- Eg Gentamicin
- Used mainly against Gram negative enteric bacteria, sepsis, TB
- Not effective against anaerobes cos needs O2 dependent transport into cytoplasm.
- Water soluble, don’t go into CNS or eye
- Partial diffusion, partly active transport into the cell–> bind to 30S ribosome–> intefere with initiation of complex peptide formation, misreading of mRNA, breakup of polysomes into monosomes.
- Poorly orally absorbed so usually given IV, t1/2 – 2-3hrs
- Renally cleared
- Once daily dosing – more effective due to concentration dependent killing, significant postantibiotic effect(actio persists beyond time when measurable drug is present). Less time in the toxic levels. More convenient – better compliance, less nursing required, can be done as outpatient.
- Narrow therapeutic index
- SE – ototoxicity, nephrotoxicity(especially if Rx for more than 5d, elderly, renal imp, higher doses). Resp paralysis via NMJ blockade at very high doses – reversed with calcium gluconate.
- Increases effect of neuromuscular blocking agents
- Eg sulfamethoxazole
- Structure is similar to PABA
- Inteferes with folate production and therfore DNA synthesis (doesn’t affect mammal cells cos we get exogenous folate)
- Bacteriostatic alone, bacteriocidal with trimethoprim.
- Cover gram positive and negative, norcadia, chlamydia, and some protozoa.
- Synergistic when used with trimethoprim cos that acts at the sequential step of folate synthesis.
- SE -fever, rash, exfoliative dermatitis, photosensitivity, nausea, vomiting, diarrhoea, stevens johnson syndrome. Can crystalise in urine –> haematuria or obstruction. Haemolysis, granulocytopenia, thrombocytopenia.
- Interferes with folate synthesis by inhibiting dihydrofolic acid reductase
- Eg ciprofloxacin, moxifloxacin
- Block bacterial DNA synthesis by inhibiting topoisomerase II(DNA gyrase) and IV.
- Cover gram positive and negative, pseudomonas
- Oral Bioavail – 80-95%, t1/2 – 3-10hrs, renally excreted
- SE – nausea, vomiting, diarrhoea, QT prolongation. Not for use in under 18yo due to damage to growing cartilage.
- Inhibits nucleic acid synthesis in anaerobes
- Good for anaerobes and protozoa esp c diff
- SE – nausea, diarrhoea, abdo pain, metalic taste, hypersensitivity, disulfram effect if taken with etOH.
- TB treatment needs multiple drugs and good compliance for at least 6mo. Isoniazid, rifampin, pyrazinamide, ethambutol. (RIPE)
- – amphotericin B – puts hole in lipid membranes of cells – toxic to humans in high levels.
- Azoles – ketaconazole etc – inhibit fungal > human cytochrome P450 so less cell wall is made.
Nystatin – like ampotericin – for local candida infections
(Same with antimalarials and antihelminthics)
Aciclovir (has been asked).
- Acyclic guanosine dervative
- HSV 1 and HSV 2 >>>>VZV, In genital herpes it shortens symptom duration by 2d and viral shedding by 7d
- 3 step activation, the first step requires viral thymidine kinase – so specific–> third step product inhibits viral DNA polymerase –> inhibits viral DNA synthesis
- Oral bioavail – 15-20%, T 1/2 – 2-3hrs, renally cleared.
- Long term suppression of recurrent genital herpes, IV for herpes encephalitis.
- Weak against cmv
- Nucleoside reverse transcriptase inhibitor
- Used in HIV/AIDS
Principles of HIV therapy
- Start treatment if CD4 count <200 or viraemia high or opportunistic infection
- Use Highly active antiretroviral therapy – multiple agents to avoid resistance.
- Nucleotide reverse transcriptase inhibitor
- Competitively inhibit HIV 1 reverse transcriptase
- Eg lamivudine – cytosine analog when incorporated it results in premature termination of DNA chain.
- Zidovudine is another example – deoxythymidine analog. Hepatic glucuronidation. Renally excreted.
- The first antiretroviral agent.
- Reduces disease progression and prolongs survival. Reduces vertical transmission.
- Non nucleoside reverse transcriptase inhibitors
- Bind directly to HIV1 reverse transcriptase to inhibit it.
- Resistance develops quickly in monotherapy.
- Delavirdine etc
- Protease inhibitor
- Resulting in immature, noninfectious viral particles
- Darunavir etc.
- Entry inhibitor
- Intefere with virus binding and entering cell via gp120
- Enfurvitide, maraviroc
- Integrase inhibitor
- Inhibits transfer of the reverse transcribed HIV DNA into chromosomes of host cells.
- Eg Raltegravir
- M2 proton pump inhibitor and inhibition of uncoating of viral RNA
- Amantadine- increase dopaminergic function, SE -acute psychosis
Disinfection vs. sterilisation (MCQ).
- Disinfection means killing microbes but does not mean all microbes
- Sterilisation is a process of killing all life forms present on a surface – done with heat, chemicals, irradiation, high pressure, filtration or a combination of the above
- Tell me about anti-TB therapy
- Inhibits bacterial DNA dependent RNA polymerase
- Tell me about the treatment of Malaria
- Plasmopodium falciparum
- Doxycycline(or clindamycin) + quinine
- Plasma podium vivax / ovale
- Hydroxychloroquine + primaquine
- P Malariae
- Plasmopodium falciparum
- Tell me about the principles of HIV treatment