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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
describe some side effects and contraindications of tetracyclines
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
name two carbapenems
Meropenem | Imipenem
27
describe the mode of action of Carbapenems
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
describe the use of Carbapenems
Broad spectrum activity against aerobic and anaerobic Gm +ve and –ve bacteria. Tend to be reserved for severe resistant infection under ID guidance
29
describe some adverse effects of Carbapenems
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
name a monobactam
Aztreonam
31
describe Monobactams
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
describe the mode of action and class of drug of vancomycin
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
describe the use of vancomycin
Orally used for c. difficle colitis Intravenously used to treat MRSA (Methicilin Resistant Staph Aureus)
34
describe some adverse effects of vancomycin
Rash / ototoxicity / nephrotoxicity
35
describe the use of metronidazole
Clinical indications: - Anaerobic infections – first line in C. difficile colitis - Abdominal sepsis
36
describe the adverse effects of metronidazole
Metallic taste Minor GI disturbance Dizziness / headache * reaction when taken with alcohol*
37
describe the mode of action of Trimethoprim
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
describe the use of Trimethoprim
Commonly used for simple UTI
39
describe the proposed mode of action of nitrofurantoin
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
when is nitrofurantoin used
Use: UTIs (not if pseudomonal or proteus)
41
describe some contraindications of nitrofurantoin
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
describe some nitrofurantoin adverse effects
Common: - GI disturbance (nausea, vomiting, diarrhoea) Important: - Peripheral neuropathy - Pulmonary fibrosis - Hypersensitivity reactions involving skin and bone marrow - Haemolytic anaemia
43
what is the drug ending for antivirals
antiVIRals -vir
44
name two herpesvirus infections
- Herpes simplex viruses 1 and 2 - Varicella zoster virus - Epstein-Barr virus - Cytomegalovirus
45
name two herpesvirus infections
- Herpes simplex viruses 1 and 2 - Varicella zoster virus - Epstein-Barr virus - Cytomegalovirus
46
what are the clinical indication for aciclovir
Herpes simplex and varicella zoster (Shingles) infections shingles requires higher dose - given orally
47
what are the clinical indications for aciclovir
Herpes simplex infections
48
describe some of the adverse effects and clinical contra-indications for aciclovir
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
describe Oseltamivir (also zanamivir)
- 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
name three anti fungal agents
Amphotericin Nystatin Fluconazole
51
describe the mode of action of amphotericin
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
Clinical indications for amphotericin
- Systemic fungal infections e.g. histoplasmosis, aspergillosis, cryptococcal meningitis - Candidiasis of the skin and mucous membranes (nystatin)
53
adverse effects and contra-indications for amphotericin
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
describe the use of nystatin
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
drug class and mode of action of fluconazole
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
clinical indications for fluconazole
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
adverse effects and contra-indications of fluconazole
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

Year 2 PODT (14 decks)

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