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PHRM 865: Theraputics V > Lecture 9: Aminoglycosides > Flashcards

Lecture 9: Aminoglycosides Flashcards

1
Q

What are the structural features that are common among the Aminoglycosides?

A
  • 1,3 - Diaminocyclitol “core”
  • Main core sturctures are Streptidine & 2-Deoxystrptamine
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2
Q

What is the Mechanism of Action for the Aminoglycodies?

A
  • Inhibit protein buosynthesis by binding to 30s subunit
  • Bind to the A-site further blocking synthesis
  • Lead to leakage of ions = cell death

affects frame shifts

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3
Q

What is the Aminoglycoside uptake mechanism?

A
  • AGs go through the outer membrane affecting the Mg & Ca salt bridges = more permeable to AGs
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4
Q

What are the Mechanisms of Resistance of the Aminoglycosides?

A
  • Metabolism: Inactived by Acetylation, Adentylation, Phosphorylation
  • Altered Ribosomes: 16s gets mutated
  • Altered AG Uptake: Stops AGs
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5
Q

What are some of the toxicities of Aminogylcosides?

Risk Factors?

A
  • Ototoxic (Tinnitus or Hearing Loss) [Irrevesible] & Nephrotoxic [Reversible]
  • Risk Factors: Taking other ototoxic drugs, renal issues, genetics, old
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6
Q

What are some of the symptoms of Aminoglycoside Ototoxicity?

A
  • Irreversible
  • Tinnitus, High-Frequnecy Hearing Loss, Vestibular Damage = Vertigo, Loss of Balance, Ataxia
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7
Q

What Aminoglycoside toxicities are Reversible and which are Irreversible?

A
  • Ototoxicity: Irreversible
  • Nephrotoxicity: Reversible
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8
Q

What are the drugs that are able to cause Nephrotoxicity of the Aminoglycosides?

A
  • Loop Diuretics [Ethacrynic Acid & Furosamide]
  • Vancomycin or Amphotericin
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9
Q

What is the potential toxic effects that Aminoglycosides can have the Respiration, and how is it revered or treated?

A
  • Respiratory Paralysis
  • Reversed by Neostigmine or Ca Gluconate BUT Ventiation might be good
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10
Q

What are some of the Risk Factors that my manifest Aminoglycosides Toxicity?

A
  • < 5d of Treatment, Old People, Renal Issues, High Doses
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11
Q

What is the main clinical use of the Aminoglycosides?

A
  • Mainly Gram (-)
  • Streptomycin treats TB
  • Gentamicin treats UTI, Burns, Pneumonias, Bone Infections
  • Amikacin good for Hospital infections

AG + Pen is good BUT DONT give at the same time

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12
Q

What is the reason that Aminoglycosides and Penicilins shouldnt be given together?

A
  • Chemical Reaction that will inactive both
  • Given in separate arms
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13
Q

What is the Aminoglycoside-induced fram shift and what are its consequences?

A
  • AGs affect 30s that causes a Frame Shift
  • Causes altered proteins
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14
Q

What is the main clinical use of Amikacin?

A
  • L-hydroxyaminobuteryl amide inhibits bacterial metabolism by R-factor
  • Good for TB, Pseudomonas Aeruginosa, Hospital Infections
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15
Q

What is the Main Clinical use of Tobramycin?

A
  • Lacks 3’-hydroxyl so NO phosphorlytion
  • Gentamicin-resistant Pseudomonas Aeruginosa
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16
Q

What is the Main Clinical Use for Gentamicin?

A
  • Most Gram (+)
  • UTI, Bone/Joint infections, Burns, Eye infections
17
Q

What is the Main Clinical Use for Neomycin B & Paromomycin?

A
  • NOT Abosrbed in GI
  • Travelers Diarrhea, Prophylactically before GI Surgery
18
Q

What is the Main Clinical Use for Streptomycin?

A
  • CURE TB –> IM injection
  • Bubonic & Tularemia
19
Q

What is the Main Clinical Use for Plazomicin?

A
  • UTI, Pyelonephritis, E. Coli, K. Pneumoniae, P. Mirabilis, E. Cloacae
20
Q

What is the reason that Amikacin is less susceptible to bacterial metabolism than Kanamycin?

A
  • L-hydroxyaminobuteryl Amide inhibits bacterail metabolism by R-factors = MORE POTENT
21
Q

What Aminoglycosides are Orally active?

A
  • Neomycin B, Paromycin, Streptomycin, Plazomicin
22
Q

What is the Polyketide biosynthesis pathway for the Macrolides?

A
  • Propionate groups being added to a chain = Methyls on alternate carbon atoms of the Ring
23
Q

What are important to know about the sturctures within Macrolides?

A
  • Desosamine: GOOD for activity
  • Cladinose: BAD for activity
24
Q

What is the reasoning that there are Methyl Groups on alternating Carbon Atoms in Macrolides?

A
  • Because of the Polyketides; they are produced by sequentail addition of propinate groups to a growing chain
  • Result: Methyl groups on alternate carbon atims in the ring
25
Q

What is the way that Erythromycin’s solubilty is increased?

A
  • Amine forms Salts??

Which will increase soluble

26
Q

What is the Mechanism of action for the Macrolides?

A
  • Inhibit synthesis by binding reversibly to the P-site of the ribsome; inhibiting RNA to go from A-site to P-Site
  • Mainly invovle 23s
27
Q

What are the Mechanism of Resistance for the Macrolides?

A
  • Lactone Ester Hydrolase: degrades Macrolides
  • Drug-induced production of RNA Methylase: A2058 on 23s of 50s
  • Mutation of A to G at A2058
  • Efflux Pump

A = Adenine
G = Guanine

28
Q

What are some of the way that the incidence of macrolides resistance can be minimized

A
  • Not using tem as much?
29
Q

What is the reason that resistacne to Pseudomonas sp. and Enterbacter sp. CANNOT be avoided?

A
  • They have intrinsic activity and cannot allow entry of the drug
30
Q

What is the way that Acidic conditions can inactivate erythromycin and how is it overcome with some of the newer macrolides?

A
  • 6-OH & 12-OH make a Ketal formation that inactives it [Erythro]
  • Clarithro: 6-OCH instead of 6-OH blocks Ketal Formation
  • Azithro: C-9 latcone replace blocks Ketal Formation
31
Q

What is the metabolism of Erythromycin?>

A
  • LIVER
  • Half life = 1.5h
32
Q

What is the basis for drug interactions with the Macrolides and which Macrolides are more likely to be involved in them?

A
  • ALL except Azithro
  • Bind and inhibit CYP3A and P450
33
Q

What is the Spectrum of Activity for the Macrolides and there main uses?

A
  • DOC: M. Pneumoniae, Leginella, Bordetella, Corynebacterium
  • Syndromes: Bronchitis, Otitis, Sinusitis, Ance
  • Prophylaxis: Endocarditis, Surgery
34
Q

What are the main side effects of Macrolides?

A
  • GI issues, Rashes, SJS, Jaundice
35
Q

What is the reasont hat Erythromycin has an oral dosage form?>

A
  • Inactivated by Gastric Acids = EC Caps or Tabs OR stable Salts [card 25]
36
Q

What is the role that Phagocytes paly in the deliveray of eytheromycin to the site of action?

A
  • Large concentrations are released

PHRM 865: Theraputics V (42 decks)

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