Antimicrobial Agents Flashcards
What are some of the ideal characteristics of an Antimicrobial Agent
- Selective toxicity against microbial target
- Minimal toxicity to host
- Kills micro-organisms
- Long plasma half-life
- Good tissue distribution
- Low binding to plasma proteins
- Oral and parental preparations
- No adverse interactions with other drugs
Name some mechanisms that antibiotics use to kill microbes
- Inhibition of cell wall synthesis
- Inhibition of protein synthesis
- Inhibition of nucleic acid synthesis
- Inhibition of folate synthesis
- Disruption of the cytoplasmic membrane
What can microbes do to develop and show a resistance to antimicrobial agents
- Production of enzymes
- Alteration in the outer membrane permeability
- Alteration of target sites
- Efflux pumps
- Alteration of metabolic pathways
Name some types of enzymes that can be produced to show resistance to antimicrobial agents
- Beta-lactamases
- Aminoglycoside - modifying enzymes
- Chloramphenicol acetyl transferase
What problems arise from human use of antibacterials
- Adverse side effects
- Drug interactions
- Rising rate of resistance
- Few organisms have become virtually untreatable
- Superinfection - candida albicans and C.Diff
What are the main features of the chemical structure of the penicillin family of drugs
- Acyl side chain
- Beta lactam ring
- Thiazolidine ring
What are the 6 groups drugs in penicillin family
- Benzylpenicillin
- Orally absorbed penicillin
- Anti-staphylococcal penicillin
- Extended spectrum penicillin
- Antipseudomonal penicillin
- B-lactamase resistant penicillins
Give an example of an orally absorbed penicillin
Penicillin V
Give an example of an anti-staphylococcal penicillin
Flucloxacillin
Give an example of an extended spectrum penicillin
Amoxicillin
Give an example of an anti-pseudomonal penicillin
Ticracillin
What is the mechanism of penicillins
Inhibiting cell wall synthesis by binding to penicillin binding proteins and inhibiting transpeptidation of peptidoglycan
How do microbes show resistance to penicillins
Resistance by beta-lactamases, failure to penetrate the outer membrane of gram negative bacteria, efflux and low affinity binding of antibacterial to target PBP
What are the potential side effects of drugs in the penicillin family
- Allergic reaction like anaphylactic reaction or delayed hypersensitivity
- GI problems like diarrhoea and enterocolitis
- Renal - interstitial nephritis or haemorrhagic cystitis
- CNS - encephalopathy or seizures - rare and occurs with renal failure or high prolonged doses
Name a beta lactamase inhibitor that can be administered with penicillins
Clavulanic acid
Describe the structure of cephalosporins
Beta lactam ring
Six membered Dihydrothiazine ring but modified at certain positions to produce different compounds
When are cephalosporins used in place of penicillins
When the patient is allergic to penicillins there is a low chance that they are also allergic to cephalosporins
Give examples of macrolides
Erythromycin, Clarithromycin and Azithromycin
What does bacteriostatic mean
Prevents the growth of bacteria
How do microbes show resistance to macrolides
- They decrease their outer membrane permeability
- efflux
- alteration in rRNA
- enzymatic inactivation by phosphotransferases
Are macrolides bacteriocidal or bacteriostatic
Bacteriostatic
What is the general mechanism of macrolides
They inhibit RNA dependent protein synthesis (50S ribosomes)
What are the potential side effects of Macrolides
- GIT symptoms
- Skin rash
- fever
- eosinophilia
- cholestatic jaundice
- transient hearing loss
- potential for increase effect of warfarin because it inhibits its metabolism and clearance
What is the spectrum of activity for macrolides
- Gram positive bacteria
- Mycoplasma
- Legionella
- Chlamydia
AY BAWS CAN I HABE DE NOTE PLZ
Macrolides can be used as an alternative to penicillin in penicillin-allergic patients
Give an example of Lincosamide
Clindamycin
Describe the general mechanism of Lincosamides
Inhibits RNA-dependent protein synthesis (50S)
How do microbes show resistance to Lincosamides
- Decrease outer membrane permeability
- Alteration in rRNA
- Alteration in 50S ribosomal proteins of the receptor sites
- Enzymatic inactivation by transferase
What is the spectrum of activity for Lincosamides
Gram positive and anaerobic bacteria
What are some side effects
- C. Diff colitis
- Allergic reaction
- Transient hepatitis
- Neutopenia
- Thrombocytopenia
Give some examples of Tetracyclines
- Tetracycline
- Chlortetracycline
- Oxytetracycline
- Doxycycline
- Tigecycline
What is the mode of action of Tetracyclines
- Inhibits bacterial protein synthesis (30S)
Are tetracyclines bacteriocidal or bacteriostatic
bacteriostatic
What is the spectrum of activity for tetracyclines
- Broad spectrum for gram positive
- Gram negative
- Intracellular organisms
How can microbes show resistance to tetracyclines
- Efflux
- Ribosomal protection protein
- Enzymatic inactivation
What are the potential side effects of Tetracyclines
- GIT symptoms
- Photosensitivity
- Pigmentation (skin, nail and sclera)
- Deposition in growing bone and teeth
- Hepatotoxicity
- Exacerbate renal impairment
- Superinfection
- Allergy
What is the general mechanism of Nitroimidazoles (metronidazole)
DNA synthesis inhibitor that interacts with nucleic acids and proteins causing breakage, destabilisation and cell death
What is the spectrum of activity for nitroimidazoles (metronidazole)
- Anaerobic
- Facultative anaerobic bacteria
- Protozoa
What are the potential side effects of Nitroimidazoles (metronidazole)
- Metallic taste
- GIT symptoms
- Peripheral neuropathy
- Disulfiram-like reaction with alcohol
- Allergic reaction
- Genitourinary
- Increase effect of warfarin
What are the effects of a disulfiram like reaction
Nausea Vomiting Flushing Tachycardia Hypotension Confusion Psychosis Sudden death
What are polyenes
Antifungal ting
Name some examples of polyenes
Amphotericin (IV)
Nystatin (PO)
What do polyenes interact with and what effect does this have on fungal cells
- Interacts with ergosterol and forms a transmembrane ion channel
- Increases membrane permeability, leakage of cell contents and cell death
How are polyenes able to show a selective action on the fungi
As the main sterol in the human cells is cholesterol and not ergosterol
How is Nystatin (polyene) administered and why
Only used topically on the skin and mucous membrane, does not get absorbed from the GI tract
What are some potential side effects of amphotericin
Anaphylaxis Nephrotoxicity GIT upset Muscle and joint pain Anaemia Cardiovascular toxicity
How can resistance be shown to polyenes
Intrinsic resistance like in dermatophytes, acquired resistance is rare
What are the 2 categories of Azole
Imidazoles
Tiazoles
What are some types of Imidazoles
- Ketoconazole
- Miconazole*
- Clotimazole
What are some types of tiazoles
- Itraconazole
- Fluconazole
- Voriconazole
- Posaconazole
- Ravuconazole
What is the general mechanism of azoles
They inhibit the synthesis of ergosterol
When should imidazoles not be used
In patients with hepatic impairment, pregnancy or breast feeding
ketoconazole is associated with fatal hepatotoxicity
What side affects and adjustments need to be made when administering Fluconazole
- Fluconazole can cause abnormal Liver Function Test (LFT)
- Fluconazole dose needs to be reduced in renal impairment
What azole is candida krusei resistant to
Fluconazole
What targets in viruses are there for antiviral agents to attack
- Attachment
- Viral entry
- Viral uncoating
- Nucleic acid synthesis
- Assemble and release of viral particle (protease and neuraminidase inhibitors)
What viruses is Aciclovir effective against
- Herpes Simplex Virus (HSV)
- Vesicular Stomatitis Virus (VSV)
What are the side effects of Aciclovir
- Skin irritation when used topically
- High dose IV can cause nephrotoxicity
- GIT disturbance
- Confusion and hallucinations
Describe the mechanism of Aciclovir
- Aciclovir = analogue of guanosine
- Phosphorylated by the thymidine kinase enzyme of HSV and VZV
- Becomes trapped in the infected cell
- Two further phosphate groups are added so becomes triphosphate by cellular kinase
- Triphosphate compound is a potent and selective inhibitor of HSV DNA polymerase
- DNA chain termination
