Antimicrobial agents Flashcards
Broadly list the antibacterial classes
- inhibit cell wall synthesis: beta lactam and glycopeptides
- protein synthesis inhibition: aminoglycosides, macrolides, tetracyclines, lincosamindes
- NA inhibitors
- DNA synthesis i - binds and inhibits DNA gyrase: nitroimidazoles, quinolones
- RNA synthesis inhibitors: rifamycin
- folic acid synthesis
- DHPS - trimethoprim and sulfamethoxazole
- DHFR - trimethoprim
Describe peniciloins
All penicillins bind to PBPs, as they are structually similar to DAla DAla, leading to inactivation of PBPs preventing peptide cross links between peptidoglycan
- - benzylpenicillin: narrow, Strep and enterococcus facealus > syphilis, L mono, N meningitidis
- flucloxaxcillin: S aureus esp methicilin sensitive
- amoxicillin.ampicinni: like benzyl, but also some G neg eg E coli and H influenzae
Describe penicillin with beta lactamase inhibitor
All penicillins bind to PBPs, as they are structually similar to DAla DAla, leading to inactivation of PBPs preventing peptide cross links between peptidoglycan
- - amox and clavulanate - broad, like amox (Strep, Entero> syph, L mono,) but with more G (E coli, H influ), below diaphragm anaerobes, S aureus
- Piper and tazo - very broad, as above but with P aeruginosa, restricted in order to prevent resistance
Describe cephalosporin
All penicillins bind to PBPs, as they are structually similar to DAla DAla, leading to inactivation of PBPs preventing peptide cross links between peptidoglycan
eVEN broader than penicilllins
not affectes by beta lactamases
- cephalexin and cefazolin: Most strep and staph, not as god strep cover as penicillins, some G neg eg E coli and Klebsiella, NO anaerobes, L mono, Enterococcus, poor CSF - not good for meningitis
- 2nd gen not generally used, cefuroxine, used for resp conditions due to strep, haemophil and moraxella cover
- ceftriaxone: more G neg, good Srep, less Staph v 1st gen, NO listeria, enteroccocus, anaerobes - same as 1st gen
- cefepine: most bacteial orgs including resisant gram negs – restricted to hospiral to treat resistant and prevent emergence of resisiance
Describe glycopeptides
- Bind DAla DAla residue preveting PBP access, preventing peptide crosslinks
- G pos only
- vancomycin and telcoplanin
- last resort against resistant gram pos – MRSA
- covers most pos
- IV in hospital
- narrow TI: nephrotoxic – needs TDM
Describe the protein synthesis inhibitors
Describe the quinolones and nitroimidazoles
Describe RNA and folic acid synthesis inhibitors
Describe the antihelminthics
Broadly describe antivirals
Antivirals
General information:
- viruses use host cell machinery and enzymes for replication
- Need to consider risk of host cell damage when using antiviral agents
- Viruses have high intrinsic rates of mutations (RNA viruses more than DNA viruses)
- Effectiveness of antiviral agents for common acute viral infections limited to within first few days of onset
Describe treatment of infleunxa
There are really only 2 mechanisms that used to kill influenza viruses
1. Neuroaminidase inhibition (stops release of new virus particles)
2. Blockade of the M2 ion channel (stops the virus incoating)
- amantadine, block M2 channel thus provents uncoating, not commly used with hgih resistance risk and Influ A only
- zanamivir, inhaled, Influ A and B, prevent neuraminidase preventing release, use for severe flu or high risk
- oseltamivir, orall, A and B, also in severe high risk or prophylaxis, similar MOa
Describe SARS COV 2 and herpes treatment
Herpes
Cell mediated immunity is important for preventing reactivation.
Resistance is uncommon and occurs in an individual on therapy (rather than from person to person spread)
- Herpes Simplex Virus 1 & 2 (HSV): Treated with nucleoside analogues
- Varicella zoster virus (VZV): Treated with nucleoside analogues
- Cytomegalovirus (CMV): Treated with nucleoside analogues
- Epstein Barr and other HSV - not treated with antivirals
Treatment is still emerging and up to date information is released regularly. Treatment is generally based on severity of disease and risk factors. For those interested the guidelines and flow charts can be found here.
SARS-CoV-2 is treated with various drug classes depending on the disease including antivirals (remdesivir, nirmatrelvir, molnupiravir), corticosteroids, immunmodulators (JAK inhibitor and IL-6 inhibitors).
Describe HIV moa and treamtne
HIV
Mechanisms of action:
Nucleoside analogues resemble cellular nucleosides and therefore terminate DNA synthesis. Although they must enter the human cell (to reach the virus) they are only used by the virus (not the human cell).
Following phosphorylation by viral and cellular enzymes, guanine analogues inhibit viral DNA polymerase and DNA synthesis.
Side effects:
nausea, vomiting, diarrhoea, headache,confusion, hallucinations (high dose), headache,dizziness, rash,hepatitis, neutropenia and bone marrow supression
Need to have a combination of at least 3 anti-retroviral drugsfrom at least 2 different classes(targeting a different parts of viral replication).
Need for early treatment with multiple antivirals- Highly Active Anti-Retroviral Therapy (HAART) for maximal viral suppression and reduce resistance
Treatment initiation
Common regimes for treatment initiation:
- 2 x NRTI PLUS integrase inhibitor OR
- 2 x NRTI PLUSNNRTI OR
- 2 x NRTI PLUS protease inhibitor
Initiation should be only be
- done by a HIV specialist
- on an individual case basis
- initiated as soon as possible in all HIV infected patients (regardless of CD4 count) to minimise morbidity and mortality and to prevent transmission.
Treatment considerations
- many drugs come in combination with other classes for compliance enhancement (1 tablet containing 3 drugs)
- most anti-retroviral agents have multiple drug interactions which need to be considered and the link below should be used
HIV aims of treatment
are very wide ranging and include:
- reduce morbidity and mortality of HIV
- improve QOL
- restore and preserve immunological function
- maximises and prolong viral load suppression
- prevent HIV transmission
note also : nucleoside and non nucleoside RTIs, protease and integrase inhibitors, fusion inhibitors, CCR5 inhbitors
Describe hepaitis treatment
Hepatitis
taken from [[The liver]]
Hepatitis B treatment
- Aim is prolonged suppression of viral replication - preferably undetectable HBV-DNA. Ultimately HBsAg seroconversion is the goal, but infrequently achievable.
- two main drug classes used to treat hepatitis B include: interferon (rarely prescribed due to compliance) and nucleoside/nucleotide analogues
#### Nucleoside analogues
Nucleoside analogues (entecavir) and nucleotide analogues (tenofovir) - mainstay of Hep B treatment
- Entecavir: Guanosine analogue inhibiting hepatitis B polymerase preventing viral DNA synthesis
- Tenofovir: inhibits viral polymerases and terminates the DNA chain after incorporation into viral DNA
- easy oral administration
- Well tolerated and high barrier to resistance
- Often required life-long
Interferon
(peginterferon alfa-2a) - not commonly used in practice
- Not recommended in cirrhosis due to risk of hepatitis exacerbation and hepatic decompensation
- Weekly injection and more side effects than oral therapy
- No drug resistance
- Defined treatment duration (48 weeks)
- Antiviral and immunomodulator activity
Hepatitis C
- To achieve a sustained virologic response (SVR), ie. virus undetectable 12weeks after finishing treatment; this indicates treatment success (cure)
- The newinterferon-free antiviral regimens use combinations of direct-acting antiviral drugs.
- cure rate >95%
- highly effective and well tolerated
- significant drug interactions. Drug interactions are particularly relevant for patients receiving concomitant treatment for HIV. Always take a detailed medication history, including non-prescribed medications, to check for interactions.
**### **Targets of direct acting antivirals for Hepatitis C
- Protease Inhibitors (…previr)
- A virus-specific proteaseconverts polyproteins into various structural and functional proteins.
- The protease does not occur in the host, and isuseful target for therapy
- Nucleotide (NS5B) polymerase inhibitor (…buvir)
- Non-nucleotide (NS5B) polymerase inhibitor (…buvir)
- NS5A inhibitors (asvir)
List the types of antifungals
- azoles: imidazoles and triazoles
- allylamines
- polyenes
- echinocandins
Describe the imidazoles
Describe the allylamines
Describe the polyenes
Describe the echinocandins
