Term
|
Definition
| size of the compartment necessary to account for the total amount of drug in the body if it were present throughout the body at the same concentration found in the plasma |
|
|
Term
| what is volume of distibution a function of? |
|
Definition
lipid vs water soulbility
plasma and tissue protein binding properties of the drug |
|
|
Term
|
Definition
| intrinsic ability of the body or its organs of elmination to remove drug from the blood or plasma |
|
|
Term
| what are the two major sites of drug elimination? |
|
Definition
kidneys and liver
renal clearance- unchanged drug
hepatic clearance-biotransformation into patent compound and metabolites
-unchanged excretion into bile |
|
|
Term
| what are other organs that participate in clearance |
|
Definition
|
|
Term
|
Definition
| rate of drug administration and the rate of elemination are egaul |
|
|
Term
|
Definition
-clearance not saturable
-rate of drug elminated directly proportional to concentration of the drug
- clearance can be estimated by calculating area under the curve (AUC) |
|
|
Term
| capacity-limited elimination |
|
Definition
clearance is saturable eusually at or near therapeutic concentration of drug
-once saturation occurs clearance rate fails to increase with increasing plasma drug concentrations
-clearance is not linear
-AUC cannot be used to describe elmination
-can result in dangerous concentrations of drug |
|
|
Term
| how is the extent of an organ's contribution to drug clearance quantified? |
|
Definition
|
|
Term
| what is extraction ratio? |
|
Definition
| compares drug concentration in plasma immediately before entering and just after exiting organ |
|
|
Term
| Organ that does not participate would have an extraction ratio closer to |
|
Definition
|
|
Term
|
Definition
•Time required to change the amount of drug in the body by one-half during elimination or during constant infusion
•Indicates time required to attain 50% steady state or to decay 50% from steady state conditions
|
|
|
Term
| Accumilation will occur provided that |
|
Definition
| the dosing interval is higher than 4 half lives |
|
|
Term
| Drug accumulation is inversely proportional to... |
|
Definition
| fraction of drug lost in each doing interval |
|
|
Term
|
Definition
| Fraction of unchanged drug reaching the systemic circulation following administration by any route |
|
|
Term
| ____ is a common measure of the extent of bioavailability |
|
Definition
AUC
= to 100 % due for intravenous drugs
* oral may be <100% due to incomplete absorption and first pass elimination |
|
|
Term
| Extent of Absorption is mainly due to |
|
Definition
| lack of absorption from the gut (i.e. digoxin) |
|
|
Term
Drug too hydrophilic?
Drug too lipophilic? |
|
Definition
i.e. atenolol - cannot cross lipid cell membrane
i.e. acyclovir - not soluble enough to cross water layer adjacent to cell |
|
|
Term
|
Definition
| reverse transporter which actively pumps drug out of gut wall and back into lumen (i.e. grapefruit juice) |
|
|
Term
|
Definition
- After absorption across gut wall drug is delivered to live via the portal system
- Metabolism by liver enzymes (most common) but can also occur in gut wall or portal circulation
-Elimination substantially decreases the amount of active drug reaching systemic circulation |
|
|
Term
| Effect of first pass hepatic elimination on bioavailability is expressed as |
|
Definition
|
|
Term
|
Definition
Determined by site of administration and drug formulation
Rate of absorption and extent of input can influence clinical effectiveness |
|
|
Term
|
Definition
| rate is independent of amount of drug remaining in gut (i.e. determined by gastric emptying or controlled release formulation) |
|
|
Term
|
Definition
| rate is proportional to gastrointestinal concentration |
|
|
Term
| Systemic clearance is not affect by |
|
Definition
|
|
Term
| Clearance can affect extent of availability because |
|
Definition
| it determine extraction ratio |
|
|
Term
| What route can over come large doses? |
|
Definition
Oral
* drug metabolites significantly increase compared with intravenous route
ex: lidocaine |
|
|
Term
|
Definition
Lidocaine
Morphine
Propranolol
Verapamil
Isoniazid
Certain tricyclic antidepressants
slow variances in bioavilability between patients due to difference in hepatic function and blood flow |
|
|
Term
|
Definition
100% Bioavailability
Most rapid onset |
|
|
Term
|
Definition
75 to less than or equal to 100
Large volumes often feasible, may be painful |
|
|
Term
|
Definition
75 to less than of equal to 100
smaller volumes than IM: may be painful |
|
|
Term
|
Definition
5 to <100
Most convenient, first pass effect may be significant |
|
|
Term
|
Definition
30 to <100
Less first pass effect than oral |
|
|
Term
|
Definition
5 to <100
Often very rapid onset |
|
|
Term
|
Definition
80 to less than or equal to 100
Usually very slow absorption; used for lack of first pass effect; prolonged duration of action |
|
|
Term
| Maximize concentration at site of action and minimize it elsewhere |
|
Definition
|
|
Term
| Prolonged exposure of drug exposure |
|
Definition
|
|
Term
|
Definition
-sublingual
-transdermal
-rectal |
|
|
Term
Drug effects immediate: may not parallel the time course of concentration
Example? |
|
Definition
Immediate= directly related to plasma concen
enalapril ACE inhibitor (t1/2=3 hours)
Even as enalapril concentrations drop the amount of ACE inhibitor does not fall accordingly, explains why despite short t1/2 enalapril is dosed once daily |
|
|
Term
| Drug effects: Delayed effects |
|
Definition
changes in drug effects often delayed in relation to changes in the plama
May reflect time required for drug to distribute from plasma to site of action
May reflect the slow turnover of a physiologic substance that is involved in expression-warfarin |
|
|
Term
| Drug effect: Cumulative Effects |
|
Definition
Drug effects may be related to cumulative action
example: renal toxicity of aminoglycosides
example: chemotherapy |
|
|
Term
|
Definition
| dosage regimen that will produce the desired therapeutic effect |
|
|
Term
|
Definition
| administrating a drug in such a way to maintain a steady state of drug in the body |
|
|
