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Pharmacology Exam 2 > Clindamycin/Tetracycline > Flashcards

Clindamycin/Tetracycline Flashcards

1
Q

What is Clindamycin synthesized from?

A

Lincomycin, a naturally occurring antibiotic

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2
Q

What do I add to Lincomycin to make Clindamycin?

A

Triphenylphosphine, chlorine in acetonitrile

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3
Q

Mechanism of change between Lincomycin to Clindamycin?

A

Inversion of configuration

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4
Q

Why is Lincomycin no longer used?

A

Toxicity

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5
Q

What is Clindamycin similar to mechanically?

A

Erythromycin (macrolide antibiotics)

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6
Q

How does Clindamycin work?

A

Inhibits protein synthesis (binds to part of 50S ribosomal subunit)

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7
Q

How does Clinda and Erythro interact?

A

Clinda binds to same site as Erythro

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8
Q

What is the result of the interaction between Clinda and Erythro?

A

Antagonism and cross resistance

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9
Q

What is Clinda most effective against?

A

Aerobic Gram + cocci

Anaerobic Gram - bacilli

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10
Q

Examples of Aerobic Gram + cocci?

A

Staph and Strep

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11
Q

Examples of Anaerobic Gram - bacilli?

A

Bacteroides and Fusobacterium

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12
Q

Best systematic use of Clinda?

A

Bone infection with Staph aureus

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13
Q

Best topical use of Clinda?

A

Severe Acne

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14
Q

What drug did Clinda replace in treating lung abscesses, anaerobic lung, and pleural space infections?

A

Penicillin

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15
Q

How do you treat Toxoplasma gondii encephalitis?

A

Clinda IV with pyrimethamine and leucovorin

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16
Q

What limits the use of Clinda to infections where it is clearly the superior agent?

A

Pseudomembranous colitis and diarrhea

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17
Q

How can Clinda be delivered?

A

Oral, IV, Topical foams/solutions

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18
Q

What metabolizes Clinda?

A

CYP 450 enzymes in liver

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19
Q

Activity of Clinda after metabolism by CYP 450?

A

Inactive

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20
Q

How much of the Clinda dose is absorbed in the GI tract?

A

90%

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21
Q

Where is Clina distributed?

A

CNS

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22
Q

Where is Clinda and metabolites excreted?

A

Bile and urine

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23
Q

What is elimination half life of Clinda?

A

1.5-5 hours

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24
Q

Potentially lethal condition caused by Clinda?

A

Pseudomembranous colitis

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25
Q

What causes the Pseudomembranous colitis?

A

Clostridium difficile toxin

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26
Q

How do you treat C. Dif?

A

Metronidazole or Vancomycin

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27
Q

What produces Tetracycline?

A

Streptomyces bacteria

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28
Q

What is Chelation?

A

Process of removing heavy metals from blood

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29
Q

Tetracycline forms stable chelates with what metals?

A

Ca, Al, Cu, and Mg

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30
Q

Problem with tetracycline chelates?

A

Insoluble, not absorbed in GI tract

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31
Q

Preferred administration route of Tetracycline?

A

Oral

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32
Q

Risk of tetracycline with children and tooth formation?

A

Can permanently stain teeth brown or gray.

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33
Q

Pain associated with injection of Tetracycline caused by?

A

Formation of insoluble calcium complexes

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34
Q

What do injectable formulations of tetra contain to reduce pain?

A

EDTA

35
Q

Epimerization causes what to Tetra?

A

Inactivates and reduces potency

36
Q

When is Epimerization of Tetra most rapid?

A

Acidic solutions of pH 4

37
Q

What does dehydration do to Tetra?

A

Inactives and makes toxic

38
Q

Fanconi syndrome?

A

Failure of reabsorption in proximal convoluted tubules

39
Q

What makes Tetra completely safe from potential for toxicity due to dehydration?

A

Lack of C-6 hydroxyl group

40
Q

Where do tetracyclines bind on ribosome?

A

30S ribosomal subunit

41
Q

What do tetracyclines inhibit?

A

Bacterial protein synthesis

42
Q

How do tetras inhibit protein synthesis?

A

Block tRNA attachment to A site of ribosome stopping the peptide growth chain

43
Q

Does tetra overlap with erythromycin binding sites like Clinda does?

A

No

44
Q

Why does tetra not inhibit host protein synthesis?

A

We don’t have tetra uptake mechanism

45
Q

How many binding sites are there on ribosome subunit for Tetra?

A

6

46
Q

Which binding site has highest occupancy for Tetra?

A

Tet1

47
Q

At what pH are tetra inactivated into lactone?

A

8.5 or above

48
Q

Most common use of Tetra?

A

Acne

49
Q

Food and milk do what to oral absorption of Tetra?

A

Lower by 50%

50
Q

Difference between tetracycline and demeclocycline?

A

Secondary C-6 hydroxyl as opposed to tertiary

51
Q

Significance of secondary hydroxyl instead of tertiary?

A

Dehydrates more slowly so less toxicity

52
Q

Food and milk do what to oral absorption of Demeclocycline?

A

Lower absorption by 50%

53
Q

What is Minocycline synthesized from?

A

Demeclocycline

54
Q

Does Minocycline have a C-6 hydroxyl group?

A

No

55
Q

Oral bioavailability of Minocycline?

A

90-100%

56
Q

Food or milk effect on Minocycline absorption?

A

Lowers by 20%

57
Q

Minocycline toxicities associated with what?

A

Vestibular system

58
Q

Oxytetracycline produced by what?

A

Strep Rimosis

59
Q

What is the most hydrophillic tetracycline?

A

Oxytetracycline

60
Q

What is oral bioavilabilty of Oxytetracycline?

A

60%

61
Q

Effect of food/milk on absorption of Oxytetracycline?

A

Lowered by 50%

62
Q

What is doxycycline synthesized from?

A

Oxytetracycline

63
Q

Why is doxy considered the tetracycline of choice by many?

A

No potential for dehydration related toxicity AND produces fewer GI problems

64
Q

Oral bioavialabilty for Doxy?

A

90-100%

65
Q

Food/milk effect on Doxy?

A

Absorption reduced 20%

66
Q

Half life of Doxy?

A

18-22 hours (one a day dosing)

67
Q

What is Chloramphenicol obtained from?

A

Strep venezuelae

68
Q

Why has use of Chloramphenicol waned?

A

Toxicities

69
Q

When would one use Chloramphenicol?

A

Benefits outweigh risks

70
Q

How does Chloramphenicol work?

A

Binds to 50S ribosomal subunit and inhibits peptide bond formation

71
Q

Where does Chloramphenicol bind on Ribosome?

A

Near site where Clinda and Erythro bind

72
Q

What does Chloramphenicol competitively work against?

A

Clinda and Erythro

73
Q

Main use of Chloramphenicol?

A

Ointment or eye drops to treat bacterial conjunctivitis

74
Q

What is chloramphenicol sodium succinate?

A

Prodrug hydrolyzed to chloramphenicol in liver

75
Q

Chloramphenicol sodium succinate used for?

A

Bacterial meningitis, typhoid fever, rickettsial infections, or intraocular infections

76
Q

Where can chloramphenicol go in the body?

A

Everywhere due to lipid solubility

77
Q

What causes resistance to chloramphenicol?

A

1) Reduced membrane permeability
2) Mutation of 50S ribosome subunit
3) Elaboration of chloramphenicol acetyltransferase

78
Q

What is the most serious toxicity of Chloramphenicol?

A

Aplastic anemia

79
Q

Highest risk of aplastic anemia with chloramphenicol due to?

A

Oral, lowest risk eye drops

80
Q

What causes bone marrow suppression in Chloramphenicol toxicity?

A

Impairment of mitochondrial function from protein synthesis inhibition

81
Q

What cancer risk is increased with Chloramphenicol?

A

Childhood Leukemia

82
Q

What is Chloramphenicol metabolized to?

A

Inactive glucuronide

83
Q

Why should neonates never be given chloramphenicol?

A

They cannot metabolize it

Pharmacology Exam 2 (9 decks)

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