DRUGS Flashcards
1
Q
Polyenes (older)
A
- Example: conventional Amphotericin B
- Mechanism: Binds to sterols in cell membrane = increase membrane permeability and forms pores. Also has effects on inhibiting oxidation
- Not affected by hepatic or renal failure
- Poor penetration thru BBB
- Spectrum: broad with low resistance
- due to toxicity not often used. Still used
- for invasive candidiasis, cryptococcal meningitis in HIV and empiric therapy in selected cases
-
ADRs:
- Nephrotoxicity - up to 80% (HSCT pts greatest risk)
- Infusion reaction (fevers, chills, rigors, hypotension)
2
Q
Flucytosine MOA
A
- converted by cytosine deaminase to 5-fluorouracil, which inhibits thymidylate synthase and disrupts fungal protein synthesis.
3
Q
Capsofungin MOA
A
- Caspofungin inhibits synthesis of beta-glucan, a major fungal cell wall component.
4
Q
Azoles MOA
A
- Example: Azole, fluconazole, posaconazole (best for zygomycosis), voriconazole (first line for invasive aspergillus)
- Spectrum - Broad: inc Aspergillus
- Mech: Inhibit C-14alpha demethylase which is required synthesis of ergosterol in fungal cell membranes –> breakdown. Then cell leakage and death occur by lytic activity of the host defence system.
- Contra/precaution: Peripheral neuropathy may worsen
- *ADRs**: Rash, HA, dizziness, GIT, hepatic derrangement, P450 inhibition
- Rare:
- thrombocytopenia (voriconazole), other blood dyscrasias
- Hepatotoxicity (30% with vori)
- Allergy
- Alopecia (prolonged courses)
- Peripheral neuropathy (prolonged courses)
- SCC in lung transplant recipients
- Voriconazole 30% visual changes - dose related, reversible
5
Q
Terbinafine MOA
A
- Inhibits squalene epoxidase
6
Q
Griseofulvin MOA
A
- interacts with microtubules to disrupt mitotic spindle.
7
Q
Trimethoprim
A
- interferes with DNA synthesis by inhibiting dihydrofolate reductase may interact with methotrexate, which also inhibits dihydrofolate reductase
- AE: myelosuppression, transient rise in creatinine via competitively inhibits the tubular secretion of creatinine resulting in a temporary increase which reverses upon stopping the drug. HyperK
- Avoid in pregnancy
8
Q
Primaquine
A
- used in non-falciparum malaria to destroy liver hypnozoites and prevent relapse.
- Should not be given to people with glucose-6- phosphate dehydrogenase (G6PD) deficiency due to the risk of haemolysis.
9
Q
Vancomycin
A
- MoA: inhibits cell wall formation by binding to D-Ala-D-Ala moieties, preventing polymerization of peptidoglycans
- Mechanism of resistance: alteration to the terminal amino acid residues of the NAM/NAG-peptide subunits (normally D-alanyl-D-alanine) to which the antibiotic binds
- Adverse effects: nephrotoxicity ototoxicity thrombophlebitis red man syndrome; occurs on rapid infusion of vancomycin
10
Q
Aminoglycosides
A
- Example: Gentamycin, Amikacin, Streptomycin
- Spectrum: Primarily Gram negative, gentamicin has pseudomonal cover
- Mech: irreversibly bind 30S ribosomal subunit = inhibit protein synthesis + damage cell membrane Concentration dependent bactericidal
- Contra: neuromuscular disease (myasthenia gravis), PHx vestibular/auditory toxicity
- Precaution: renal/elderly/preg
- ADRs: Renal, ototoxicity, neuromuscular blockade - inc resp depression Rx with Ca gluconate. Includes permanent deafness esp in DNA A1555G mutation
11
Q
Voriconazole
A
- High cover spectrum
- Fluconazole resistant Candida
- Moulds
- Aspergillus spp (esp terreus)
- Fusarium
- Scedosporium apiospermum
12
Q
Fluconazole
A
- Treatment of candidaemia in non-neutropenic patients who are haeomdynamically stable
- Sensitive Canidida
13
Q
Itraconazole
A
- Broader spectrum -> yeasts and moulds
- Oral bioavailablity
- new formulaiton - suba-itraconzaole (pH polymeric matrix)
- Oral - signififcant GI side effects
- Drug-drug interactions
- Uses
- alt prophylaxis post allogenic HSCT
- Sequential therapy for IA (rarely with the advent of other azoles
- Alt 2nd or 3rd line agent for Scedosporium
- Alt for treatment of Dermatophytes
14
Q
Carbapenems
A
- Example: Ertapenem, imipenem, meropenem
- Spectrum = BROAD: gram positive, negative, anaerobes, ESBLs, pseudomonas. No MRSA activity
- Mech: inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins
- Usually bactericidal
- Contra: avoid Rx with valproate (lowers Val)
-
ADRs: GIT, headache, C diff, anaphylaxis
- Imipenem: neurotoxicity
- Ertapenem: neurotoxicity inc seizures
- Stenotrophomonas maltophilia - intrinsically resistant and can be opportunistic infection with prolonged Rx
- Note Ertapenem does not have anti-pseudomonal activity
15
Q
Tetracyclines
A
Example: Tetracycline, Doxycycline
- Mech: reversibly binding to 30S ribosome subunit - inhibits bacterial protein synthesis
- Bacteriostatic
- Contra/Precaution: SLE (may worsen), contraindicated with oral retinoids (increased risk of BIH), children (discolour teeth, reduce bone growth)
- Safe in first 18 weeks of pregnancy
- ADRs: GIT, tooth discolouration, reduced bone growth in kids <8, photosensitivity
- Rare ADRs: photo-onycholysis/nail discolouration, oesophageal ulcers, C. diff, hepatitis/fatty liver, benign intracranial hypertension, allergy, TEN, worsening of SLE, serum sickness-like reactions
16
Q
Mechanisms of Resistance
- Penicillins
- Aminoglycosides
- Chloramphenicol
- Tetracyclines
- Sulphonamides
- Vancomycin
A
20
Q
Mechanisms of Antibiotic Resistance
A
21
Q
Mechanisms of Antibiotic Resistance
A
22
Q
Mechanism of Vancomycin Resistance
A
23
Q
Palivizumab
A
24
Q
Ribavirin adverse effects
(used in Hep C)
A
