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Primary Pharmacology > Antimicrobia Therapy > Flashcards

Antimicrobia Therapy Flashcards

1
Q

What are the four main targets for Antimicrobials

A

Cell wall synthesis
Cell membrane permeability
Protein synthesis
Nucleic acid synthesis

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2
Q

Characteristics of bacterial cell wall
Difference in gram pos and neg

A

Stops lysis in hypotonic environment
Made of n acetyl glucosamine, acetyl muramic acid and a polypeptide with multiple cross links
Several layers thick in gram neg
Hundereds of layers think in gram pos

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3
Q

Why do antifungals cause severe side effects in high doses

A

Target sterols which are present in both fungal and human cell membranes

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4
Q

How do antibiotics that effect protein synthesis avoid damaging human cells? How do they differ between bacteriostatic and bacteriosidal

A

Bacteria have different subunit size (50 and 30s vs human 60 and 40s)
Those that reversibly inhibit protein synthesis - static
Those that bind to 30s - cidal

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5
Q

Examples of antibiotics effecting nucleic acid synthesis and how

A

Rifampicin - inhibits dna dependant rna polymerase
Quinolones - inhibit dna synthesis and disrupt coiling
Aciclovir - block active site of enzymes on dna stoping synthesis

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6
Q

Mechanisms of aquisition of Antimicrobial resistance

A

Spontaneous mutation
Plasmid transfer
Chromosome transfer
Bacteriophages
Conjugation

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7
Q

Mechanisms of Antimicrobial resistance

A

Enzymatic destruction - eg beta lactamase
Altered target site - eg mRNA altered penicillin binding proteins, VRE altered peptidoglycan wall
Protection of target site - quinolone resistance by protecting dna gyrase
Overproduction of target - sulphonamides and trimethoprim resistance
Bypass metabolic pathways - enterococci utilising folate from difference source resisting trimethoprim
Bind up abx
Decreased permeability - pseudomonas blocking abx Ingres though pores
Abx efflux - eg quinolone and macrolide resistance

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8
Q

What is MRSA resistant to

A

Meticillin
Flucloxacillin
Cephalosporins

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9
Q

Groups of beta lactam abx

A

Penicillins
Cephalosporins
Carbapenems
Monobactams,

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10
Q

How do beta lactams work

A

Bind to penicillin binding proteins stopping cell wall synthesis
Osmotic lysis occurs
Additionally cause synergistic reaction with other classes of abx as increase permeability of cell thus other abx can enter more easily

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11
Q

Proportion of people with penicillin allergy and anaphylaxis
Mortality of penicillin anaphylaxis

A

Allergy 1-10%
Anaphylaxis 0.05%
Mortality 10%!

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12
Q

Side effect of penicillins in very high doses eg for meningitis

A

Convulsions

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13
Q

Spectrum of benzylpenicillin
Route
Distribution

A

Mainly gram positive, anaerobes and certain gram negative cocci
Given parenterally
Widely distributed, only through bbb if inflamed

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14
Q

Spectrum of amoxicillin
Uses

A

Similar to benzylpenicillin but with some more gram neg such as haemophius influenza and enterococci
LRTI and faecal strep infections

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15
Q

Spectrum of flucloxacillin
Effect of beta lactamase
Distribution
Side effects

A

Unaffected by beta lactamase but narrower spectrum than benpen
Highly protein bound so limited distribution
Can cause cholestatic jaundice and hepatitis

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16
Q

Half lives of benpen, Amos and fluclox

A

Benpen 30 mins
Amox 1 hr
Fluclox 45 mins

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17
Q

Spectrum of pip taz vs amoxicillin
Side effects

A

Also cover apps pseudomonas
Due to Tazobactam also active agains beta lactamase producing organisms
Sodium overload

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18
Q

Side effects of coamoxiclav

A

Choelostatic jaundice and hepatitis

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19
Q

Examples of cephalosporins and generation

A

Cephalexin 2nd
Cefuroxime 2nd
Cefotaxime 3rd
Ceftriaxone 3rd
Cefixime 3rd
Ceftazidime 3rd
Cefpirome 4th
Ceftarline 5th

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20
Q

Spectrum of cephalexin
Oral bioavailability
Excretion and t1/2

A

Gram positive cocci and some enterobacteria
Bioavailability nearly 100%
Excretion in urine, t1/2 50mins

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21
Q

Spectrum of cefuroxime
Bioavailability
Excretion and half life

A

More active than cephalexin in enterobacteriaceae and h influenzae
Not absorbed orally, must be given iV
Excreted in urine with t1/2 80mins

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22
Q

Spectrum of cefotaxime
Metabolism
T1/2

A

Large spectrum including many gram negative and against penicillin resistant strains
Limited effect on anaerobes, minimal effect on pseudomonas
Metabolised and renally excreted
80mins

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23
Q

Which antibiotic must be added to cover listeria meningitis

A

Amoxicillin

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24
Q

Differences between ceftriaxone and cefotaxime

A

Ceftriaxone has very similar spectrum but much longer t1/2 allowing for outpatient iV therapy

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25
Q

Examples of carbapenems

A

Ertapenem
Imipenem
Meropenem

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26
Q

How do carbapenems differ in mechanism from other beta lactams
Consequence

A

Specifically target pbp2 resulting in faster bacterial death and less endotoxin release

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27
Q

Why can carbapenems have a long dose interval despite relatively short t1/2

A

They continue to have a prolonged inhibition of bacterial growth even when concentration fallen beneath minimum inhibitory concentration

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28
Q

Adsverse effects of carbapenems

A

Neutropenia
Neurotoxicity

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29
Q

Spectrum of imipenem
Meropenem

A

Huge, nearly all gram neg and pos including anaerobes
Poor intracellular penetration limits action agains intracellular infections

Meropenem Is similar but more against gram neg and less against gram pos

30
Q

Example of a monobactam abx
Spectrum

A

Astreonam
Gram neg aerobic

31
Q

Cross sensitivity between penicillin and aztreonam for allergy
Why

A

Little (but use with caution)
Only has one beta lactam ring not 2

32
Q

Example of glycopeptide abx
How do they work
Spectrum - why

A

Teicoplainin, vancomycin
Prevent bacterial wall synthesis thus are slowly bacteriocidal
Only effects gram positive, large and polar thus not able to penetrate outer membrane of gram neg

33
Q

T1/2 of vancomycin

A

6-8hrs

34
Q

When to monitor vancomycin;

A

Pre dose

35
Q

Adverse effects of vancomycin

A

Hypersensitivity, nephrotoxicity, ototixicity, neutropenia, red man syndrome (histamine release on rapid infusion)

36
Q

Symptoms and course of red man syndrome

A

Itching, causing, angioedema, hypotension, tachycardia
NO bronchospasm
Normally resolves within 1 hr of stoping vancomycin infusion

37
Q

Half life of teicoplainin
Why

A

47 hrs
Heavily protien bound

38
Q

Examples and mechanism of Aminoglycosides

A

Gentamicin, streptomycin, amikacin
Bind to 30s sub unit inhibiting protein synthesis - causes cell membrane leaking and are bacteriocidal

39
Q

Mechanisms of resistance to Aminoglycosides

A

Altered binding site
Reduced uptake
Aminoglycosides modifying enzymes

40
Q

How can risk of ototoxicity and nephrotoxicity be reduced with Aminoglycosides

A

Monitor levels
Slow iV injection

41
Q

Is Aminoglycosides mediated nephro and otoxicity reversible

A

Nephro is reversible
Oto is not

42
Q

Tissue penetration of gentamicin

A

Poor

43
Q

Oral bioavailability of gentamicin

A

1%

44
Q

Special bug treated with amikacin or streptomycin

A

TB

45
Q

Example and mechanism of macrolides

A

Clarithromycin, erythromycin
Bind to 50s subunit inhibiting protein synthesis probably stopping translocation

46
Q

Mechanism of resistance to macrolides

A

Altered binding site
Drug inactivation
Efflux of drug

47
Q

Effect of renal and hepatic disease on erthyromycin

A

Renal little limpact (t1/2 from 1.5 to 5 hrs)
Hepatic failure causes accumulation as it is mainly inactivated and excreted in bile

48
Q

Side effects of ertythromycin

A

GI upset
Hepatotoxicity
Ototoxicity
Cardiotoxicity
Intrahepatic choleostasis

49
Q

Examples and mechanism of tetracyclines

A

Doxycycline, tetracycline
Bind to 30s and prevent binding of tRNA
Prevents protein synthesis and is bacteriostatic

50
Q

Methods of resistance to tetracyclines

A

Decreased cell entry
Increased efflux
Ribosomal protection
Checmial modicaiton

51
Q

Infections that are best treated with tetracyclines

A

Chlamydia
Rickettsial
Q fever
Cholera
Lymes disease
Anthrax
Plague

52
Q

What dietary intake impairs tetracycline absorption

A

Best in fasted stated
Impaired by ferrous ions

53
Q

Side effects of tetracycline

A

GI
Photosensitivity
Dental discolouration in children
Hepatotoxicity
Nephrotoxicity
Leukopenia
Thrombocytopenia
Bacterial and fungal superinfections
Nephrotoxicity - aggregation if existing , nephritis, nephro genie diabetes insipidus

54
Q

How does chloramphenicol work
Spectrum

A

Binds to 50s subunit thus bacteriostatic
At high concentrations bacteriocidal against h influenza and n meningitisis
Broad spectrum including mycobacteria

55
Q

Absorption and distribution of chloramphenicol

A

Well absorbed
Widly distributed inc into CNS and eye

56
Q

Adverse effects of chloramphenicol

A

Bone marrow suppression
Grey baby syndrome - myocardial depression and circulatory collapse in prem neonates
Optic neuritis
Ototoxicity

57
Q

How is chloramphenicol given

A

Usually topical eg into eye
Rarely systemic (meningitis with proven severe penicillin allergy)

58
Q

Mechanism of fusidic acid
Spectrum

A

Inhibit bacterial cell protein synthesis
Active vs most gram positive bacteria and gram neg cocci

59
Q

Why is fusidic acid good for spots etc

A

Penetrates pus, abscesses and wound exudate well

60
Q

Side effects of fusidic acid

A

Abnormal liver function
Thrombophlebitis

61
Q

Examples and mechanism of quinolones

A

Ciprofloxacin, levofloxacin, moxifloxacin
Inhibit dna gyrase which causes supercoiling of dna

62
Q

General spectrum of quinolones

A

Good vs most gram negative

63
Q

Hepatic effects of Ciprofloxacin

A

Inhibits cyp450

64
Q

Class of metronidazole
Mechanism

A

Nitroimidazole

Destroys dna, only do this when reduced by the very low redox values in anaerobic bacteria and Protozoa

65
Q

Effect of metronidazole on other substances

A

Disulfarim like reaction with alcohol
Potentiates warfarin
Impairs phenytoin and lithium clearance
Interferes with OCP and digoxin

66
Q

How does rifampicin work
Spectrum

A

Inhibit bacterial dna dependant rna polymerase stopping transcription
Particularly against gram pos and mycobacteria
Good intracellular penetration so active vs legionella and Q fever

67
Q

Adverse effects of rifapicin

A

GI
Hepatotoxicity
Thrombocytopenia
Renal failure
Induces metabolism of ocp, anticoagulants, digoxin
Red urine

68
Q

Mechanism of trimethoprim

A

Inhibits dihydrofolate reductase thus inhibiting dna synthesis

69
Q

Mechanism of sulphonamides

A

Inhibit folic acid synthesis at an earlier stage than trimethoprim

70
Q

What is cotrimoxazole

A

Trimethoprim with a sulphonamide

71
Q

Side effects of sulphonamides

A

Renal damage
Rashes
Bone marrow depression
Yphypersisitivity and vasculitis

72
Q

What are the antimycobacterials

A

Ethambutol, isoniazid, pyrazinamide

Primary Pharmacology (18 decks)

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