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Pharmacology > Infection > Flashcards

Infection Flashcards

1
Q

Name some examples of aminoglycosides?

A

Gentamycin, amikacin, neomycin

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2
Q

What are the common indications for aminoglycosides?

A

Systemic aminoglycosides (gentamycin, amikacin) are used to treat severe infections, particularly those caused by gram-negative anaerobes (including Pseudomonas aeruginosa):
1. Severe sepsis
2. Pyelonephritis and complicated UTIs
3. Biliary and other intraabdominal sepsis
4. Endocarditis
Topical aminoglycosides (e.g. neomycin) are used to treat
5. Bacterial skin, eye or external ear infections

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3
Q

What is the spectrum of activity for aminoglycosides?

A

Mainly Gram-negative aerobic bacteria
They also have some activity against staphylococci and mycobacteria, but other agents are preferred in practice
They are inactive against streptococci and anaerobes, so should be combined with penicillin and/or metronidazole when the organism is unknown

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4
Q

How do amoinoglycosides work?

A

They bind reversibly to bacterial ribosomes

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5
Q

What are the important adverse effects of aminoglycosides?

A

Nephrotoxicity and ototoxicity as they accumulate in renal tubular epithelial cells and cochlear and vestibular hair cells where they trigger apoptosis and cell death
Nephrotoxicity- reduced urine output, rising serum creatinine and urea and is potentially reversible
Ototoxicity- Often not noticed until after resolution of the acute infection, where the patient may complain of hearing loss, tinnitus and/or vertigo

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6
Q

What are the warnings for aminoglycosides?

A

Monitor carefully in neonates, elderly patients and those with renal impairment
They can impair neuromuscular transmission and so should not be given to people with myasthenia gravis unless unavoidable

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7
Q

What are the important interactions with aminoglycosides?

A

Ototoxicity is more likely if aminoglycosides are co-prescribed with loop diuretics or vancomycin
Nephrotoxicity is more likely if they are co-prescribed with ciclosporin, platinum chemotherapy, cephalosporins or vancomycin

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8
Q

How are aminoglycosides prescribed?

A

In severe infection, given by intermittent IV infusion, usually OD
The dose is calculated from the patients weight and renal function
Adjusted body weight= ideal BW +0.4 x (actual BW- ideal BW)
Dose is reduced in severe renal impairment

The dose interval is determined by drug level monitoring, with subsequent doses being administered only when plasma concentrations have fallen to a safe level. It is usually 24 hours for people with normal renal function and 36-48 hours in renal impairment

Treatment duration should be as short as possible to avoid toxicity

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9
Q

How are aminoglycosides administered?

A

For IV, they should be diluted (e.g. in 50ml sodium chloride 0.9%) and infused slowly (e.g. over 30 mins). This prevents exposure of the ear to a high conc bolus of aminoglycosides

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10
Q

How is aminoglycoside treatment monitored?

A

For efficacy, monitor symptoms and signs e.g. pyrexia and CRP
For safety, renal function should be measured before and during therapy
The plasma drug dose concentration is usually measured 18-24 hours after the first dose
The next dose should only be administered if these have fallen to a safe level with a low risk of toxicity (e.g. gentamycin <1mg/ml)

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11
Q

Name some antifungal drugs

A

Nystatin, clotrimazole, fluconazole

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12
Q

What are antifungal drugs prescribed for?

A
  1. Treatment of local fungal infections including of the oropharynx, vagina or skin. They may be applied topically (nystatin, clotrimazole) or taken orally (fluconazole)
  2. Systemic treatment of invasive or disseminated fungal infections
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13
Q

What are the important adverse effects of anti-fungal meds?

A

Nystain or clotrimazole are used topically at the site of infection , so have few adverse effects apart from occasional local irritation where applied
Fluconazole is taken orally so has systemic AEs- GI upset, headache, hepatitis, hypersensitivity causing skin rash
Rare- severe hepatic toxicity, prolonged QT interval predisposing to arrhythmias, severe hypersensitivity reactions, including cutaneous reactions and anaphylaxis

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14
Q

What are the warnings for prescribing anti-fungals?

A

Fluconazole should be prescribed with caution in patients with liver disease because of the risk of hepatic toxicity
A dose reduction is required in moderate renal impairment
Fluconazole should be avoided in pregnancy due to the risk of fetal malformation

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15
Q

What are the important interactions for antifungal drugs?

A

Fluconazole increases in plasma conc and increases risk of AEs when prescribed with drugs that are metabolised by CYP enzymes, inc carbamazepine, phenytoin, warfarin, diazepam, simvastatin, sulphonylureas

It may reduce the anti platelet effects of clopidogrel

Increases risk of arrhythmias if prescribed with drugs that prolong the QT interval- amiodarone, antipsychotics, quinine, quinolone, marcrolide antibiotics, SSRIs

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16
Q

How are antifungal drugs prescribed?

A

Nystain is administered topically as an oral suspension for oropharyngeal candidiasis (thrush) at a dose of 100,000 units QDS for 7 days or until 48 hours after lesions have resolved

Clotrimazole is used to treat fungal infections of the skin and genital tract, such as tinea (ringworm, inc athletes foot), and candida

For skin/mucosal infections, clotrimazole 1% cream is applied 2-3 times a day until 1-2 weeks after infection has resolved

Oral fluconazole is prescribed as a single dose of 150mg for vaginal candidiasis. For other mucosal infections, e.g. oropharynx, oesophagus, airways, it is prescribed at 50mg daily for a more prolonged course

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17
Q

How is oral nystain prescribed?

A

After food
Held in the mouth to allow good contact with the lesions
Remove dentures

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18
Q

What should be monitored during fluconazole prescription?

A

Liver enzymes before and during prolonged courses of treatment

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19
Q

Name an example of an antiviral drug?

A

Aciclovir

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20
Q

What are antivirals used for?

A
  1. Treatment of acute episodes of herpes virus infections (including herpes simplex- cold sores, genital ulcers, encephalitis) and (varicella-zoster- chickenpox, shingles)
  2. Suppression of recurrent herpes simplex attacks where these are occurring at a frequency of 6 or more per year
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21
Q

How do antivirals work?

A

Aciclovir enters the herpes-infected cells and inhibits the herpes-specific DNA polymerase, stopping further viral DNA synthesis and therefore replication

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22
Q

What are the common adverse effects of antivirals?

A

Headache, dizziness, GI disturbances and skin rash
IV aciclovir commonly causes inflammation and phlebitis at the injection site and can cause crystal-induced acute renal failure

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23
Q

What are the warnings for prescribing antiviral drugs?

A

It does cross the placenta and is expressed in breast milk so caution is advised in pregnant women and women who are breastfeeding
However the benefits of treatments can outweigh the risks

Aciclovir is excreted by the kidneys, so the dose and/or frequency of administration should therefore be reduced in severe renal impairment

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24
Q

Are there any interactions with aciclovir?

A

No

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25
Q

How is aciclovir prescribed?

A

Acute episodes of oral and genital herpes simplex can be treated with aciclovir topically (5 times a day for 5-20 days) or orally (200mg 5 times a day)
Treatment should ideally be started in the prodromal phase
In recurrent infections, suppressive treatment (400mg 12-hourly) may be given

Herpes simplex encephalitis requires high-dose IV therapy (10-15mg/kg 8-hourly)

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26
Q

What needs to be monitored with high-dose IV aciclovir treatment?

A

Renal function

27
Q

Name some examples of cephalosporins and carbapenems?

A

Cefalexin, cefotaxime, meropenem, ertapenem

28
Q

What are cephalosporins and carbapenems prescribed or?

A
  1. Oral cephalosporins are second and third line options for treatment of urinary and respiratory tract infections
  2. Parenteral cephalosporins and carbepenems are reserved for infections that are very severe or complicated, or caused by antibiotic-resistant organisms
29
Q

Do cephalosporins and carbapenems have a broad or narrow spectrum of action?

A

They have a broad spectrum of action

They have a beta-lactam ring and weaken bacterial cell walls, resulting in bacterial cell lysis, swelling and death

30
Q

What are the important adverse effects of cephalosporins and carbapenems?

A

GI upset
Antibiotic-associated colitis- by killing gut flora
Hypersensitivity
Neurological toxicity inc seizures

31
Q

What are the warnings for cephalosporins and carbapenems?

A

In caution for people at risk of C.diff infection e.g. hospital patients and elderly, due to risk of colitis
CI’d in Allergy
Used in caution in patients with epilepsy
Dose reduction required in renal impairment

32
Q

What are the important interactions for cephalosporins and carbapenems?

A
  • They can enhance the effect of warfarin by killing got flora that synthesise vit K
  • cephalosporins may increase nephrotoxicity of aminoglycosides
  • carbapenems reduce plasma conc and efficacy of valproate
33
Q

How are cephalosporins and carbapenems prescribed?

A

cephalosporins are usually prescribed for 6-12 hourly administration e.g. IV cefotaxime 2g 6-hourly for bacterial meningitis. Can rarely be administered orally

Carbapenems are only available IV e.g. meropenem 1-2g IV 8-hourly

34
Q

How are cephalosporins and carbapenems monitored?

A

Check the infection resolves by symptoms, signs (resolution of pyrexia) and blood tests (falling CRP and WCC)

35
Q

What is chloramphenicol used for?

A
  1. Bacterial conjunctivitis using eye drops or ointment
  2. Otitis externa using ear drops
  3. Rarely used systemically for life-threatening infections
36
Q

What is the spectrum of activity for chloramphenicol?

A

It has a broad activity against many gram-positive, gram-negative, aerobic and anaerobic organisms

37
Q

How does chloramphenicol work?

A

It is bacteriostatic (stops bacterial growth) which helps the immune system to clear the organisms

38
Q

What are the important AEs for chloramphenicol?

A

Stinging, burning and itching when applied topically

Systemic administration- bone-marrow toxicity risk

  • dose-related bone marrow suppression
  • aplastic anaemia

Grey baby syndrome is circulatory collapse in an exposed neonates who are unable to metabolise and excrete the drug
Optic and peripheral neuritis may occur with prolonged systemic administration

39
Q

What are the warning for prescription of chloramphenicol?

A

CI’d in people with hypersensitivity reactions, and a personal or family history of bone marrow disorders
CI’d systemically in 3rd trimester of pregnancy, breastfeeding and children under 2
Dose adjustment in hepatic impairment

40
Q

Are there any interactions for chloramphenicol?

A

No

41
Q

How is chloramphenicol prescribed?

A

Prescribed for topical administration as eye or ear drops or eye ointment

For eye infections, drug application needs to be frequent as tears and blinking remove the drug. Eye drops (0.5%) should be prescribed initially as one drop every 2 hours when awake, with frequency reduced to 3-4 times a day as symptoms resolve

Eye ointment (1%) stays in the eye longer, so should be applied 3-4 times daily. Rx should be continued 48 hours after healing for both.

For otitis externa, 3-4 ear drops (5-10%, higher conc than eye drops as less risk systemic absorption) are administered to the affected ear 2-3 times daily for up to 1 week

42
Q

What needs to be monitored for systemic treatment with chloramphenicol?

A

FBC

Drug stopped if any signs of myelosuppression are evident

43
Q

Name some examples of macrolides?

A

Clarithromycin, erythromycin, azithromycin

44
Q

What are the common indications for macrolides?

A
  1. Treatment for respiratory, skin and soft tissue infections as an alternative to penicillin when use is contraindicated e.g. by allergy
  2. In severe pneumonia added to a penicillin to cover atypical organisms including Legionella pneumophila and Mycoplasma pneumoniae
  3. Eradication of Helicobacter pylori (e.g. causing peptic ulcer disease) in combination with a PPI and either amoxicillin or metronidazole
45
Q

Do macrolides have a broad or narrow spectrum of activity?

A

Broad for erythromycin
Synthetic macrolides e.g. clarithromycin and azithromycin have increased activity against gram-negative bacteria, particularly H. influenzae

46
Q

How do macrolides work?

A

They inhibit bacterial protein synthesis which is bacteriostatic

47
Q

What are the important AEs of macrolides?

A

Most commonly seen with erythromycin
They are irritant, causing nausea, vomiting, abdo pain and diarrhoea when taken orally and thrombophlebitis when given IV

Allergy
Antibiotic-associated colitis
Liver abnormalities inc cholestatic jaundice, prolongation of the QT interval
Ototoxicity

48
Q

What are the warnings for prescribing macrolides?

A

Macrolide hypersensitivity

Caution in severe hepatic impairment and dose reduction in severe renal impairment

49
Q

What are the interactions for macrolides?

A

Increased plasma conc and risk AEs with drugs that are metabolised by CYP enzymes- warfarin, statins
Should be prescribed in caution in patients taking othr drugs that prolong the QT interval or cause arrhythmias- amiodarone, antipsychotics, quinine, quinolone antibiotics, SSRIs

50
Q

How are macrolides prescribed?

A

Erythromycin- 250-500mg 6-hourly for infections (due to short half-life)
Clarithromycin 250-500mg 12-hourly
Azithromycin- 250-500mg daily
All available in IV preparations

51
Q

How are macrolides administered?

A

Orally- with or without food (although food may improve GI tolerability)
IV- diluted in a large volume before infusing in large proximal vein over at least 60 mins

Oral are 50x cheaper than IV so switch to oral as soon as tolerated

52
Q

What is metronidazole used for?

A
  1. Antibiotic-associated colitis caused by the Gram-positive anaerobe C.Difficile
  2. Oral infections such as dental abscess or aspiration pneumonia caused by Gram-negative anaerobes from the mouth
  3. Surgical and gynaecological infections caused by Gram-negative anaerobes from the colon, for example Bacteroides fragilis
  4. Protozoal infections including trichomal vaginal infection, amoebic dysentery and giardiasis
53
Q

What is the spectrum of activity for metronidazole?

A

Anaerobic bacteria and protozoa

54
Q

What are the important adverse effects of metronidazole?

A

It can cause GI upset and immediate or delayed hypersensitivity reactions
When used at high doses for prolonged courses, it can cause neurological adverse effects such as peripheral and optic neuropathy, seizures and encephalopathy

55
Q

What are the warnings for metronidazole?

A

Dose should be reduced in people with severe liver disease
Alcohol should NOT be drunk until 48 hours after treatment as the combination can cause a ‘disulfiram-like’ reaction, including flushing, headache, nausea and vomiting

56
Q

What are the important interactions for metronidazole?

A

Can reduce the metabolism of warfarin (increased bleeding risk) and phenytoin (increased toxicity risk)
Also increases toxicity of lithium

57
Q

How is metronidazole prescribed?

A

The oral route is used for GI infections or where the patient is not systemically unwell
A typical dose would be 400mg orally 8-hourly

The IV route, 500mg IV 8-hourly, is used for severe infection on patients can’t tolerate by mouth

Rectal is an alternative for oral, it can also be prescribed as a gel for topical administration to treat vaginal infection such as BV or infected skin ulcers

58
Q

What needs to be measured if metronidazole treatment exceeds 10 days?

A

FBC and LFTs

59
Q

Which other antibiotics can alcohol reduce the effectiveness of?

A

Doxycycline and erythromycin

60
Q

What is nitrofurantoin prescribed for?

A
  1. Nitrofurantoin is a first-choice for acute, uncomplicated lower UTI (alternatives are trimethoprim, amoxicillin, cephalexin)
  2. It can also be used for prophylaxis of UTI in patients with recurrent infections
61
Q

What are the important adverse effects of nitrofurantoin?

A

GI upset
Immediate and delayed hypersensitivity reactions
It can turn urine dark yellow or brown
Less commonly- chronic pulmonary reactions, hepatitis, peripheral neuropathy
In neonates, haemolytic anaemia may occur because immature red blood cells are unable to mop up nitrofurantoin- stimulated superoxides, which damages RBCs

62
Q

What are the warnings for nitrofurantoin?

A

It should not be prescribed for pregnant women towards term or for babies in the first 3 months of life
Contraindicated in patients with renal impairment
Cautioned in long-term prevention, as chronic use increases the risk of adverse effects, particularly in elderly patients

63
Q

How is nitrofurantoin prescribed?

A

Only available for oral administration
50-100mg 6-hourly, usually 3 day course for uncomplicated UTI in women and 7 days for men or complicated infection

For prevention of recurrent UTI, a single nightly dose of 50-100mg is prescribed

It should be taken with food or milk to minimise GI upset

Pharmacology (9 decks)

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