Antibiotics and Antifungals Flashcards
What is the main Indication of Penicillin?
Streptococcal infections
- Tonsilitis
- Pneumonia
- Endocarditis
Meningococcal infections
- Meningitis
- Septicaemia
Clostridial Infections
- Gas Gangrene
List some examples of Penicillins:
- Phenoxymethylpenicillin
- Amoxicillin
- benzylpenicillin
What is the MOA of Penicillin?
- Has Beta-lactam ring which is responsible for their bactericidal activity.
- Inhibit the enzymes responsible for cross-linking peptidoglycan in bacterial cell wall, to then weaken the cell wall, which prevents them from maintaining an osmotic gradient. This leads to uncontrolled entry of water into bacteria causing cell swelling, lysis and death.
What are the side effects of Penicillin?
- allergy
- GI upset
- Colitis
- acute liver injury
Which drug does Penicillin interact with?
Methotrexate- as penicillin reduce the renal excretion of methotrexate meaning there is an increased risk of toxicity.
What is the main indications for prescribing Amoxicillin?
- community acquired pneumonia.
- otitis media
- sinusitis
- UTI
- H. Pylori
What is the MOA of Amoxicillin?
- Has Beta-lactam ring which is responsible for their bactericidal activity.
- Inhibit the enzymes responsible for cross-linking peptidoglycan in bacterial cell wall, to then weaken the cell wall, which prevents them from maintaining an osmotic gradient. This leads to uncontrolled entry of water into bacteria causing cell swelling, lysis and death.
List some of the side effects from using amoxicillin:
- GI upset (nausea/ vomitting)
- colitis (c. difficile)
- Allergy
Which drug does Amoxicillin interact with?
Can kill normal gut flora that synthesise vitamin K meaning that broad-spectrum penicillins can enhance the anticoagulant effect of warfarin.
What is the main indication of Flucloxacillin?
- Staphylococcal infection
- Skin and soft tissue infections e.g. cellulitis
- Osteomyelitis and septic arthritis
- Other infections, including endocarditis
What is the MOA of Flucloxacillin?
- Has Beta-lactam ring which is responsible for their bactericidal activity.
- Inhibit the enzymes responsible for cross-linking peptidoglycan in bacterial cell wall, to then weaken the cell wall, which prevents them from maintaining an osmotic gradient. This leads to uncontrolled entry of water into bacteria causing cell swelling, lysis and death.
- Acyl-side chain protects the beta lactam ring from the beta lactamases (produced by the bacteria to de activate penicillin) which makes it effective from beta lactamase producing staphylococci.
List some side effects of Flucloxacillin:
- GI upset
- Allergy
- Liver toxicity
What are the main indications to prescribe Tetracyclines?
- acne vulgaris
- LRTIs e.g., infective exacerbations of COPD, pneumonia
- Chlamydial infections: PID
- malaria/ lyme disease/ typhoid
Give an example of a tetracycline and its indication:
Doxycycline which is first line for Chlamydia and Pneumonia.
What is the MOA of tetracyclines?
Inhibits protein synthesis by binding onto the 30s subunit of the bacteria’s ribosome which interferes with the addition of amino acids to expanding polypeptide chains.
List some side effects of Tetracyclines:
- GI upset (nausea/ vomiting/ diarrhoea)
- discoloration of teeth enamel
- HTN
- Hepatotoxicity
- ulceration
- Oesophageal irritation
Who is Tetracyclines contraindicated in?
- Pregnancy
- breastfeeding
- <12 years
What 2 drugs do Tetracycline interact with?
- Bind to divalent cations therefore should not be given within 2 hours of calcium, antacids or iron which can prevent antibiotic absorption.
- Can enhance anticoagulant effect of warfarin by killing normal gut bacteria synthesizing Vit K.
What are Macrolides indicated in?
- respiratory, skin and soft tissue infections
- H. Pylori
What is the MOA of Macrolides?
- Inhibit bacterial protein synthesis by binding to the 50s subunit of ribosome which blocks translocation (that is required for the elongation of the polypeptide chain) which in turn will stop bacterial growth.
What are some examples of macrolides?
- Clarithromycin
- Erythromycin (suitable for pregnant women)
What are the common side effects of taking macrolides:
- GI upset
- abdominal pain
- diarrhoea
- Thrombophlebitis when IV
- allergy
- colitis
- ototoxicity
What are the Key interactions of Macrolides?
Erythromycin and clarithromycin (NOT azithromycin) inhibit CYP enzymes which increases plasma concentrations and the risk of adverse effects with drugs metabolized by CYP enzymes e.g. with:
- Warfarin: there is an increased risk of bleeding
- Satins: increased risk of myopathy
Prescribe with caution when taking other drugs that prolong the the QT interval or cause arrhythmias e.g. amiodarone, antipsychotic, quinine, quinolone antibiotics and SSRIs
Give an example of a Fluroquinolone?
Ciprofloxacin
Moxifloxacin
Levofloxacin
What are Fluoroquinolones indicated in?
- Gram negative UTI
- Sever Gastroenteritis (shigella campylobacter)
- LRTIs
- Ciprofloxacin gonorrohea
What is the MOA of Fluroquinolone?
- inhibits DNA synthesis to then kill bacteria.
What are the common side effects of fluoroquinolones?
- GI Upset (nausea/ diarrhoea)
- allergy
- colitis (c. difficile)
- Neurological effects: Lowering of seizure threshold and Hallucinations
- Inflammation and rupture of muscle tendons.
Who are fluoroquinolones contraindicated in?
- those who suffer seizures.
- Children and young adults (potential risk of arthropathy)
- Those with other risk factors for Q-T prolongation (e.g. cardiac disease/electrolyte disturbance)
What other drugs does Fluoroquinolone interact with?
Absorption of fluoroquinolone is reduced by drugs containing divalent cations e.g.,
- Ca
- Antacids
Ciprofloxacin inhibits certain cytochrome P450 enzymes which increases risk of toxicity with drugs like THEOPHYLINE.
Addition of NSAIDs increases risk of seizures.
Addition of PREDNISALONE increases risk of tendon rupture.
Caution in patients taking drugs that prolong the PROLONG THE QT interval or cause arrhythmias e.g.:
- Amiodarone
- Antipsychotics
- Quinine
- Macrolide antibiotics
- SSRIs
What are Cephalosporins indicated in?
- UTI
- Respiratory tract infections
What is the MOA of Cephalosporins?
- Broad spectrum for gram negative (staph and strep)
- has a Beta-lactam ring (bactericidal)
- cephalosporins can bind to penicillin-binding proteins that make up the cell wall structure and inhibit their activity causing a breakdown of cellular infrastructure of bacterium.
- Inhibit the enzymes responsible for cross-linking peptidoglycan in bacterial cell wall, to then weaken the cell wall, which prevents them from maintaining an osmotic gradient. This leads to uncontrolled entry of water into bacteria causing cell swelling, lysis and death.
What are the main side effects of cephalosporins?
- Abdominal pain
- Diarrhoea
- nausea
- colitis (c.difficile)
- allergy
- haemolytic anaemia
- neurological toxicity at high doses
What other drugs does Cephalosporins interact with?
- Can enhance anticoagulant effect of warfarin by killing normal gut flora that synthesize Vit K.
- Can increase nephrotoxicity of aminoglycosides.
What is Trimethoprim used for?
- 1st line for UTI
- acne
- Respiratory tract infections
- Prostatitis
What is the MOA of Trimethoprim?
- Folate antagonist: Inhibits bacterial folate synthesis which slows bacterial growth (bacteriostasis).
- due to resistance, must give a sulfonamide drug in combination for more complete inhibition of folate synthesis.
What are the main side effects of Trimethoprim?
- GI Upset (nausea, diarrhoea)
- sore mouth
- skin rash
- allergy
- hyperkalaemia
- Haematological disorders such as: Megaloblastic anaemia, Leucopenia, Thrombocytopenia
In who is trimethoprim contraindicated in?
- 1st trimester of pregnancy
- folate deficiency (caution)
- caution: neonates, HIV, elderly
What does Trimethoprim interact with?
Using with potassium-elevating drugs (e.g., Aldosterone antagonists, ACEi, ARBs) predisposes to hyperkalaemia.
Risk of adverse haematological effects increased by use with:
- Folate antagonists (e.g. methotrexate)
- Drugs that increase folate metabolism (e.g. phenytoin)
Can enhance the effect of warfarin (by killing normal gut flora that synthesis vitK).
What are the main indications for using Vancomycin:
- gram positive infections: endocarditis
- c. difficile
what is the MOA of Vancomycin:
- Inhibits growth and cross-linking of peptidoglycan chains which inhibits synthesis of cell walls of Gram+ bacteria and then lyses and kills bacteria (bactericidal)
- bind to terminal D-alanyl-D-analnine residues of the NAg and NAM peptides to inhibit transglycosylation causing bactericidal activity.
What are the main side effects of Vancomycin?
- Thrombophlebitis
- allergy
- ototoxicity
- red man syndrome- (erythema, Hypotension, Bronchospasm); this involves mast cell degranulation, but not due to antigen-ab interaction.
Who in Vancomycin contraindicated in?
- Elderly
- Renal impairment
What drug does Vancomycin interact with?
Increases risk of ototoxicity and nephrotoxicity when prescribed with:
- Aminoglycosides
- Loop diuretics
- Ciclosporin (immunosuppressant drug)
What are the main indication for prescribing Metronidazole?
- c. difficile
- oral infection
- aspiration pneumonia
- Trichomonas Vaginalis
What is the MOA of Metronidazole?
- Specific to anaerobic bacteria (because Aerobic cannot reduce the drug) and protozoa.
- enters anaerobic bacteria via passive diffusion where it is reduced to Nitroso free radical that binds to DNA causing reduced protein synthesis which then causes widespread damage, DNA degradation and cell death (bactericidal)
What are the main side effects of Metronidazole?
- GI upset (nausea, vomiting)
- Allergy
- Peripheral and optic neuropathies
- seizures
- Encephalopathy
Who is Metronidazole contraindicated in?
- Reduce dose in pts with severe liver disease, Because it is metabolised by hepatic CYP enzymes
- Alcohol should NOT be drunk as Metronidazole inhibits acetaldehyde dehydrogenase (clears the intermediate alcohol metabolite acetaldehyde from the body)
What drug interacts with Metronidazole:
Has some inhibitory effect on CYP enzymes which:
- reduces metabolism of warfarin, which increases risk of bleeding
- Reduces metabolism of phenytoin which increases risk of toxicity, including impaired cerebellar function
Reverse interaction can occur with CYP inducers (e.g. phenytoin, rifampicin) reduced plasma conc and impaired antimicrobial efficacy
Increases the risk of toxicity with lithium.
What is the main indication of Nitrofurantoin:
- UTI
What is the MOA of Nitrofurantoin:
Metabolised (reduced) in bacterial cells by nitrofuran reductase in which, tts active metabolite damages bacterial DNA to causes cell death (bactericidal).
What are the main side effects of Nitrofurantoin:
- GI Upset (Nausea and diarrhoea)
- Allergy
- Can turn urine dark yellow/ brown.
- in those with Chronic pulmonary reactions can cause hepatitis, peripheral neuropathy.
- in neonates can cause haemolytic anaemia
- alopecia, cyanosis
How would you treat Active Tuberculosis?
RIPE
