Pharmacokinetics&Pharmacodynamics Flashcards
is currently defined as the study of the time course of drug absorption, distribution, metabolism, and excretion (ADME).
•How body handles the drug
Kinetics
refers to the relationship between drug concentration at the site of action and the resulting effect, including the time course and intensity of therapeutic and adverse effects.
•Effect of drug on body
Pharmacodynamics
application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient
Clinical pharmacokinetics
What factors influence drug absorption (8)
Molecular wt Blood flow Solubility Concentration Disintegration and dissolution Partition coefficient Transporters pH partition theory (Henderson-Hasselbalch)
Sublingual route?
Nitroglycerine
Rectal routes?
Antiemetic
Opioids
BZ
Antipyretics
Pulmonary routes?
Beta agonists
Anti muscarinic
Volatile anesthetics
Corticosteroids
Faster or slower onset for drugs with high pKa (low pH)
Faster
Why are pro drugs used?
Improve how the intended drug is absorbed, distributed, metabolized, or excreted (more soluble to create parenteral form or improve oral absorption)
-lack intrinsic efficacy. Classically pretreatment with this reduces the maximum response (Emax) – they diminish maximal efficacy
functioning to remove receptors from the system (since they can not be recovered by administering agonist)
-bind to the same receptor site as an agonist but they dissociate very slowly (or not at all) from the receptor site. Covalent binding is frequently involved and no displacement of this by an agonist is possible
Irreversible competitive antagonists
What kind of efficacy does an agonist display?
Positive
- to a receptor at the same site as the agonist normally binds. This binding prevents the agonist from binding. Competitive antagonists are also described as surmountable.
- shifts the log dose response curve for a full agonist to the right (a parallel shift) – note that the maximum response possible (Emax) is unchanged if sufficient agonist is given to overcome this. The ED50 is increased however.
- can be displaced (surmounted or overcome) if sufficient agonist is administered
Reversible competitive antagonists
What kind of efficacy does an antagonist display?
Zero
What kind of efficacy does an inverse agonist display?
Negative
What 2 properties do partial agonists have?
- Produce max response (which is weaker than tissue max)
2. Capable of ‘displacing’ full agonist (antagonizing it)
agonists bind to a receptor and produce a molecular response with a subsequent cellular response
Full
agonists bind to a receptor BUT even the highest drug concentration is incapable of producing a sufficient molecular response to generate the cellular response seen following administration of a full agonist
Partial
agonists have a higher binding affinity for a receptor in the resting state than in the active state (unlike antagonists which bind equally at both states). They abrogate the intrinsic constitutive activity of the free unoccupied receptor
Inverse
What determines to a large dress the quantitative relationship between drug dose and pharmacological effect?
Receptors
relates drug dose to the size of the response in a single individual
•It also reflects the maximal efficacy of a drug
Graded dose response relationship
relates drug dose to the proportion of individuals displaying a desired pharmacologic response
•It also reflects the variability of responsiveness among individuals
Quantal dose response relationships
What can both graded and quantal dose response curve show us?
Potency and selectivity of drug action
relative term which represents the amount of one drug required to produce a desired level of effect to the amount of a different drug required to produce the same effect (observe EC50 or ED50)
Potency
relative term which represents the amount of one drug required to produce a desired level of effect to the amount of a different drug required to produce the same effect
Efficacy
What is a special case of tolerance (acute tolerance)
Tachyphylaxis
Hyporeactivity resulting from chronic drug exposure. Clinically cross-tolerance is common between drugs producing similar pharmacologic effect
Tolerance
How can drug absorption be described?
Extent of absorption (total amount entering systemic)
Rate of absorption (how quickly drug enters systemic)
Common drugs with relevant first pass clearance (4)
Ca channel blockers
Beta blockers
Diuretics
Lidocaine
How do you inspect rate of absorption?
Tmax and Cpmax
How to you inspect extent of absorption?
AUC
Fraction absorbed into the systemic circulation is the drug’s what?
Bioavailability
Describes how a Substance distributes itself between 2 immiscible solvents
Partition coefficient (absorption and distribution)
What links drug concentration to the amount of drug in the body?
Apparent volume of distribution (V)
Inactive precursors that are metabolized to active metabolites
Pro drugs
What phase of metabolism is CYPs mainly for?
Phase I
Expect a decrease in elimination rate constant of object drug - increased half life
Inhibition
Expect increase in elimination rate - decreased half life
Induction
Larger or small inhibitors encountered in clinical practice?
Larger
Larger or smaller number of inducers are encountered in clinical practice?
Smaller
What kind of stereoisomers is etomidate?
R(+)
What kind of stereoisomers is bupivacaine?
Local anesthetic, Na channel blocker
What kind of stereoisomers is ketamine?
Race mate
How to calculate volume of distribution
Dose/resulting concentration
used when it is desirable to rapidly establish a therapeutic concentration of drug in the body, instead of waiting for the drug to accumulate from a series of maintenance doses.
Loading dose
When does elimination begin?
as soon as first drug molecule enters the central compartment
as soon as first drug molecule enters the central compartment
First order rate kinetics
A constant amount of drug is eliminated per unit time regardless of the amount of drug in the body
Zero order rate kinetics
What is the half life equation?
.693/ke
