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Clinical Pharmacology > 11.1 Antimicrobials > Flashcards

11.1 Antimicrobials Flashcards

1
Q

What is meant by multi-drug resistance?

A

Non-susceptibility to at least one agent in three or more antimicrobial categories

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2
Q

What is meant by extensively drug resistant?

A

Non-susceptibility to at least one agent in all but two or fewer antimicrobial categories

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3
Q

What is meant by pan drug resistant?

A

Non-susceptibility to all agents in all antimicrobial categories

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4
Q

What are the key points of antimicrobial stewardship?

A

Appropriate use of antimicrobials
Optimal clinical outcomes
Minimize toxicity and other adverse events
Reduce the costs of health care for infections
Limit the selection for antimicrobial resistant strains.

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5
Q

What are the persuasive interventions of antibiotic stewardship?

A 
Education
Consensus
Opinion leaders
Reminders
Audit
Feedback
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6
Q

What are the restrictive interventions of stewardship intention?

A

Restricted susceptibility reporting
Formulary restriction
Prior authorisation
Automatic stop orders

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7
Q

What are the structural interventions of antibiotic stewardship?

A

Computerised records
Rapid lab test
Expert systems
Quality monitoring

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8
Q

What is used to guide antibiotic choice?

A

History/presenting complaint

Follow local guidelines

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9
Q

Why should local guidelines by used over NICE guidelines when prescribing antibiotics?

A

as regional sensitivity/resistance is a thing

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10
Q

Before treating an infection with antimicrobials, what should be done?

A

microbiological samples obtained pertinent to the suspected infection; this will allow laboratory testing for
sensitivity and resistance, thus allow you to give more focused treatment

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11
Q

What is considered in antibiotic guidelines?

A

Which pathogens are most likely causative for a given infection type
What are the characteristics of these pathogens, i.e. Gram +ve vs. Gram –ve, Anaerobic vs. Aerobic?
Does it reach the site of infection?

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12
Q

What must a clinician consider before prescribing an antibiotic advised by the local guidelines?

A

Is the drug available in the right formulation?
What is the half-life/dosing frequency?
Does it interact with other drugs?
Are there toxicity concerns?
Does the antibiotic require therapeutic drug monitoring?
Does your patient have an allergy to the drug?

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13
Q

What antimicrobials affect cell wall synthesis?

A

Penicillins
Vancomycin
Cephalosporins

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14
Q

What antibiotics affect folic acid metabolism?

A

Trimethoprim

Sulfonamides

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15
Q

What antibiotics affect protein synthesis (30s inhibitors)

A

Tetracyclines
Gentamicin
Streptomycin
Nitrofurans

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16
Q

What antibiotics affect protein synthesis (50s inhibitors)

A

Erythromycin (Macrolides)

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17
Q

What is the mechanism of action of beta lac tam antibiotics?

A

Interfere with the synthesis of the bacterial cell wall peptidoglycan
Generally bactericidal
1. Antibiotic binds to penicillin-binding protein on bacteria
2. Inhibit the transpeptidation enzyme (responsible for linking the peptidoglycan chains to form rigid cell walls)
3. Disruption of bacterial cell wall structure.

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18
Q

What are the three main sub groups of beta lactams?

A

Penicillin
Cephalosporins
Carbapenems

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19
Q

What are common examples of penicillins?

A

Phenoxymethylpenicillin (Penicillin V)
Flucloxacillin (Beta lactamase resistant)
Amoxicillin (Broad spectrum)
Co-amoxiclav

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20
Q

What is the role of clavulanic acid?

A

Beta-lactamase inhibitor. Inhibits beta-lactamase breaking down beta-lactate antibiotic molecular structure

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21
Q

What combination of drugs is co-amoxiclav?

A

Amoxicillin

Clavulanic acid

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22
Q

What cautions should be taken before administering penicillin?

A

Individual sensitivity testing often required, particularly in secondary care

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23
Q

What are the clinical applications of penicillins?

A 
Bacterial meningitis
Bone and joint infections
Skin and soft tissue infections
Otitis media
Pneumonia
UTIs
STIs
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24
Q

What are examples of cephalosporins?

A

Cefalexin
Ceftriaxone
Cefuroxime
Cefotaxime

25
Q

What must be considered before presribingcephalosporins in secondary care?

A

Individual sensitivity testing

26
Q

What are the clinical applications of cephalosporins?

A 
Septicaemia
Pneumonia
Meningitis
Biliary tract infections
UTIs (especially in pregnancy or in patients unresponsive to other drugs)
Sinusitis
27
Q

What antibacterial affect bacterial protein synthesis?

A 
Tetracyclines
Aminoglycosides
Macrolides
Oxazolidinones
Lincosamides
Nitrofurans
28
Q

What is the mechanism of action of tetracyclines?

A

Following uptake into susceptible organisms by active transport, tetracyclines act by inhibiting protein synthesis
Bind to bacterial ribosomes, preventing binding of tRNA to it, thus preventing the initiation of protein synthesis
Bacteriostatic

29
Q

What are common examples of tetracyclines?

A

Doxycycline

Tetracycline

30
Q

What are the clinical applications of tetracyclines?

A

Respiratory tract infections (particularly atypical organisms)
Acne
Chlamydia
Lyme disease

31
Q

Why shouldn’t tetracyclines be given to children under 12, pregnant and breastfeeding women?

A

As causes staining of developing teeth

32
Q

What is the mechanism of action of macrolides?

A

Inhibit bacterial protein synthesis by an effect on ribosomal translocation Bactericidal/bacteriostatic

33
Q

What are common examples of macrolides?

A

Erythromycin
Clarithromycin
Azithromycin

34
Q

What are the clinical applications of macrolides?

A

The antimicrobial spectrum of macrolides is very similar to that of penicillin
Also active against atypical respiratory pathogens

35
Q

Give an example of a nitrofuran?

A

Nitrofurantoin

36
Q

What is the mechanism of action of nitrofurantoin?

A

Works by being reduced to multiple reactive intermediates by nitrofuran reductase inside the bacterial cell
These intermediates then attack ribosomal and DNA proteins within the bacteria, as well as inhibit the Citric acid cycle

37
Q

Why is nitrofurantoin one of the first line agents in treating urinary tract infections?

A

Up to 50% of an oral dose Nitrofurantoin is excreted in the urine in unchanged form
This allows Nitrofurantoin to concentrate within urine, leading to more effective levels within the bladder than in other tissue compartments

38
Q

What is the mechanism of action of quinolones?

A

Inhibit topoisomerase II (a bacterial DNA gyrase), the
enzyme that produces a negative supercoil in DNA and
thus permits transcription or replication

39
Q

What are common examples of quinolones?

A

Ciprofloxacin

Levofloxacin

40
Q

What are the clinical applications of quinolones?

A 
Very good cover of Gram negative organisms, as well as atypical organisms
and Gram positives 
Clinical applications:
Complicated UTIs 
Pseudomonas aeruginosa cover Gonorrhoea
41
Q

What are the important ADR of quinolones?

A

Tendinitis +/- rupture
Aortic dissection
Central nervous system effects (inc. Convulsions)

42
Q

What is the mechanism of action of trimethoprim?

A

Folate antagonist: Reversible inhibitor of dihydrofolate reductase, which is responsible for the production of Tetrahydrofolic acid necessary for the biosynthesis of bacterial nucleic acids and proteins
Binds with a much stronger affinity to bacterial dihydrofolate reductase than human
Bacteriostatic/bactericidal

43
Q

What are the clinical applications of trimethoprim?

A

UTIs

44
Q

When are trimethoprim contraindicated?

A

In pregnancy, has tetragenic effects on fetus

45
Q

What organisms is metronidazole effective against?

A

Protozoa and anaerobic bacteria

46
Q

What advice must be given to a patient taking metronidazole?

A

Has disulfiram-like action, advise patients to avoid using alcohol when on the antibiotic as would get severe hangover.

47
Q

What are the most commonly used antivirals?

A

Aciclovir (DNA Polymerase Inhibitors)

Oseltamivir (Neuraminidase Inhibitors)

48
Q

What is the mechanism of action of acyclovir?

A

Activated predominantly in infected cells as it is phosphorylated and activated by viral enzyme thymidine. When active, acyclovir inhibits the viral DNA polymerase.

49
Q

What are the clinical applications of acyclovir?

A 
Herpes simplex infections (genital herpes, encephalitis) 
Varicella zoster (chicken pox, shingles)
50
Q

When is acyclovir advised to treat herpes simplex virus?

A

Predominantly to treat serotype HSV-2 (genital infections. Not used to treat HSV-1/ herpes labialis in healthy patients. May be used prescribed orally in HSV-1 depending on severity, frequency and persistence of the lesions, and if the patients are immunocompromised

51
Q

What is the routine treatment of genital herpes?

A

First episode:
Oral Aciclovir within 5 days of the start of the episode or while new lesions are forming
Recurrent episodes:
Episodic antiviral treatment – if attacks are infrequent (<6/year)
Either 800mg TDS for 2 days or 200mg 5x/day for 5 days. Consider self-initiated treatment, to allow for early start
Suppressive antiviral treatment – if attacks are more frequent (≥6/year) OR causing psychological distress OR affecting the person’s social life
400mg BD OR 200mg QDS. If breakthrough recurrences occur, the dosage should be increased. Continue treatment for max. 1 year, after which it should be stopped to assess recurrence

52
Q

What are notable sites for CYP450 enzymes?

A 
Liver
Small intestine
Lungs 
Placenta
Kidneys
53
Q

What are the most significant CYP enzymes?

A

CYP3A4

CYP2DP

54
Q

Why should metronidazole not be prescribed alongside warfarin?

A

Warfarin is an anticoagulant that is metabolised by CYP2C9
Metronidazole is a CYP2C9 inhibitor
Inhibiting the enzyme will slow down warfarin metabolism and cause warfarin overdose.

55
Q

What medications should not be prescribed alongside macrolides and why?

A

Macrolides inhibit CYP3A4, and should not be prescribed alongside drugs that are metabolised by this enzyme such as verapamil (CCB) and simvastatin. If prescribed together would cause CCB overdose (orthostatic hypotension) and statin overdose (myopathy and rhabdomyolysis on rare occasions)

56
Q

Describe the enterohepatic circulation

A

Begins with drug absorption across the intestine into the portal circulation, followed by uptake into the
hepatocytes. Next, drug and or conjugated metabolites
are secreted into the bile and returned to the intestine,
where drug can be reabsorbed into the circulation

57
Q

How do oral antibiotics reduce the absorption rates of certain drugs?

A

Oral antibiotics can eliminate gut flora and lessen the enzymes involved in the metabolism of drugs in bile. Reduce absorption rates of drugs that are absorptive due via secondary absorption in bile due to the enterohepatic circulation. For example antibiotics, NSAIDs, hormones, opiods, digoxin, warfarin.

58
Q

What advice should be given to females on the contraceptive pill when taking antibiotics?

A

Oral antibiotics can lower the rates of enterohepatic recycling and cause lower blood concentrations of oestrogen and progesterone in patients on oral contraceptives. Increases the risk of becoming pregnant. Should use additional barrier contraceptive methods whilst on antibiotics.

Clinical Pharmacology (26 decks)

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