Antibiotics

Question 1

Name anaerobic antibiotics

Answer 1

Metronidazole

Orala or IV or Gel

Question 2

Indications of using metronidazole

Answer 2

1) C.Diff (gram +ve) - this is 1st line
2) Oral infections - due to gram -ve in the mouth
3) Aspiration pneumonia
4) Surgical and gynae infections due to gram -ve anaerbobes from the colon
5) Protozoal infections e.g. trichomonal vaginosis, dysentry, giardasis

Question 3

Mechanisms of metronidazole

Answer 3

Passively diffuses into anaerobic bacterial cells
Reduced to generate a nitroso free radical
Binds to DNA
Reduces syntheses causing widespread damage - DNA degradation and cell death

Question 4

Why doesnt metronidazole work on aerobic bacteria

Answer 4

As they dont reduce it to a nitrosos free radical

Question 5

Is there resistance to metronidazole

Answer 5

Generally low resistance

But can be resistanct due to decreased uptake and decreased generation of nitroso free radicals

Question 6

ADverse effects of metronidazole

Answer 6

1) GI Upset
2) Hypersensitivity
3) Neuro effects –> if at high doses or prolonged courses e.g. peripheral and optic neuropathy, seizures and encephalopathy

Question 7

Warnings of metronidazole

Answer 7

Metabolised by hepatic CP450 ensymes –> reduce dose in hepatic impairment

Inhibits acetalderhyde dehydrogenase enzye –> this clears intermediate alcohol metabolite –> hence if you drink a disulfram-like reaction occurs –> flushing, headach, nausea and vomiting

Question 8

What cant you do whilst taking metronidazole

Answer 8

Drink alcohol

Question 9

Interactions of metronidazole

Answer 9

1) inhibitory effect on CP450 en`ymes
2) Excitory effect on CP450 inducers
3) Increased risk of lithium toxicity

Question 10

What do we measure if we treat longer than 10 days on metronidazole

Answer 10

Measure FBC and LFTs

Question 11

Indications of nitrofurantoin

Answer 11

1) Uncomplicated lower UTI - 1st line

Reaches therapeutic concentration in the urine through renal excretion

Question 12

Action of nitrofurantoin

Answer 12

Metabolised in bacterial cells by nitrofuran reuctase

Its active metabolite damages bacterial DNA causing cell death

Question 13

what organisms is nitrofurantoin active against

Answer 13

Gram +ve (staph. saprophyticus) and gram -ve (E. Coli) that cause UTIs commonly

Question 14

What bacteria are resistant to nitrofurantoin

Answer 14

Bacteria with reduced nitrofuran reductase activity

Also less common causes of UTIs e.g. Klebsiella, Proteus have intrinsic resistant

Relatively rare for E. Coli to develop resistance

Question 15

Adverse effects of nitrofurantoin

Answer 15

1) GI upset
2) Hypersensitivity
3) Chronic pulmonary reactions - pneumonitis, fibrosis
4) Hepatitis and peripheral neuropathy
5) haemolytic aneamia in neonates –> as immature RBCs are unable to mop up nitrofurantoin stimulated superoxides which damages RBCs
6) can turn urine dark yellow or brown

Patiet whousl warn if any unexplained symtpoms e.g.breathlessness

Question 16

Contrainidcatinos of nitrofurantoin

Answer 16

1) Pregnancy towards term
2) Under 3 months old
3) Renal impairment - as impaired excretion increases its toxicity and decreases its efficacy

Question 17

Caution of using nitrofurantoin in who

Answer 17

Long term UTI prevention –> high risk of adverse effects

Question 18

Interactions of nitrofurantoin

Answer 18

No significant interactions

Question 19

How can we minimise GI upset in nitrofurantoin

Answer 19

Take with food or mulk

Question 20

Why shouldn’t we prescribe nitrofurantoin for pyelonephritis

Answer 20

As tissue concentrations are low

Use co-amoxiclav or gentamicin instead

Question 21

What does co-trimoxazole contain

Answer 21

Trimethoprim and sulfamethoxazole

Question 22

Indications of trimethprim

Answer 22

1) UTI - 1st line for uncomplicated

2) Pneuocytis Pneumonia - use co-trimoxazole

Question 23

Action of trimethoprim

Answer 23

Inhibits bacterial folate synthesis by inhibiting dihydrofolate reductase

Bacteria are unable to use external folate for DNA synthesis –> therefore inhibiting it is bacteriostatic

Question 24

What organisms is trimethoprim effective against

Answer 24

Broad spectrum against gram -ve and gram +ve - Particularly E. Coli

BUT widespread bacterial resistance

Question 25

How do sulfonamide antibiotics work

Answer 25

Inhibits bacterial folate syntheisis - but inhibits dihydropteroate syhnthetase as structual analoge of PABA

Question 26

Why do we combine trimethoprim and sulfomethoxazole?

Answer 26

As both are bacteriostatic and in combination they cause more inhibition making it bacteriacidial

Question 27

Adverse effects of trimethoprim

Answer 27

1) GI upset - common 2) Skin rash - 3-7% 3) Severe hypersensitivity reactions 4) Haematological disorders --> as a folate anatgonists can cause megaloblastic aneamia, leucopenia and thrombocytopenia 5) Hyperkaelamia and eleation of plasma creatinine

Question 28

Why can trimethoprim cause megaloblastic anaemia, leucopenia and thromboyctopenia

Answer 28

As it is a dihydrofolate reductase inhibitor hence this means that it reduces the amount of folate available

Question 29

Contraindications of using trimethoprim

Answer 29

1) 1st trimester --> increased risk of foetal abnormalities

Question 30

Caution in which patients when using trimethoprim

Answer 30

1) Folate deficiency - more susceptible to haematological effects 2) Renal impairment ---> may need dose reduction as exreted mostly unchanged by the kidneys 3) Neonates, elderly, HIV infection --> more susceptible to adverse effects

Question 31

Interactions of trimethoprim

Answer 31

1) Potassium raising drugs --> predisposes to hyperkaleamia 2) Folate antagonists (e.g. methotrexate) and drugs that increase folate metabolism (e.g. phenytoin) --> increase the risk of adverse effects 3) Enhances warfarin --> as it kills the gut flora that synthesise vitamin K

Question 32

What would use as prophylaxis for UTIs

Answer 32

Low dose trimethoprim

Question 33

What do we need to monitor if we give long term trimethoprim

Answer 33

FBC monitoring | For the early detection of haematological disorders

Question 34

What is the relationship between trimethoprim and creatnine

Answer 34

Trimethoprim competitively inhibits creatinine secretion in the renal tubules This causes a small reversible increase in creatining without reducing GFR Hence this means trimethoprim is less effective in those with renal impairment as it is outcompeted by creatinine for secretion into the urinary tract

Question 35

Name a glycopeptide

Answer 35

Vancomycin

Question 36

Indications for vancomycin

Answer 36

1) Gram +ve infections --> if severe infection and penicillines cant be used 2) Antibiotic associated colitis due to C. Diff - 2nd line to metronidazole

Question 37

Action of glycopeptides

Answer 37

Inhibit frowth and cross-linking of peptidoglycan chains --> hence inhibiting the synthesis of the cell wall of gram +ve bacteria

Question 38

Why are glycopeptides inactive against gram -ve bacteria

Answer 38

Due to a different cell walll structure

Question 39

Adverse effects of glycopeptides

Answer 39

1) Thrombophlebitis --> common at infusion site 2) Red Man Syndrome --> general erythema, hypotension and bronchospasm Anaphylactoid reactions are NOT antigen-mediated hence they are not true allergies They are due to the non-specific degranulation of mast cells 3) Nephrotoxicity --> when IV 4) Ototoxicity --> report any changes in hearing 5) Blood disorders: Neutropenia and thrombocytopenia

Question 40

Warnings of using glycopeptides

Answer 40

Caution and dose reduction in elderly and renal impairment

Question 41

Interactions of glycopeptides

Answer 41

1) Aminoglycosides, loop diuretics and ciclorpin Increased risk of ototoxicity/nephrotoxicity if used together!!

Question 42

What is vancomycin good for C. Diff reatment

Answer 42

As it is a large hydrophilic molecule so is poorly absorbed across lipid membranes

Question 43

Indications for tetracyclines

Answer 43

1) Acne vulgaris 2) LRTI --> including COPD exacerbations and atypical pneumonia 3) Chlamydia 4) Typhoid, anthrax, malaria and Lyme Disease

Question 44

Action of tetracyclines

Answer 44

Bind to 30S ribosome --> inhibits bacterial protein synthesis Relatively broad spectrum but widspread resistance due to a pump that allows bacteria to pump out tetracyclines

Question 45

Adverse effects of tetracylcines

Answer 45

1) GI upset - take with food to reduce risk 2) Hypersesntivity 3) Oesophageal irritation, ulceration and dysphagia 4) Photosensitivity 5) Discououration and/or hypoplasia of tooth enamel in chilren 6) Intracreanial hypertesnin --> headaches and visual disturbatnces

Question 46

Contraindication of tetracyclines

Answer 46

1) Pregnancy 2) Breastfeeding 3) Under 12 As tetracylicnes bind to teeth and bones during development

Question 47

When should we also avoid tetracyclines

Answer 47

Renal impairment | Their anti-anabolic effect can raise plasma urea and reduced excretion increase the risk of adverse effects

Question 48

Interactiosn of tetracyclines

Answer 48

Bind to divalent cations --> seperate 2 horus from calcium, antacids or Iron Wargarin --> exacerbates antcoagulant efffects as kills normal gut flora

Question 49

How should you take a tetracycilne tablet

Answer 49

Swallow whole with plenty of water to avoid oesophageal irritation

Question 50

Name macrolides

Answer 50

Clarithromycin erythryomycin Azithromycin

Question 51

Indicatinos of macrolides

Answer 51

1) Respiratory and soft tissue infections (penicillin alternative) 2) Severe pneumonia --> add to penicilin to cover atypical 3) H. Pylori eradicated --> incombo with either PPI and amoxicillin or metronidazole

Question 52

Action of macrolides

Answer 52

Inhibits bacterial protein synthesis --> binds to the 50S ribsosome and blocks translocation. This prevents elondation of polypeptide It is bacteriostatic so the immune system can then kill it and remove it from the body

Question 53

What organisms does each type of macrolide have on?

Answer 53

``` Eryhtormucin --> broad spectrum against +ve and -ve Synthetic molecules (clarithromycin + azithromycin) hace increaesd activity against gram -ve (particularly H. Infunenzae) ```

Question 54

Adverse efecs of macrolides

Answer 54

Most ommon and sever 1) Macrolides are irritant --> nause, ovmitng, thrombophlebiti 20 Antibitoics associated colitis 2) Liver abnormlaities 4) Prolongation of the QT interval 5 Ototoxicity

Question 55

Contrainidication ofsing macrolides

Answer 55

1) Macrolide hypersensitivity

Question 56

Caution of using macrolides

Answer 56

Severe hepatic and renal impairment

Question 57

Interactino of macrolides

Answer 57

1) the drugs are metablised by the P450 enzymes (ecept emma) | 2) Drugs that prolong the QT intervatl e.g. amiodarone, antipsychoics and quinin , SSRI

Question 58

Do macrolides cover penicillin resistant organsimis

Answer 58

Yes they cover things such as legionella that cause pneumonia but not other organisms that cause LRTI

Question 59

Name quinolones

Answer 59

Ciprofloxacin Moxifloxacin Levofloxacin

Question 60

Indicitatios for use of quinolones

Answer 60

Generally reserved for 2nd or 3rd line treatment due to potential for rapid resistance and C. Diff 1) UTI 2) Severe GI infection e.g. Shigella or campulobacter --> ciprofloxacin 3) LRTI - use moxi or levo 4) Pseudomonas aureginos

Question 61

What antibitoic should we treat pseudomonas with

Answer 61

Ciprofloxacin - this is the only oral antibiotic with action against it

Question 62

Action of quinonones

Answer 62

Inhibit DNA synthesis - particularly active against anaerbovin gram -ve hence useful in UTI and GI infections Moxi and levo hace enhaved activity against gram _ve hence can be used to treat LRTIs that are caused by gram_ve and -ve

Question 63

How does rapid resistance arise to quinolones

Answer 63

Prevent intracellular accumumlation be reducing permeablility/increasing efflux Mutations in target enzymes

Question 64

Adverse effects of quinonlones

Answer 64

1) GI Upset 2) Hypersesnitivty 3) Neuro adverse effects --> lower the seizure thresholod 4) INflammation and rupture of muscle tendons 5) Prolong the QT interval --> Arrhythmias risk --> particularly moxi 6) Promote C. Diff

Question 65

Warnings of using quinolones

Answer 65

At risk of seizures Growing - increased risk of arthropaty Risk factosr for QT prolongation e.g. electroloye disturbances or cardiac diseases

Question 66

Interactions of quinolones

Answer 66

1) Drugs containing divalent cations --> e.g. calcium and atacids --> these decrease its absorption and efficacy 2) Cipro inhibits certain CP450 enzymes 3) Co-prescription with NSAIDS --> high risk of seizures 4) Co-prescription with prednisolone increaess risk of tendon rupture 5) Caution with other drugs that prolong the QT interval or cause arrhytmias e.g. amiodarone, antipsychotic, SSRIs, macrolides, quinine

Question 67

What happens if co-prescription of quinolones and prednisolone

Answer 67

Increased chance of tendon rupture