Pharm: Principles of Drug Action
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- Define First Order kinetics
- process by which a constant percentage of substrate is metabolized per unit time (i.e half life)
- Define zero order kinetics
-
a constant amount of drug is metabolized per unit time
(i.e alcohol) - what is an agonist?
- a drug that binds to and activates a receptor
- what is a full agonist?
- a drug that binds to a recptor and has the ability to produce 100% of the maximal response
- what is a partial agonist?
- drugs that bind but produce less than 100% of the maximal possible biological response no matter how high their concentration
- what are antagonists?
- drugs that bind to receptors or other drugs and INHIBIT a biological response
- What does a competitive antagonist do?
- it binds reversibly to the same active site as the agonist, shifts the dose response curve to the right, increases the ED50
- How can a competitive antagonist be overcome?
- by increasing the concentration of the agonist; the maximal efficacy of the drug will not change
- what does a non competitive antagonist do?
- It binds irreversibly to a different site on the nzm than the agonist; it cannot be overcome by increasing the concentration of the drug; lowers Emax
- How does a non competitive antagonist effect the efficacy of a drug?
- it reduces the maximum efficacy will be reduced
- Define efficacy
- the ability to produce a biological effect
- Define potency
- a measure of the amount of drug needed to cause a biological effect; demonstrated by the ED50
- What is Kd?
- the conc. of drug yeilding 50% occupancy of the receptor; dissociation constant
- What is EC50?
- the drug concentration that produces 50% of the maximal possible response in a graded dose-response curve
- What is volume of distribution (Vd)?
- the apparent volume into which a drug is able to distribute
- Vd =
-
= total drug in the body/ plasma concentration of drug
= x/Cp - What is the significance of a large Vd?
- a large Vd signifies that most of the drug is being sequestered in some organ or compartment
- What is maintenance dose?
- a dose of drug given to achieve a therapeutic plasma concentration over an extended period of time
- Maintenance Dose =
-
= Clearance x desired steady state concentration
= CL x Css - What is loading dose?
- In some clinical situations the desired plasma concentration must be acheived quickly. In these cases a single loading dose is injected, followed by a routine maintenance dose
- Loading Dose =
- = Vd x desired Cp
- Define peak and trough concentrations
- maximum and minimum plasma concentrations, which are observed during dosing intervals
- What variables affect peak and trough concentrations?
- they will fluctuate around the steady state plasma concentration
- What is the steady state plasma concentraion (Css)?
- the point at which the rate of drug availability is equal to the rate of drug elimination
- How does frequency of dosing affect Css?
- it doesn't
- How many half lives are required to reach Css?
- approximately 4.3
- What is clearance (CL)?
- volume of plasma cleared of drug per unit time
- What is therapeutic index?
- the ratio of a drug's toxic dose to its therapeutic dose
- What do pharmacokinetics describe?
- Where the drug goes and how much needed for desired effect.
- What factors affect pharmacokinetics?
- Absorption, distribution, metabolism, and excretion.
- What affects absorption?
- Rate is affected by route of drug administration and extent is determined by metabolism and lipid solubility.
- What affects the distribution?
- Diffusion across gradient, lipid/water partitioning, charge and pH.
- Are drugs more likely to be trapped in ionized or neutral form?
- Ionized, since ions don't easily cross membranes.
- What is first pass metabolism?
- The reduction in bioavailability in orally administered drugs because of metabolism in the liver.
- What is the half-life of a drug?
- half-life = 0.693 * Vd/CL
- What are pharmacodynamics?
- This term describes how a drug works. This is determined by 1) drug-receptor interactions; 2) duration of drug action.
- What are the 2 phases in drug metabolism?
- Phase I = conversion of drug to more polar or reactive compound; Phase II = increase water solubility to increase water solubility.
- What are the cytochrome P-450 group of enzymes?
- Enzymes located in the smooth ER which help catabolize drugs.
- What is an alkanizing agent?
- bicarbonate
- What is and acidifying agent?
- ammonium chloride
- What are some factors that affect Vd?
- disease (obesity, renal disease), size (capillary permeability), lipid solubility, and charge
- What are the 3 basic reactions in Phase I of drug metabolism?
- oxidation, reduction, and hydrolysis
- P-450 is responsible for which Phase I reaction?
- oxidation
- What are 4 reactions in Phase II drug metabolism?
- glucoronidation, sulfation, acetylation and glutathione conjugation
- Which is the most important organ in drug metabolism?
- Liver is most important, followed by the kidney
- What are the 2 components of the cytochrome P-450 enzyme system?
- oxidase and reductase
- What are examples of P-450 inducers?
- barbiturates, ethanol, which enhance the metabolism of warfarin (anticoagulant) and tylenol (analgesic), respectively.
- What are examples of P-450 inhibitors?
- cimetidine and allopurinol, which decrease the metabolism of valium and tolbutamide, respectively
- what is an inverse agonist?
- inhibits receptor by locking it in an inactive conformation