Medications Flashcards
Quinolones
Ciprofloxacin
Norfloxacin
Levofloxacin
Pharmacokinetics
Absorption - Good absorption, reduced by co-administration with Ca, Mg, Fe
Distribution - excellent CSF penetration, limited protein binding
Metabolism - Limited metabolism
Excretion - largely unchanged
Pharmacodynamics
Bactericidal via inhibition of DNA-Gyrase (interfering with the coiling of DNA strands)
Significant post-antibiotic effect
ADRs
Decrease seizure threshold
Haemolytic if G6PD
Can increase plasma theophylline levels
Metronidazole
Inhibitors of potent anaerobes and protozoa ie. Clostridium, Bacteroides, Treponema Pallidum, Campylobacter
Pharmacokinetics:
Absorption - 100% oral bioavailability
Distribution - Minimal Protein Binding, wide distribution including CSF, prostate, pleural fluid, cerebral abscess
Metabolism - Metabolised to active compounds by liver
Excretion - Excreted in the urine, half life of active drug unchanged in renal insufficiency due to hepatic clearance being rate limiting
Pharmacodynamics
Unclear. Bactericidal
ADRs
Nausea
Rarely; rash, pancreatitis and peripheral neuropathy
Glycopeptides
eg: Teicoplanin, Vancomycin, (and weird ones like telavancin, bleomycin, ramoplanin, and decaplanin).
- Naturally occurring Compounds (Originally produced in soil based bacteria), active against virtually all gram-positive bacteria
- Large molecular size prevents penetration of the lipid Layer of gram-negative bacteria
Pharmocokinetics
Absorption - Not orally absorbed, so IV route is the only option
Distribution - Variable protein binding
Bone and CSF penetration of Vancomycin is very poor, better with teicoplanin
Metabolism - Not metabolised
Excretion - excreted unchanged, narrow therapeutic range, therefore monitoring of levels is required
Peak governed by the dose, trough governed by the interval.
Pharmacodynamics
This is a glycopeptide synthase inhibitor so glycopeptide can’t be formed in the bacterial walls.
ADRs
Renal - possible toxicity if co-administered with gentamicin
Red man syndrome - histamine release, hypotension, tachycardia, and diffuse rash. Reduce rate of infusion
Rare neutropaenia and thrombocytopaenia
Vancomycin
Glycopeptide synthase inhibitor, particularly for MRSA and orally against C.Diff
Absorption - Parenteral only, ideally infusion in ITU.
Distribution - Variable protein binding
Bone and CSF penetration very poor, better with teicoplanin
Metabolism - Not metabolised
Excretion - excreted unchanged, narrow therapeutic range, therefore monitoring of levels is required
Peak governed by the dose, trough governed by the interval.
Pharmacodynamics
This is a glycopeptide synthase inhibitor so glycopeptide can’t be formed in the bacterial walls.
ADRs
Renal - possible toxicity if co-administered with gentamicin
Red man syndrome - histamine release, hypotension, tachycardia, and diffuse rash. Reduce rate of infusion
Rare neutropaenia and thrombocytopaenia
Teicoplanin
Glycopeptide synthase inhibitor, like vancomycin but longer duration of action and greater potency.
Longer duration of action means can do BD loading doses for 48hrs and then OD. Also means can be given IM
Better bone and CSF penetration than Vancomycin
Absorption - Parenteral only, ideally infusion in ITU.
Distribution - 90% protein binding
Metabolism - Not metabolised
Excretion - excreted unchanged, narrow therapeutic range, therefore monitoring of levels is required
Peak governed by the dose, trough governed by the interval (so increase interval in renal impairment)
Pharmacodynamics
This is a glycopeptide synthase inhibitor so glycopeptide can’t be formed in the bacterial walls.
ADRs
Fewer side effects than vancomycin, particularly less red man syndrome and renal dysfunction.
Renal - possible toxicity if co-administered with gentamicin
Red man syndrome - histamine release, hypotension, tachycardia, and diffuse rash. Reduce rate of infusion
Rare neutropaenia and thrombocytopaenia
Lincosamides
Clindamycin
Semi-synthetic, bacteriostatic agent acting on the 50s ribosomal unit to disrupt protein synthesis. This means it can compete with Macrolides and chloramphenicol for binding sites
Absorption- good oral bioavailability
Distribution - good penetration, particularly bone and joint. CSF penetration very poor,
Metabolism - Hepatic, produces active and inactive metabolites
Excretion - Renal and some biliary. Needs renal adjustment
Pharmacodynamics
Bacteriostatic, bactericidal against some staph/strep
inhibits 50s ribosomal subunit
ADRs
Diarrhoea, C.Diff risk
Fever, rash, eosinophilia, and thrombocytopaenia
Oxazolidinones
Linezolid - a novel protein synthesis inhibitor at the 50s subunit like macrolides, chloramphenicol and clindamycin but doesn’t interact.
Absorption - 100% oral bioavailability
Distribution - limited protein binding, good penetration into all compartments.
Metabolism - Hepatic metabolism to inactive metabolites
Excretion - Urinary excretion of inactive metabolites so doesn’t need dose adjustment. Interestingly, doesn’t need dose adjustment in hepatic failure either!
Can reduce plasma levels with high flux RRT
Pharmacodynamics
50s ribosome subunit bacterial protein synthesis inhibitor
Suppresses bacterial toxin production
ADR
Diarrhoea and nausea in 4%
Thrombocytopaenia, peripheral neuropathy and lactic acidosis reported
Macrolides
Protein synthesis inhibitors originally Erythromycin, then clarithromycin and azithromycin (better absorption, fewer side effects) joined the party.
Useful if penicillin allergy as similar, broader, spectrum of activity.
Unlike penicillin has been shown effective against Legionella pneumophila, mycoplasma, mycobacteria, some rickettsia, and chlamydia.
Pharmacokinetics
Absorption - Good oral bioavailability
Distribution - Good lung, limited CSF, variable protein binding
Metabolism - Primarily hepatic
Excretion - Significant excretion unchanged, so needs dose reduction in renal injury
Pharmacodynamics
Primarily Bacteriostatic Protein synthesis inhibitors, prevent peptidyltransferase from adding the peptide to the next amino acid. Act on the 50s Ribosome.
ADRs
Diarrhoea (prokinetics).
Cardiovascular (prolong QT interval)
CYP 450 so augment theophylline, warfarin and digoxin.
Clarithromycin
Macrolide
Protein synthesis inhibitor, bind to the 50s ribosome
Better strep, listeria and legionella cover than erythromycin
fewer GI side effects
Azithromycin
Macrolide antibiotic
Protein synthesis inhibitor, binds to the 50s subunit
Notably improved bioavailability, longer half life —> once daily dosing
Better gram -ve cover.
Pharmacokinetics
Absorption - Good oral bioavailability
Distribution - Good lung, limited CSF, variable protein binding
Metabolism - Primarily hepatic
Excretion - Significant excretion unchanged, so needs dose reduction in renal injury
Pharmacodynamics
Primarily Bacteriostatic Protein synthesis inhibitors, prevent peptidyltransferase from adding the peptide to the next amino acid. Act on the 50s Ribosome.
ADRs - much better profile than other macrolides (erythromycin)
Diarrhoea (prokinetics).
Cardiovascular (prolong QT interval)
CYP 450 so augment theophylline, warfarin and digoxin.
Carbapenems
Imipenem and Meropenem
The broadest spectrum Beta-lactams
Imipenem
First carbapenem - B-lactam
Broad cover
Absorption: prolonged >3hr infusions
Distribution: wide
Metabolism: Partially metabolised by renal dehydropeptidase; cilastin given concurrently to block the metabolic pathway
Accumulates in renal failure —> dose adjustment
Excretion: unchanged in urine
ADRs
Hepatotoxicity: transaminitis in 5-10%, acute liver failure rarely
Meropenem
Broad cover
No need for cilastrin like imipenem. Better gm-ve cover, worse gm+ve cover
Absorption: prolonged >3hr infusions
Distribution: wide
Metabolism: largely unchanged, Accumulates in renal failure —> dose adjustment
Excretion: unchanged in urine
ADRs
Hepatotoxicity: transaminitis in 5-10%, acute liver failure rarely
Aminoglycosides
Gentamicin, amikacin, (neomycin and tobramycin)
Bind to the ribosomal 30s subunit, blocking protein synthesis. This binding can be irreversible which explains the long post antibiotic effect.
Best when cell membrane weakened by other beta lactams.
WIDE gm -ve cover, limited (staph, some strep) gm +ve cover, no anaerobic cover.
Synergistic with beta lactams and vancomycin
Pharmacokinetics:
Absorption: paerenteral only
Distribution: limited as large polar molecules c low protein binding. Poor intracellular, CSF and Sputum penetration. need active transport to enter cells, so worse in acidosis/hypoxia.
Metabolism: Not metabolised;
Excretion: unchanged in urine. Some is reabsorbed in the proximal tubule and this can cause a Fanconi like syndrome as the large polar molecules clog things up…
Pharmacodynamics:
Bactericidal.
Significant post-antibiotic effect
Single doses with extended interval dosing.
ADRs
Narrow therapeutic range
Ototoxicity related to PEAK plasma concentrations, worse in renal failure and frusemide use.
Can cause ATN
Muscular weakness by reducing the pre-junction release and post junctional sensitivity at NMJs, so avoid in Myasthenia Gravis.
Beta-Lactams
Bactericidal; beta lactam ring binds to and inhibits bacterial transpeptidases, inhibiting cell wall synthesis.
Pharmacokinetics
Absorption - mostly parenteral; Amos/fluclox orally
Distribution - variable protein binding, good penetration but needs inflammation to penetrate CNS/bone.
Metabolism - Excreted mostly unchanged.
Excretion - short half life (yet T>MIC dependent bacteriocidal activity). Best to use infusion. Renal excretion impaired by probenecid which has the effect of prolonging half life of most beta lactams
Dose adjustment required in renal impairment.
Pharmacodynamics
30s subunit of the bacterial ribosome, inhibits cell wall synthesis through inhibition of bacterial transpeptidases
No post antibiotic effect
Synergistic with aminoglycosides (enable penetration)
Guanosine analogues
Anti-viral classes including Acyclovir and Ganciclovir
Activity against HSV, VZV, EBV
Ganciclovir also against CMV
Pharmacokinetics
Absorption - Unpredictable orally, ~25%
Distribution - low protein binding and therefore wide distribution inc CNS.
Metabolism - partial hepatic
Excretion - active tubular excretion; blocked by probenecid. Accumulates in renal failure.
Pharmacodynamics
Acyclovir gets converted by thymidine kinase intracellularly to aciclovir triphosphate which is incorporated into the DNA (in place of deoxyguanosine triphosphate). This —> DNA chain termination.
Thymidine kinase not in CMV infected cells. An alternative viral kinase —> phosphorylation of Ganciclovir in CMV affected cells.
ADR
Extravasation —> thrombophlebitis
If dehydrated, can crystallise in the renal tubules —> renal impairment
Neuro: Tremors, confusion, seizures, coma in accumulation.
Ganciclovir —> bone marrow suppression
Neuraminidase Inhibitors
Oseltamivir, Zanamivir, Peramivir
Sialic acid analogues. Competitively inhibit neuraminidase on cell surface of host cells. Viral neuraminidase is how progeny cells break away to infect further cells. This is stopped, slowing the spread and allowing the immune system to kill the virus.
Pharmacokinetics
Absorption: good oral bioavailability; Zanamivir available as IV preparation.
Distribution: Widely distributed
Metabolism: First pass metabolism converts most osteltamivir to its active metabolite
Excretion: Renally cleared; dose adjustment required
ADRs
Nausea and vomiting
Azoles
initially imidazoles like ketoconazole
Then triazoles like fluconazole, itraconazole
Then gen 2 triazoles like voriconazole
14a methylation inhibitor prevents ergosterol formation, crucial for fungal membrane formation.
Active against Candida, cryptococcus, histoplasma,
Itraconazole, voriconazole active against aspergillus too.
Pharmacokinetics
absorption: good
Distribution: fluconazole; low protein binding and good CNS penetration
All the others are highly protein bound so poor CNS penetration
Metabolism: Hepatic metabolism to inactive compounds
Excretion: Biliary excretion.
Pharmacodynamics
They block a CYP450 process (14a methylation) which disrupts synthesis of ergosterol. This is required for membrane formation. human equivalent isn’t really sensitive.
ADR:
Some impact on CYP450; enhances effect of warfarin
GI irritation
Inhibition of steroid synthesis
Polyene
Amphotericin B - the oldest antifungal, but little resistance. Brutal side effect profile.
Broad spectrum antifungal (extracted from Streptomyces Nodosus)
Effective for Aspergillus, candida, cryptococcus
Resistance is rare
Pharmacokinetics
Absorption: IV only
Distribution: Highly protein bound (limited distribution into CSF)
Metabolism: hepatic to inactive metabolites
Excretion: no adjustment required
Pharmacodynamics
Binds to ergosterol component of fungal cell walls and makes pores.
Fungicidal. Dose dependent (faster at killing at higher doses)
ADRs:
Renal failure in up to 80%!!!
Blood dyscrasias, seizures, hypokalaemia, hypomagnesaemia, hyperchloraemic acidosis.
Nausea, vomiting, muscle pain, chills and rigors.
Echinocandins
Caspofungin, micafungin, anidulofungin - penicillin of antifungals (because they disrupt B-Glucan, which is like peptidoglycan in cell walls).
Broad antifungal, less resistance in candida species than azoles.
inhibit the 1,3/3-D-Glucan synthase enzyme, inhibiting cell wall synthesis. Fungicidal against candida, fungistatic against aspergillus.
Pharmacokinetics
Absorption: IV administration only
Distribution: big molecule, highly protein bound, therefore Limited distribution to eye, CNS< or urine.
Metabolism: not CYP450 dependent so less drug interaction
Caspofungin and anidulofungin degrade spontaneously
Micafungin hepatic ally metabolised
Excretion: no dose adjustment needed
Minimal side effects. GI upset, histamine release, elevated liver enzymes
Quinine
Primarily acts on the eryhtrocytic stage or parasite development where it interferes with the parasite’s ability to digest haemoglobin. Quinine and quinidine also inhibit the spontaneous formation of beta-haematin, a toxic product of breakdown.
Pharmacokinetics: Absorption: 75% oral bioavailability Distribution: widely distributed Metabolism: hepatic transformation to polar molecules Excretion: renal, t0.5 10-12hrs
Side effects:
Long QT
blurred vision
Hypoglycaemia
Eplerenone
- Steroidal antimineralocorticoid; Selective Aldosterone Receptor Antagonist
- (SARA), but more selective than spiro for the mineralocorticoid receptor.
- Reduces cardiovascular risk in patients following MI
Eplerenone is contraindicated in patients with hyperkalaemia, severe renal impairment (creatinine Cl less than 30 ml/min), or severe hepatic impairment (Child-Pugh score C)
No big issues with androgen blocking that spiro has.
half the potency relative to spiro; double the dose required.
Clonidine
Imidazolone compound
acts by stimulating the pre-synaptic alpha 2 adrenoceptors, thereby decreasing noradrenaline release from both central and peripheral sympathetic nerve terminals
