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PR3151 > drug points (antibiotics) > Flashcards

drug points (antibiotics) Flashcards

1
Q

PKPD target for time-dependent bacterial killing (beta-lactams)

A

Normal: 40-70% of dosing interval > MIC
Critically ill OR Sites of poor penetration: 50-100% of dosing interval > 4-5x of MIC

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2
Q

If patient CrCl < 30ml/min, PO ciprofloxacin dose recommended is 250mg q12h or 500mgq24h, which one to choose?

A

500mg q24h (ciprofloxacin is a concentration-dependent killing drug: 500mg q24h gives a higher peak and hence better kill)

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3
Q

What drug can be used with a time-dependent killing antibiotic to block excretion (hence optimise T%>MIC)

A

Probenecid

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4
Q

Rate and extent of killing in concentration-, time- and exposure- dependent kill is related to _______, _______ and ________ respectively

A

Antibiotic concentration; Amount of time antibiotic concentration is above MIC of organism; Overall drug exposure (AUC vs MIC)

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5
Q

IV Vancomycin 500mg q12h vs Vancomycin 1g q24h: Which will give higher AUC in the same patient?

A

Same AUC (Same patient –> same clearance –> both drugs give same 24h AUC)

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6
Q

What to optimise in dosing strategy for concentration-, time- and exposure-dependent kill respectively?

A

Concentration - Peak/Cmax:MIC ratio
Time - T%>MIC
Exposure - AUC:MIC ratio

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7
Q

Amoxicillin is a _____ of penicillin. It is formed by adding _____ group to penicillin, which improves coverage against ________ bacteria and confers _______ enabling PO route.

A

semisynthetic derivative; amino; gram-negative; acid resistance

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8
Q

Which antibiotics have poor/no oral bioavailability? (3)

A

Ceftriaxone (no PO bioavailability), Meropenem (no PO bioavailability), Gentamicin (F <1%)

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9
Q

Which antibiotics’ absorption is affected by food? (3)

A

Amoxicillin clavulanate (Clavulanic acid: absorption enhanced by administration with food),
Doxycycline (Oral F=95% but reduced by 20% with high fat meal/milk),
Ciprofloxacin (reduced absorption with milk/dairy products, indigestion remedies e.g. antacids, medicines or supplements that contain aluminium/calcium/iron/magnesium/zinc, medicines that act as binder e.g. Lanthanum/Sevelamer; TO AVOID milk feed 1-2 hrs before and after)

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10
Q

Antibiotics with POOR (3) and GOOD (2) cerebrospinal fluid (CSF) penetration respectively

A

POOR: Amoxicillin clavulanate, Doxycycline, Gentamicin;
GOOD: Ceftriaxone, Meropenem

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11
Q

Antibiotics that are highly protein bound (2)

A

Ceftriaxone, Doxycycline

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12
Q

Antibiotics with high volume of distribution (3)

A

Clarithromycin, Doxycycline, Ciprofloxacin

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13
Q

For ceftriaxone, higher concentrations in CSF are achieved when ______.

A

meninges are inflamed

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14
Q

Antibiotics that undergo no/minimal hepatic metabolism (4)

A

Amoxicillin, Ceftriaxone, Doxycycline, Gentamicin

NOTE: but amoxicillin clavulanate undergoes hepatic metabolism as clavulanic acid undergoes extensive hepatic metabolism

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15
Q

Antibiotic that mainly undergoes biliary/faecal excretion (1)

A

Doxycycline (the other 6 antibiotics mainly undergo renal excretion)

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16
Q

Which antibiotics do not require dosage adjustment in both renal or hepatic impairment? Why? (2)

A

(1) Ceftriaxone; it is eliminated by both renal and biliary excretion, hence is more tolerant to either kidney or liver impairment (alternative route concept).
NOTE: Have to take caution in patient with both renal and hepatic impairment

(2) Doxycycline; it is mainly eliminated by biliary excretion -> reduces impact of renal impairment on clearance + not significantly affected by hepatic impairment though partially metabolised by liver

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17
Q

Tmax and Half-life of Amoxicillin clavulanate

A

Tmax: ~1.5h
Half-life: ~1h

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18
Q

MOA of Amoxicillin Clavulanate (talk about MOA of amoxicillin and clavulanic acid respectively)

A

Amox: Bind to penicillin-binding protein (PBP) to inhibit peptidoglycan (PG) hence bacterial cell wall synthesis -> bacteria lyse and die;
Clav: Inhibit beta-lactamases that hydrolyse beta-lactam ring in amox. -> prevent inactivation of amox.

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19
Q

What bacteria can amoxicillin clavulanate cover that amoxicillin cannot?

A

MSSA and Gram-negative bacteria (beta-lactamase producing)
[incl. Bacteroides fragilis (anaerobe), Haemophilus influenzae, Escherichia coli, Klebsiella sp, Proteus mirabilis]

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20
Q

Indications of amoxicillin clavulanate (5); How does its distribution relate to its indications?

A

Acute otitis media, Acute bacterial rhinosinusitis, Lower respiratory tract infection, Skin and soft tissue infection, Urinary tract infection

Distributed into most body tissues and fluids e.g. Middle ear effusions, Maxillary sinus secretions, Lungs, Urinary tract

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21
Q

Common side effects of Amoxicillin clavulanate

A

Diarrhoea (most common), Rash, Nausea, Vomiting, Vaginal mycosis/Vaginitis, Candidiasis

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22
Q

Both C. difficile- and non-C. difficile-associated diarrhoea are significant adverse reactions of amoxicillin clavulanate caused disruption of _____ by _______ (abx component) and stimulation of ______ by _______ (abx component).

A

gut/intestinal microbiota; amoxicillin; small bowel motility; clavulanic acid

23
Q

Immediate hypersensitivity reactions caused by Amoxicillin clavulanate (3)

A

Urticaria, Angioedema, Anaphylaxis

24
Q

Contraindications of Amoxicillin clavulanate (4)

A
  1. Hypersensitivity (to amoxicillin, clavulanic acid, other beta-lactam abx or any formulation component)
  2. History of cholestatic jaundice or hepatic dysfunction with amoxicillin/clavulanate potassium therapy

For Augmentin XR:
3. Severe renal impairment (CrCl <30 mL/min)
4. Patients on haemodialysis

25
Q

Antibiotics that cannot be used/used with caution in pregnancy (6)

A

Foetal risk cannot be ruled out: (1) Ceftriaxone, (2) Ciprofloxacin
Avoid use in pregnancy: (3) Meropenem, (4) Clarithromycin, (5) Gentamicin, (6) Doxycycline

26
Q

Antibiotics that cannot be used/used with caution in lactation (5)

A

Present in breastmilk so monitor for thrush and diarrhoea: (1) Meropenem, (2) Clarithromycin, (3) Gentamicin
Avoid use in lactation: (4) Doxycycline
Infant risk cannot be ruled out: (5) Ciprofloxacin

27
Q

Ceftriaxone: Tmax of IV and IM; Half-life in normal adults vs with renal impairment

A

Tmax
IV: 30min, IM: 2-3hrs

Half-life
Normal: 5-9hrs, Renal impairment: 12-16hrs
-> long half-life compared to other cephalosporins; highly penetrable into meninges/eyes/inner ear, hence only need low dose

28
Q

Indications for Ceftriaxone (main 3)

A

Lower respiratory tract infections, Skin and soft tissue infections, Urinary tract infection (complicated)

29
Q

For IM injection of Ceftriaxone, what to dissolve the abx in? For what purpose?

A

1% lidocaine hydrochloride solution; Local anesthetic to numb the pain

Note: Not more than 1g should be injected at one site

30
Q

For IV injection of Ceftriaxone, what to dissolve the abx in? Administer over how long? If infusion, infuse over how long?

A

Sterile water for injection;
Administer IV over 2-4 min;
Infuse IV over at least 30min

NOTE: DO NOT use with lidocaine as they cannot go into blood vessels –> heart; IV lidocaine only for ventricular arrhythmia

31
Q

Indications for Meropenem (main 3)

A

Intra-abdominal infections, Skin and skin structure infections, Meningitis (CNS infection)

32
Q

Meropenem is an empiric treatment for?

A

Presumed infections in adult patients in febrile neutropenia (monotherapy OR in combination with anti-viral or anti-fungal agents)

33
Q

Indications for Clarithromycin (6)

A

H. pylori ulcers, Pneumonia, Cellulitis, Rhinosinusitis, Otitis, Pharyngitis

34
Q

Indications for IV (2) and PO (7) Doxycycline respectively

A

IV: Infections susceptible to doxycycline, Inhalational anthrax

PO: Infections susceptible to doxycycline, Inhalational anthrax, Relapsing fever tick-borne, Prophylaxis (traveller’s diarrhoea, malaria), Rosacea, Acne vulgaris, Periodontitis

35
Q

Tmax (IM and IV) and Half-life of Gentamicin

A

Tmax
IM: 30-90min
IV: 30min after 30min infusion

Half-life: ~2h

36
Q

Indications for Gentamicin (8)

A

Bacterial meningitis/sepsis
Infection of eye/bone/skin/subcutaneous tissue
Infective endocarditis
Peritonitis
GI tract infections
Respiratory tract infections (severe)
Surgical antibiotic prophylaxis
UTI

37
Q

Tmax (PO) and Half-life of Ciprofloxacin

A

Tmax: 0.5-2 hrs
Half-life: 4-6 hrs

38
Q

Indications for Ciprofloxacin (5 FDA approved, 3 off-label)

A

FDA approved: Infection of
(1) lungs
(2) digestive system
(3) urinary system
(4) bones and joints
(5) eyes and ears

Off-label:
(1) Chronic obstructive pulmonary disease, Acute exacerbation
(2) Peritoneal dialysis catheter-related infection
(3) Surgical prophylaxis

38
Q

is amoxicillin time/concentration/exposure dependent killing?

A

time dependent killing

39
Q

Is ceftriaxone time/concentration/exposure dependent killing?

A

time dependent killing

40
Q

use ceftriaxone in combination (with ampicillin) for which bacteria?

A

enterococcus faecalis

41
Q

is ceftriaxone present in breast milk? What to look out for in neonates who consume?

A

yes, monitor for GI disturbances since oral bioavailability is low

42
Q

Is clarithromycin time/concentration/exposure dependent killing?

A

exposure dependent killing

43
Q

Is doxycycline time/concentration/exposure dependent killing?

A

exposure dependent killing

44
Q

Is vancomycin time/concentration/exposure dependent killing?

A

exposure dependent killing

45
Q

Is gentamicin time/concentration/exposure dependent killing?

A

exposure dependent killing

46
Q

Is ciprofloxacin time/concentration/exposure dependent killing?

A

concentration dependent killing

47
Q

Which antibiotic is indicated for CNS infection?

A

Meropenem

48
Q

Antibiotic contraindicated in Myasthenia Gravis patients?

A

Ciprofloxacin (potential neural damage)

49
Q

When to use 5mg/kg and when to use 7mg/kg for gentamicin? What is the rationale behind?

A

5mg/kg for UTI since excretion via urine and unchanged drug will reach intended site of action.
7mg/kg for abdominal infection.

Rationale: use higher doses at sites with poor penetration

50
Q

Antibiotics with risk of QTc prolongation (2)

A

Clarithromycin
Ciprofloxacin

51
Q

What are the 2 dose-dependent adverse reactions arising from gentamicin use? Are they reversible?

A

Nephrotoxicity - usually reversible
Ototoxicity - irreversible

52
Q

Why are anaerobes not susceptible to gentamicin?

A

Gentamicin relies on oxygen-dependent active transporters to enter the bacterial plasma membrane.

PR3151 (7 decks)

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