Drugs Flashcards
5 major classes of antifungals
Polyenes, Azoles, Pyrimidines, Echinocandins, Allylamines
Which classes of antifungals act on cell membrane?
Polyenes, Azoles, Allylamines
Which class of antifungal act on cell wall?
Echinocandins
Which class of antifungal act on DNA?
Pyrimidines
Mechanism of polyenes
bind to ergosterol –> cell lysis
Polyenes (2)
Amphotericin B, Nystatin
Way of administration of Amphotericin B
IV
Empirical IV antifungal
Amphotericin B
Coverage of Amphotericin B (6)
Candida, Cryptococcus, Aspergillus, Mucoromycetes, Coccidiodes, Histoplasma
Side effects of Amphotericin B (4)
Renal toxicity, fever, n/v, phlebitis
Which antifungal requires close RFT monitoring?
Amphotericin B
Describe the renal toxicity of Amphotericin B (3)
- dose-dependent
- renal wasting of K, Mg, HCO3-
- renal tubular acidosis
Salt of original Amphotericin B
Amphotericin B deoxycholate
What is the formulation to reduce side effects of Amphotericin B?
Liposomal formulation
Nystain usage (way of administration) (3)
- Oral & oesophageal candidiasis (oral swish and swallow)
- Vaginal candidiasis (topical)
- Sclerosing agent (IV)
2 Types of Azoles
Imidazoles, Triazoles
Mechanism of Azoles
inhibit cytochrome-P450 dependent 14-demethylase –> stop conversion from lanosterol to ergosterol
Side effects of Azoles (2)
CYP450 inhibitor, Hepatotoxicity
Which classes of antifungal requires LFT monitoring? (2)
Azoles, Pyrimidines
Which 2 pathogens are intrinsically resistant to Azoles?
Candida glabrata, Candida krusei
Triazole with good CNS penetration and is used for long term treatment of Cryptococcal meningitis
Fluconazole
Antifungal with transient visual change as a common side effect
Voriconazole
Triazole that cover zygomycetes
Posaconazole
Antifungal with haematological suppression as side effect
5-flurocytosine
Antifungal that induces resistance rapidly if given as monotherapy (synergism with?)
5-flurocytosine, synergistic with amphotericin B
Way of administration of 5-Flurocytosine
oral
Echinocandins (3)
Caspofungin, Micafungin, Anidulafungin
卡士普 米卡 安妮杜拉
Way of administration of Echinocandins
IV (daily dose)
Mechanism and coverage (2, effect) of Echinocandins
inhibit 1,3 D-glucan synthase –> inhibit cell wall synthesis
Coverage: Candida (fungicidal), Asperigillus (fungistatic)
Antifungal class that is ineffective in UTI and CNS infections due to questionable penetration
Echinocandins
Allylamines (2)
Terbinafine, Naftifine
Mechanism of Allylamines
inhibit squalene monoxygenase –> inhibit ergosterol synthesis
Antifungals available as OTC nail lacquer
Amorolfine 阿莫羅芬, Ciclopirox
Why liposomal formulations of amphotercin B cannot be made manually?
risk of precipitation, instability
Which 2 non β lactams commonly cause C. difficile colitis?
Quinolones, Clindamycin
Which 3 non β lactams cause renal toxicity?
Glycopeptides, Aminoglycosides, Polymyxins
Which 2 non β lactams cause ototoxicity?
Aminoglycosides, Glycopeptides (rare)
Which non β lactam causes neuromuscular block as a rare side effect?
Aminoglycosides
Which non β lactam cause peripheral neuropathy and optic neuropathy?
Oxazolidinones
Which 2 non β lactams cause CNS toxicity?
Polymyxins, Quinolones (rare)
Which non β lactam causes teeth discoloration, depresses bone growth and thus is contraindicated in children <8y?
Tetracyclines
Which non β lactam causes cartilage injury and is thus contraindicated in children <16y?
Quinolones
Which 2 non β lactams cause thrombocytopenia?
Glycopeptides, Oxazolidinones (prolonged use)
Which non β lactam causes acute haemolytic anaemia?
Co-trimoxazoles
Which non β lactam causes aplastic anaemia, which could be fatal?
Chloramphenicols
Which 3 non β lactams can cross placenta and is thus terotogenic?
Aminoglycosides, Metronidazoles, Chloramphenicols
Which non β lactam causes red man syndrome?
Vancomycin
Which non β lactam cause photosensitivity and SJS?
Co-trimoxazoles
Which 2 non β lactams potentiate effects of Warfarin?
Ofloxacin, Metronidazoles
Side effects of Aminoglycosides (4)
nephrotoxicity, ototoxicity, neuromuscular block, terotogenic
Side effects of Linezolid (3)
thrombocytopenia, peripheral neuropathy, optic neuropathy
Side effects of Tetracyclines (2)
Teeth discoloration, depress bone growth
Side effects of Septrin (3)
Acute haemolytic anaemia, photosensitivity, SJS
Side effects of Vancomycin (4)
nephrotoxicity, ototoxicity (rare), neutropenia & thrombocytopenia, red man syndrome
Which non β lactam causes tendinopathy?
Quinolones
Side effects of Quinolones (6)
GI distress, C. difficile colitis, cartilage injury, tendinopathy, CNS toxicity, arrhythmia
Side effects of Polymyxins (2)
nephrotoxicity, CNS toxicity
Side effects of Chloramphenicals (2)
aplastic anaemia, terotogenic
Side effect of Spectinomycin
discomfort at injection site
Mechanism of Glycopeptide
bind D-ala-D-ala tail –> stop elongation fo peptidoglycan
Usage of vancomycin
[IV] MRSA systemic infection
[oral] C. difficile colitis
Which 2 non β lactam have post-antibiotic effect?
Aminoglycosides, Quinolones
Mechanism of Aminoglycosides
cause misreading of mRNA –> - protein synthesis
Glycopeptides (2)
Vancomycin, Teicoplanin
Aminoglycosides (5)
Streptomycin, Gentamicin, Amikacin, Netilmicin, Neomycin
Which Aminoglycoside is available in topical, eye drops, and oral form?
Neomycin
Which Aminoglycoside has the least ototoxicity?
Netilmicin
Mechanism of Linezolid
inhibit protein sythesis initiation
Usage of Linezolid
MRSA infection in vancomycin failure / allergy
Mechanism of Macrolides
block 50s formation –> block a.a. elongation –> inhibit protein sythesis
Prescription precaution of oral Macrolide
1h before meal or 2h after meal
Macrolides (3)
Erithromycin, Clarithromycin, Azithromycin
Mechanism of Tetracyclines
reversibly binding to 30s –> inhibit protein synthesis
Tetracyclines (2)
Doxycycline, Tigecycline
Septrin full form
Trimethoprim-Sulfamethoxazole
Mechanism of Septrin
inhibit folic acid synthesis
Quinolones (5) (in ascending order of GPB activity)
Ofloxacin < Ciprofloxacin < Levofloxacin < Moxifloxacin < Gemifloxacin
Mechanism of Quinolones
inhibit bacterial DNA synthesis (DNA gyrases, DNA topoisomerases IV)
DDI of Ofloxacin
enhance effect of Warfarin
Mg or Al containing antacids, Fe containing drugs interfere with absorption
Mechanism of Metronidazole
intermediate reacts with DNA
Mechanism of Polymyxins
penetrate into outer cell membrane –>
competitively replace cations —> combine with negatively charged phospholipids —> disrupt cell membrane integrity
Lincosamide (2)
Lincomycin, Clindamycin
Which 5 non β lactams are bacteriostatic instead of bacteriocidal?
Oxazolidinones, Macrolides, Tetracyclines
Spectinomycin, Fusidic acid
Which non β lactam acts on cell wall?
Glycopeptides
Which non β lactam acts on cell membrane?
Polymyxins
Which 3 non β lactams act on DNA?
Co-trimoxazoles, Quinolones, Metronidazoles
Which non β lactams mainly target on GPB? (3)
Glycopeptides, Oxazolidinones, Lincosamides
Which non β lactams mainly target on GNB? (2)
Aminoglycosides, Quinolones
Which non β lactams mainly target on anaerobes?
Metronidazoles
Which non β lactams cover atypical bacteria? (3)
Tetracyclines, Chloramphenicals, Macrolides
Which non β lactam cover intracellular organisms?
Tetracyclines
Usage of Spectinomycin
Nesseria gonorrhoeae infection
Usage of Co-trimoxazoles (2)
Toxoplasma gondii, Pneumocystis jirovecii
Which 2 non β lactams are contraindicated in children?
Tetracyclines, Quinolones
Traditional anti-TB drugs (4)
Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), Ethambutol (E)
Which anti-TB drug causes peripheral neuropathy and vitamin B6 may be co-administered?
Isoniazid
Which ABx causes orange discoloration of urine?
Rifampicin
Which anti-TB drug is a P-450 inducer?
Rifampicin
Mechanism of Rifampicin
inhibit DNA-dependent RNA polymerase
Which anti-TB drug develops resistance rapidly when given as monotherapy?
Rifampicin
Which anti-TB drug causes polyarthralgia?
Pyrazinamide
Which anti-TB drug causes ocular toxicity? Describe
Ethambutol
↓ visual acuity and loss of colour vision
Treatment regimen of active TB
2 month HRZE + 4 month HR
What ABx is used for TB treatment when isoniazid is contraindicated?
Replace isoniazid with levofloxacin
Which ABx are bacteria with VanA gene resistant to?
Glycopeptides
Which ABx are bacteria with mcr-1 gene resistant to?
Polymyxins
(mobilised colistin resistance)
Which ABx are bacteria with gyrA, parC genes resistant to?
Quinolones
Which ABx are bacteria with erm gene resistant to?
Macrolides
Which ABx commonly require TDM? (3)
vancomycin, gentamicin, amikacin…
Which Co-trimoxazole inhibit dihydrofolate reductase?
Trimethoprim
Which Co-trimoxazole inhibit dihydropteroate synthetase?
Sulfamethoxazole
Which ABx are bacteria with rpoB gene resistant to?
Rifampicin
Mechanism of beta-lactams
mimic D-ala-D-ala residues –> transpeptidase binds to penicillin instead of D-ala-D-ala –> inhibit synthesis of peptidoglycan –> inhibit cell wall synthesis
Augmentin full form
Amoxicillin + Clavulanic acid
Tazocin full form
Piperacillin + Tazobactam
Oral form of penicillin
Penicillin V
Oral form of Aminopenicillins
Amoxicillin
Which beta lactam requires co-administration of weekly vitamin K?
Cefoperazone + Sulbactam
Which type of adverse drug reaction does allergy belong to?
Type B
Risk factors for penicillin allergy (4)
- frequent, repeated course of penicillin
- parenteral administration
- hereditary factors
- Hx of SJS, toxic epidermal necrolysis, drug hypersensitivity syndrome
Test to determine whether the patient has antibiotic allergy and procedure
Graded challenge:
- stop pre-treated with anti-histamines / glucocorticoids
- starting dose = 1/4 or 1/10 of full dose –> observe for 30~60 mins
- proceed to full dose –> observe for another 30~60 mins
Indication for desensitization test (2)
definite / suspected history of Type I allergy, and alternative ABx not available
Which beta lactam does not need renal adjustment as most of it is not excreted via urine? (Via what?)
Ceftriaxone (bile)
Example of synergism & antagonism of antiotics with penicillin
Synergism: Aminoglycosides (enable entry of drugs)
Antagonism: Bacteriostatic agents (inhibit bacteriocidal effect of beta-lactams)
Time-dependent killing v.s. Concentration-dependent killing
Time-dependent: ↑ frequency of dose –> ↑ killing (e.g. β-lactams)
Concentration-dependent: ↑ dosage –> ↑ killing (e.g. Aminoglycosides)
What is post-antibiotic effect?
persistent suppression after ABx exposure, even when concentration < min inhibitory concentration (MIC)
Calculation of post-antibiotic effect
PAE = T - C
(T = time of regrowth by 1 log of organisms after ABx removal)
(C = time for growth in control by 1 log)
Trough level v.s. Peak level in ABx TDM
Trough level: correspond to toxicity (adjusted by frequency)
Peak level: correspond to clinical outcomes (adjusted by dosage)
Which gene does MRSA belong making it resistant to penicillin? (Effect)
mecA (modification of penicillin-binding protein)
4 resistance mechanisms against beta-lactams
- Permeability barrier
- Efflux pump
- Modification of penicillin-binding protein
- β-lactamase
3 types of β-lactamases & Treatment
- ESBL (Carbapenem)
- AmpC β-lactamase (4th GC)
- Carbapenemase (?)
Which type of β-lactamase does New Delhi Metallo-beta-lactamase belong to?
Carbapenemase
How do bacteria acquire resistance gene? (3)
Transformation (from environment)
Conjugation (via pilus)
Transduction (via bacteriophage)
Types of vaccines (4+2)
Live attenuated, Inactivated, Subunit, Toxoid
mRNA, vector
Toxoid vaccines (2)
Tetanus, Diphtheria
Subunit vaccines (3)
HBV, HPV, acellular Pertussis
Inactivated vaccines (3+4)
Pneumoccocus, Hib, Meningococcus ACYW
HAV, Polio (IM), Rabies, Influenza (injected)
Order the immunogenicity of the 3 MC vaccine types by descending order
Live attenuated > Inactivated > Subunit
Example of vector used for vector vaccines
Adenovirus
Vaccine adverse reactions: common (3+1) & rare (2)
Common:
- discomfort at injection site, fever, malaise
- anaphylaxis
Rare:
- GBS
- reversion to virulence
Can pregnency get vaccination? (live attenuated, inactivated)
Live attenuated: ⨉
Inactivated: ok
3 types of aims of vaccination programme
eradication, elimination, containment
HK Childhood immunization programme: details
BCG: 0
HBV: 0,1,6
DTaP-IPV: 2,4,6,18,P1,P6
PCV13: 2,4,12
MMRV: 12,18
HPV [for girls only]: P5,P6
What is DTaP-IPV?
Diphtheria, Tetanus, acellular Pertussis & Inactivated Poliovirus vaccine
Which vaccine is patients with renal failure on dialysis suggested to take?
HBV
What vaccines should patients with BM transplant take?
all childhood vaccination
What type of vaccine is Sinovac?
Inactivated
What type of vaccine is BioNtech? What is its mechanism?
mRNA
mRNA encoding spike protein –> induce human cells to make spike protein
Side effects of Amantadine, Rimantadine
insomnia, drowsiness
Which influenza drug is intranasal?
Zanamivir
Which influenza drug is available for patients >12y only?
Baloxavir
Mechanism of anti-herpesviridae drugs
DNA polymerase inhibitor –> chain termination of DNA synthesis
Why acyclovir has a good safety profile?
require 3-time phosphorylation to be activated, with first step being viral thymidine kinase
Number of dosage of acyclovir per day
5
Antiviral for CMV
Ganciclovir
Side effects for virus-specific immunoglobulin (3)
HSR, blood-borne pathogens, IC formation
Antiviral for genital warts / genital herpes resistant to acyclovir
Imiquimod (Aldara)
Antibiotics prophylaxis for different surgical wounds
Clean: not required except
- Neurosurgery: Ceftrixone
- Knee implant: Cefazolin
Clean-contaminated: Cefazolin
Contaminated: Cefuroxine + Metronidazole
Dirty: case-by-case
When should surgical prophylaxis be given? After how much time should dosing be repeated? What surgery requires addition (for how long)?
30~60mins before incision, single dose IV
2x half life of the drug
Cardiothoracic surgery (72 hours after surgery)
Post-exposure prophylaxis for influenza A
Oseltamivir
Post-exposure prophylaxis to HIV
(Tenofovir + Emtricitabine) + Raltegravir
Example of dual NRTI drugs for HIV
Tenofovir + Emtricitabine
Example of integrase strand-transfer inhibitor for HIV
Raltegravir
2 anti-herpesviridae drugs with higher oral availability
Valaciclovir, Famiciclovir
How to prevent red man syndrome caused by vancomycin?
slow infusion
Which antibiotic is used in the susceptibility test for MRSA?
cefoxitin
What is the D test for antibiotic susceptibility? (which ABx used and what does it test for?)
erythromycin + clindamycin
clindamycin-resistant Staphylococci
Special susceptibility tests for ESBL (2)
keyhole effect + double disk synergy test
Resistance mechanism towards quinolone
Single point mutation
At quinolone resistant determining region (QRDR) (e.g. gyrA, parC)
Resistance mechanism to polymyxin
mcr1 gene mutation —> modify lipid A of LPS with pEtN (phospho-ethanolamine) —> neutralise overall negative charges —> positively charged polymyxin cannot bind to LPS
Resistance metabolism to septrin
Mutation in synthase gene —> decrease permeability and increase efflux
Advantages and disadvantages of live attenuated vaccine (2+2)
Highly immunogenic, long lasting
Risk of reversion to virulence, require cold temperature to maintain viability
Which penicillin gives rash as side effects?
Amoxicllin / Ampicillin