Pharmacokinetics and Pharmacodynamics

Question 1

Mathematical description of plasma concentration-time course

Answer 1

Pharmacokinetics

Question 2

What are components of the dosage regimen?

Answer 2

Dosage
Route of administration
Frequency
Duration of administration

Question 3

What is an optimum dosage regimen?

Answer 3

Effective and Nontoxic (within the therapeutic window)

Without prolonged drug residues in tissue of food animals

Question 4

Time to peak plasma concentration

Answer 4

Rate of absorption (tmax)

Question 5

_______________ is the fraction of the dose which reaches the systemic circulation intact

Answer 5

Systemic bioavailability

Question 6

How is systemic bioavailability calculated?

Answer 6

Systemic bioavailability (F%)= (AUC extravascular x100) / (AUC IV)

AUC= area under the plasma concentration-time curve

Question 7

What is the one-compartment model?

Answer 7

All tissues and organs that the drug penetrates (good enough reason to use penetrate???) behave as if they were in ready equilibrium with the blood

Question 8

What is the two-compartment model?

Answer 8

Peripheral and central compartments behave differently

Initial decent (distribution phase): distribution from central compartment to peripheral compartment

Second decent (elimination phase): metabolism and excretion of the drug

Question 9

_________________ is estimated by the distribution phase half-time(t1/2a) in the two compartment model

Answer 9

Rate of distribution

Question 10

_______________ is measured by the apparent volume of distribution

Answer 10

Extent of distribution (Vd)

Question 11

what is the volume of fluid which would be required to contain the amount of the drug in the body if it were uniformly distributed, and the concentration in that fluid was equal to the concentration of the plasma

Answer 11

Apparent volume of distribution (Vd)

Question 12

How is apparent volume of distribution calculated?

Answer 12

IV: Vd (L/kg)= amount of drug in body (Dose)/ plasma drug concentration (cp)

Extravascular: Vd= dose x F% / Cp

Question 13

Vd < 1L/kg means?

Answer 13

Drug has limited distribution (tends to stay in plasma)

Question 14

Vd = 1L/kg means?

Answer 14

Drug has a wide distribution (concentration of drug in tissue is the same as the plasma)

Question 15

Vd > 1L/kg means?

Answer 15

Drug has a very wide distribution (concentration is greater in the tissue than plasma)

Question 16

___________ is the time required for the body to eliminate one-half of the drug it contains

Answer 16

Half life

Question 17

Elimination in first order kinetics means?

Answer 17

Rate of removal of drug from the plasma is proportional to concentration present at a given time (a constant percent of drug is eliminated per unit time)

Question 18

What is elimination by zero-order kinetics?

Answer 18

Rate of elimination remains constant regardless of the amount of body in the drug (a constant amount of drug is eliminated per unit time)

Question 19

Aspirin in cats follows (first/zero) order kinetics of elimination ?

Answer 19

Zero

Question 20

What determines the rate at which plasma concentration of a drug rises during constant IV infusion to attain a steady state concentration ?

Answer 20

Half life

Question 21

Plasma concentration when the maintenance rate of drug administration is equal to the rate of elimination

Answer 21

Steady state plasma concentration / plateau

Question 22

How many half life’s does it take for a drug to reach 90% of the steady-state concentration

Answer 22

3.3

Question 23

What percent of the steady state concentration is achieved after 4 half lives ?

Answer 23

93.75%

Question 24

T/F: A faster rate of infusion will change the time needed to achieve steady state concentration

Answer 24

False

The drug will have a higher steady state concentration if the rate of infusion is faster

Question 25

Rate of drug elimination from the body, by all routes, relative to the concentration of drug in the plasma

Answer 25

Total body clearance CL(B) = CL (r) + CL (nr)

Question 26

What is plasma clearance?

Answer 26

Volume of plasma cleared of the drug per unit time

Question 27

How is plasma clearance calculated?

Answer 27

CL (p)= rate of elimination(mg/min)/ plasma drug concentration (mg/mL)

Question 28

How is rate of elimination calculated?

Answer 28

Rate of elimination (mg/min) = urine flow (mL/min) x concentration of drug in urine (mg/mL)

Question 29

How is total body clearance calculated?

Answer 29

CL (B)= Vd x k / T1/2 K= 0.693

Question 30

Fraction of the drug removed from the perfusion blood by an organ

Answer 30

Extraction ratio E= C(A) - C(v) / C(A) ``` C(A) = concentration of drug in arterial blood entering the organ C(v)= concentration of drug in venous blood leaving the organ ```

Question 31

Organ clearance

Answer 31

CL(organ)= extraction ratio x blood flow to the organ

Question 32

What are examples of drugs that have high hepatic extraction ratios??

Answer 32

Lidocaine, propranolol, diazepam, and nitroglycerin

Question 33

What is the maintenance dose

Answer 33

Dose required to maintain steady state plasma concentrations Dose x F / dosing interval = CL(B) x C(p-ss)

Question 34

What is the loading dose ?

Answer 34

Dose required to achieve therapeutic concentration quickly Loading dose = Vd x desired serum drug concentration

Question 35

To adjust a dose and dose interval due to renal disease, the calculation is?

Answer 35

Adjusted dose= normal dose x (patient renal clearance/normal renal clearance) Adjusted interval= normal dose interval x (normal renal clearance / patients renal clearance)

Question 36

What are the targets for drug action?

Answer 36

Physical interactions: -non-specific effects Biological interaction: - non receptors - receptors (single transduction)

Question 37

What are non specific effects of drug action due to physical interactions?

Answer 37

Osmotic diuretics (attract water) Antacids that act by direct neutralization of acid in the GItract Radioactive iodine

Question 38

What are non-receptor targets of drug action through biological interaction?

Answer 38

Ion channels -physically obstruct or modulate opening and closing Enzymes - compete for binding sites or produce abnormal metabolites Carrier proteins - alter proteins and inhibit their actions

Question 39

What are the receptor interactions for drug action?

Answer 39

Specific recognition sites fore endogenous chemical messengers : Ion channels (inotropic receptors) G protein coupled (metabotrophic receptors) Kinase linked Nuclear receptors (transcription factor receptors)

Question 40

Drugs that bind ligand-gated channels have what affect?

Answer 40

Allows/prevents ions passing through Eg Nicotinic ACh r)eceptors or GABA receptors (neurotransmitters

Question 41

What is a G protein coupled receptor and what affects does its activation have?

Answer 41

Transducer an extracellular signal to an intracellular one -ligand binds to the receptor which displaces GDP from the Gprotein and it is replaced with GTP GTP regulates enzyme/ion channel activity GTP->GDP stops the action

Question 42

What are the intracellular systems of a Gprotien coupled receptor?

Answer 42

- cAMP: adenylyl cylase catalyzes ATP to cAMP-> protein kinase A - PIP2: phospholipase C -> cleaves PIP2 to IP3 and DAG -> IP3 works on ER to release Ca and DAG activates membrane protein kinase C

Question 43

What are the Gprotein subunits?

Answer 43

S- stimulators I- inhibitory q- couples to PLC

Question 44

If a drug couples to G(s) protein receptor what affect will it have?

Answer 44

Positive Increase cAMp Phosphorylation cellular constituents

Question 45

If a drug couples of G(i) protein receptor what will the effects be?

Answer 45

Negative Decrease cAMP Increased outward K+ and close Ca and K channels

Question 46

If a drug couples of G(q) protein receptor what effect will it have?

Answer 46

Positive Couple to phospholipase C Increase Ca release from SER

Question 47

Drugs that bind to kinase-linked receptors will have what affect?

Answer 47

Extracellular receptor -> intracellular kinase domain ->phosphorylation and activation of proteins => insulin, IGF-1, cytokines (generally growth promoting hormones and factors)

Question 48

_________________ receptors are in the cytoplasm and on binding they will trans locate to nucelus to bind to DNA and alter specific gene transcription

Answer 48

Nuclear receptors

Question 49

How are receptors up regulated ?

Answer 49

Increased number at cell surface

Question 50

How are receptors down regulated ?

Answer 50

Decrease in number of receptors and effect Internalization Recycling Sequestration Degradation

Question 51

____________ is a gradual decrease in responsiveness to a drug when given repeatedly over days to months

Answer 51

Tolerance

Question 52

___________________ is an acute tolerance that develops over a short period of time

Answer 52

Tachyphylaxis

Question 53

What are the types of ligand?

Answer 53

Agonist Antagonist Inverse agonist Mixed agonist-antagonist

Question 54

what is an agonist

Answer 54

Mimics the effect of an endogenous ligand | Affinity and efficacy

Question 55

What is the difference between a full agonist and a partial agonist?

Answer 55

Full agonist- spare receptors (receptor reserve) and titrational effect (Eg Methadone) Partial agonist- binds to receptor but does not cause as much effect as a full agonist, still blocks that receptor from full agonist binding "ceiling effect" (once fill effect is reached adding more will not cause a change) (Eg Buprenorphine)

Question 56

A ___________ binds to the same receptor, prevents an agonist from binding, and inhibits the effects of the receptor

Answer 56

Antagonist Naloxone

Question 57

What time of antagonism is reversible and has concentration-dependent binding

Answer 57

Competitive

Question 58

What type of antagonism is irreversible and prevents action of antagonist at ANY concentration.

Answer 58

Noncompetitive | 'Covalently bound to receptor'

Question 59

___________ binds to the same receptor site and produces the opposite effect as agonist. Give an example

Answer 59

Inverse agonist B- carboline

Question 60

___________________ acts as an agonist on one type of receptor and as an antagonist on other types of receptors. Give an example.

Answer 60

Mixed agonist-antagonist Butorphanol - k opioid agonist (sedation) and u opioid antagonist (analgesic)

Question 61

__________ is the concentration of a drug needed to produce the effect

Answer 61

Potency

Question 62

Point at which increasing concentration does not yield greater response

Answer 62

Maximal effect (ceiling)

Question 63

What is the efficacy of a drug

Answer 63

Maximal effect a drug can have Partial agonist may never be able to achieve full efficacy

Question 64

What is the effective concentration

Answer 64

50% of maximal response in vitro | Relates to the concentration of the drug at the site

Question 65

What is the effective dose

Answer 65

Desired effect in 50% of the population | Relates to the dose given to individuals and observed effect

Question 66

What is the does between the lethal dose and the effective dose?

Answer 66

Therapeutic index TI=LD50 / ED50

Question 67

___________ means that the dose required to cause death is close to the dose required to have a therapeutic effect

Answer 67

Narrow therapeutic index

Question 68

________________ means that the dose required to cause death is much higher than the dose required to have a therapeutic effect

Answer 68

Wide therapeutic index

Question 69

How is the standard safety margin calculated?

Answer 69

SSM= (LD1-ED99) / ED99

Question 70

___________ is the time required after drug administration for a response to be observed (latent period)

Answer 70

Onset of action

Question 71

____________ is the length of time that a drug is effective

Answer 71

Duration of action