Questions - Answer Bassam Qq 1 .Docx

7/28/2019 Questions - Answer Bassam Qq 1 .Docx

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Pharm acokinetics and pharm acodynam ics

1. What is meant by the terms

Pharmacology : pharmakon meaning drug and logos meaning study.

It is the study of substances that interact with living systems through chemical

processes, especially by binding to regulatory molecules and activating or inhibiting

normal body processes

Dru g : Any substance that brings about a change in biologic function through itschemical action and used for treatment, prevention and diagnosing disease

condition.

ion trapping: weak acids can be eliminated by alkalinization of the urine, whereaselimination of weak bases may be increased by acidification of the urine

First-pass effect: Drugs which absorbed orally are initially transported to the liver via portalvein. The greater the first-pass effect, the less the agent will reach the systemic circulation

and less drug action

bioavailability: is the percentage of dose given that reaches the systemic circulation inunchanged form.

receptor: is a specialized macromolecule (Protein or glycoprotein) presenceon thecell surface or intracellularly that interacts with a drug and initiates the chain of

biochemical events leading to the drug s observed effects orit is any biologic

molecule to which a drug binds and produces a measurable response.Agonists :isan agent that can bind to a receptor and mimics the response to theendogenousligand or drug .e.g phenylephrine is an agonist at -adrenoceptors .

Or is a drugcapable of fully activating the effector system when it binds to the

receptor.

antagonists : are drugs that bind to the receptor, but do no t activate it

Pharmacological antagonist : a drug that blocks the action of epinephrine at itsreceptors by occupying those receptors without activating themChemical antagonist: an antagonist that interacts directly with the agonist and not at

all or only incidentally, with the receptorpartial agonist : can antagonize theeffects of a full agonist because it hasHighaffinity but low intrinsic activity or have efficacies(intrinsic activities) greaterthan zero, but less than that of a full agonist For example, aripiprazole, an atypicalneuroleptic agent, is a partial agonist at selected do pamine receptors.


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Competitive: If both the antagonist and the agonist bind to the same site on the

receptor .Noncompetitive: If the antagonist binds to a site other than where the agonist binds,

the interaction is noncompetitive.

therapeutic index: is the ratio of the dose that producestoxicity to the dose that produces a clinically desired

T.I= TD50/ ED50

2. What is the relationship between displacement and

volume of distribution of a drug?

The impact of drug displacement from albumin

depends on both the Vd and the therapeutic index ofthe drug

1- I f Vd , TI leads to no- important (change in free-

drug concentration in the plasma is not significant)

2- If Vd , TI leads to intermediate - important (the increase in free drug in

the plasma is more profound)

3- If Vd , TI leads to intermediate - important (this increase in drug

concentration may have significant clinical consequences.)

4- I f Vd , TI leads to very - important (Sever dangerous)

3. What is the importance of the Henderson-Hasselbalch equation in the

Pharmacology?

This equation is useful in determining how much drug will be found on

either side of a membrane


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e.gExample: Salicylic acid has a pKa of ~3.

Example: Morphine has a pKa of ~ 8.

4. What are the implications of hepatic enzyme induction and inhibition in

terms of drug metabolism and elimination from the body?

5. Does protein binding speed or slow drug distribution to sites of action?


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Choose the ONE best answer

Enteral administration of drug means that the drug is given

A. IV B. IMC. Transversally

D. through the GIT

Abou t receptor, all these sentences are true except:

A. Most drugs don't interact with receptors

B. Determine selective therapeutic and toxic effects of the drug.

C. Determine the quantitative relations between dose of a drug and pharmacologiceffect

D. Interaction of receptors with ligands involves the formation of chemical bonds..

Bound drugs to plasma albuminA. are pharm acologically inactive

B. act on target sites in the tissues

C. elicit a biologic response

D. are available to the processes of elimination

Mr. Jones, a newly admitted patient, has a history of liver disease. In planning Mr. Jonescare the nurse mu st consider that liver disease may resu lt in a (an) .

A. increase in the excretion rate of a dru g

B. impaired ability to metabolize or detoxify a drug

C. necessity to increase the dosage of a drug

D. decrease in the rate of drug absorption

A patient is treated with drug A, which has a high affinity for albumin and is administered

in amounts that do not exceed the binding capacity of albumin. A second drug, B, is added

to the treatment regimen. Drug B also has a h igh affinity for album in but is adm inistered inalbumin. Which of the following occurs

after administration of drug B?

A. An increase in the tissue concentrations of drug A.

B. A decrease in the tissue concentrations of drug A.

C. The tissue concentrations of drug A is not changed.

The addition of glucuronic acid to a drug :A. Decreases its water solub ility.B. Usually leads to inactivation of the drug.

C. Is an example of a Phase I reaction.

D. Involves cytochrome P450.

A drug w ith a half-life of 12 hours is administered by continuous IV infusion. How long will

it take for the drug to rea ch ninety percen t of its final steady-state level?

A. 18 hours.

B. 24 hours.

C. 30 hours.D.

40 hours.E. 90 hours.


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Which o f the following statem ents is correct?

If 10 mg of Drug A produces the same response as 100 mg of Drug B ;A. Drug A is more potent than Drug B.

B. Drug B is more po tent than Drug A.

C. Drug A is more efficacious than Drug B.D. A and c

EC50 mainly reflexes a drug's:

A. maximal effectB. potency

C. lethality

D. ease of elimination

E. safety

Receptors are usually:

A. LipidsB. Proteins

C. D N A Two m ost important sites for drug elimination:A. pulmonary and liver

B. liver and gastrointestinal tractC. kidney and liver

D. skin and liver

E. pulmonary and kidney

Ion-trapping in the kidney:A. Weak acids are usually excreted slower in alkaline urine

B. Weak b ases are usu ally excreted faster in acidic urine

C. bothD. Neither

Definition: Therapeutic Index

A. ED50/LD50

B. potency/selectivityC. EC50/LD50D. TD50/ED50

Most common drug permeation mechanism:A. passive diffusion in aqueous or lipid medium

B. active transport

Lipid solubility and drugs :

A. more of the weak acid drug will be in the lipid-soluble form at alkaline pH.B. more of the weak acid drug will be in the lipid soluble form at acid pH.C. more of the weak base drug w ill be in the lipid soluble form at alkaline pH

D. A & CE. B & C


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Most comm on mechanism of drug permeation:A. endocytosis

B. carrier-mediated transport

C. active-transport

D. passive diffusion

E. none of the above

General term having to do with actions of the body on the drug:

A. pharmacodynamics

B. pharmacogenetics

C. pharmacokinetics

D. absorption

E. none of the above

General term having to do with drug actions on the body:

A. pharmacokinetics

B. pharmacodynamicsC. pharmacogenetics

D. placebo

E. all of the above

Drug-transport system described as "energy requiring":

A. glomerular filtration

B. facilitated diffusionC. active transport

D. B & C

E. A, B & C

Drug transport:

A. Very hydrophilic drugs may not be well absorbed

B. Excessively lipid-soluble (hydrophobic) drugs may not be soluble enough to cross a

water layer near the cell membraneC. Both

D. Neither

Number of half-lives required to go from one steady-state to another:

A. 1

B. 2

C. 4D. 8

Drug m echanism/mechanisms which may increase the amount of cytochrome P450

enzyme:

A. increased enzyme degradation rateB. increase enzyme synthesis rate

C. bothD. neither

.


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1. Drug NomenclatureA. Chemical Name ; describe chemical structure Not Particularly Useful!

B. Generic Name ; a name assigned to drug that can be used by anyone (not

proprietary)C. Trade Name; Proprietary name given to the drug by the manufacturer

Much more useful

2. Drug sources1) Plant sources; e.g. Morphine, digoxin.

2) Animal sources; e.g. Insulin, and antitoxic sera.

3) Minerals; e.g. magnesium sulfate, ferrous sulfate.

4) Chemical or Synthetic sources ; Most of drugs are chemical e.g. aspirin

5) Micro-organisms; Bacteria and fungi e.g. Penicillin (from fungi)

, tetracycline (from bacteria)

6) Genetic Engineering; e.g. antibodies, interferons

3. Pregnancy CategoriesA: Controlled studies in pregnancy .

B: Animal studies show no risk; Inadequate human data.

C: Animal studies show risk, inadequate human data.

D: Human data show risk, benefit may outweigh risk.

X: Animal or human data positive for risk. Use unwarranted.

PharmacokineticsDrug Absorption

4. Absorption of drugs in an aqueous solution is fast, whereas that from depot

preparations is slow such as haloperidol decanoate.

5. The rate and efficiency of absorption depend on the route of administration.For IV delivery, absorption is complete.

6. Factors wh ich influence on drug absorption1) Transport; Act ive vs. passive2) PH alterations3) Rou te of adm inistration4) Dosage forms

5) Phy sical factors

6) Blood flow at the s ite of abso rptionBlood flow to the organ -----

Blood flow to the organ -----

7) Surface area of absorptiona. Surface area of absorption ---------


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8) Contact time of absorption site e.g. if gastric emptying is delayed or

enhanced

7. Most drugs are either weak acids or weak bases and can exist in either the

ionized (less lipid soluble) or unionized (more lipid soluble) form depending

on the pH of the surrounding environment.

8. Depending on their chemical properties, drugs may be absorbed from the GI

tract by either passive diffusion, facilitated d iffusion, active transport,endocytosisorexocytosis.

Drug Bioavailability9. Factors that influence bioavailability

1) First-passhepatic metabolism

2) Solubil ity of the drugFor a drug to be readily absorbed, it must be largely hydrophobic and some

solubility in aqueous solutions.

3) Ch em ical instabili tySome d rugs, such as penicillin G, are unstable in the pH of the gastriccontents. Others, such as insulin , are destroyed in the GI tract by degradativeenzymes.

4) Complexation Tetracyclines and Ca ++5) Nature of the drug formu lation:

Some factors such as particle size, salt form can influence the ease of

dissolution and, therefore, alter the rate of absorption

Drug Distribution10. Factors affecting drug distribution

A. Blood flow

B. Capillary permeability

C. Capillary permeability is determined by capillary structure and by the

chemical nature of the drug ; e.g., molecular weight, solubility of the drug in

lipid or in water, ionization ,

D. Protein binding

Drugs that bind to plasma proteins may be restricted in distribution.

11. If a drug has a very large molecular weight or binds extensively to plasma

proteins is effectively trapped within the plasma (vascular) compartment.

12. If a drug has a low molecular weight but is hydrophilic, it can move through

the endothelial slit junctions of the capillaries into the interstitial fluid.

13. If a drug has a low molecular weight and is hydrophobic, not only can it move

into the interstitium through the slit junctions, but it can also move throughthe cell membranes into the intracellular fluid.


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14. The volume into which drugs distribute is called the apparent volume of

distribution, or Vd.

where C = the plasma concentration of the drug and D = the total amount of drug

in the body. For example, if 25 mg of a drug (D = 25 mg) are administered

15. Effect of a large Vd on the half-life of a drug

A ny factor that increases the volume of distribution can lead to an increase in the

half-life and extend the duration of action of the drug.

Protein-Drug binding16. Drug molecules may bind to plasma proteins (usually albumin).

17. Bound drugs are pharmacologically inactive; only the free, unbound drug can

act on target sites in the tissues, elicit a biologic response, and be available to

the processes of elimination.

18. The binding of drugs to albumin is reversible and may show low capacity (one

drug molecule per albumin molecule) or high capacity (a number of drug

molecules binding to a single albumin molecule).

19. Drugs can also bind w ith varying affinities.

Drug Metabolism20. The process of metabolism transforms lipophilic drugs into more polar readily

excretable products.

21. Metabolism occurs mainly in the liverbut also occur in other sites, such as

the kidney and the intestines.

22. Some agents are initially administered as inactive compounds (pro-drugs) and

must be metabolized to their active forms.

23. Phase I reactions function to convert lipophilic molecules into more polar

molecules by introducing or unmasking a polar functional group, such as OHor NH2.

24. Phase I metabolism may increase, decrease, or leave unaltered the drug's

pharmacologic activity.

25. PhaseIIconsists of conjugation reactions.

26. A subsequent conjugation reaction with an endogenous substrate, such as

glucuronic acid, sulfuric acid, acetic acid, or an amino acid, results in polar,

usually more water-soluble compounds that are most often therapeutically

inactive.


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27. Drugs already possessing an OH, HN2, or CO OH group may enter Phase I I

directly and become conjugated without prior Phase I metabolism. The highly

polar drug conjugates may then be excreted by the kidney or bile.

28. Not all drugs undergo Phase I and II reactions in that order. For example,

isoniazidis first acetylated (a Phase II reaction) and then hydrolyzed toisonicotinic acid (a Phase I reaction).

Drug elim ination

29. There are two major routes of elimination; 1-Metabolism 2-Excretion

30. The liver contributes to drug loss through metabolism and/or excretion into

the bile.

31. The action of many drugs, especially lipophilic compounds, is terminated by

enzymatic conversion, or metabolism, to biologically inactive derivatives.32. In most cases, the enzymatic conversion forms a more hydrophilic compound

that can be more readily excreted in the urine.

Excretion

33. Removal of a drug from the body occurs via a number of routes,

34. These routes include the kidney, bile, intestine, lung , sweat or milk in

nursing mothers .

35. The most important being through the kidney into the urine.

36. To be excreted by the kidney, drugs need to be reasonably hydrophilic so that

they will remain in the fluid that becomes the urine.37. Most drugs are excreted by the kidneys and eliminated unchanged or as

metabolites in the urine.

38. Others are excreted in bile, reabsorbed from the small intestine, returned to

the liver (called enterohepatic recirculation), metabolized, and eventually

excreted in urine.

39. The lungs mainly remove volatile substances, such as anesthetic gases.

40. The skin has minimal excretory function.

41. Transport systems of tubular secretion shows low specificity and cantransport many compounds; thus, competition between drugs for these

carriers can occur within each transport system (for example, probenecid).

42. The drug elimination is determined primarily by the drug s rates of

metabolism and excretion .

43. A drug with a short half-life requires more frequent administration than one

with a long half-life.


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44. The half-life of a drug is increased by

1) Diminished renal plasma flow or hepatic blood flow.

2) Decreased metabolism.

3) Reabsorption through the enterohepatic circulation

45. The half-l ife of a drug m ay decrease by

1) Increased hepatic blood flow,

2) Decreased protein binding,

3) Increased metabolism.

46. A drug will reach steady-state in about 4-5 half-lives.

47. The sole determinant of the rate that a drug approaches steady state is the

t1/2or ke, and this rate is influenced only by the factors that affect the half-

life.

48. Although increasing the rate of infusion of a drug increases the rate at which

any given concentration of drug in the plasma is achieved, it does not

influence the time required to reach the ultimate steady-state concentration.

49. loading dose

1) A loading dose is an initial higher dose of a drug that may be given at

the beginning of a course of treatment before dropping down to a

lower maintenance dose.

2) A delay in achieving the desired plasma levels of drug may be

clinically unacceptable.

3) Therefore, a loading dose of drug can be injected as a single dose to

achieve the desired plasma level rapidly, followed by an infusion to

maintain the steady state (maintenance dose).

50. Most drugs are given at intervals shorter than five half-lives and are

eliminated exponentially with time.

Pharmacokinetics51. Most drugs exert their effects, both beneficial and harmful, by interacting

with receptors.52. Receptor is a specialized macromolecule (Protein or glycoprotein) present on

the cell surface or intracellularly that interacts with a drug and initiates the

chain of biochemical events leading to the drug s observed effects or it is any

biologic molecule to which a drug binds and produces a measurable

response.

53. Not all drugs exert their effects by interacting with a receptor; for example,

antacidschemically neutralize excess gastric acid, reducing the symptoms of

heartburn.

54. Receptors


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1) Determine selective therapeutic and toxic effects of the drug.

2) Determine the quantitative relations between dose of a drug and

pharmacologic effect.

55. Interaction o f receptors with ligands involves the formation of chemical

bonds.56. These chemical bonds are most commonly electrostatic and hydrogen bonds,

as well as weak interactions involving van der Waals forces.

57. The bonds are usually reversible, except for a handful of drugs (for example,

phenoxybenzamine, and acetylcholinesterase inhibitors in the

organophosphate class that covalently bond to their targets).

58. The size, shape, and charge distribution of the drug molecule determines

which of the myriad binding sites in the cells and tissues of the patient can

interact with the ligand.

59. The metaphor of the lock and key is a useful concept for understanding theinteraction of receptors with their ligands (lock-an d-key model ).

60. Sensitivity of cell to the agonist concentration depends on affinity of receptor

for drug, in addition to, total receptor concentration.

61 . These receptors may be divided into four families:

I. Ligand-gated ion channels,

II. G protein coupled receptors,

III. Enzyme -linked receptors, and

IV . Intracellular receptors

1) The type of receptor a ligand will interact with depends on the nature

of the ligand.

2) Hydropholic ligands interact with receptors that are found on the cell

surface (families 1, 2, and 3).

3) In contrast, hydrophobic ligands can enter cells through the lipid

bilayers of the cell membrane to interact with receptors found inside

cells (family 4).

62. A graph of graded dose-response relationship is

known as a graded dose-response curve.

63. Two important properties of drugs can be

determined by graded dose response curves,

potency and efficacy.

64. Potency is the amount of drug necessary to produce

an effect of a given magnitude.

65. It is determined mainly by:

a. Affinity of receptor for the drug


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b. E ff iciency with which drug-receptor interactions is coupled to

response

66. EC50

used to determine potency (Used to compare com pounds w ithin classes ofdrugs).

The lower the dose needed to produce a response, the more potent the drug.

The sm al ler the EC50

, the more potent the drug.

67. Efficacy is the largest response or maximal effect (Emax) of a drug can

produce when it interacts with a receptor

68. Affinity describes the strength of the interaction (binding) between a ligand

and its receptor.

69. The therapeutic index of a drug is the ratio of the dose that produces toxicity

to the dose that produces a clinically desired or effective response in a

population o f individuals: T.I= TD50/ ED 50

of the population.

70. The therapeutic index is a measure of a drug's safety, because a larger value

indicates a wide margin between doses that are effective and doses that are

toxic.

Choice of administration route of drug depend on 1. The ph ysical properties

2. chem ical properties3. The therapeutic objectives.

71. The three major parenteral routes are I.V, I.M, S.C

72. if 100 mg of a drug are administered orally and 20mg o f this drug are

absorbed unchanged, the bioavailability is 20 percent.

73. The most common route of drug administration Oral Route


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Questions - Answer Bassam Qq 1 .Docx