Semester 1 Public Drugs Flashcards
SALVARSAN
- First chemotherapy drug to treat Syphilis.
- Discovered by Paul Ehrlich whilst looking for a cure for sleeping sickness.
- Mixture of a trimer and pentamer structures that contain ARSENIC.
- High arsenic content made the drug highly toxic.
- A PRODRUG which is oxidised to oxophenarsine.
- Oxophenarsine reacts with thiol grops in proteins - targets bacteria due to the fact they replicate their cells quicker than humans.
NEOSALVARSAN
- A sulphur group added to salvarsan in order to make the drug more soluble and therefore less toxic.
TETRACYLCINES
- Integrated - Doxycycline for Malaria Prophylaxis
- Integrated - Minocycline for Neisseria meningtidis
These bind directly to the ribosome to inhibit protein synthesis. Binding so that elongation factor TU is unable to bring the next amino acid to the ribosome.
These are both semi-synthetic tetracyclines.
ContraIndicated in children because it stains tooth enamel.
Resistance to Tetracyclines
is membrane associate, but mutations in the S10 can also give rise to resistance
AMINOGLYCOSIDES
- Gentamicin
- Streptomycin
- TOBRAMYCIN
Very hydrophilic so are given IV because they cannot cross the gut wall.
Narrow Therapeutic Index - Nephrotoxicity
Work by binding to the 30S ribosomal subunit. Binding so that the A site is inhibited and the genetic code is misread.
Good for gram negative - which is usually more difficult to treat.
Tobramycin - for the treatment of Pseudomonas aeruginosa infections. Inhaled.
This aminoglycoside also binds to the 50S as well as the 30S, preventing them from combining.
LINEZOLID (oxazolidinone)
Inhibits the INITIATION stage, and prevents the 50S and the 30S subunit from binding together.
Active against MRSA - drug is kept back to fight hospital acquired infections.
MACROLIDES
- erythromycin
2nd Gen
- Azithromycin
- Clarithromycin
blocks the 50S subunit
gram positive bacteria
azithromycin & clarithromycin are much more hydrophobic and therefore ore stable in the stomach than erythromycin
Side Effects of Macrolides
Generally, not very well tolerated
- Gut Motile Agonists (sickness/diarrhoea) - can give azithromycin instead
- Taste not masked easily - esterify the drug to make a prodrug, so that it is taste free and can be hydrolysed in the blood. THIS MEANS THAT THE MEDICINE WILL THEN HAVE TO STAY IN THE FRIDGE OR IT MAY BE HYDROLYSED IN THE BOTTLE. Erythromycin hydrolyses within 10 mins.
- Metabolised by Cytochrome P450 3A4
CHLORAMPHENICOL
Gram Positive or Negative
Formulated as EYE DROPS
CLINDAMYCIN/LINCOMYCIN
bind to the same place as macrolides - 50S subunit
Clindamycin is used for
- ANAEROBIC INFECTIONS of soft tissue
- AEROBIC INFECTIONS of the resp tract
TOXIC SHOCK SYNDROME - alongside vancomycin
PROTOZOAL INFECTIONS - alongside chloroquinine/quinine
FUSIDIC ACID
Gram Negative Infections
Given as eye drops - or a gel for conjunctivitis
Binds to elongation factor G to stall protein synthesis
B Lactam Ring Containing Antibiotics include:
Penicillins
Cephalosporins
Carbapenems
They work by targeting the transpeptidase and the carboxypeptidase enzymes
Penicillin G
Only to be administered IV because it is acid labile
Sensitive to B Lactamases produced by bacteria
Ampicillin (Penicillin)
Semisynthetic
Able to take orally, not as acid labile
Sensitive to B Lactamases produced by bacteria
Amoxicillin (Penicillin)
Semisynthetic
Resistant to Class 1 of B Lactamases produced by bacteria
Taste Masked - good for children
- Chlamydia trachomitis
- Non gonococcal urethritis
Methicillin/Flucloxacillin (Penicillin)
Resistant to all B Lactamses produced by bacteria
Not readily taste masked
Cephalosporins
1st Gen - BARELY USED
2nd Gen - gram negative activity, problems with resistance showing
3rd Gen - good gram negative activity, good for serious illnesses and can be injected (Ceftriaxone)
Carbapenems
Broad Spec Antibiotics and resistant to MOST B Lactamses produced by bacteria
Its the reserve antibiotic
VANCOMYICN
Works by pushing apart the peptidoglycan chains so that they cannot be cross-linked.
Serious Gram Positive Infections - but doesn’t cross the gut wall.
MSRA
Clostridium difficile
Teicoplanin works in a similar way to vancomycin
SULFONILAMIDES
Gram positive cocci (pneumococci/meningococci)
TRIMETHOPRIM
Resembles a part of the pteridine structure (what bacteria make the tetrahydrofolate from)
Blocks the bacterial dihydrofolate reductase - has higher affinity for it than the human one
Used for UTIs
Can be used in combination with other sufonilamides (co-trimoxazole - sulphamethoxazole)
Pyrimethamine
- a dihydrofolate reductase inhibitor
- is an antimalarial - chlorophenyl ring makes it too hydrophobic to be able to cross bacterial walls
Methotrexate
- a dihydrofolate reductase inhibitor in HUMANS, inactive against bacteria because they don’t have AA transporters
- glutamate on the group enables it to be actively transported by amino acid transporters
- similar in structure to folic acid means that it will also be taken up into cells
- Anticancer Agent
- Rheumatoid Arthritis
- IBD - an immunomodulator (also be supplemented with folic acid). Given instead of Azathioprine for maintenance treatment in CD . Given as an IM injection.
- Terminate pregnancy
Drug Interaction - interacts with Penicillin, penicillin blocks methotrexate’s elimination
QUINOLONES
MOA: blocks subunit A of DNA Gyrase that usually supercoils DNA into bacterial cells
1st Gen - 3rd Gen, starts off just gram negative but then activity against gram positive improves
2nd Generation Quinolones - Fluoroquinolones, including Ciprofloxaicin
- for respiratory tract infections BUT NOT pneumococcal pneumonia
- interactions - CYP450 1A2
3rd Generation Quionolones - Levofloxacin
- Broad Spectrum
- Active against Strep (gram positive)
DNA Strand Breakers
MOA: highly reactive molecules that attack DNA strand breakers and produce radicals that cause cleavage of the sugar phosphate backbone of DNA.
Nitrofurantoin
- Narrow Spectrum
- UTIs
Metronidazole
- Can’t drink alcohol
- H pylori
- C difficile (400mg TDS for 7 - 10 days)
Antivirals for Influenza
Zanamivir / Oseltamivir
- Transition state inhibitors that target the neuraminidase proteins on the virus
- Targeting Neuraminidase - only slowing the progression of the disease whilst trying to find some antibodies for the Haemagluttinin proteins
Treatment for Chlamydia Trachomitis
- Azithromycin 1g as a single dose
- Doxycycline 100mg BD for 7 days
- Erythromycin 500mg BD for 14 days
Treatment for Gonococcal Urethritis
- Ceftriaxone IM and Azithromycin PO
- Cefixime PO and Azithromycin PO
(Cephalosporin and Macrolide)
Treatment for Non Gonococcal Urethritis
- Treat as for Chalmydia
- Azithromycin 1g as a single dose
- Doxycycline 100mg BD for 7 days
- Erythromycin 500mg BD for 14 days
Treatment for Bacterial Vaginosis
Overgrowth of anaerobic organisms rather than the lactobacilli that usually maintains the pH of the vagina
Metronidazole BD for 7 days (DNA Strand Breaker)
Clindamycin BD for 7 days
Treatment for Trichmoniasis
a PROTOZOAL infection
Metronidazole 2g as a single dose
Metronidazole 400mg BD for 7 days
Aciclovir
for the treatment of genital herpes
MOA: replaces the normal substrate for DNA synthesis
- purine analogue
- inhibits DNA polymerase
- higher affinity for viral kinases rather than cellular kinases
Side Effects: Nausea Diarrhoea Headache Tremor Delirium
Treatment for Syphillis
Penicillin G
Doxycycline 100mg BD for 14 days
Amphotericin B
a POLEYNE anti-fungal
- binds to ergosterol in the cell membrane of fungi
- forms pores
- Oral Infections
- IV systemic Infections
- Toxic to the kidneys
Nystatin
a POLEYEN anti-fungal
- binds to ergosterol in the cell membrane
- Candida albicans infections of the skin
Azole Fungals
Fluconazole
Inhibits the CYP450 14alphademethylase enzyme, which stops the conversion of squalene to ergosterol
- Good oral absorption
- Cryptococcal meningitis
- Severe oral/oesophageal candidiasis
