Aminoglycosides

Eg Gentamicin
bacteriocidal
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

Sulfonamides.

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.

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
“nitromidazole”
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)

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

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 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