Antibiotics Flashcards
Penicillin - Example
- benzylpenicillin
- phenoxymethylpenicillin
Penicillin - Indication
- Streptococcal Infections: tonsilitis, pneumonia, endocarditiis , skin/soft tissue infections
- Meningococcal infection: meningitis and septicaemia
- Clostridial infection such as tetanus
Is penicillin narrow or broad spectrum?
Narrow
Penicillin - MOA
Penicillin act by inhibiting the peptidoglycans in the bacterial cell wall which weakens the cell walls. They cannot maintain an osmotic gradient and this leads to uncontrolled entry of water. The cells begin to swell and eventually lysing and dying.
What gives Penicillin it’s antibiotic properties?
Penicillin contains a B-lactam ring which is responsible for their bacteriacidal activity.
What do side chains on B-lactam ring do?
The side chains can be linked to the B-lactam ring and influence the nature of the antibiotic determining the antibacterial spectrum and other properties of the drug.
How do bacteria resist Penicillin?
bacteria resist the action of penicillin by synthesising B-lactamases which break down the B-lactam ring and thus
What are side effects of Penicillin?
- Penicillin allergy = presents as a skin rash 7-10 days after first exposure and 1-2days after repeat exposure
- Less common : anaphylactic reaction- Characterised by hypotension, bronchial and laryngeal spasm/oedema and angioedema.
- Central nervous system toxicity which usually happens in high doses of penicillin or where severe renal impairment delays excretion = pt usually has convulusions or coma
What are the contraindications of Penicillin?
- a history of penicillin allergy
2. renal impairment - reduced dose required because other can lead to a delay in excretion leading to toxicity.
What are the interactions of Penicillin?
reduces renal excretion of methotrexate increasing the risk of toxicity.
Broad spectrum penicillin - Examples
Amoxicillin and co-amoxiclav.
Broad spectrum penicillin - Indication
- Susceptible infections such as
- community acquired pneumonia
- otitis media
- UTIs
- sinusitis - H.Pylori associated peptic ulcers
- Severe-resistant hospital acquired infections - usually co-amoxiclav
Broad spectrum penicillin- MOA
How does it differ to other kinds of penicillin?
Some MOA of weakening bacterial cell wall leading to cell swelling and lysis of the bacteria. Bactericidal properties brought about by the B-lactam ring.
They way it differs is that it’s synthesised with additional amino group to the B-lactam ring side chain ehich broadens the activity against aerobic Gram negative bacteria
Broad spectrum penicillins - Side Effects
- GI upset including nausea and diarrhoea
- penicillin allergy which usually presents as a skin rash or can lead to delayed or immediate IgE-mediated anaphylactic reaction
- Acute liver injury/jaundice or hepatitis may develop during or shortly after co-amoxiclav and is usually self-limiting once the Tx is stopped.
- less commonly antibiotic-associated colitis
Broad spectrum penicillins - Contraindication
- History of allergy
- pt in risk of C.difficile infection - hospitalised pts and elderly
- penicillin associated liver injury
- severe renal impairment - dose should be reduced (risk of crystalluria)
Broad spectrum penicillins - Interaction
They can enhance to anticoagulant effect of warfarin by killing normal gut flora that synthesise vitamin K
Macrolides - Examples
- clarithromycin
- erythromycin
- azithromycin
Macrolides - Indications
- Respiratory, skin and soft tissue infections = usually as an alternative to penicillin
- Severe pneumonia - added to penicillin to cover atypical pathogens such as legionella pneumophila and mycoplasma pneumoniae.
- H.Pylori eradication Tx in combination with PPI and either amoxicillin and metronidazole
Macrolides - Spectrum of activity
erythromycin is relatively broad spectrum active against gram-positive and some gram-negative pathogens
synthetic macrolides such as clarithromycin and azithromycin have increased activity against gram-negative pathogens particularly haemophilus influenzae
Macrolides - MOA
Type of Abx
Macrolides inhibit bacterial protein synthesis. They do this by binding to the 50S subunit of the bacterial ribosome blocking translocation (needed to elongate polypeptide/protein).
it is a bacteriostatic antibiotic = prevents the growth/multiplication of bacteria thus providing the immune system with more time to kill and remove bacteria.
Macrolide - Side Effects
most common and severe in eythromycin
side effects:
1. irritant causing nausea, vomiting, abdo pain and diarrhoea and also thrombophlebitis when given via IV.
- allergy
- antibiotic associated coiltis
- liver abnormalities such as cholestatic jaundice
- prolongation of QT interval thus predisposing arrythmias
- ototoxicity at high doses
Macrolide - Contraindication /Caution
- History of hypersensitivity/allergy
- severe hepatic impairment
- severe renal impairment
Macrolide - Interaction
- Macrolide inhibit CYP enzymes : increases conc of drugs metabolised by them
Tetracycline - Examples
- doxycycline
- lymecycline
Tetracycline - Indication
- Acne Vulgaris = presence of inflamed papules, pustules and/or cysts
- Lower respiratory Tract infections (LRTI) = includes infective exacerbations of COPD, pneumonia and atypical pneumonia
- Chlamydial infection = includes pelvic inflammatory disease
- Other infections = typhoid, anthrax, malaria and Lyme disease
Tetracycline - MOA
- Tetracycline inhibit the bacterial protein synthesis.
- They bind to the 30S subunit found specifically in bacteria preventing transcription & translation.
- They are therefore deemed as bacteriostatic antibiotics.
Tetracycline - Spectrum of activity
Tetracyclines are relatively broad spectrum active against many gram-positive and gram-negative bacteria including chlamydia, mycoplasma and spirochaetes. However, their utility is limited by increase if resistance.
Tetracycline - Side Effects
Most commonly causes by nausea, vomiting and diarrhoea. (slightly lower risk of coilitis)
Hypersensitivity reactions occur which can be either immediate or delayed.
tetracycline specific:
1. oesophageal irritation, ulceration and dysphagia
- photosensitivity and discolouration of skin and/or hypoplasia of tooth enamel
- Less common: hepatotoxicity and intracranial hypertension (leading to headaches and visual disturbance)
Tetracycline - Contraindications
Avoid use in infancy/childhood (under 12yrs) because it can have an effect on teach and bone during development
for this reason should not be given in pregnancy or breastfeeding
Tetracycline - Caution
- renal impairment as anabolic effect raises serum urea and reduced excretion = more risk of adverse effects.
Tetracycline - Interactions
tetracyclines bind to divalent cations and therefore shouldn’t be given within 2 hours of calcium, antacids or iron preventing antibiotic absorption.
Tetracyclines enhance the anticoagulant effect of warfarin killing gut bacteria which synthesise vit K.
Trimethoprim - Indications
- Uncomplicated UTI = alternatives include Nitrofurantoin and amoxicillin.
- Prophylaxis of recurrent UTI.
also Tx option for:
- acne
- respiratory tract infections
- Pneumocystis pneumonia in immunocompromised pt = co-trimoxazole
Trimethoprim - MOA
trimethoprim inhibits bacterial folate synthesis.
folate is needed for essential functions such as DNA synthesis and it must be their own folate
therefore, this slows down bacterial growth = bacteriostasis
Trimethoprim - Side Effects
- GI upset (nausea, vomiting and sore mouth)
- skin rash
- more rare but can cause hypersenstivity recations including anaphylaxis, drug fever and erythema multiform.
- can impair haematopoiesis causing haematological disorders e.g. megaloblastic anaemia, leucopenia and thrombocytopenia.
- hyperkalaemia and elevated plasma creatinine
Trimethoprim - Contraindications
First trimester of pregnancy, because folate antagonist is associated with increased risk of fetal abnormalities.
Trimethoprim - Caution
- folate deficiency - more susceptible to haematological effects.
- renal impairment - excreted by the kidneys and so reduced dose is used.
- neonates, elderly, and HIV patients
Trimethoprim - Interactions
- potassium-elevating drugs (aldosterone antagonists, ACEi, ARBs) predisposes to hyperkalaemia
- use with other folate antagonists (methotrexate) and drugs that increase folate metabolism (Phenytoin) increases the risk of adverse haematological effects
- Trimethoprim can enhance the anticoagulant effect of warfarin by killing normal gut flora that synthesis Vit K.
Trimethoprim - Spectrum of activity
Broad spectrum
Nitrofurantoin - Indications
- acute uncomplicated LUTI (alternatives are trimethoprim, amxocillin and cefelaxin)
- Prophylaxis of reccurent UTI.
Nitrofurantoin - MOA
Free Radicals
- Nitrofurantoin is metabolised (reduced) in bacterial cells by nitrofuran reductase.
- Its active metabolite damages bacterial DNA and causes cell death (bactericidal).
Nitrofurantoin - Side Effects
- GI upset (nausea and diarrhoea)
- immediate and delayed hypersensitivity reactions
- dark yellow/brown coloured urine
less common
- chronic pulmonary recations (pneumonitis and fibrosis)
- hepatitis
- peripheral neuropathy
neonates = haemolytic anaemia - immature RBCs can’t mop up superoxides formed by nitrofurantoin damaging the RBCs.
Nitrofurantoin - Contraindications
- pregnant women towards term or babies in the first 3 months of life
- renal impairment - impaired excretion increases risk of toxicity and lower drug conc reduces efficacy
Nitrofurantoin - Caution
Chronic use in prophylaxis increases risk of adverse effect esp in elderly,
Nitrofurantoin - Interactions
None
Flucloxacillin - Class of druh
Penicillin, penicillin-resistant
Flucloxacillin - Indications
Usually used in combined Tx for a staphylococcal infection
- skin and soft tissue infections = e.g. cellulitis (usually combined with benzylpenicillin)
- Osteomyelitis and septic arthritis
- Other infections including endocarditis
Flucloxacillin - MOA
Follow the similar MOA through targeting the peptidoglycan in bacterial cell walls.
Side chains an acyl side chain protects the B-lactam ring from B-lactamases making the antibiotic more effective agaisnt B-lactamse-producing staphylococci.
Flucloxacillin - Spectrum of Activitiy
Narrow spectrum against Gram-positive staphylococci.
Flucloxacillin - Side Effects
- Minor GI upset
- penicillin allergy - usually presents as a skin rash
- life-threatening anaphylactoid reaction
- Liver toxicity - including cholestasis and hepatitis (can occur up to 2months after Tx is completed)
Flucloxacillin - Contraindications
- xhistory of penicillin allergy
- renal failure - reduced dose
- xprior flucloxacillin-related hepatotoxicity
- use with caution with hepatic impairment
Flucloxacillin - Interactions
reduces renal excretion of methotrexate which increases the risk of toxicity.
Vancomycin - Indication
1) Gram- positive infection (endocarditis)
2) Abx- associated colitis caused by C.diff
Vancomycin - Spectrum of acitvity
Narrow
Vancomycin - MOA
Vancomycin inhibits growth and cross-linking of peptidoglycan chains, inhibiting synthesis of the cell wall of Gram-positive bacteria, thus lysing and killing the bacteria (bactericidal).
Vancomycin - Side Effects
Most common:
- thrombophlebitis
Severe:
- ‘red man syndrome’ : erythema, hypotension, bronchospasm
Allergy
IV:
- nephrotoxicity, ototoxicity , thrombocytopenia
Vancomycin - Contraindications
NONE
Vancomycin - Caution
Renal impairment & elderly
Vancomycin - Interactions
- Increase otoxicity & nephrotoxicity with aminophycoside, loop diuretic, ciclosporin
