plasma proteins (becoming active) and stays in the intravascular compartment; the overall plasma concentration change can be significant |
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Definition
| Effect of competition on a small Vd drug |
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Term
| Since the liver produces albumin and liver disease would cause decreased albumin concentration, there would be less drug binding with liver disease and thus a greater concentration of free drug and possible toxicity |
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Definition
| Effect of liver disease on free drug concentration |
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Term
| More drug active in the plasma than expected based on dose and toxicity could occur |
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Definition
| Effect of protein deficiency on free drug concentration |
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Term
| Tissue binding--Redistribution--Infection--Inflammation--Patient differences |
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Definition
| Pathologic and pathophysiologic mechanisms that may alter drug distribution |
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Term
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Definition
| Rate of drug metabolism is directly proportional to the concentration of free drug
A constant fraction of drug is eliminated over time
Most drugs follow this |
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Term
| Zero-order ("nonlinear") kinetics |
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Definition
| Rate of metabolism remains constant over time
Constant amount of drug eliminated per time
Select drugs follow this (EtOH, aspirin, phenytoin/Dilantin) |
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Term
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Definition
Function to convert lipophilic molecules into more polar molecules by introducing or unmasking a polar function group (i.e., -OH, -NH2, -SH, -CO2) via oxidation reactions
Most reactions involve the CYP 450 enzyme system of the liver
Pharmacologic activity can be decreased, increased, or remain unchanged
If the metabolite end product is sufficiently polar, it can be excreted by the kidneys. Many metabolites are still too lipophilic to be retained in the kidney tubules |
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Term
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Definition
Uses conjugation reactions to create an end product with greater polarity (therefore less likely to be taken up by the cells)
In conjugation reactions, endogenous substances combine with a drug compound. Glucuronidation is a common route of biotransformation of drugs and endogenous compounds. This method is underdeveloped in neonates. Other types of biotransformation include sulfation, methylation, and acetylation.
After conjugation reactions, most drugs do NOT retain therapeutic actions |
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Term
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Definition
| network of enzymes, mostly located in the liver (some in the GI tract), that metabolize endogenous (i.e., steroids and lipids) and exogenous substances |
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Term
| 3A4, 2D6, 2C9/10/19, 1A2, 2E1 |
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Definition
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Term
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Definition
| Tricyclic antidepressants (TCAs), Warfarin (Coumadin), Theophylline, Caffeine |
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Term
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Definition
| Non-steroidal anti-inflammatories (NSAIDs), Oral hypoglycemic, Warfarin (Coumadin), |
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Term
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Definition
| Proton Pump Inhibitors (PPIs--treat acid reflux), Antiepileptic drugs |
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Term
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Definition
| Beta blockers, Antidepressants (TCAs, SSRIs, Antipsychoitics, Codeine |
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Term
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Definition
| Anesthetics, Acetaminophen (Tylenol), Ethanol |
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Term
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Definition
| Antibiotics—Macrolides, Benzodiazepines (BZDs), Immunosuppressants, HIV antivirals, Calcium Channel Blockers (CCBs), Statins, Stains, Hormones (estrogen, progesterone), Many other miscellaneous |
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Term
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Definition
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Term
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Definition
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Term
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Definition
| PPIs, some antidepressants (SSRIs, TCAs) |
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Term
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Definition
| HIV antivirals, macrolide antibiotics, azole antifungals, grapefruit juice, CCBs |
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Term
| Overall common CYP450 inhibitors |
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Definition
| Cimetadine (Tagamet®), Grapefruit juice, Amiodarone |
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Term
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Definition
| foods (broccoli, brussels sprouts, other), tobacco smoke |
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
| HIV antivirals, Barbiturates (Phenobarbital), Carbamazepine, Phenytoin (Dilantin®), Rifampin |
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Term
| Overall common CYP450 inducers |
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Definition
| Phenobarbital, Phenytoin, Rifampin, Carbamazepine (Tegretol®) |
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Term
Decreased plasma drug concentration
Decreased drug activity (if metabolite is inactive)
Increased drug activity if metabolite is active
Decreased therapeutic drug effect |
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Definition
| Consequences of increased drug metabolism via induction |
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Term
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Definition
| sum of the renal clearance, hepatic clearance, and other clearance mechanisms; it is not possible to accurately measure the sum of all clearance mechanisms involved |
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Term
Kidney into the urine is most common
Bile
Intestine
Lung
Milk in nursing mothers |
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Definition
| Routes of drug elimination |
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Term
| Proximal tubular secretion |
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Definition
| Responsible for transport of certain cations and anions via active transport systems (carrier mediated, requires energy, saturation is possible). The systems show low specificity so competition for transport mechanisms may occur |
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Term
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Definition
| Drugs enter through blood flow to the kidneys and the unbound (free) drug flows through the capillaries into primary urine |
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Term
| Concentration increases, exceeds that of the perivascular space (due to reabsorption of water from filtrate); Drug may passively diffuse out of the lumen and back into systemic circulation (but NOT if the drug is in polar form) |
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Definition
| Action of drug in distal convoluted tubule |
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Term
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Definition
| Altering the pH of the drug to minimize it diffusing back into systemic circulation and enhancing clearance. Keeps medication ionized and decreases reabsorption back into systemic circulation. |
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Term
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Definition
| Concentration of drug leaving the kidneys divided by the concentration of drug entering the kidneys. It is the decline in drug concentration from the arterial to the venous side of the kidney. Can also be calculated by multiplying elimination constant by the volume of distribution. |
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Term
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Definition
| equal to the plasma clearance, which is the volume of plasma from which all drug is cleared in a given time, measured in mL/min |
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Term
| Kidney dysfunction--Liver dysfunction--Decreased metabolism or metabolism inhibition |
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Definition
| Clincal situations that increase the half-life of a drug (decreased hepatic or rental blood flow) |
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Term
| Decreased protein binding due to drug interactions or hypoalbuminemia--Increased metabolism due to metabolism induction |
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Definition
| Clinical situations that decrease the half-life of a drug (increased hepatic blood flow) |
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Term
| Steady-state concentration |
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Definition
| Rate of elimination equals the rate of administration--plasma concentration of a drug is constant |
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Term
| Steady-state concentration is directly proportional to the infusion rate |
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Definition
| Relationship of steady state concentration and infusion rate |
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Term
| Steady-state concentration of the drug and the rate at which steady state is approached are not affected by the frequency of dosing |
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Definition
| Effect of dosing frequency on steady-state concentration and the rate at which steady-state is approached |
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Term
| Steady-state concentration is inversely proportional to the clearance of the drug--any factor that decreases clearance increases steady-state concentration |
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Definition
| Relationship between steady-state concentration and clearance |
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Term
| Rate of drug exit from the body increases proportionately as the plasma concentration increases, and at every point in time it is proportional to the plasma concentration of the drug |
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Definition
| Kinetics of constant IV infusions |
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Term
| Half life is the sole determinant of the rate that a drug approaches steady state; this rate is influenced only by factors that affect the half-life |
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Definition
| Relationship between half-life and the rate of approach to steady state |
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Term
| The circulating level of drug decreases exponentially with time |
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Definition
| Kinetics of single IV injection |
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Term
| When a drug is given repeatedly at regular intervals, the plasma concentration increases until steady-state is reached |
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Definition
| Kinetics of multiple IV injections |
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Term
| Kinetics are similar, but the fraction absorbed (bioavailability) must be taken into consideration. |
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Definition
| Difference of repeated IV dosing and PO administered drugs |
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