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Pharmacology Exam 2 > Clindamycin/Tetracycline > Flashcards

Clindamycin/Tetracycline Flashcards

(83 cards)

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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
What causes the Pseudomembranous colitis?
Clostridium difficile toxin
26
How do you treat C. Dif?
Metronidazole or Vancomycin
27
What produces Tetracycline?
Streptomyces bacteria
28
What is Chelation?
Process of removing heavy metals from blood
29
Tetracycline forms stable chelates with what metals?
Ca, Al, Cu, and Mg
30
Problem with tetracycline chelates?
Insoluble, not absorbed in GI tract
31
Preferred administration route of Tetracycline?
Oral
32
Risk of tetracycline with children and tooth formation?
Can permanently stain teeth brown or gray.
33
Pain associated with injection of Tetracycline caused by?
Formation of insoluble calcium complexes
34
What do injectable formulations of tetra contain to reduce pain?
EDTA
35
Epimerization causes what to Tetra?
Inactivates and reduces potency
36
When is Epimerization of Tetra most rapid?
Acidic solutions of pH 4
37
What does dehydration do to Tetra?
Inactives and makes toxic
38
Fanconi syndrome?
Failure of reabsorption in proximal convoluted tubules
39
What makes Tetra completely safe from potential for toxicity due to dehydration?
Lack of C-6 hydroxyl group
40
Where do tetracyclines bind on ribosome?
30S ribosomal subunit
41
What do tetracyclines inhibit?
Bacterial protein synthesis
42
How do tetras inhibit protein synthesis?
Block tRNA attachment to A site of ribosome stopping the peptide growth chain
43
Does tetra overlap with erythromycin binding sites like Clinda does?
No
44
Why does tetra not inhibit host protein synthesis?
We don't have tetra uptake mechanism
45
How many binding sites are there on ribosome subunit for Tetra?
6
46
Which binding site has highest occupancy for Tetra?
Tet1
47
At what pH are tetra inactivated into lactone?
8.5 or above
48
Most common use of Tetra?
Acne
49
Food and milk do what to oral absorption of Tetra?
Lower by 50%
50
Difference between tetracycline and demeclocycline?
Secondary C-6 hydroxyl as opposed to tertiary
51
Significance of secondary hydroxyl instead of tertiary?
Dehydrates more slowly so less toxicity
52
Food and milk do what to oral absorption of Demeclocycline?
Lower absorption by 50%
53
What is Minocycline synthesized from?
Demeclocycline
54
Does Minocycline have a C-6 hydroxyl group?
No
55
Oral bioavailability of Minocycline?
90-100%
56
Food or milk effect on Minocycline absorption?
Lowers by 20%
57
Minocycline toxicities associated with what?
Vestibular system
58
Oxytetracycline produced by what?
Strep Rimosis
59
What is the most hydrophillic tetracycline?
Oxytetracycline
60
What is oral bioavilabilty of Oxytetracycline?
60%
61
Effect of food/milk on absorption of Oxytetracycline?
Lowered by 50%
62
What is doxycycline synthesized from?
Oxytetracycline
63
Why is doxy considered the tetracycline of choice by many?
No potential for dehydration related toxicity AND produces fewer GI problems
64
Oral bioavialabilty for Doxy?
90-100%
65
Food/milk effect on Doxy?
Absorption reduced 20%
66
Half life of Doxy?
18-22 hours (one a day dosing)
67
What is Chloramphenicol obtained from?
Strep venezuelae
68
Why has use of Chloramphenicol waned?
Toxicities
69
When would one use Chloramphenicol?
Benefits outweigh risks
70
How does Chloramphenicol work?
Binds to 50S ribosomal subunit and inhibits peptide bond formation
71
Where does Chloramphenicol bind on Ribosome?
Near site where Clinda and Erythro bind
72
What does Chloramphenicol competitively work against?
Clinda and Erythro
73
Main use of Chloramphenicol?
Ointment or eye drops to treat bacterial conjunctivitis
74
What is chloramphenicol sodium succinate?
Prodrug hydrolyzed to chloramphenicol in liver
75
Chloramphenicol sodium succinate used for?
Bacterial meningitis, typhoid fever, rickettsial infections, or intraocular infections
76
Where can chloramphenicol go in the body?
Everywhere due to lipid solubility
77
What causes resistance to chloramphenicol?
1) Reduced membrane permeability 2) Mutation of 50S ribosome subunit 3) Elaboration of chloramphenicol acetyltransferase
78
What is the most serious toxicity of Chloramphenicol?
Aplastic anemia
79
Highest risk of aplastic anemia with chloramphenicol due to?
Oral, lowest risk eye drops
80
What causes bone marrow suppression in Chloramphenicol toxicity?
Impairment of mitochondrial function from protein synthesis inhibition
81
What cancer risk is increased with Chloramphenicol?
Childhood Leukemia
82
What is Chloramphenicol metabolized to?
Inactive glucuronide
83
Why should neonates never be given chloramphenicol?
They cannot metabolize it

Pharmacology Exam 2 (9 decks)

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