Antibiotic Classes Flashcards
Name 1 e.g. of a tetracycline antibiotic and 2 indications for their use
-Doxycycline, lymecycline
Indications for use of doxycycline, name 2:
- acne (inflamed pustules/papules/cysts)
- lower RT infections e.g. infective exacerbations of COPD (H.influenzae, pneumonia, and atypical pneumonia (mycoplasma, chlamydia psittaci, coxiella burnetti)
- chlamydial infection inc. pelvic inflamm disease
- other infections e.g. typhoid, anthrax, malaria, lyme disease..
Tetracyclins have quite a ____-spectrum of activity against ___ and ___ organisms.
Their use is limited by increasing ____ ___
- broad spec vs gram + and gram - organisms
- limited by bacterial resistance
Tetracyclins MOA
- they inhibit bacterial _____ ____.
- they bind to the 30S _____ subunit found in bacteria, which prevents binding of ____ to ___
- this prevents the _____ of new ___ ___ to growing ____ ___ chains
- this is _____ (stops bacterial growth) so assists immune system in killing and removing bacteria
- what is the main MOA of resistance to this class which has developed?
- inhibit protein synthesis
- bind to ribosomal subunit, prevents tRNA binding to mRNA
- prevents the addition of new amino acids to the growing polypeptide chains
- this is bacteriostatic
- efflux pump (allows bacteria to pump out tetracyclines-preventing cytoplasmic accumulation)
Name 4 SEs of tetracycline use
- nausea
- vomiting
- diarrhoea
- hypersensitivity reactions (1%)
- oesophageal irritation, ulceration and dysphagia
- photosensitivity (sunburn reaction when skin exposed to light)
- discolouration +/- hypoplasia of tooth enamel in children
- hepatotoxicity, intracranial hypertension are rare
Tetracyclines bind to divalent cations, therefore should not be given within 2hrs of
-___
-___
or __
as this would prevent antibiotic absorption
- calcium
- antacids
- iron
How can tetracyclines enhance Warfarin’s anticoag. effect?
-they kill normal gut bacteria that synthesis vitamin K so there is less vitamin K concentration and Warfarin’s action is more potent as a result,
In acne rx, an 8week course of doxycyline is give, what is the length of dose for infective COPD exacerbation?
-5-7days
Metronidazole works against what bacteria/protozoa?
-anaerobic
Metronidazole is reduced in anaerobic bacteria which generates a nitroso free radical that binds to DNA -> degradation and death. Suggest 2 indications for it’s use.
- antibiotic associated collitis (caused by gram+ anaerobe c.diff)
- oral infection/abscess or aspiration pneumonia (caused by gram - anaerobes in mouth)
- surgical and gynae infections caused by anaerobes from colon
- protozoal infections e.g. TV, amoebic dysentery and giardiasis
Due to it’s metabolism, people with severe disease of what organ should not be prescribed metronidazole?
- liver
- CYP450 metabolised
It is contraindicated to have what alongside the abx Metronidazole due to SEs of: flushing, headache, N&V (_____-like reaction)
- CI: ALCOHOL
- (disulfiram-like reaction)
Interactions:
Metronidazole increases the risk of toxicity of what medication?
-Lithium
Vancomycin indications, there are 2:
- rx gram + infection if severe or resistant/allergic to penicillins
- rx of antibiotic associated colitis caused by C. diff (2nd line after Met)
Vancomycin has a narrow spectrum vs gram + bacteria, suggest 2
- staphlococcus aureus (and MRSA)
- streptococcus
- C. difficile
Vancomycin inhibits growth and cross-linking of peptidoglycan chains so inhibits what?
-the synthesis of the cell wall of Gram + bacteria (hence lysing and killing the bacteria)
What is the most common adverse effect of vancomycin infusion?
Another adverse effect if infused too rapidly is “___ ___ syndrome” characterised by what?
- most common = thrombophlebitis at infusion site
- Red Man Syndrome = generalised erythema, +/- hypotension, bronchospasm
What 2 organs is Vancomycin toxic to? What effect can Vancomycin have on parameters you’d check in a full blood count?
- nephrotoxic (-> renal failure, interstitial nephritis)
- ototoxic (tinnitus, hearing loss)
- blood: neutropenia, thrombocytopenia
Amikacin (systemic) and neomycin (topical) belong to what class of antibiotics? NB: especially effective against gram negative aerobes
-Aminoglycosides (like gentamicin)
Aminoglycosides are useful against gram + aerobes e.g. P_____ _____
-suggest 3 indications for their use:
- Pseudomonas aeruginosa
- severe sepsis
- intra-abdo sepsis
- pyelonephritis
- endocarditis
- topical for bacterial skin, eye, ear infections
Aminoglycosides bind irreversibly to what in bacterial to inhibit protein synthesis?
-to bacterial ribosomes 30S subunit
Ototoxicity secondary to aminoglycosides is often a later, irreversible complication. However, nephrotoxicity can be noticed earlier and may be reversed. What would make you worried about nephrotoxity?-
- reduced urine output
- rising creatinine and urea
Aminoglycosides are renally excreted. Suggest 3 pt groups you need to be cautious about prescribing these in?
- neonates
- elderly patients
- those with renal impairment
- myasthenia gravis (they impair neuromuscular transmission)
Chloramphenicol is a broad spectrum antibiotic. Drops are used for ______ and otitis___.
- conjunctivitis
- otitis externa
Common adverse effect of chloramphenicol is what sx upon application of drops?
And what can happen if neonates are exposed (unable to metabolise and excrete –> what syndrome?)
- stinging, burning, itching on application
- Grey Baby Syndrome due to circulatory collapse
Penicillin e.g. Benzylpenicillin, phenoxymethylpenicillin
-give 2 indications and state it’s MOA
- rx for streptococcal infection e.g. tonsillitis, pneumonia, endocarditis..
- rx for meningococcal infection
- rx for clostridial infection e.g. gas gangrene
- inhibit enzymes responsible for crosslinking peptidoglycans in bacterial cell walls
What toxicity can occur with v high-dose penicillin therapy or accumulation due to renal impairment?
-Neurological toxicity
Flucloxacillin is a penicillinase-resistant penicillin, suggest 2 indications:
-it has a narrow spectrum of activity against gram … s____
- skin and soft tissue infections e.g. cellulitis
- osteomyelitis & septic arthritis
- endocarditis
- vs. gram + staphylococci
What rare but serious organ toxicity can occur with flucloxacillin therapy/up to 2 months after completion of treatment? Suggest how this may manifest?
-liver toxicity
-e.g. cholestasis, hepatitis
NB: prior fluclox-related hepatotoxicity is a CI to future use
Macrolides e.g. Clarithromycin, erythromycin, azithromycin are often used in place of penicillin if allergy is present. They are useful in what type of infection to cover what? And are used with a PPI and amox/metronidazole in treatment of what?
- in severe pneumonia added to penicillin to cover atypical organisms (e.g. legionella, mycoplasma)
- treatment to eradicate H. pylori
MOA of macrolides (suffix -___)
suffix = omycin
- they inhibit protein synthesis by binding to the 50S ribosome subunit
- here they block translocation so is bacteriostatic/stops growth
Macrolides e.g. erythromycin are irritants.
Given orally can cause –>
Given IV can cause –> ____
orally: nausea, vomiting, abdo pain, diarrhoea
IV: thrombophlebitis
Macrolide e.g. erythromycin SEs:
- in bowel can cause abx-associated ____
- in liver can cause c_____ j___
- can predispose to arrhythmias as _____ the ___
- high doses can be o____
- colitis
- cholestatic jaundice
- prolongs the QT interval
- ototoxic
CI to macrolide use is history of macrolide hypersensitivity
they interact with other medications due to their i____ effect on the CYP enzymes
inhibitors of CYP enzymes
Name 3 medications that prolong the QT interval
hence use with caution co-cominantly as higher risk of arrythmias
- macrolides e.g. erythromycin
- amiodarone
- antipsychotics
- quinine
- quinolone antibiotics
- SSRIs
Broad spec penicillin include amoxicillin and co-amoxiclav
-amox is commonly used for CAP, otitis media, sinusitis and UTIs
-co-amox is commonly used for severe, resistant HAI
What is co-amoxiclav and how is it more effective vs. resistant infections?
-Amoxicillin plus the B-lactamase inhibitor Clavulanic Acid gives the more powerful activity vs. resistant strains
2 bowel SE of broad-spec penicillin like co-amoxiclav include
NB: cholestatic jaundice/hepatitis rarely occurs but resolves on stopping rx
- GI upset: nausea, diarrhoea
- abx-associated colitis
- death of normal flora –> Clostridium difficile
What is the mechanism by which broad spec penicillin e.g. co-amoxiclav enhance the anticoagulant effect of Warfarin?
- they kill normal gut flora that synthesises vitamin K
- less vitamin K, stronger effect of Warfarin
Aciclovir treats and supresses recurrent herpesviridae infections. it inhibits the herpes-specific __ ______ stopping further viral DNA synthesis
DNA Polymerase
Aciclovir SEs: headache, dizziness, GI changes, rash if IV -> phlebitis
-what renal complication is associated with high IV doses, how can you reduce this risk?
- Precipitation in the renal tubules –> crystal induced acute renal failure
- ensure good hydration, slow rate of infusion to reduce risk
What is important to know about aciclovir and pregnancy/breastfeeding?
- it can cross placenta and is expressed in breast milk so use with caution
- but infections e.g. viral encephalitis, varicella pneumonia and genital herpes have signif risks to mother and foetus, benefit often > risk
Aciclovir is excreted by what hence reduce dose to avoid damage when
- kidneys
- reduce dose in renal impairment
IV cephalosporins/carbapenems are reserved for severe/complicated infections/caused by resistant organisms. Their MOA is similar to penicillin. but where are these classes derived from?
- from naturally occurring anti-microbials produced by fungi/bacteria
- inhibits enzymes that cross-link the peptoglycans of cell wall -> swell, lyse, die
If carbapenems are prescribed in high doses/to pts with renal impairment what other organ can be implicated and how may this present?
What condition should you prescribe these meds with caution?
- Neurological toxicity
- Presents w seizure
- renal impairment and Epileptic Patients, be cautious
Cephalosporins/carbapenems share similar structure as Penicillin. Therefore suggest 2 GI possible SEs.
NB: hypersensitivity reactions can occur and cross-reactivity in penicillin allergic pts so CI = severe penicillin allergy
- GI upset: Nausea, diarrhoea
- Abx-associated colitis
- killed gut flora-> overgrowth -> Clostridium Difficile
Carbapenems and valporate, what is the interaction? hence risk of what?
- Carbapenams reduce plasma concentration and efficacy of valproate
- risk of seizure in epileptic pts
Cephalosporins.
- oral e.g. = cef
- IV e.g. = cef
oral = cefalexin
IV = cefotaxime
(tip: lex =relaxed, taxime = taxing)
Carbapenems e.g. meropenem,ertapenem can only be given
IV
Antipseudomonal Penicillin is the mighty combo:
-Piperacillin with Tazobactam (Tazocin)
Antipseudomonal Penicillin is Tazocin, reserved for severe infections, abx resistance/broad-spec of potential organisms likely/immunocompromised pt.
Suggest 3 clinical infections that may be treated with this med?
- lower resp tract infections
- urinary tract infections
- intra-abdominal sepsis
- skin and soft tissue infections
Antipseudomonal Penicillin is Tazocin is made of piperacillin and tazobactam so has the same 3 GI SEs/risks as penicillins, what are these?
- GI upset: Nausea, diarrhoea
- Abx-associated colitis
- killed gut flora-> overgrowth -> Clostridium Difficile
All penicillin reduces the renal excretion of which medication (that is an inhibitor of dihydrofolate reductaseso prevents cellular replication)
so levels can reach toxicity (use w caution)
Methotrexate
Like with other penicillin anti-pseudomonal Tazocin can enhance the ______ effect of ____ by killing normal GI flora that synthesis ______ __
- enhance anticoagulant effect of Warfarin
- vitamin K
Quinolones have what suffix, give 2 examples
-used as 2nd/3rd line agent because of what 2 reasons?
- floxacin
e. g. ciprofloxacin, moxifloxacin, levofloxacin - not 1st line due to: potential for rapid emergence of resistance and association w Clostridium Difficile
Quinolones are not used 1st line due to: potential for rapid emergence of resistance and association w Clostridium Difficile
But suggest 2 clinical infections they are used to treat:
- UTI (mainly gram negative)
- Severe Gastroenteritis (shigella/campylobacter e.g.)
- Lower Resp Tract infection
Ciprofloxacin (a quinolone) is unusual as it has significant activity against p_____ ____
Pseudomonas Aeruginosa
Quinolones kill bacteria by inhibiting DNA synthesis . Bacteria rapidly develop resistance, suggest 2 ways they do this?
- prevent intracellular accumulation by:
- reducing permeability
- increasing efflux
- develop protective mutations in target enzymes
Odd SE of Quinolones:
- 1 neuro
- 1 muscular skeletal
- one cardiac (esp. w moxifloxacin)
- neuro = lowered seizure threshold and risk of hallucinations
- MSK = inflamm and rupture of muscle tendons
- cardiac = prolonged QT interval (arrythmia risk)
Quinolones and cephalosporins are the bs-abx most commonly associated with which GI complication?
-Clostridium Difficile Colitis
Use Quinolones (-floxacin) with caution in those at risk of seizures, children and those w other risks of QT prolongation. Why caution w children?
- they are growing, greater risk of arthropathy
- remember MSK risk - tendon inflammation/rupture
Drugs containing divalent cations reduce absorption + efficacy of Quinolones (-flozacin) suggest 1 such drug
- calcium
- antacids
Ciprofloxacin inhibits certain cp450 enzymes increasing risk of toxicity with some drugs, most notably the respiratory medication t____
Theophylline
Quinolone co-prescription with:
- NSAIDs increases the risk of _____
- _____ increases the risk of tendon rupture
- NSAIDs + quinolones -> greater seizure risk
- Prednisolone + quinolones -> greater tendon rupture risk
Trimethoprim is used for acute and prophylaxis of?
-other uses inc: acne, resp infections and prostatitis
Acute lower urinary tract infection + prophylaxis of recurrent UTI
As a folate antagonist, Trimethoprim can impair haematopoiesis leading to haem disorders such as?
-leucopenia, thrombocytopenia, megaloblastic anaemia
What electrolyte abnormality can trimethoprim use precipitate? Therefore avoid use with other drugs that have same effect.
-can cause hyperkalaemia (and elevation of creatinine)
When is Trimethoprim CI and specifically why?
- 1st trimester pregnancy
- as folate antagonist, is associated with risk of NT defects and cleft lip/palate
Phenytoin has what effect that increases the risk of adverse haematological effects if used with trimethoprim?
-Phenytoin increases folate metabolism
Trimethoprim competitively inhibits creatinine secretion by the renal tubules.
Leads often to a small reversible rise in serum creatinine conc, but no change in eGFR.
-Why is trimethoprim less effective for UTI rx in pts w renal impairment?
-because the increased serum creatinine conc in renal impaired patients competes with trimethoprim for secretion into the urinary tract
Nitrofurantoin is 1st line for acute, uncomplicated lower UTI and prophylaxis of. Is it effective against clinical infections elsewhere in body? Why
- no
- it requires concentration in the urine by renal excretion for therapeutic effect
Nitrofurantoin is active vs most organisms that cause uncomplicated UTIs:
e. g. gram negative: __ ____
e. g. gram positive: staphylococcus s_____
- gram neg = Escherichia Coli
- gram pos = staph saprophyticus
Nitrofurantoin is metabolised in bacterial cells by nitrofuran reductase. its active metabolite damages bacterial DNA -> death. some bacteria have intrinsic resistance to nitrofurantoin e.g. k___ _and p____ species)
-e.g. Klebsiella and Proteus
What visible urine change can Nitrofurantoin have?
-turns it dark yellow/brown
Nitrofurantoin can cause GI upset, delayed hypersensitivity… and rarely
-what effect on lung?
-liver?
-nerves?
NB: all these SEs are more likely w prolonged administration
- chronic pulmonary reactions: inflammatory pneumonitis and fibrosis
- liver: hepatitis
- nerves: peripheral neuropathy
In neonates nitrofurantoin can cause what because immature RBCs can’t mop up superoxides.
Therefore suggest 2 CIs to it’s prescription
- haemolytic anaemia
- CI:
Fungal cell membranes contain ergosterol, triazole antifungals inhibit it’s synthesis. Name such a topical antifungal:
-clotrimazole
Fluconazole common SEs: ___ ____, headache, h____ and h_____ -> rash
-GI upset (N&V, diarrhoea), headache, hepatitis, hypersensitivity
Fluconazole common SEs = -GI upset (N&V, diarrhoea), headache, hepatitis, hypersensitivity
-name 2 rare but possibly fatal SEs
- severe hepatic toxicity (LFTs before and during prolonged rx)
- prolonged QT interval –> arrythmia predisposition
- severe hypersensitivity (cutaneous reactions) or anaphylaxis
What is the one CI to fluconazole prescription?
CI: PREGNANCY (risk of foetal malformation)
FLuconazole is an _____ of the cytochrome p450 enzymes
(therefore will have what effect on carbamazepine, phenytoin, warfarin, diazepam, simvastatin, sulphonylureas… if co-prescribed?)
- Fluconazole is a CYP450 inhibitor
- so the concentrations of the listed medications will increase (risk of toxicity
