Term
|
Definition
| Absorption, distribution, metabolism and excretion of a drug. |
|
|
Term
|
Definition
| Pharmacologic effect of a drug. |
|
|
Term
| A weak acid drug will be better absorbed at ____ pH. |
|
Definition
| Low pH, such as in the stomach. Remember when pH < pKa, the weak acid will retain its proton and be in the uncharged form, which is more easily absorbed. |
|
|
Term
| Other factors that affect absorption of compounds (4) |
|
Definition
| Solubility in aqueous solution, dissolution rate if solid, surface area of absorption site and rate of blood flow. |
|
|
Term
|
Definition
| Efficiency of delivery, defined as fraction of administered dose that reaches the circulation in an unchanged form. IV is defined as 100%. |
|
|
Term
|
Definition
| Drugs absorbed through the GI tract will first be delivered through the portal circulation to the liver which is a major site of drug metabolism and will clear a percentage of the dose. |
|
|
Term
| Enteral routes of drug administration |
|
Definition
Oral, most common but have to deal with first-pass metabolism and possibility of GI irritation.
Rectal, mainly used for patients unable or unwilling to swallow pills.
Sublingual and buccal, avoids first-pass metab by traveling directly into head/neck circulation. |
|
|
Term
| Parenteral routes of drug administration |
|
Definition
IV, max bioavailability and can do continuous infusion, has the risk of infection and vascular wall irritation.
SubQ, self-administration is possible, but circulation at injection site is critical.
IM, injection site can serve as a depot for drug that is release when muscle is active, limited volume.
Topical/transdermal, depends on lipid solubility of drug, may be irritating, may be slowly absorbed.
Pulmonary, usually for local (lung) applications, for anesthesia can easily control depth of anesthesia.
Intrathecal, injection to CSF, commonly used for selective spinal block, epidurals. |
|
|
Term
|
Definition
Rate = -ke x C
rate in (mg/mL)/min
ke in 1/min
C is concentration |
|
|
Term
| Time course of elimination |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
Relates the conc of the drug in the compartment to the dose introduced.
Vd = dose / C0; alternatively: Vd = amount of drug in body / plasma drug concentration |
|
|
Term
|
Definition
Elimination rate (mg/min) = CL x C
CL in mL/min
C is concentration |
|
|
Term
| Equation relating three pharmacokinetic parameters |
|
Definition
|
|
Term
| For a drug with a high Vd, a dose will raise plasma concentration considerably or minimally? |
|
Definition
Minimally, recall the equation for concentration change is:
Change in conc = dose / Vd |
|
|
Term
|
Definition
| Conversion of active, lipophilic molecules to (usually) less active, polar molecules that can be more easily excreted. |
|
|
Term
|
Definition
| Convert parent drug to a more polar metabolite by introducing or unmasking a polar functional group. |
|
|
Term
|
Definition
| Polar substances acquired earlier are conjugated to endogenous polar substances (such as glucuronic acid, sulfuric acid, acetic acid or glycine) to make a highly polar molecule for excretion. |
|
|
Term
|
Definition
| A drug given in an inactive form but is converted in the body to an active form. |
|
|
Term
| Top two sites in body for drug metabolism |
|
Definition
Site - Relative Activity
Liver - 100
Lung - 20
Kidney - 8
Intestine - 6
Skin - 1
Brain - 0.5 |
|
|
Term
| Phase I reactions are mostly catalyzed by enzymes on _______. Two main types of these enzymes are ________. |
|
Definition
| SER, also known as microsomes. NADPH-cytochrome P450 oxidase and cytochrome P450 (CYP450). |
|
|
Term
|
Definition
| A substrate induces enzyme activity that then increases metabolism of other compounds that that particular CYP works on. (Drug level decreases) |
|
|
Term
|
Definition
| A substance competes for active sites on a CYP, decreasing metabolism of other compounds or drugs that that particular CYP works on. (Drug level increases) |
|
|
Term
| Factors affecting excretion of drugs from kidney (3) |
|
Definition
| Anything that affects glomerular filtration rate (GFR), plasma protein-bound compound cannot be filtered, and pH of the urine, as uncharged weak acids or bases can be reabsorbed back into the blood stream but charged species cannot. |
|
|
Term
| Enterohepatic recirculation |
|
Definition
| Drugs are often conjugated in the liver and excreted via the biliary system, however many gut flora have enzymes that can cleave off the conjugate and if the resultant compound is sufficiently lipid-soluble it can be reabsorbed into the portal circulation. |
|
|
Term
| "Test" metabolites and determining metabolism rates |
|
Definition
| Give a patient a "test" metabolite, i.e. a compound that is metabolized by the same CYP450 that the drug you are concerned about is. Check urine ratios of metabolites to determine efficiency of conversion. |
|
|
Term
| Influence of disease on metabolism |
|
Definition
| Various disease states can affect the rates of metabolism of drugs. For example, liver damage will affect drugs metabolized by the liver, similarly kidney damage can increase drug levels. Impaired cardiac function can also impair metabolism of drugs that are metabolized quickly by the liver ("flow-limited" metabolism). |
|
|
