Treatment of infections Flashcards

1
Q

describe the mode of action of penicillins

A

Target: Bacterial penicillin-binding proteins/transpeptidase enzymes

Action: Inhibitor

Effect: Inhibit cross-linking of NAMA/NAG peptide chains in the peptidoglycan bacterial cell wall

Overall effect: Weakening of bacterial cell wall leading to lysis (bacteriocidal)

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2
Q

list some types of penicillin

A

change R side chain

Benzylpenicillin (poor GI absorption and susceptible to β-Lactamases)

Broader spectrum – Amoxicillin
(combined with β-Lactamase inhibitor clavulinic acid- Co-Amoxiclav) – rope-a-dope*

β-Lactamase resistant - Flucloxacillin

Extended spectrum – Piperacillin /Ticarcillin
(combined with β-Lactamase inhibitors (e.g. Tazobactam) to make Tazocin / Timentin)

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3
Q

briefly describe the pharmacokinetics of penicillins

A

Oral absorption variable

Widely distributed in body fluids - likely to reach infection no matter where it is

Mainly renal excretion (tubular secretion)

Short plasma half-life

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4
Q

describe the uses of some penicillins

A

Benzylpenicillin
- Bacterial meningitis

Amoxicillin

  • Resp Infections
  • UTI
  • Otitis media
  • (most widely used)

Flucloxacillin
- Cellulitis

Piperacillin

  • Severe infection / pseudomonas
  • can be used in septic shock
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5
Q

describe some adverse effects of penicillins

A

Generally very few adverse effects

  • Hypersensitivity
  • Skin rash / fever
  • Anaphylaxis
  • Oral – antibiotic associated diarrhoea
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6
Q

describe the mode of action of Cephalosporins

A

smilier to penicillins

Target: Bacterial penicillin-binding proteins/transpeptidase enzymes

Action: Inhibitor

Effect: Inhibit cross-linking of NAMA/NAG peptide chains in the peptidoglycan bacterial cell wall

Overall effect: Weakening of bacterial cell wall leading to lysis (bacteriocidal)

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7
Q

list some of the uses of cephalosporins

A

Use has decreased in last few years

Cefotaxime / Ceftriaxone
- Meningitis

Ceftazidime
- Bronchiectasis infections (depending on organism)

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8
Q

briefly describe the pharmacokinetics of Cephalosporins

A

Most need to be given parenterally

Excreted by the kidney (ceftriaxone 40% bile)

“10%” (probably <1%) cross-sensitivity with penicillins
- This figure is being re-analysed and is probably a lot lower for 2nd and 3rd generation cephalosporins

Occassional nephrotoxicity / alcohol intolerance

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9
Q

name some macrolides

A

Erythromycin

Clarithromycin

Azithromycin

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10
Q

describe the mode of action of macrolides

A

protein synthesis inhibitor

Target: 50s subunit of bacterial ribosome

Action: Reversibly bind

Effect: Prevent transfer of bacterial tRNA from A-site to P-site on the ribosome, thus preventing elongation of the polypeptide chain (bacteriostatic)

Overall effect: Inhibit bacterial protein synthesis

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11
Q

list some adverse effects of macrolides

A

Common:

  • GI upset (nausea, vomiting, abdominal discomfort, diarrhoea)
  • Taste/smell disturbance
  • hypersensitivity reactions

Important:
- QT interval prolongation - arrhythmias

Contra-indications and cautions
- Caution in hepatic and renal impairment (avoid if severe) (due to effect on cytochrome P450 system) and in patients with predisposition to QT interval prolongation

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12
Q

name some quinolones and what are their endings

A

-floxacin

Ciprofloxacin
Levofloxacin
Moxifloxacin

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13
Q

describe the mode of action of Quinolones

A

Target: Bacterial DNA gyrase (topoisomerase II)

Action: Inhibitor

Effect: Inhibit supercoiling of the bacterial DNA double helix

Overall effect: Prevent bacterial DNA replication, transcription, repair and recombination

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14
Q

describe some clinical indications of Quinolones

A

Quinolones are active against gram –ve and gram +ve bacteria, particularly gram –ve enteric coliforms.

Urinary tract infection

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15
Q

describe some adverse effects of Quinolones

A

GI upset – Caution re c. diff risk

Hypersensitivity

Rarely convulsions – caution in epilepsy (or if on theophylline / NSAIDs)

Caution QT prolongation

Inhibits CYP450 increasing theophylline toxicity

FDA July 2016 re: possible temporary or permanent disability added to SPC

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16
Q

name two aminoglycosides

A

Gentamicin

Tobramycin

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17
Q

describe the mode of action of aminoglycosides

A

Target: Bacterial 30s ribosomal subunit

Action: Inhibits normal ribosomal functioning in 3 ways:

Effect: Interfere with the initiation complex of peptide formation, induce misreading of mRNA, break up ribosomal clusters (polysomes)

Overall effect: Block bacterial protein synthesis leading to cell death (bacteriocidal)

NB. Aminogylcosides require oxygen-dependent transport to enter the bacterial cell and are
therefore ineffective against anaerobes.

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18
Q

describe the uses of aminoglycosides

A

Effective against aerobic Gm-ve and some Gm+ve organisms

Especially in Gm-ve sepsis (Gent) in combination with a penicillin (synergy)

Tobramycin for Pseudomonas infections often in combination with another anti-pseudomonal antibiotic

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19
Q

briefly describe the pharmacokinetics of aminoglycosides

A

Highly polar molecules – therefore IV admin

Variable penetration into body fluids

Eliminated by kidney T1/2 2-3 hours

Elimination mirrors eGFR

MUST reduce dose and frequency in renal impairment to prevent dose dependent side effects

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20
Q

describe the adverse effects and interactions of aminoglycosides

A

Important:
> Nephrotoxicity (usually reversible when drug stopped)
> Ototoxicity (usually irreversible) (rare before 2 weeks of treatment)
- damage of sensory cells in the vestibulo-cochlear apparatus
- Deafness and/or vertigo/ataxia

Contra-indications and cautions:

  • Caution in renal impairment and extremes of age
  • Avoid in pregnancy and in patients with myasthenia gravis

Interactions:

  • Loop diuretics e.g. Furosemide (increased risk of ototoxicity – do not co-prescribe)
  • Vancomycin (increased risk of ototoxicity)
  • NSAIDs (increased risk of nephrotoxicity)
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21
Q

describe Therapeutic drug monitoring in aminoglycosides

A

Safety: Renal function should be measured at baseline, re-check U+E regularly during treatment; ask
patient to report any changes in hearing or balance to detect ototoxicity

Serum aminoglycoside levels should be checked regularly – scheduling of monitoring varies depending on single-dose or multiple dose regimens. Blood samples should be taken 1 hour after IV or IM administration (peak concentration) and just before the next dose (trough concentration).
If peak is high, reduce dose. If trough is high, increase dosage interval (+/- reduce dose).

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22
Q

name two tetracyclines

A

Tetracycline

Doxycycline

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23
Q

describe the mode of action of tetracyclines

A

Target: Bacterial 30s ribosomal subunit

Action: Reversibly binds to the 30s ribosomal subunit blocking tRNA binding

Effect: Inhibit aminoacyl tRNA and mRNA ribosomal complex formation therefore inhibit bacterial protein synthesis

Overall effect: Bacteriostatic effect

24
Q

describe clinical indications for tetracyclines

A

Broad spectrum bacteriostatic antibiotics

Usually given orally as an alternative for community acquired pneumonia or cellulitis

25
Q

describe some side effects and contraindications of tetracyclines

A

Contraindications:

  • Chelate Calcium – NEVER to pregnant women/breast feeding mothers / children
  • Caution in hepatic impairment

Adverse effects:
Common:
- GI disturbance
- Dysphagia, oesophageal irritation

Important:

  • Tooth staining, dental hypoplasia – ‘tetracycline teeth’ (tetracyclines chelate calcium and are deposited in growing bones and teeth, avoid in children and pregnant/breastfeeding women)
  • Hepatotoxicity (particularly in pregnancy)
  • Blood disorders
26
Q

name two carbapenems

A

Meropenem

Imipenem

27
Q

describe the mode of action of Carbapenems

A

β-lactam antibiotics

Target: Bacterial penicillin-binding proteins/transpeptidase enzymes

Action: Inhibitor

Effect: Inhibit cross-linking of NAMA/NAG peptide chains in the peptidoglycan bacterial cell wall

Overall effect: Weakening of bacterial cell wall leading to lysis (bacteriocidal)

28
Q

describe the use of Carbapenems

A

Broad spectrum activity against aerobic and anaerobic Gm +ve and –ve bacteria.

Tend to be reserved for severe resistant infection under ID guidance

29
Q

describe some adverse effects of Carbapenems

A

Common:
 Abdominal pain; diarrhoea; disturbances in liver function
tests; headache; nausea; pruritus; thrombocythaemia; vomiting
Important:
 Hypersensitivity reactions – skin rash, fever, anaphylaxis
 Antibiotic associated colitis
- Neurotoxicity including seizures, especially with high dose/renal failure/CNS disease

30
Q

name a monobactam

A

Aztreonam

31
Q

describe Monobactams

A

Resistant to most β-lactamases
Only given IV
Effective only against Gm-negative aerobic rods (e.g. pseudomonas) – targeted Rx
Adverse effects – GI upset similar to other β-lactams but rarely cross-sensitivity

32
Q

describe the mode of action and class of drug of vancomycin

A

Drug Class: Glycopeptide antibiotics

Target: Terminal moieties of the NAMA and NAG peptides

Action: Binding

Effect: Irreversibly block the elongation of peptidoglycan chains by preventing the incorporation of NAMA and NAG peptide subunits

Overall effect: Inhibit bacterial cell wall synthesis leading to cell death (bactericidal)

33
Q

describe the use of vancomycin

A

Orally used for c. difficle colitis

Intravenously used to treat MRSA (Methicilin Resistant Staph Aureus)

34
Q

describe some adverse effects of vancomycin

A

Rash / ototoxicity / nephrotoxicity

35
Q

describe the use of metronidazole

A

Clinical indications:

  • Anaerobic infections – first line in C. difficile colitis
  • Abdominal sepsis
36
Q

describe the adverse effects of metronidazole

A

Metallic taste
Minor GI disturbance
Dizziness / headache
* reaction when taken with alcohol*

37
Q

describe the mode of action of Trimethoprim

A

Target: Bacterial dihydrofolate reductase
Action: Inhibitor
Effect: Inhibits reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF), an essential precursor in the thymidine synthesis pathway – interference with this pathway inhibits bacterial DNA synthesis
Overall effect: Limits bacterial reproduction

38
Q

describe the use of Trimethoprim

A

Commonly used for simple UTI

39
Q

describe the proposed mode of action of nitrofurantoin

A

Mode of Action: Poorly understood.
It is thought to inhibit a number of bacterial enzymes including those involved in bacterial carbohydrate metabolism and those involved in cell wall synthesis.

40
Q

when is nitrofurantoin used

A

Use: UTIs (not if pseudomonal or proteus)

41
Q

describe some contraindications of nitrofurantoin

A

DO NOT USE if septicaemia (poor serum levels)

DO NOT USE if renal impairment (less effective and potentially increased risk of peripheral neuropathy)

Caution in:

  • Anaemia
  • Diabetes mellitus
  • Vitamin B12 and folate deficiency
  • Pulmonary disease
  • Hepatic and renal impairment
  • Any condition associated with peripheral neuropathy (severe and irreversible neuronal damage may result)
42
Q

describe some nitrofurantoin adverse effects

A

Common:
- GI disturbance (nausea, vomiting, diarrhoea)

Important:

  • Peripheral neuropathy
  • Pulmonary fibrosis
  • Hypersensitivity reactions involving skin and bone marrow
  • Haemolytic anaemia
43
Q

what is the drug ending for antivirals

A

antiVIRals

-vir

44
Q

name two herpesvirus infections

A
  • Herpes simplex viruses 1 and 2
  • Varicella zoster virus
  • Epstein-Barr virus
  • Cytomegalovirus
45
Q

name two herpesvirus infections

A
  • Herpes simplex viruses 1 and 2
  • Varicella zoster virus
  • Epstein-Barr virus
  • Cytomegalovirus
46
Q

what are the clinical indication for aciclovir

A

Herpes simplex and varicella zoster (Shingles) infections

shingles requires higher dose - given orally

47
Q

what are the clinical indications for aciclovir

A

Herpes simplex infections

48
Q

describe some of the adverse effects and clinical contra-indications for aciclovir

A

Common:

  • GI disturbance e.g. nausea, vomiting, diarrhoea
  • Headache

Important:

  • Neurotoxicity e.g. dizziness, confusion, hallucinations, convulsions
  • Acute renal failure

Contra-indications and cautions:
- Caution in the elderly and those with renal impairment

49
Q

describe Oseltamivir (also zanamivir)

A
  • Neuraminidase is an essential viral glycoprotein for virus replication and release
  • High homology of neuraminidase in influ A + B
  • Pro-drug
  • Activated by liver on 1st pass
  • Used if <36 hours or post-exposure in high risk patients (elderly, chronic organ disease, DM)
  • ? Slight reduction in duration (1 day)
  • ?? Slight reduction in complication rates??
  • Nausea / GI upset / headache common

used for treatment of influenza virus

50
Q

name three anti fungal agents

A

Amphotericin
Nystatin
Fluconazole

51
Q

describe the mode of action of amphotericin

A

Target: Ergosterol in fungal cell membrane

Action: Binding

Effect: The drug molecule has a hydrophilic core which creates a transmembrane ion channel (i.e. a pore) in the fungal cell membrane, increasing its permeability

Overall effect: Polyene antifungals cause leakage of intracellular macromolecules and ions including potassium, leading to gross disturbances in ion balance and fungal cell death

52
Q

Clinical indications for amphotericin

A
  • Systemic fungal infections e.g. histoplasmosis, aspergillosis, cryptococcal meningitis
  • Candidiasis of the skin and mucous membranes (nystatin)
53
Q

adverse effects and contra-indications for amphotericin

A

Adverse effects

Common:
- GI disturbance e.g. nausea, vomiting, diarrhoea, electrolyte disturbances – hypokalaemia and hypomagnesaemia

Important:
The following apply to amphotericin only:
- Nephrotoxicity
- Neurotoxicity including peripheral neuropathy and encephalopathy
- Cardiotoxicity including arrhythmias and blood pressure changes
- Anaphylaxis

Contra-indications and cautions:
- Avoid in pregnancy and renal impairment

54
Q

describe the use of nystatin

A

Polyene macrolide

Similar to amphotericin

Too toxic for systemic

Used topically for candida infections (Thrush)

No absorption from skin or mucous membranes

If swallowed – nausea / vomiting

55
Q

drug class and mode of action of fluconazole

A

Drug Class: Triazole antifungals

Mode of action:

  • Target: Fungal cytochrome P450 3A enzyme (responsible for converting lanosterol to ergosterol)
  • Action: Inhibitor
  • Effect: Depletion of ergosterol, a key component of the fungal cell membrane – this alters the fluidity of the membrane and thus interferes with membrane-associated enzymes
  • Overall effect: Inhibition of fungal cell replication
56
Q

clinical indications for fluconazole

A

Clinical indications:

  • Candidal infections including vaginal and mucosal candidiasis and candidaemia
  • Prevention of fungal infections in immunocompromised patients
  • Dermatological fungal infections e.g. tinea pedis, pityriasis versicolor
  • Systemic fungal infections including histoplasmosis, cryptococcosis, etc.
57
Q

adverse effects and contra-indications of fluconazole

A

Adverse effects:

Common:
- GI disturbance e.g. nausea, diarrhoea, rash and headache

Important:
- Hepatotoxicity (especially with itraconazole)
- Paraesthesia, peripheral neuropathy (itraconazole)
- Toxic epidermal necrolysis, Stevens-Johnson syndrome (more likely in AIDS patients)
Contra-indications and cautions
- Caution in renal and hepatic impairment (avoid if risk of toxicity outweighs potential benefit) and in those susceptible to congestive heart failure
- Avoid in pregnancy and active liver disease
- Discontinue if patient develops signs or symptoms of hepatic disease