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Drugs, Microbes, Host-The Elements of Chemotherapy

1. Which is mismatched:

A) Fleming - penicillin
B) Domagk - sulfonamide
C) Ehrlich - tetracycline
D) Florey and Chain - penicillin
E) none of the choices are correct

2. Salvarsan was:

A) discovered in the mid-1900's
B) used to treat syphilis
C) formulated from the red dye prontosil
D) first discovered as a product of Penicillium notatum
E) discovered by Robert Koch
Arsphenamine, also known as Salvarsan and 606, is a drug that was used beginning in the 1910s to treat syphilis and trypanosomiasis

3. Substances that are naturally produced by certain microorganisms that can inhibit or destroy other microorganisms are called:

A) antibiotics
B) narrow-spectrum drugs
C) semisynthetic drugs
D) synthetic drugs
E) broad-spectrum drugs

4. Antimicrobics effective against a wide variety of microbial types are termed:

A) antibiotics
B) narrow-spectrum drugs
C) semisynthetic drugs
D) synthetic drugs
E) broad-spectrum drugs

5. Antibiotics are derived from all the following except:

A) Penicillium
B) Bacillus
C) Staphylococcus
D) Streptomyces
E) Cephalosporium

6. Important characteristics of antimicrobic drugs include:

A) low toxicity for human tissues
B) high toxicity against microbial cells
C) do not cause serious side effects in humans
D) stable and soluble in body tissues and fluids
E) all of the choices are correct

7. Broad-spectrum drugs that disrupt the body's normal flora often cause:

A) nephrotoxicity
B) superinfections
C) allergic reactions
D) drug toxicity
E) all of the choices are correct

8. Penicillins and cephalosporins:

A) interfere with elongation of peptidoglycan
B) are metabolic analogs of PABA and block folic acid synthesis
C) attach to the 30S ribosomal subunit and disrupt protein synthesis
D) damage cell membranes
E) bind and block peptidases that cross-link glycan molecules, thereby interrupting the completion of the cell wall.

9. Sulfonamides:

A) interfere with elongation of peptidoglycan
B) are metabolic analogs(competition) of PABA for the active site of enzyme that synthesis; therefore blocking folic acid synthesis.
C) attach to the 30S ribosomal subunit and disrupt protein synthesis
D) damage cell membranes
E) block peptidases that cross-link glycan molecules

10. Aminoglycosides:

A) interfere with elongation of peptidoglycan
B) are metabolic analogs of PABA and block folic acid synthesis
C) attach to the 30S ribosomal subunit and disrupt protein synthesis
D) damage cell membranes
E) block peptidases that cross-link glycan molecules

11. Ampicillin, amoxicillin, mezlocillin, and penicillin G all have:

A) a beta-lactam ring
B) resistance to the action of penicillinase
C) a semisynthetic nature
D) an expanded spectrum of activity
E) all of the choices are correct

12. A chemical that inhibits beta-lactamase enzymes is:

A) synercid
B) penicillinase
C) aztreonam
D) clavulanic acid
E) imipenem

13. All of the following pertain to cephalosporins except:

A) have a beta-lactam ring
B) greater resistance to beta-lactamases
C) newer generations have activity against gram negatives
D) many administered by injection not orally
E) are synthetic drugs

14. Which antimicrobic does not inhibit cell wall synthesis?

A) gentamicin
B) vancomycin
C) cephalosporins
D) penicillins
E) clavamox

15. Gram negative rods are often treated with:

A) penicillin G
B) vancomycin
C) aminoglycosides
D) synercid
E) isoniazid

16. This drug is used to treat cases of tuberculosis:

A) penicillin G
B) vancomycin
C) aminoglycosides
D) synercid
E) isoniazid

17. Which antimicrobic does not interfere with protein synthesis?

A) aminoglycosides
B) tetracyclines
C) erythromycin
D) trimethroprim
E) chloramphenicol

18. Which of these drugs have the most narrow spectrum?

A) tetracycline
B) isoniazid
C) erythromycin
D) aminoglycosides
E) cephalosporins

19. All of the following pertain to fluoroquinolones except:

A) broad spectrum
B) include ciprofloxacin and levofloxacin
C) are nephrotoxic
D) used to treat respiratory, urinary, and sexually transmitted infections
E) readily absorbed from intestines

20. Antimicrobics that are macrolides:

A) disrupt cell membrane function
B) include tetracyclines
C) include azithromycin, clarithromcyin, and erythromycin
D) are very narrow-spectrum drugs
E) are hepatotoxic

21. The drug that can cause aplastic anemic, and is used to treat typhoid fever and brain abscesses is:

A) chloramphenicol
B) clindamycin
C) ciprofloxacin
D) bacitracin
E) gentamicin

22. The drug used against intestinal anaerobic bacteria, that can also alter normal flora causing antibiotic-associated colitis is:

A) chloramphenicol
B) clindamycin
C) ciprofloxacin
D) bacitracin
E) gentamicin

23. The antifungal drug that can be used to treat serious systemic fungal infections is:

A) nystatin
B) griseofulvin
C) amphotericin B
D) sulfa drugs
E) metronidazole

24. The drug used for several protozoan infections is:

A) nystatin
B) griseofulvin
C) amphotericin B
D) sulfa drugs
E) metronidazole

25. Mebendazole, niclosamide, and ivermectin are drugs used to treat _____ infections.

A) bacterial
B) fungal
C) protozoan
D) helminthic
E) virus

26. Ketoconazole, fluconazole, clotrimazole, and miconazole are broad-spectrum azoles used to treat _____ infections.

A) bacterial
B) fungal
C) protozoan
D) helminthic
E) virus

27. There are fewer antifungal, antiprotozoan, and antihelminth drugs compared to antibacterial drugs because fungi, protozoa, and helminths:

A) do not cause many human infections
B) are not affected by antimicrobics
C) are so similar to human cells that drug selective toxicity is difficult
D) are parasites found inside human cells
E) because their cells have fewer target sites compared to bacteria

28. Which of the following is not a mode of action of antivirals?

A) block penetration
B) block transcription and translation
C) inhibit DNA synthesis
D) block maturation
E) bond to ergosterol in the cell membrane

29. An antiviral that is a guanine analog would have an antiviral mode of action that:

A) blocks penetration
B) blocks transcription and translation
C) inhibits DNA synthesis
D) blocks maturation
E) bonds to ergosterol in the cell membrane

30. Antivirals that target reverse transcriptase would be used to treat:

A) influenza A virus
B) HIV
C) herpes zoster virus
D) respiratory syncytial virus
E) hepatitis C virus

31. Acyclovir is used to treat:

A) influenza A virus
B) HIV
C) herpes zoster virus
D) respiratory syncytial virus
E) hepatitis C virus

32. The cellular basis for bacterial resistance to antimicrobics include:

A) bacterial chromosomal mutations
B) synthesis of enzymes that alter drug structure
C) prevention of drug entry into the cell
D) alteration of drug receptors on cell targets
E) all of the choices are correct

33. The multidrug resistant pumps in many bacterial cell membranes cause:

A) bacterial chromosomal mutations
B) synthesis of enzymes that alter drug structure
C) prevention of drug entry into the cell
D) alteration of drug receptors on cell targets
E) all of the choices are correct

34. Side effects that occur in patient tissues while they are on antimicrobic drugs include all the following except:

A) development of resistance to the drug
B) hepatotoxicity
C) nephrotoxicity
D) diarrhea
E) deafness

35. A superinfection results from:

A) build up of a drug to toxic levels in the patient
B) the wrong drug administered to the patient
C) an immune system reaction to the drug
D) decrease in most normal flora with overgrowth of an unaffected species
E) all of the choices are correct

36. Drug susceptibility testing:

A) determines the patient's response to various antimicrobics
B) determines the pathogen's response to various antimicrobics
C) determines if normal flora will be affected by antimicrobics
D) determines if the drug is increasing to toxic levels in a patient
E) none of the choices are correct

37. A clinical microbiologist makes serial dilutions of several antimicrobics in broth, then incubates each drug dilution series with a standard amount of a patient's isolated pathogen. What is this microbiologist setting up?

A) Kirby-Bauer
B) antibiogram
C) E-test
D) MIC
E) therapeutic index (TI)

38. A ratio of the dose of the drug that is toxic to humans versus the minimum effective dose for that pathogen is assessed to predict the potential for toxic drug reactions. This is called the:

A) Kirby-Bauer
B) antibiogram
C) E-test
D) MIC
E) therapeutic index (TI)

39. When a patient's immune system reacts adversely to a drug, this serious side effect is called a superinfection.

A) True
B) False

40. The most important antibiotic of the penicillin family is penicillin G.

A) True
B) False

41. Species of Bacillus produce bacitracin and the polymyxins.

A) True
B) False

42. Ciprofloxacin is used to treat viral respiratory infections.

A) True
B) False

43. Resistance factor plasmids are transferred to other bacterial cells during transformation, transduction, and conjugation.

A) True
B) False

44. The MIC is the smallest concentration of an antimicrobic required to inhibit the growth of the microbe.

A) True
B) False

45. Drugs that are hepatotoxic cause damage to a patient's kidneys.

A) True
B) False

46. The Kirby-Bauer test uses an agar surface, seeded with the test bacterium, to which small discs containing a specific concentration of several drugs are placed on the surface.

A) True
B) False

47. An antimicrobic with a low therapeutic index is a safer choice compared to a drug with a high therapeutic index.

A) True
B) False

_____ are plasmids that contain genes for resistance to a drug.

...

49. Sulfonamides are analogs of PABA and, as a result, they inhibit _____ synthesis.

...

50. Drugs that insert on the _____ ribosomal subunit prevent peptide bond formation or inhibit translocation of the subunit during translation.

...

51. Drugs that act by mimicking the normal substrate of an enzyme, thereby blocking its active site, are called _____.

...

52. All _____ consist of a thiazolidine ring, a beta-lactam ring, and an R group.

...

53. The major source of naturally produced penicillin is the mold _____.

...

54. The _____ are drugs that deposit in developing teeth and cause a permanent brown discoloration.

...

55. Polyene drugs bind to fungal _____ and cause loss of selective permeability.

...

56. Primaquine and chloroquine are drugs used in the treatment of _____.

...

57. If pathogen A is more resistant to an erythromycin disc on a Kirby-Bauer plate compared to pathogen B, then pathogen A will have a _____ zone of inhibition compared to pathogen B.

...

58. Discuss the problems with development of antifungal, antiprotozoan, antihelminth, and antiviral drugs compared to the antbacterial drugs. Discuss at least 3 different modes of action that have been developed for these drugs.

...

59. Describe how the therapeutic index of a drug is determined and explain its function.

...

60. Discuss 5 factors that have influenced the increasing development of resistant microbial strains.

...

Describle the Principals of Antimicrobial Therapy

-Adminstering of a drug to an infected person that destroys the infective agent without harming the host's cells.
-Antimicrobial drugs are produced naturally, synthtically , or semi-sythtically. (semi- due to the bacteria becoming resistant.

Physician Sir alander Fleming discovered what?

He accidently discovered penicillin when his keen eye noticed that colonies of bacteria were being lysed by a fungal contaminat.

What did Gerhanrd Domagk discovered?

1930's launched a breakthrough in therapy that marked the true beginnning of broad-scaled usage of antimicrobial durgs - He discovered the substance called sulfonamide-the first sulfa drug.

Scientist Paul Ehrlich discovered what?

The first scientist to formulate basic theroetical concepts in chemotherapy in the late 1800's. He observed that certain dyes affixed themselves to specific mircroorganisms and not to normal tissues.

Chemist Howard Florey and Ernst Chain

After a decade of Fleming understanging of penicillian they worked out methods for industrial production of penicillian to help in the war effort.

Terminology of chemotherapy
What is Antibiotics?

are common metabolic products of aerobic spore-forming bacteria and fungi.
-Bacteria in genera Streptomyces(streptomycin) and Bacillus (bacitracin)
-molds in genera Penicillium and Cephalosporium
-By inhibiting the other microbes in the same habitat, anitbiotic producers have less competition for nutrients and space.

Terminology of Chemotherapy
What is narrow -spectrum drugs (limited spectrum)?

Antimicrobials effective against a limited array of microbial types; for example, a drug effective mainly on gram-positive bacteria. ( Azithromycin, Clarithromycin, Clindamycin)

Terminology of Chemotherapy
What is Semisynthetic Drugs

Drugs that chemically modified in the laboratory after being isolated from natural sources:

Terminology of Chemotherapy
Synthetic drugs

Antimicrobial compounds synthetic in the laboratory through chemical reactions.

Terminology of chemotherapy
What is Antimicrobials

All-inclusive term for any antimicrobial drug, regardless of its origin.

What is Selectively toxic?

Antimicrobial drugs should be ---- drugs should kill or inhibit microbial cells without simultaneously damaging host tissues.This concept should be central to chemotherapy.
- As the characteristics of the infectious agents become more similar to the vertebrate host cell, complete selective toxicity becomes more difficult to achieve and more side effects are seen in the host.

Antimicrobial Drugs That Disrupt Cell Membrane Function

A cell with a damaged membrane dies from disruption in metabolism or lysis.
These drugs have specificity for a particular microbial group, based on differences in types of lipids in their cell membranes.
Polymyxins interact with phospholipids and cause leakage, particularly in Gram-negative bacteria.
Amphotericin B and nystatin form complexes with sterols on fungal membranes which causes leakage. (check liver enzymes)

Drugs That Inhibit Nucleic Acid Synthesis

May block synthesis of nucleotides, inhibit replication or stop transcription
Chloroquine binds and cross-links the double helix; quinolones inhibit DNA helicases.
Antiviral drugs that are analogs of purines and pyrimidines insert in viral nucleic acid, preventing replication.

Drugs That Block Protein Synthesis

Ribosomes of eucaryotes differ in size and structure from procaryotes; antimicrobics usually have a selective action against procaryotes; can also damage the eucaryotic mitochondria
Aminoglycosides (streptomycin, gentamycin) insert on sites on the 30S subunit and cause misreading of mRNA.
Tetracyclines block attachment of tRNA on the A acceptor site and stop further synthesis

Drugs that Affect Metabolic Pathways

Sulfonamides and trimethoprim block enzymes required for tetrahydrofolate synthesis (synthesis of folic acid) needed for DNA and RNA synthesis.
Competitive inhibition - drug competes with normal substrate for enzyme's active site
Synergistic effect - an additive effect, achieved by multiple drugs working together, requiring a lower dose of each, ex. Affects the cell wall, affects the cell membrane, and nucleic acid production

Must know - Survey of Major Antimicrobial Drug Groups

Antibacterial drugs
Antibiotics - penicillin, streptomycin
synthetic drugs - amoxicillin, doxycycline
Antifungal drugs - Nystatin, Amphotericin B, Candicin
Antiprotozoan drugs - metronidazole (Flagyl, treats mixed infections), hydroxychloroquine (malaria)
Antiviral drugs - acyclovir, Zovirax, valacyclovir,Valtrex
About 260 different antimicrobial drugs are classified in 20
drug families

Penicillin and Its Relatives

Large diverse group of compounds
Could be synthesized in the laboratory
More economical to obtain natural penicillin through microbial fermentation and modify it to semi-synthetic forms
Penicillium chrysogenum - major source
All consist of 3 parts:
1) thiazolidine ring
2) BETA-LACTAM RING - DESTROYS THE CELL WALL, (ex. Beta-lactamase & Penicillinase are enzymes secreted by bacteria that make them resistant.
3) variable side chain dictating microbial activity

Cephalosporins

Account for majority of all antibiotics administered
Cephalosporin compounds were first isolated from cultures of Cephalosporium acremonium from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu
Synthetically altered beta-lactam structure
Relatively broad-spectrum
Resistant to most penicillinases, & cause fewer allergic reactions
Some are given orally; many must be administered parenterally (taken into the body in a manner other than through the digestive canal)
Generic names have root - cef, ceph, or kef.

Semisynthetic penicillins

ampicillin, carbenicillin and amoxicillin have broader spectra - Gram-negative enteric rods

Cephalosporins- 4 generations exist: each group more effective against Gram-negatives than the one before with improved dosing schedule and fewer side effects

first generation - cephalothin, cefazolin - most effective against Gram-positive cocci and few Gram-negative
second generation - cefaclor, cefonacid - more effective against Gram-negative bacteria
third generation - cephalexin, ceftriaxone - broad-spectrum activity against enteric bacteria with beta-lactamases
fourth generation - cefepime - widest range; both Gram- negative and Gram-positive

Additional Beta-lactam Drugs - Carbapenems

imipenem - broad-spectrum drug for infections with aerobic and anaerobic pathogens; low dose, administered orally with few side effects

Additional Beta-lactam Drugs - Monobactams

aztreonam -newer narrow-spectrum drug for infections by Gram-negative aerobic bacilli; may be used by people allergic to penicillin

Non Beta-lactam Cell Wall Inhibitors - bacitracin

narrow-spectrum produced by a strain of Bacillus subtilis; used topically in ointment

Non Beta-lactam Cell Wall Inhibitors - vancomycin

narrow-spectrum, most effective in treatment of Staphylococcal infections in cases of penicillin and methicillin resistance or if patient is allergic to penicillin; toxic and hard to administer; restricted use

Non Beta-lactam Cell Wall Inhibitors - isoniazid (INH) -

works by interfering with mycolic acid synthesis; used to treat infections with Mycobacterium tuberculosis,Penicillin G was used until the bacteria became resistant

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