Y10. Pharmacopeia: Antimicrobials

---

PAST QUESTIONS – T02. Anti-Microbial Drugs (Click to Open)

---

CICMWrecks Tables (Click to Open)

MASTER TABLES	Level 1 Antibiotics
	Level 3 Antibiotics
	Antivirals and Antifungals (Level 3)
	Antiseptics and Disinfectants (Level 3)
INDIVIDUAL TABLES	Ceftriaxone
	Piperacillin – Tazobactam
	Benpen | Fluclox | Amp (Limited)
	Ceftriaxone | Meropenem (Limited)
	Amp | Gent | Vanc | Cipro (Limited)
	Benpen | Metro | Clinda (Limited)
	Benpen | Fluconazole (Limited)
	Vancomycin | Flucloxacillin
	Ciprofloxacin
	Vancomycin
	Piperacillin-Tazobactam | Ciprofloxacin
	Fluconazole | Amphotericin

---

MASTER TABLES

---

LEVEL 1 ANTIBIOTICS

Pharmacopeia - Level 1 Antibiotics

	AMPICILLIN	FLUCLOXACILLIN	BENZYL PENICILLIN	AMOXICILLIN - CLAVULANIC ACID	PIPERACILLIN	TAZOBACTAM	PIPERACILLIN -TAZOBACTAM	CEPHALEXIN	CEFAZOLIN	CEFTRIAXONE	CEFOTAXIME	CEFEPIME	MEROPENEM	VANCOMYCIN	GENTAMICIN	CIPROFLOXACIN	MOXIFLOXACIN	METRONIDAZOLE
GROUP	ANTIBIOTIC: PENICILLIN	ANTIBIOTIC: PENICILLIN	ANTIBIOTIC: PENICILLIN	ANTIBIOTIC: PENICILLIN	ANTIBIOTIC: PENICILLIN	ANTIBIOTIC: BETA LACTAMASE INHIBITOR	ANTIBIOTIC: PENICILLIN	ANTIBIOTIC: CEPHALOSPORIN	ANTIBIOTIC: CEPHALOSPORIN	ANTIBIOTIC: CEPHALOSPORIN	ANTIBIOTIC: CEPHALOSPORIN	ANTIBIOTIC: CEPHALOSPORIN	ANTIBIOTIC: CARBAPENEM	ANTIBIOTIC: GLYCOPEPTIDE	ANTIBIOTIC: AMINOGLYCOSIDE	ANTIBIOTIC: QUINOLONE	ANTIBIOTIC: QUINOLONE	ANTIBIOTIC: NITROIMIDAZOLE
CICM Level of Understanding	Level 1	Level 1	Level 1	Level 1	Level 1	Level 3	Level 1	Level 1	Level 1	Level 1	Level 1	Level 1	Level 1	Level 1	Level 1	Level 3	Level 3	Level 3
INTRODUCTION	Betalactam	Narrow spectrum, semisynthetic anti-staphylococcal penicillin	Narrow spectrum naturally occurring penicillin	Extended spectrum aminopenicillin	Piperacillin is a penicillin antibiotic combined with tazobactam to treat piperacillin-resistant, piperacillin/tazobactam¬ susceptible, β-lactamase generating strains of several bacteria.	Tazobactam is a beta lactamase inhibitor administered with antibiotics such as piperacillin and ceftolozane to prevent their degradation, resulting in increased efficacy.	Antipseudomonal penicillin	1st Generation Cephalosporin	1st Generation Cephalosporin	3rd Generation Cephalosporin	3rd Generation Cephalosporin	4th generation Cephalosporin	Carbapenem (contain a fused beta-lactam & a -5-member ring system that differs from penicillins because it is unsaturated and contains a carbon instead of a sulphur atom)	Tricyclic glycopeptide antibiotic produced by streptococcus orientalis	Aminoglycoside	Quinolone	Quinolone	Nitroimidazole
USES		useful for treating staphlococci which are resistant to benpen due to beta-lactamase activity . It is well absorbed from the gut but is given IV if the infection is serious. It should not be used if the organism is sensitive to benpen as benpen is more bacteriocidal.			Piperacillin is used in the treatment of: 1. urinary and respiratory tract infections 2. intra-abdominal and biliary tract sepsis 3. gynaecological and obstetric infections 4. infections of skin, soft tissue, bone, and joints 5. septicaemia 6. meningitis and for 7. perioperative prophylaxis.	When combined with other antibiotics, a variety of infections, including serious and life-threatening infections may be treated	used to treat a variety of infections, including those caused by aerobic and facultative gram-positive and gram-negative bacteria, in addition to gram-positive and gram-negative anaerobes. E.g: cellulitis, diabetic foot infections, appendicitis, and postpartum endometritis infections.			used for the treatment of infections caused by susceptible Gram-positive and Gram-negative bacteria, including infections of the abdomen, bones and joints, CNS, skin and skin structures, genito-urinary tract (including gonorrhoea), respiratory tract, gynaecological infections, Lyme disease.			broader spectrum of action than other beta lactams used in serious infections only Unlike other carbapenems Meropenems do not require coadministration with cilastatin because it is not degraded by renal dipeptidase	It possesses a broad spectrum of activity against gram positive bacteria including MRSA. Acts synergistically with aminoglycosides, cephalosporins and rifampicin (although synergy testing required as vancomycin + cephalosporin may act antagonistically against some strains of staph epidermis)	aminoglycoside of choice because of its lower cost and reliable activity against GNB. It is often used in combination with a beta lactam antibiotic for serious but uncultured infections. They also have limited gram positive coverage including staph and some strep
PHARMACEUTICS (PC)		PO/IV. Tablet/Powder for reconstitution			In vials containing 1/2 g and infusion bottles containing 4 g of piperacillin sodium. A fixed-dose combination with tazobactam is also available. The adult intravenous dose is 4 g 6 to 8 hourly (each gram should be infused over 3–5 minutes), and the intramuscular dose 2 g 6 to 8 hourly.	In vials with Piperacillin (500mg/4g Piperacillin or 250mg/2g) or ceftolozane Tazobactam shows little antibacterial activity by itself, and for this reason, is generally not administered alone		Capsules 250, 500mg Powder for oral suspension	White/pale yellow powder for injection	White powder for IV- yellowish solution. Can precipitate with Ca2+ containing solutions	Powder for IV injection. Does NOT precipitate in calcium containing solutions	Powder for reconstitution and IV injection (pale white –yellow)	IV: White crystals for reconstitution- 500mg or 1gm. Very expensive	Store at 2-8 degrees, clear solution. Slowly due to vessel irritation (& risk of red man syndrome). Monitoring required to avoid toxic levels (aiming serum conc 15+/-3).	clear solution for injection. Requires monitoring of levels especially if there is any renal impairment, to prevent complications	PO and IV, topical eye drops and ointment	PO and IV
PC: Chemical					A semi-synthetic penicillin.	penicillanic acid sulfone derivative
PC: Presentation
PHARMACODYNAMICS (PD)
PD: Main Action					Bactericidal broad-spectrum antibiotic that is effective against many beta-lactamase-producing organisms.	Tazobactam broadens the spectrum of piperacillin and ceftolozane by making them effective against organisms that express beta-lactamase and would normally degrade them.
PD: Mode of Action	Contains a beta lactam ring structure. Betalactam antibiotics inhibit the growth of sensitive bacteria by inactivating transpeptidase enzymes located in the bacterial cell membrane, inhibiting crosslinkage of peptidoglycans and thus impairing cell wall synthesis	Beta lactam ring binds to penicillin binding protein (transpeptidase) and prevents crosslinking of bacterial peptidoglycan inhibits cell wall synthesis Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested Less bactericidal but stable to staph beta-lactamases	β lactam antibiotic Binds to penicillin binding protein (transpeptidase) and prevents crosslinking of bacterial peptidoglycan impairs cell wall synthesis	β lactam antibiotic Binds to penicillin binding protein (transpeptidase) and prevents crosslinking of bacterial peptidoglycan impairs cell wall synthesis	Piperacillin binds to cell wall PBPs and inhibits their activity It affects • PBP 1A/B which are involved in the crosslinking of cell wall peptidoglycans • PBP 2 which is involved in the maintenance of the rod shape PBP 3 which is involved in septal synthesis.	Irreversible inhibition of beta-lactamase enzymes. In addition, tazobactam may bind covalently to plasmid-mediated and chromosome-mediated beta-lactamase enzymes.	β lactam antibiotic Binds to penicillin binding protein (transpeptidase) and prevents crosslinking of bacterial peptidoglycan impairs cell wall synthesis	Beta lactam ring binds to multiple penicillin binding proteins (carboxy/endo/ transpeptidase) and prevents crosslinking of bacterial peptidoglycan inhibits cell wall synthesis BROADER SPECTRUM Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested Configuration: Stability against Betalactamases	Beta lactam ring binds to multiple penicillin binding proteins (carboxy/endo/ transpeptidase) and prevents crosslinking of bacterial peptidoglycan inhibits cell wall synthesis BROADER SPECTRUM Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested Configuration: Stability against Betalactamases	Beta lactam ring binds to multiple penicillin binding proteins (carboxy/endo/ transpeptidase) and prevents crosslinking of bacterial peptidoglycan inhibits cell wall synthesis BROADER SPECTRUM Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested Configuration: Stability against Betalactamases	Beta lactam ring binds to multiple penicillin binding proteins (carboxy/endo/ transpeptidase) and prevents crosslinking of bacterial peptidoglycan inhibits cell wall synthesis BROADER SPECTRUM Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested Configuration: Stability against Betalactamases	Beta lactam ring binds to multiple penicillin binding proteins (carboxy/endo/ transpeptidase) and prevents crosslinking of bacterial peptidoglycan inhibits cell wall synthesis BROADER SPECTRUM Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested Configuration: Stability against Betalactamases	Binds to several penicillin binding protein and prevents crosslinking of bacterial peptidoglycan inhibits cell wall synthesis BROADEST SPECTRUM Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested Configuration: Stability against Betalactamases and ESBLs	Inhibits Glycopeptide synthetase  prevents peptidoglycan formation in bacterial cell well (Unlike penicillins, prevents the transfer and addition of the muramylpentapeptide building blocks that make up the peptidoglycan molecule itself.) May also alter membrane permeability and selectively inhibit RNA synthesis. Antimicrobial activity Dependent on Duration above MIC, not concentration	bactericidal Binds to the bacterial 30S ribosomal subunit to inhibit protein synthesis and thus bacterial growth	Bacteriocidal antimicrobials that block DNA replication by blocking tropoisomerase enzymes, which are essential for the supercoiling, replication and separation of circular bacterial DNA	Bacteriocidal antimicrobials that block DNA replication by blocking tropoisomerase enzymes, which are essential for the supercoiling, replication and separation of circular bacterial DNA	Converted to active form or nitroso free radical by obligate anaerobes. Inhibits DNA synthesis. Causes DNA degradation
PD: Route & Doses
PD: Metrics (Onset/ Peak/ Duration)								250-500mg QID (BD for UTI)	1-2g q 8hr	1g daily (2g BD for meningitis)	1-2g q8hr	1-2g q8hr
PD: Effects					Metabolic/other Piperacillin has a lower sodium content than other disodium penicillins and causes less fluid and electrolyte derangements; serum potassium levels may decrease after the administration of the drug.
PD: Spectrum of Activity	Moderate spectrum Semisynthetic Can penetrate some gram negative outer membranes, but susceptible to betalactamases. Often given with clauvanic acid Targets Strep, Listeria, Enterococcus, Haemophilus	narrow spectrum but is useful for treating staphlococci which are resistant to benpen due to beta-lactamase activity It should not be used if the organism is sensitive to benpen as benpen is more bactericidal	Narrow-Spectrum Natural Penicillin Highly bactericidal, only gram positives/anaerobes, susceptible to betalactamases Targets GPC: Streptococci, Meningococcus Listeria (GPB) GNC: Neisseria, Clostridia Treponemma (Spiral) Synergistic effects with aminoglycosides	Gram +ve and some gram –ve cover - Covers strep and enterococcus - Variety of gram –ves including enterobacter, haemophilus, H. pylori Covers listeria	In vitro, it shows activity against the Gram-negative organisms Escherichia coli, Haemophilus influenzae, and Klebsiella, Neisseria, Proteus, Shigella, and Serratia spp.; anaerobes, including Bacteroides and Clostridium spp.; and the Gram-positive enterococci Staphylococcus, and Streptococcus spp. It is particularly effective against Pseudomonas, indole-positive Proteus, Streptococcus faecalis, and Serratia marcescens.	Tazobactam is predominantly effective against the OHIO-1, SHV-1, and TEM groups of beta-lactamases, but may also inhibit other beta-lactamases.	Pseudomonas Beta-lactamase producing bacteria Gram negatives Anaerobes	Bacteriocidal Active against: - Most GPC (not MRSA, enterococcus, staph epidermidis) - Some E. Coli, Klebsiella, Proteus - Oral anaerobes (Except B. Fragilis)	Bacteriocidal Active against: - Most GPC (not MRSA, enterococcus, staph epidermidis) - Some E. Coli, Klebsiella, Proteus - Oral anaerobes (Except B. Fragilis)	Bacteriocidal Active against: - GP cocci (including pen resistant pneumococcus), sensitive staph - Extended G-ve cover (aerobes)- enterobacter resistance is rapid - Inferior anaerobe cover compared to second generation * ESCAPPMs can induce resistance so treatment failures can occur	Bacteriocidal Active against: same as ceftriaxone Not Active against: same as ceftriaxone	Bacteriocidal Active against: - Same as ceftriaxone (GPC + gram negatives) - More activity against Enterbacter and other ESCAPPMs and pseudomonas	v.broad spectrum, gram positive, gram negative (incl pseudomonal) and anaerobic coverage (resistant to beta lactamases and cephalosporinases)	active against most gram positive bacteria (including staphlycocci, streptococci, enterococci, listeria monocytogenes, clostridium sp, and Bacillus sp.), with limited gram negative activity.	provide good gram negative coverage and some gram positive most often used against enteric infections and in sepsis usually used in combination with a beta lactam	Broad spectrum Active against both gram positive and gram negative bacteria particularly effective against GNB (E.Coli, H.influenza, Klebsiella, Legionella, Moraxella, Proteus, and Pseudomonas) Less effective against Gram-positive bacteria (such as MSSA, Strep pneumoniae, and Enterococcus faecalis) than newer fluoroquinolones	1. Gram positives - Better strep pneumonia cover 2. Gram negatives - Including salmonella, Neisseria, pseudomonas, E. Coli 3. Anaerobes - Modest including B. Fragilis 4. Atypicals Legionella, mycoplasma, Rickettsia, Chlamydia	Active against anaerobes (including clostridium, N.Gonorrhoea, N.Menigitidis, Bacterioides and Fusobacterium) and protozoa (trichomonas, Giardia)
PD: Resistance Mechanism	Bacteria produce beta lactamases, which hydrolyse and inactivate the antibiotic Resistance MRSA Many Staph -Betalactamase prod	MRSA develop or acquire the gene mecA which synthesizes an additional penicillin binding protein that enables it to continue cell wall synthesis in the presence of a beta lactam drug	Resistance MRSA Many Staph -Betalactamase prod Gram Negatives				Certain gram-negative bacilli infections with beta-lactamase producing organisms cannot be treated with piperacillin-tazobactam, due to a gene mutation conferring antibiotic resistance			cephalosporinases hydrolyse β-lactam rings. PBP modification. Enterobacter: Change in porins – Impermeable.			Carbapenemases Metallobetalactamases (Sternotrophomonas) Efflux pumps. Pseudomonas: Change PBP, diminish permeability thru porin modification	VanA resistance – gene mutation leading to decreased affinity of peptidoglycan precursors for vancomycin. Induced by exposure to vanc / teicoplanin Van B resistance – similar but only induced by vancomycin; strains may remain susceptible to teicoplanin	Alteration in access to target site – membrane impermeability / transport defect in the active transport. Lack of O2-transport channels: Anaerobes Multiple enzymes which block gentamicin (acetytransferases, adenyltransferases, phosphotransferases)	Alteration in target enzyme – changes to the DNA binding surface of DNA supergyrase infers resistance Alteration in drug entry – altered expression of outer membrane porin proteins that form channels for passive diffusion of ciprofloxacin Increase in efflux of drug – expression of nonspecific energy dependent efflux pumps which remove drug	Alteration in target enzyme – changes to the DNA binding surface of DNA supergyrase infers resistance Alteration in drug entry – altered expression of outer membrane porin proteins that form channels for passive diffusion of moxifloxacin Increase in efflux of drug – expression of nonspecific energy dependent efflux pumps which remove drug	reduced rate of uptake, by efflux or by reducing the rate of metronidazole reductive activation increased DNA repair efficiency
PD: Side Effects / Toxicity		Up to 10% of the population have allergies to penicillins. Due to the high percentage excreted renally unchanged dose adjustment is required in low urine output states. Severe cholestatic hepatitis has been reported idiosyncratically.	GIT– abdominal pain, N/V/D, pseudomembranous colitis, hepatitis HAEM- agranulocytosis CNS- confusion, seizure, encephalopathy HYPERSENSITIVITY- rash, anaphylaxis	1. Cholestatic jaundice 2. Hypersensitivity 3. Maculopapular rash 4. Increased risk of C Dif Interstitial nephritis	• Gastrointestinal upsets • abnormalities of liver function tests • allergic reactions • transient leucopenia and neutropenia Deterioration in renal function has been reported in patients with pre-existent severe renal impairment	• Nausea, vomiting, and diarrhea are frequent manifestations of an overdose. • Neuromuscular excitability or seizures may also occur with high intravenous doses or renal failure. There is no specific antidote • Anaphylaxis Nephrotoxicity	1. Hypokalaemia (lower sodium concentration so hypernatraemia less likely) 2. Piptaz + vancomycin associated with increased AKI 3. LFT derangement Neutropenia	Generally well tolerated Hypersensitivity reactions (10% cross reactivity with penicillin allergies), thrombophlebitis, interstitial nephritis, low prothrombin, flushing and headaches with EtOH.	Generally well tolerated Hypersensitivity reactions (10% cross reactivity with penicillin allergies), thrombophlebitis, interstitial nephritis, low prothrombin, flushing and headaches with EtOH.	highly protein bound and is able to displace bilirubin from albumin binding sites, causing bilirubin; should be avoided in jaundiced neonates. Pseudolithiasis or Biliary sludge due to a precipitate of Calcium-ceftriaxone seen occasionally.	Generally well tolerated Hypersensitivity reactions (10% cross reactivity with penicillin allergies), thrombophlebitis, interstitial nephritis, low prothrombin, flushing and headaches with EtOH. Third generation cephalosporins are particularly associated with antibiotic associated colitis.	Generally well tolerated Hypersensitivity reactions (10% cross reactivity with penicillin allergies), thrombophlebitis, interstitial nephritis, low prothrombin, flushing and headaches with EtOH.	May cause injection site irritation. May cause seizures similar to Benpen but only in susceptible patients. Caution in renal patients due to large amount excreted unchanged. Should not be used concurrenly with probenecid. Can cause confusion	Hypersensitivity reactions including anaphylaxis. Rapid infusion is associated with histamine release - red-man syndrome. Ototoxicity rare, dose related. Nephrotoxicity has declined with improved formulations, usually resolves with cessation of drug	ototoxicity nephrotoxicity (worse with loop diuretics or pre-existing renal disease) pre-jn Ach release   post-jn sensitivity to Ach NMBD activity can cause paralysis. May cause C.Diff.	1. CNS Toxicity- GABA antagonists and may precipitate seizures in epileptic patients, particularly in presence of NSAIDs 2. Tendonitis and tendon rupture 3. QT prolongation- Low risk of Torsade’s in absence of other predisposing factors 4. Hemolysis in G6PD 5. Photosensitivity 6. Arthralgias and cartilage toxicity (generally avoided in children) 7. Dysglycaemia (hyper and hypoglycaemia)	1. CNS Toxicity- GABA antagonists and may precipitate seizures in epileptic patients, particularly in presence of NSAIDs 2. Tendonitis and tendon rupture 3. QT prolongation- Low risk of Torsade’s in absence of other predisposing factors 4. Hemolysis in G6PD 5. Photosensitivity 6. Arthralgias and cartilage toxicity (generally avoided in children) 7. Dysglycaemia (hyper and hypoglycaemia)	GIT– abdominal pain, N/V/D, jaundice, pancreatitis HAEM- leukopenia CVS– T wave flattening, QT prolongation CNS– ataxia, seizures, insomnia, paraesthesia HYPERSENSITIVITY– rash OTHER– metallic taste
PHARMACOKINETICS (PK)
PK: Absorption	BA 62%	bioavailabilty 50–70% routes of administration PO, IV or IM doses Usually given QID or TDS in up to 2g/day	Orally not absorbed (need penicillin V)	Rapid oral absorption with 90/60% bioavailability	Poorly absorbed when administered orally and is hydrolysed by gastric acids.		Poorly absorbed orally Peak plasma concentrations occur immediately after the completion of intravenous infusion. Following several doses of piperacillin-tazobactam infusions every 6 hours, peak concentrations were similar to those that were measured after the initial dose.	Rapid and complete absorption, which is not effected by food.	IV or IM admin.	Well absorbed when given IM IV/IM Dose is 1-2g daily or BD On/dur serum peak in 2-3hrs (IM)	Poor oral absorb – given IV or IM only.	IV or IM only.	IV route only Dose is 500mg-1g TDS On/dur peak at 1hr	bioavailabilty Oral: Poor; I.M.: Erratic; Intraperitoneal: ~38% IV. dose loading 20mg/kg then 1-1.5g daily based on levels	BA no oral absorption, rapid and complete IM. IV (poor lipid solubility) doses 3-10mcg/kg depending on severity onset / duration 30mins	Good oral absorption (80%) Undergoes first pass Coadministration of calcium or magnesium reduces absorption	90% oral absorption Coadministration of calcium or magnesium reduces absorption	50% PO BA 75% Rectal BA
PK: Distribution	penetration into CSF occurs with inflamed meninges only	penetration into CSF occurs with inflamed meninges only	CSF and bone penetration if inflammation present		High concentrations are found in most tissues and body fluids.		Widely distributed in body tissues and fluids. Meningeal distribution of piperacillin-tazobactam increases with inflammation, but is otherwise low		Widely distributed.	Crosses the BBB, improved with inflam	Widely distributed and crosses the BB in meningitis. Good tissue penetration	Widely distributed	Crosses BBB with CSF conc = plasma	Distributes widely in body tissue and fluids, except for CSF, improved CSF penetration with inflamed meninges	lip sol low - reduces gut absorption some CSF penetration with inflamed meninges (30%)	High CSF and tissue penetration	High CSF and tissue penetration	Widely distributed to all tissues
Protein binding (PK: Distribution)	20% PB	up to 95% PB	60% PB	20% PB	16% PB		30% PB	10% PB	80% PB	85 – 95% PB Highly protein bound, non-linear dose response	35-50% PB		2% PB Minimally protein bound	~50% PB	<30% PB	30% PB	30% PB	10% PB
Volume of distribution (PK: Distribution)		Vd ~0.28 L/kg	Vd <1L/kg	Vd <1L/kg	Vd 0.32 L/kg		Vd <1L/kg			small Vd 0.5L/kg			small Vd 0.3 L/kg	Vd: 0.4-1 L/kg	Vd 0.2-0.3 L/kg	Vd 2-3L/kg		Vd 0.75 L/kg
PK: Metabolism	Some Hepatic Metabolism	Hepatic- active metab	Inactive metabolite penicollic acid	Both metabolized in the liver, amoxicillin 30%, clavulonic acid 70%	Not metabolized in man.		Piperacillin is not metabolized in man. Tazobactam is mainly metabolized to M1, an inactive metabolite.	Minimal metabolism	Minimal metabolism	minimally hepatic	Active metabolite desacetyl-cefotaxime in the liver		partially hepatic	Little or no metabolism	not metabolised	Little hepatic metabolism	Little hepatic metabolism	Hepatic Oxidation and glucuronidation
PK: Excretion	Mostly unchanged in urine. Rest is feces and bile	excretion Urine (50-65% as unchanged drug)	90% excreted in urine by tubular secretion 25% unchanged	- High clearance (both 250ml/min)	Bile: 20% Renal: Rest (by glomerular filtration and tubular secretion)		Renal: 80% unchanged + metabolite	90% excreted unchanged in urine	Renally cleared Plasma T1/2 = 1 hr	excreted mostly unchanged in urine and bile	Mainly renal clearance	85% eliminated unchanged in the urine	excreted in urine 70% unchanged	excretion via kidneys unchanged Not effectively removed by dialysis	excretion urine as unchanged drug	Active tubular secretion	Renal excretion	Renal excretion 60% unchanged
- Clearance (PK: Excretion)
- Half Life (PK: Excretion)		half life 0.75–1 hours, prolonged in anuria/renal impair			Elimination half-life: 36–72 minutes		Half-life of Piperacillin-tazobactam: 0.7 to 1.2 hours	Plasma T1/2 = 1hr		half life 8 hours enabling daily dosing	Plasma T1/2 = 1-1.5 hrs	Plasma T1/2 = 2 hrs	half life 1-1.5 hrs renal failure significantly increases half life	half life Biphasic half life, prolonged in renal fail. Mean t1/2 4-6hrs	half life 1.5-3 hrs, +++ in renal impairment (up to 70hrs)	T1/2= 3 hours (renal dose adjustment required)	T1/2= 12 hours Renal dose adjustment not required	T1/2 = 6-10hrs Renal dose adjustment not required
SPECIAL POINTS					The dose of piperacillin should be reduced in the presence of renal impairment; the drug is 30–50% removed by haemodialysis.		Removed by haemodialysis			PK changes in Critical Illness: ---------------- D: Vd ↑’s in critical illness loading dose (LD = Vd x desired concentration) may increase Beta lactams are hydrophobic - Vd less effected than hydrophilic drugs Protien binding - albumin is generally reduced in critical illness → ↑ Ceftriaxone plasma conc → ↓ dose M: minimal change due to lack of metabolism E: excreted in urine mostly unchanged → renal impairment will significantly increase elimination half times (dose should not exceed 2gm/day) Protein binding of ceftriaxone reduces CRRT clearance (nil dose adjustment required)			PK changes in Critical Illness: ---------------- D: Vd ↑’s in critical illness loading dose (LD = Vd x desired concentration) may increase Beta lactams are hydrophobic - Vd less effected than hydrophilic drugs M: minimal change due to lack of metabolism E: excreted in urine mostly unchanged → renal impairment will significantly increase elimination half times (dose reduction required) Low protein binding → Meropenem is cleared via CRRT →↑dose freq

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

LEVEL 3 ANTIBIOTICS

Pharmacopeia - Level 3 Antibiotics

	ERYTHROMYCIN	CLARITHROMYCIN	AZITHROMYCIN	CLINDAMYCIN	DOXYCYCLINE	TRIMETHOPRIM - SULFAMETHOXAZOLE (CO-TRIMOXAZOLE)	TAZOBACTAM
GROUP	ANTIBIOTIC: MACROLIDE	ANTIBIOTIC: MACROLIDE	ANTIBIOTIC: MACROLIDE	ANTIBIOTIC: LINCOSAMIDE	ANTIBIOITIC: TETRACYCLINE	ANTIBIOTIC: ANTIFOLATE + SULFONAMIDE	ANTIBIOTIC: BETA LACTAMASE INHIBITOR
CICM Level of Understanding	Level 3	Level 3	Level 3	Level 3	Level 3	Level 3	Level 3
INTRODUCTION						Sulphamethoxazole (an intermediate half life, slow oral absorbing sulfonamide) and trimethoprim	Tazobactam is a beta lactamase inhibitor administered with antibiotics such as piperacillin and ceftolozane to prevent their degradation, resulting in increased efficacy.
USES				• Clindamycin is used to treat serious anaerobic and gram positive infection (not enterococcus) and also has MRSA and Plasmodium falciparum cover (but not p. vivax or gram negative aerobes) • Can be used (along with primaquine) to treat PCP • Can be used to treat toxin mediated septic syndromes including necrotizing fasciitis and toxic shock syndrome • MOA: inhibits bacterial synthesis by disrupting the function of 50S ribosomal subunit. Can be bacteriostatic or bacteriocidal depending on concentration and microbe being treated
PHARMACEUTICS (PC)	Topical, oral, IV	PO, IV	PO, IV		PO and IV		In vials with Piperacillin (500mg/4g Piperacillin or 250mg/2g) or ceftolozane Tazobactam shows little antibacterial activity by itself, and for this reason, is generally not administered alone
PC: Chemical							penicillanic acid sulfone derivative
PC: Presentation
PHARMACODYNAMICS (PD)
PD: Main Action							Tazobactam broadens the spectrum of piperacillin and ceftolozane by making them effective against organisms that express beta-lactamase and would normally degrade them.
PD: Mode of Action	Inhibits 50s subunit to prevent protein synthesis Bacteriocidal/static	Inhibits 50s subunit to prevent protein synthesis Bacteriocidal/static	Inhibits 50s subunit to prevent protein synthesis Bacteriocidal/static	Inhibitor of bacterial 50S ribosomal subunit Prevents protein synthesis	Inhibit bacterial protein synthesis by binding the 30S subunit of the ribosome to prevent tRNA access	MOA: Selectively inhibits bacterial dihydrofolate reductase, which inhibits purine synthesis and therefore DNA synthesis	Irreversible inhibition of beta-lactamase enzymes. In addition, tazobactam may bind covalently to plasmid-mediated and chromosome-mediated beta-lactamase enzymes.
PD: Route & Doses
PD: Metrics (Onset/ Peak/ Duration)
PD: Effects
PD: Spectrum of Activity	1. Gram positives 2. Anaerobes Obligate intracellular organisms (legionella, mycoplasma)	1. Gram positives (better strep and listeria cover) 2. Anaerobes 3. Obligate intracellular organisms (legionella, mycoplasma) 4. Gram negatives- including Helicobacter	1.Gram positives 2. Anaerobes 3. Obligate intracellular organisms (legionella, mycoplasma) 4. Gram negatives including Moraxella, Neisseria, H. Influenzae	Aerobic G+ cocci including MRSA (except enterococci) Anaerobic G- bacilli Most aerobic G- bacilli are resistant including pseudomonas (except Capnocytophagia canimorus)	1. Gram Positives - Includes staph and MRSA - Strep cover variable 2. Gram negatives - Not pseudomonas or proteus 3. Atypical and spirochetes - Mycoplasma, chlamydia, rickettsia, spirochetes 4. Protozoa - Including plasmodium falciparum prophylaxis	1. Gram positives- including MSSA and MRSA (though increasing resistance) 2. Gram negatives- including Moraxella, Klebsiella, haemophilus and some E. Coli 3. Non-bacterial pathogens- pneumocystis and toxoplasma	Tazobactam is predominantly effective against the OHIO-1, SHV-1, and TEM groups of beta-lactamases, but may also inhibit other beta-lactamases.
PD: Resistance Mechanism
PD: Side Effects / Toxicity	1. Must be avoided in porphyria 2. Nausea, vomiting, diarrhea 3. Hypersensitivity 4. QT prolongation and increased risk of torsade’s 5. Inhibits CYP3A4 (increased warfarin, carbamazepine, ciclosporin, valproate, tacrolimus, digoxin) Inhibits p-glycoprotein	1. Nausea, vomiting, diarrhea 2. Hypersensitivity 3. QT prolongation and increased risk of torsade’s 4. Inhibits CYP3A4 (increased warfarin, carbamazepine, ciclosporin, valproate, tacrolimus, digoxin) Inhibits P-glycoprotein	1. Nausea, vomiting, diarrhea 2. Hypersensitivity 3. Less QT prolongation 4. Inhibits CYP3A4 (increased warfarin, carbamazepine, ciclosporin, valproate, tacrolimus, digoxin) Inhibits P-glycoprotein	- Pseudomembranous colitis due to c.diff - Contact dermatitis - Metallic taste - Anaphylaxis	1. Exacerbate MG 2. Exacerbate SLE 3. Dental staining and hypoplasia in unerrupted teeth 4. Photosensitivity 5. Nausea/Vomiting/Diarrhoea 6. Oesophagitis Hepatic toxicity	1. Megaloblastic anaemia through to aplastic anaemia and neutropenia 2. Sulfa cross reactivity hypersensitivity 3. Dermatological reactions - Uncomplicated maculopapular through to life threatening TENs (SMX) 4. Pseudorenal failure- trimethoprim inhibits proximal secretion of creatinine 5. Hyperkalaemia and hyponatraemia - Believed to be an anti-aldosterone effect - Risk highest in renal failure or patients with HIV/AIDs 6. AIN or crystalluriea (SMX) 7. Potentiates warfarin	• Nausea, vomiting, and diarrhea are frequent manifestations of an overdose. • Neuromuscular excitability or seizures may also occur with high intravenous doses or renal failure. There is no specific antidote • Anaphylaxis Nephrotoxicity
PHARMACOKINETICS (PK)
PK: Absorption	10-60% absorption Undergoes first pass metabolism	50% absorption	37% oral absorption	IV or PO	Well absorbed orally	100% BA
PK: Distribution	Poor CSF penetration but good lung penetration	Poor CSF penetration but good lung penetration	Poor CSF penetration but good lung penetration	Wide distribution including bone but not CSF	Widely distributed with a small amount of CSF penetration	Trimethoprim is more lipid soluble than sulphamethoxazole, and therefore has a larger Vd. The drugs are combined as 1:5 parts trimethoprim:sulphamethoxazole. This results in a plasma concentration ratio of 1:20, which is optimal for synergism
Protein binding (PK: Distribution)	85% PB	8% PB	12-50% PB	90% PB	50% PB	TMP 45% PB SMX 66% PB
Volume of distribution (PK: Distribution)	Vd 0.3-1.2L/kg		Vd 0.5L/kg			TMP Vd 2 L/kg SMX Vd 0.23 L/kg
PK: Metabolism	Hepatic demethylation	Hepatic metabolism via N-dealkalylation	Hepatic metabolism to inactive metabolites	Hepatic metabolism	Hepatically metabolized	TMP 5-15% to inactive metab SMX Extensive metabolism – major metab acetyl derivative
PK: Excretion	Renally excreted (15% unchanged)	Renally excreted (33% unchanged) 10% in bile	Major route of excretion is bile 12% unchanged in the urine	Biliary. Long post antibiotic effect leads to clostridium overgrowth	Biliary excretion. Does not require renal dose adjustment	Both eliminated renally (TMP unchanged, SMX as metabolites)
- Clearance (PK: Excretion)
- Half Life (PK: Excretion)	T1/2= 1.5 hours	T1/2= 5-6 hours	T1/2 of 68 hours		T1/2 12-16 hours	TMP 11hrs SMX 9 hrs Dose reduction if CrCl < 30 ml/min
SPECIAL POINTS

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

ANTIVIRALS AND ANTIFUNGALS (LEVEL 3)

Pharmacopeia - Antivirals and Antifungals (Level 3)

	ACICLOVIR	NEURAMINIDASE INHIBITORS	GANCICLOVIR	AZOLES	AMPHOTERICIN B	CASPOFUNGIN
GROUP	Antiviral	Antiviral	Antiviral	Antifungal	Antifungal	Antifungal
CICM Level of Understanding	Level 3	Level 3	Level 3	Level 3	Level 3	Level 3
INTRODUCTION	Synthetic nucleoside analogue	Oseltamivir and Zanamivir		Triazoles: Fluconazole, Itraconazole, Voriconazole, Posaconazole Imidazoles: Clotrimazole, Ketoconazole	Polyene
USES
PHARMACEUTICS (PC)
PC: Chemical
PC: Presentation
PHARMACODYNAMICS (PD)
PD: Main Action
PD: Mode of Action	- Inhibits nucleic acid synthesis - Cells infected with HSV or VZV contain virally encoded thymidine kinase that converts acyclovir to acyclovir monophosphate. This is then converted to an active triphosphate that inhibits viral DNA polymerase and acts as a chain terminator - Thymidine kinase in non-infected cells has a low affinity for acyclovir - Whilst useful for HSV and VZV, it does not eradicate them and is only useful if given at the start of an infection	inhibit neurominidase resulting in impaired viral release from infected cells. Neurominidase cleaves the sialic acid on the cell membrane allowing viral budding.		Azoles disrupt ergosterol production by interacting with 14-alpha demthylase, a cytochrome P450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of fungal cell membranes, inhibition of its synthesis leads to increased cell permeability causing leakage of contents.	Polyenes specifically target fungal membranes. They bind ergosterol, which is the principal sterol in fungal membranes as opposed to cholesterol found in host membranes. This interference creates a transmembrane channel and the resultant change in permeability allows leakage of intracellular components
PD: Route & Doses
PD: Metrics (Onset/ Peak/ Duration)
PD: Effects
PD: Spectrum of Activity	Herpes Simplex (1 and 2) and Varicella Zoster. Lacks CMV cover			Fluc: Candida Cryptococcus Coccidia (No activity against histoplasma, blasto, sporotrichosis, Aspergillus, mucormycosis)	Broad antifungal cover including candida, Cryptococcus, aspergillus and zygomyces
PD: Resistance Mechanism				Fluc: Some candida species, Decreased drug concentration Target site alteration Up-regulation of target enzyme Development of bypass pathways
PD: Side Effects / Toxicity	Renal - Rapid IV administration may precipitate renal failure Thrombophlebitis - Highly irritating to veins and extravasation may lead to ulcers CNS - Tremors, confusion, seizures and coma in rapid infusion	1. Psychiatric symptoms 2. N/V/D 3. Bronchospasm		Fluc: N/V/D, Abdominal pain Headache Skin rash Reversible alopecia Rare: Hepatic failure, SJS Should be avoided in Pregnancy Drug interactions: (inhibitor of CYP3A4, CYP2C9)	Dose related nephrotoxicity Infusion related reactions (hypotension, fever, rigors)
PHARMACOKINETICS (PK)
PK: Absorption	Erratic intestinal absorption and low bioavailability (25%). Oral valine-esterified prodrug valacyclovir improves absorption			Well absorbed orally (except miconazole)	only administered IV
PK: Distribution	Widely distributed			Fluc – good CSF penetration Itra, Keto – no CSF penetration	Poor tissue penetration. Negligable CSF or urine penetration.
Protein binding (PK: Distribution)				Itra, Keto – 99% PB	Highly protein bound
Volume of distribution (PK: Distribution)
PK: Metabolism	Oral valine-esterified prodrug valacyclovir is rapidly hydrolyzed in the blood			Fluc not metabolized well Itra, Keto – metabolized by liver	Metabolised by the liver
PK: Excretion	actively excreted in the kidneys unchanged (blocked by probenecid)			Fluc – Urine unchanged Itra, Keto – Excreted bile	poorly characterized but does not accumulate in renal failure
- Clearance (PK: Excretion)
- Half Life (PK: Excretion)
SPECIAL POINTS				potent CYP inhibitors with a wide range of drug interactions (including warfarin)

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

ANTISEPTICS AND DISINFECTANTS (LEVEL 3)

Pharmacopeia - Antiseptics & Disinfectants (Level 3)

	ALCOHOL	CHLORHEXIDINE	IODINE	GLUTARALDEHYDE
CICM Level of Understanding	Level 3	Level 3	Level 3	-
Main Action	Likely act by denaturing proteins	Cationic biguanide -strongly adsorbs to bacterial membranes causing leakage of small particles and precipitation of cytoplasmic proteins	Oxidative damage.	Alkylation of micro-organism proteins or nucleic acids
Advantages	Evaporative effects are useful when sinks with running water are not available	Resistant to inactivation by blood and organic material Low skin irritation	1. Sporicidal 2. Cheap 3. Broad spectrum Most effective for intact skin	Used for sterilization of equipment that cannot withstand high temperatures
Limitations	1. Flammable- must be allowed to dry fully before diathermy or laser surgery 2. Corneal damage 3. Skin drying 4. Ineffective against C. Dif spores	1. Neurotoxic 2. Delayed effect 3. No direct spore activity	1. Hypersensitivity reactions 2. Delayed onset without residual activity 3. Stains clothes and dressings	1. Once activated have a shelf life of 14 days 2. Failure of activity may occur due to excessive dilution or exposure to organic material (frequently reused) 3. Irritating to eyes and respiratory mucosa 4. Slow activity
Onset / Duration	Onset: Rapid Duration: Lack residual action because they evaporate completely	Onset: Delayed Duration: Sustained residual activity	Onset: Iodine is bacteriocidal in 1 minute and kills spores in 15 minutes. However in povidine compounding it has a delayed onset Duration: No sustained effect	Onset: 2.4% glutaraldehyde achieve disinfection in 45 minutes
Spectrum of Activity	- Gram positives and negatives - Acid fast bacteria are susceptible - Lipophilic viruses may be susceptible - Many fungi	- Bacteria (G+ve>G-ve) - Moderate fungal and viral activity - Inhibits spore germination	- Bacteria (G+ve and –ve and acid fast) - Sporicidal - Viruses - Fungi	- Bacteria (G+ve and –ve and acid fast) - Spores - Viruses - Fungi
Ineffective Against:	Spores and prions Hydrophilic viruses are less susceptible	Spores and prions Hydrophilic viruses are less susceptible	Prions Hydrophilic viruses	Prions
SPECIAL POINTS	Optimal bacteriocidal concentration is 60-90%	Can be combined with 70% alcohol Preferred antiseptic for central venous access Not absorbed orally		Used to sterilize fiber optic endoscopes and respiratory therapy equipment

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

INDIVIDUAL TABLES

---

Ceftriaxone

Pharmacopeia - Level 1 Antibiotics

	CEFTRIAXONE
GROUP	ANTIBIOTIC: CEPHALOSPORIN
CICM Level of Understanding	Level 1
INTRODUCTION	3rd Generation Cephalosporin
USES	used for the treatment of infections caused by susceptible Gram-positive and Gram-negative bacteria, including infections of the abdomen, bones and joints, CNS, skin and skin structures, genito-urinary tract (including gonorrhoea), respiratory tract, gynaecological infections, Lyme disease.
PHARMACEUTICS (PC)	White powder for IV- yellowish solution. Can precipitate with Ca2+ containing solutions
PC: Chemical
PC: Presentation
PHARMACODYNAMICS (PD)
PD: Main Action
PD: Mode of Action	Beta lactam ring binds to multiple penicillin binding proteins (carboxy/endo/ transpeptidase) and prevents crosslinking of bacterial peptidoglycan inhibits cell wall synthesis BROADER SPECTRUM Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested Configuration: Stability against Betalactamases
PD: Route & Doses
PD: Metrics (Onset/ Peak/ Duration)	1g daily (2g BD for meningitis)
PD: Effects
PD: Spectrum of Activity	Bacteriocidal Active against: - GP cocci (including pen resistant pneumococcus), sensitive staph - Extended G-ve cover (aerobes)- enterobacter resistance is rapid - Inferior anaerobe cover compared to second generation * ESCAPPMs can induce resistance so treatment failures can occur
PD: Resistance Mechanism	cephalosporinases hydrolyse β-lactam rings. PBP modification. Enterobacter: Change in porins – Impermeable.
PD: Side Effects / Toxicity	highly protein bound and is able to displace bilirubin from albumin binding sites, causing bilirubin; should be avoided in jaundiced neonates. Pseudolithiasis or Biliary sludge due to a precipitate of Calcium-ceftriaxone seen occasionally.
PHARMACOKINETICS (PK)
PK: Absorption	Well absorbed when given IM IV/IM Dose is 1-2g daily or BD On/dur serum peak in 2-3hrs (IM)
PK: Distribution	Crosses the BBB, improved with inflam
Protein binding (PK: Distribution)	85 – 95% PB Highly protein bound, non-linear dose response
Volume of distribution (PK: Distribution)	small Vd 0.5L/kg
PK: Metabolism	minimally hepatic
PK: Excretion	excreted mostly unchanged in urine and bile
- Clearance (PK: Excretion)
- Half Life (PK: Excretion)	half life 8 hours enabling daily dosing
SPECIAL POINTS	PK changes in Critical Illness: ---------------- D: Vd ↑’s in critical illness loading dose (LD = Vd x desired concentration) may increase Beta lactams are hydrophobic - Vd less effected than hydrophilic drugs Protien binding - albumin is generally reduced in critical illness → ↑ Ceftriaxone plasma conc → ↓ dose M: minimal change due to lack of metabolism E: excreted in urine mostly unchanged → renal impairment will significantly increase elimination half times (dose should not exceed 2gm/day) Protein binding of ceftriaxone reduces CRRT clearance (nil dose adjustment required)

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

Piperacillin – Tazobactam

Pharmacopeia - Level 1 Antibiotics

	PIPERACILLIN -TAZOBACTAM
GROUP	ANTIBIOTIC: PENICILLIN
CICM Level of Understanding	Level 1
INTRODUCTION	Antipseudomonal penicillin
USES	used to treat a variety of infections, including those caused by aerobic and facultative gram-positive and gram-negative bacteria, in addition to gram-positive and gram-negative anaerobes. E.g: cellulitis, diabetic foot infections, appendicitis, and postpartum endometritis infections.
PHARMACEUTICS (PC)
PC: Chemical
PC: Presentation
PHARMACODYNAMICS (PD)
PD: Main Action
PD: Mode of Action	β lactam antibiotic Binds to penicillin binding protein (transpeptidase) and prevents crosslinking of bacterial peptidoglycan impairs cell wall synthesis
PD: Route & Doses
PD: Metrics (Onset/ Peak/ Duration)
PD: Effects
PD: Spectrum of Activity	Pseudomonas Beta-lactamase producing bacteria Gram negatives Anaerobes
PD: Resistance Mechanism	Certain gram-negative bacilli infections with beta-lactamase producing organisms cannot be treated with piperacillin-tazobactam, due to a gene mutation conferring antibiotic resistance
PD: Side Effects / Toxicity	1. Hypokalaemia (lower sodium concentration so hypernatraemia less likely) 2. Piptaz + vancomycin associated with increased AKI 3. LFT derangement Neutropenia
PHARMACOKINETICS (PK)
PK: Absorption	Poorly absorbed orally Peak plasma concentrations occur immediately after the completion of intravenous infusion. Following several doses of piperacillin-tazobactam infusions every 6 hours, peak concentrations were similar to those that were measured after the initial dose.
PK: Distribution	Widely distributed in body tissues and fluids. Meningeal distribution of piperacillin-tazobactam increases with inflammation, but is otherwise low
Protein binding (PK: Distribution)	30% PB
Volume of distribution (PK: Distribution)	Vd <1L/kg
PK: Metabolism	Piperacillin is not metabolized in man. Tazobactam is mainly metabolized to M1, an inactive metabolite.
PK: Excretion	Renal: 80% unchanged + metabolite
- Clearance (PK: Excretion)
- Half Life (PK: Excretion)	Half-life of Piperacillin-tazobactam: 0.7 to 1.2 hours
SPECIAL POINTS	Removed by haemodialysis

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

Benzyl penicillin | Flucloxacillin | Ampicillin
(Limited)

Pharmacopeia - Level 1 Antibiotics

	BENZYL PENICILLIN	FLUCLOXACILLIN	AMPICILLIN
PD: Spectrum of Activity	Narrow-Spectrum Natural Penicillin Highly bactericidal, only gram positives/anaerobes, susceptible to betalactamases Targets GPC: Streptococci, Meningococcus Listeria (GPB) GNC: Neisseria, Clostridia Treponemma (Spiral) Synergistic effects with aminoglycosides	narrow spectrum but is useful for treating staphlococci which are resistant to benpen due to beta-lactamase activity It should not be used if the organism is sensitive to benpen as benpen is more bactericidal	Moderate spectrum Semisynthetic Can penetrate some gram negative outer membranes, but susceptible to betalactamases. Often given with clauvanic acid Targets Strep, Listeria, Enterococcus, Haemophilus
PD: Resistance Mechanism	Resistance MRSA Many Staph -Betalactamase prod Gram Negatives	MRSA develop or acquire the gene mecA which synthesizes an additional penicillin binding protein that enables it to continue cell wall synthesis in the presence of a beta lactam drug	Bacteria produce beta lactamases, which hydrolyse and inactivate the antibiotic Resistance MRSA Many Staph -Betalactamase prod

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

Ceftriaxone | Meropenem
(Limited)

Pharmacopeia - Level 1 Antibiotics

	CEFTRIAXONE	MEROPENEM
GROUP	ANTIBIOTIC: CEPHALOSPORIN	ANTIBIOTIC: CARBAPENEM
CICM Level of Understanding	Level 1	Level 1
PHARMACODYNAMICS (PD)
PD: Mode of Action	Beta lactam ring binds to multiple penicillin binding proteins (carboxy/endo/ transpeptidase) and prevents crosslinking of bacterial peptidoglycan inhibits cell wall synthesis BROADER SPECTRUM Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested Configuration: Stability against Betalactamases	Binds to several penicillin binding protein and prevents crosslinking of bacterial peptidoglycan inhibits cell wall synthesis BROADEST SPECTRUM Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested Configuration: Stability against Betalactamases and ESBLs
PD: Spectrum of Activity	Bacteriocidal Active against: - GP cocci (including pen resistant pneumococcus), sensitive staph - Extended G-ve cover (aerobes)- enterobacter resistance is rapid - Inferior anaerobe cover compared to second generation * ESCAPPMs can induce resistance so treatment failures can occur	v.broad spectrum, gram positive, gram negative (incl pseudomonal) and anaerobic coverage (resistant to beta lactamases and cephalosporinases)
PHARMACOKINETICS (PK)
PK: Absorption	Well absorbed when given IM IV/IM Dose is 1-2g daily or BD On/dur serum peak in 2-3hrs (IM)	IV route only Dose is 500mg-1g TDS On/dur peak at 1hr
PK: Distribution	Crosses the BBB, improved with inflam	Crosses BBB with CSF conc = plasma
Protein binding (PK: Distribution)	85 – 95% PB Highly protein bound, non-linear dose response	2% PB Minimally protein bound
Volume of distribution (PK: Distribution)	small Vd 0.5L/kg	small Vd 0.3 L/kg
PK: Metabolism	minimally hepatic	partially hepatic
PK: Excretion	excreted mostly unchanged in urine and bile	excreted in urine 70% unchanged
- Clearance (PK: Excretion)
- Half Life (PK: Excretion)	half life 8 hours enabling daily dosing	half life 1-1.5 hrs renal failure significantly increases half life
SPECIAL POINTS	PK changes in Critical Illness: ---------------- D: Vd ↑’s in critical illness loading dose (LD = Vd x desired concentration) may increase Beta lactams are hydrophobic - Vd less effected than hydrophilic drugs Protien binding - albumin is generally reduced in critical illness → ↑ Ceftriaxone plasma conc → ↓ dose M: minimal change due to lack of metabolism E: excreted in urine mostly unchanged → renal impairment will significantly increase elimination half times (dose should not exceed 2gm/day) Protein binding of ceftriaxone reduces CRRT clearance (nil dose adjustment required)	PK changes in Critical Illness: ---------------- D: Vd ↑’s in critical illness loading dose (LD = Vd x desired concentration) may increase Beta lactams are hydrophobic - Vd less effected than hydrophilic drugs M: minimal change due to lack of metabolism E: excreted in urine mostly unchanged → renal impairment will significantly increase elimination half times (dose reduction required) Low protein binding → Meropenem is cleared via CRRT →↑dose freq

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

Ampicillin | Gentamicin | Vancomycin | Ciprofloxacin
(Limited)

Pharmacopeia - Level 1 Antibiotics

	AMPICILLIN	GENTAMICIN	VANCOMYCIN	CIPROFLOXACIN
GROUP	ANTIBIOTIC: PENICILLIN	ANTIBIOTIC: AMINOGLYCOSIDE	ANTIBIOTIC: GLYCOPEPTIDE	ANTIBIOTIC: QUINOLONE
PD: Mode of Action	Contains a beta lactam ring structure. Betalactam antibiotics inhibit the growth of sensitive bacteria by inactivating transpeptidase enzymes located in the bacterial cell membrane, inhibiting crosslinkage of peptidoglycans and thus impairing cell wall synthesis	bactericidal Binds to the bacterial 30S ribosomal subunit to inhibit protein synthesis and thus bacterial growth	Inhibits Glycopeptide synthetase  prevents peptidoglycan formation in bacterial cell well (Unlike penicillins, prevents the transfer and addition of the muramylpentapeptide building blocks that make up the peptidoglycan molecule itself.) May also alter membrane permeability and selectively inhibit RNA synthesis. Antimicrobial activity Dependent on Duration above MIC, not concentration	Bacteriocidal antimicrobials that block DNA replication by blocking tropoisomerase enzymes, which are essential for the supercoiling, replication and separation of circular bacterial DNA
PD: Spectrum of Activity	Moderate spectrum Semisynthetic Can penetrate some gram negative outer membranes, but susceptible to betalactamases. Often given with clauvanic acid Targets Strep, Listeria, Enterococcus, Haemophilus	provide good gram negative coverage and some gram positive most often used against enteric infections and in sepsis usually used in combination with a beta lactam	active against most gram positive bacteria (including staphlycocci, streptococci, enterococci, listeria monocytogenes, clostridium sp, and Bacillus sp.), with limited gram negative activity.	Broad spectrum Active against both gram positive and gram negative bacteria particularly effective against GNB (E.Coli, H.influenza, Klebsiella, Legionella, Moraxella, Proteus, and Pseudomonas) Less effective against Gram-positive bacteria (such as MSSA, Strep pneumoniae, and Enterococcus faecalis) than newer fluoroquinolones
PD: Resistance Mechanism	Bacteria produce beta lactamases, which hydrolyse and inactivate the antibiotic Resistance MRSA Many Staph -Betalactamase prod	Alteration in access to target site – membrane impermeability / transport defect in the active transport. Lack of O2-transport channels: Anaerobes Multiple enzymes which block gentamicin (acetytransferases, adenyltransferases, phosphotransferases)	VanA resistance – gene mutation leading to decreased affinity of peptidoglycan precursors for vancomycin. Induced by exposure to vanc / teicoplanin Van B resistance – similar but only induced by vancomycin; strains may remain susceptible to teicoplanin	Alteration in target enzyme – changes to the DNA binding surface of DNA supergyrase infers resistance Alteration in drug entry – altered expression of outer membrane porin proteins that form channels for passive diffusion of ciprofloxacin Increase in efflux of drug – expression of nonspecific energy dependent efflux pumps which remove drug

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

Benzyl penicillin | Metronidazole | Clindamycin
(Limited)

Pharmacopeia - Antibiotics

	BENZYL PENICILLIN	METRONIDAZOLE	CLINDAMYCIN
GROUP	ANTIBIOTIC: PENICILLIN	ANTIBIOTIC: NITROIMIDAZOLE	ANTIBIOTIC: LINCOSAMIDE
PD: Mode of Action	β lactam antibiotic Binds to penicillin binding protein (transpeptidase) and prevents crosslinking of bacterial peptidoglycan impairs cell wall synthesis	Converted to active form or nitroso free radical by obligate anaerobes. Inhibits DNA synthesis. Causes DNA degradation	Inhibitor of bacterial 50S ribosomal subunit Prevents protein synthesis
PD: Spectrum of Activity	Narrow-Spectrum Natural Penicillin Highly bactericidal, only gram positives/anaerobes, susceptible to betalactamases Targets GPC: Streptococci, Meningococcus Listeria (GPB) GNC: Neisseria, Clostridia Treponemma (Spiral) Synergistic effects with aminoglycosides	Active against anaerobes (including clostridium, N.Gonorrhoea, N.Menigitidis, Bacterioides and Fusobacterium) and protozoa (trichomonas, Giardia)	Aerobic G+ cocci including MRSA (except enterococci) Anaerobic G- bacilli Most aerobic G- bacilli are resistant including pseudomonas (except Capnocytophagia canimorus)
PD: Side Effects / Toxicity	GIT– abdominal pain, N/V/D, pseudomembranous colitis, hepatitis HAEM- agranulocytosis CNS- confusion, seizure, encephalopathy HYPERSENSITIVITY- rash, anaphylaxis	GIT– abdominal pain, N/V/D, jaundice, pancreatitis HAEM- leukopenia CVS– T wave flattening, QT prolongation CNS– ataxia, seizures, insomnia, paraesthesia HYPERSENSITIVITY– rash OTHER– metallic taste	- Pseudomembranous colitis due to c.diff - Contact dermatitis - Metallic taste - Anaphylaxis

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

Benzyl Penicillin | Fluconazole
(Limited)

Pharmacopeia - Antibiotics

	BENZYL PENICILLIN	FLUCONAZOLE
GROUP	ANTIBIOTIC: PENICILLIN	ANTIFUNGAL: AZOLE
PD: Mode of Action	β lactam antibiotic Binds to penicillin binding protein (transpeptidase) and prevents crosslinking of bacterial peptidoglycan impairs cell wall synthesis	fluorinated bis-triazole reduction of ergosterol synthesis by inhibition of fungal cytochrome P450 enzymes (greater affinity for fungal than for human)
PD: Spectrum of Activity	Narrow-Spectrum Natural Penicillin Highly bactericidal, only gram positives/anaerobes, susceptible to betalactamases Targets GPC: Streptococci, Meningococcus Listeria (GPB) GNC: Neisseria, Clostridia Treponemma (Spiral) Synergistic effects with aminoglycosides	Candida Cryptococcus Coccidia (No activity against histoplasma, blasto, sporotrichosis, Aspergillus, mucormycosis)
PD: Side Effects / Toxicity	GIT– abdominal pain, N/V/D, pseudomembranous colitis, hepatitis HAEM- agranulocytosis CNS- confusion, seizure, encephalopathy HYPERSENSITIVITY- rash, anaphylaxis	N/V/D, Abdominal pain Headache Skin rash Reversible alopecia Rare: Hepatic failure, SJS Should be avoided in Pregnancy Drug interactions: (inhibitor of CYP3A4, CYP2C9)

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

Vancomycin | Flucloxacillin

Pharmacopeia - Level 1 Antibiotics

	VANCOMYCIN	FLUCLOXACILLIN
GROUP	ANTIBIOTIC: GLYCOPEPTIDE	ANTIBIOTIC: PENICILLIN
CICM Level of Understanding	Level 1	Level 1
INTRODUCTION	Tricyclic glycopeptide antibiotic produced by streptococcus orientalis	Narrow spectrum, semisynthetic anti-staphylococcal penicillin
USES	It possesses a broad spectrum of activity against gram positive bacteria including MRSA. Acts synergistically with aminoglycosides, cephalosporins and rifampicin (although synergy testing required as vancomycin + cephalosporin may act antagonistically against some strains of staph epidermis)	useful for treating staphlococci which are resistant to benpen due to beta-lactamase activity . It is well absorbed from the gut but is given IV if the infection is serious. It should not be used if the organism is sensitive to benpen as benpen is more bacteriocidal.
PHARMACEUTICS (PC)	Store at 2-8 degrees, clear solution. Slowly due to vessel irritation (& risk of red man syndrome). Monitoring required to avoid toxic levels (aiming serum conc 15+/-3).	PO/IV. Tablet/Powder for reconstitution
PC: Chemical
PC: Presentation
PHARMACODYNAMICS (PD)
PD: Main Action
PD: Mode of Action	Inhibits Glycopeptide synthetase  prevents peptidoglycan formation in bacterial cell well (Unlike penicillins, prevents the transfer and addition of the muramylpentapeptide building blocks that make up the peptidoglycan molecule itself.) May also alter membrane permeability and selectively inhibit RNA synthesis. Antimicrobial activity Dependent on Duration above MIC, not concentration	Beta lactam ring binds to penicillin binding protein (transpeptidase) and prevents crosslinking of bacterial peptidoglycan inhibits cell wall synthesis Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested Less bactericidal but stable to staph beta-lactamases
PD: Route & Doses
PD: Metrics (Onset/ Peak/ Duration)
PD: Effects
PD: Spectrum of Activity	active against most gram positive bacteria (including staphlycocci, streptococci, enterococci, listeria monocytogenes, clostridium sp, and Bacillus sp.), with limited gram negative activity.	narrow spectrum but is useful for treating staphlococci which are resistant to benpen due to beta-lactamase activity It should not be used if the organism is sensitive to benpen as benpen is more bactericidal
PD: Resistance Mechanism	VanA resistance – gene mutation leading to decreased affinity of peptidoglycan precursors for vancomycin. Induced by exposure to vanc / teicoplanin Van B resistance – similar but only induced by vancomycin; strains may remain susceptible to teicoplanin	MRSA develop or acquire the gene mecA which synthesizes an additional penicillin binding protein that enables it to continue cell wall synthesis in the presence of a beta lactam drug
PD: Side Effects / Toxicity	Hypersensitivity reactions including anaphylaxis. Rapid infusion is associated with histamine release - red-man syndrome. Ototoxicity rare, dose related. Nephrotoxicity has declined with improved formulations, usually resolves with cessation of drug	Up to 10% of the population have allergies to penicillins. Due to the high percentage excreted renally unchanged dose adjustment is required in low urine output states. Severe cholestatic hepatitis has been reported idiosyncratically.
PHARMACOKINETICS (PK)
PK: Absorption	bioavailabilty Oral: Poor; I.M.: Erratic; Intraperitoneal: ~38% IV. dose loading 20mg/kg then 1-1.5g daily based on levels	bioavailabilty 50–70% routes of administration PO, IV or IM doses Usually given QID or TDS in up to 2g/day
PK: Distribution	Distributes widely in body tissue and fluids, except for CSF, improved CSF penetration with inflamed meninges	penetration into CSF occurs with inflamed meninges only
Protein binding (PK: Distribution)	~50% PB	up to 95% PB
Volume of distribution (PK: Distribution)	Vd: 0.4-1 L/kg	Vd ~0.28 L/kg
PK: Metabolism	Little or no metabolism	Hepatic- active metab
PK: Excretion	excretion via kidneys unchanged Not effectively removed by dialysis	excretion Urine (50-65% as unchanged drug)
- Clearance (PK: Excretion)
- Half Life (PK: Excretion)	half life Biphasic half life, prolonged in renal fail. Mean t1/2 4-6hrs	half life 0.75–1 hours, prolonged in anuria/renal impair
SPECIAL POINTS

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

Ciprofloxacin

Pharmacopeia - Level 1 Antibiotics

	CIPROFLOXACIN
GROUP	ANTIBIOTIC: QUINOLONE
CICM Level of Understanding	Level 3
INTRODUCTION	Quinolone
USES
PHARMACEUTICS (PC)	PO and IV, topical eye drops and ointment
PC: Chemical
PC: Presentation
PHARMACODYNAMICS (PD)
PD: Main Action
PD: Mode of Action	Bacteriocidal antimicrobials that block DNA replication by blocking tropoisomerase enzymes, which are essential for the supercoiling, replication and separation of circular bacterial DNA
PD: Route & Doses
PD: Metrics (Onset/ Peak/ Duration)
PD: Effects
PD: Spectrum of Activity	Broad spectrum Active against both gram positive and gram negative bacteria particularly effective against GNB (E.Coli, H.influenza, Klebsiella, Legionella, Moraxella, Proteus, and Pseudomonas) Less effective against Gram-positive bacteria (such as MSSA, Strep pneumoniae, and Enterococcus faecalis) than newer fluoroquinolones
PD: Resistance Mechanism	Alteration in target enzyme – changes to the DNA binding surface of DNA supergyrase infers resistance Alteration in drug entry – altered expression of outer membrane porin proteins that form channels for passive diffusion of ciprofloxacin Increase in efflux of drug – expression of nonspecific energy dependent efflux pumps which remove drug
PD: Side Effects / Toxicity	1. CNS Toxicity- GABA antagonists and may precipitate seizures in epileptic patients, particularly in presence of NSAIDs 2. Tendonitis and tendon rupture 3. QT prolongation- Low risk of Torsade’s in absence of other predisposing factors 4. Hemolysis in G6PD 5. Photosensitivity 6. Arthralgias and cartilage toxicity (generally avoided in children) 7. Dysglycaemia (hyper and hypoglycaemia)
PHARMACOKINETICS (PK)
PK: Absorption	Good oral absorption (80%) Undergoes first pass Coadministration of calcium or magnesium reduces absorption
PK: Distribution	High CSF and tissue penetration
Protein binding (PK: Distribution)	30% PB
Volume of distribution (PK: Distribution)	Vd 2-3L/kg
PK: Metabolism	Little hepatic metabolism
PK: Excretion	Active tubular secretion
- Clearance (PK: Excretion)
- Half Life (PK: Excretion)	T1/2= 3 hours (renal dose adjustment required)
SPECIAL POINTS

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

Vancomycin

Pharmacopeia - Level 1 Antibiotics

	VANCOMYCIN
GROUP	ANTIBIOTIC: GLYCOPEPTIDE
CICM Level of Understanding	Level 1
INTRODUCTION	Tricyclic glycopeptide antibiotic produced by streptococcus orientalis
USES	It possesses a broad spectrum of activity against gram positive bacteria including MRSA. Acts synergistically with aminoglycosides, cephalosporins and rifampicin (although synergy testing required as vancomycin + cephalosporin may act antagonistically against some strains of staph epidermis)
PHARMACEUTICS (PC)	Store at 2-8 degrees, clear solution. Slowly due to vessel irritation (& risk of red man syndrome). Monitoring required to avoid toxic levels (aiming serum conc 15+/-3).
PC: Chemical
PC: Presentation
PHARMACODYNAMICS (PD)
PD: Main Action
PD: Mode of Action	Inhibits Glycopeptide synthetase  prevents peptidoglycan formation in bacterial cell well (Unlike penicillins, prevents the transfer and addition of the muramylpentapeptide building blocks that make up the peptidoglycan molecule itself.) May also alter membrane permeability and selectively inhibit RNA synthesis. Antimicrobial activity Dependent on Duration above MIC, not concentration
PD: Route & Doses
PD: Metrics (Onset/ Peak/ Duration)
PD: Effects
PD: Spectrum of Activity	active against most gram positive bacteria (including staphlycocci, streptococci, enterococci, listeria monocytogenes, clostridium sp, and Bacillus sp.), with limited gram negative activity.
PD: Resistance Mechanism	VanA resistance – gene mutation leading to decreased affinity of peptidoglycan precursors for vancomycin. Induced by exposure to vanc / teicoplanin Van B resistance – similar but only induced by vancomycin; strains may remain susceptible to teicoplanin
PD: Side Effects / Toxicity	Hypersensitivity reactions including anaphylaxis. Rapid infusion is associated with histamine release - red-man syndrome. Ototoxicity rare, dose related. Nephrotoxicity has declined with improved formulations, usually resolves with cessation of drug
PHARMACOKINETICS (PK)
PK: Absorption	bioavailabilty Oral: Poor; I.M.: Erratic; Intraperitoneal: ~38% IV. dose loading 20mg/kg then 1-1.5g daily based on levels
PK: Distribution	Distributes widely in body tissue and fluids, except for CSF, improved CSF penetration with inflamed meninges
Protein binding (PK: Distribution)	~50% PB
Volume of distribution (PK: Distribution)	Vd: 0.4-1 L/kg
PK: Metabolism	Little or no metabolism
PK: Excretion	excretion via kidneys unchanged Not effectively removed by dialysis
- Clearance (PK: Excretion)
- Half Life (PK: Excretion)	half life Biphasic half life, prolonged in renal fail. Mean t1/2 4-6hrs
SPECIAL POINTS

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

Piperacillin-Tazobactam | Ciprofloxacin

Pharmacopeia - Level 1 Antibiotics

	PIPERACILLIN -TAZOBACTAM	CIPROFLOXACIN
GROUP	ANTIBIOTIC: PENICILLIN	ANTIBIOTIC: QUINOLONE
CICM Level of Understanding	Level 1	Level 3
INTRODUCTION	Antipseudomonal penicillin	Quinolone
USES	used to treat a variety of infections, including those caused by aerobic and facultative gram-positive and gram-negative bacteria, in addition to gram-positive and gram-negative anaerobes. E.g: cellulitis, diabetic foot infections, appendicitis, and postpartum endometritis infections.
PHARMACEUTICS (PC)		PO and IV, topical eye drops and ointment
PC: Chemical
PC: Presentation
PHARMACODYNAMICS (PD)
PD: Main Action
PD: Mode of Action	β lactam antibiotic Binds to penicillin binding protein (transpeptidase) and prevents crosslinking of bacterial peptidoglycan impairs cell wall synthesis	Bacteriocidal antimicrobials that block DNA replication by blocking tropoisomerase enzymes, which are essential for the supercoiling, replication and separation of circular bacterial DNA
PD: Route & Doses
PD: Metrics (Onset/ Peak/ Duration)
PD: Effects
PD: Spectrum of Activity	Pseudomonas Beta-lactamase producing bacteria Gram negatives Anaerobes	Broad spectrum Active against both gram positive and gram negative bacteria particularly effective against GNB (E.Coli, H.influenza, Klebsiella, Legionella, Moraxella, Proteus, and Pseudomonas) Less effective against Gram-positive bacteria (such as MSSA, Strep pneumoniae, and Enterococcus faecalis) than newer fluoroquinolones
PD: Resistance Mechanism	Certain gram-negative bacilli infections with beta-lactamase producing organisms cannot be treated with piperacillin-tazobactam, due to a gene mutation conferring antibiotic resistance	Alteration in target enzyme – changes to the DNA binding surface of DNA supergyrase infers resistance Alteration in drug entry – altered expression of outer membrane porin proteins that form channels for passive diffusion of ciprofloxacin Increase in efflux of drug – expression of nonspecific energy dependent efflux pumps which remove drug
PD: Side Effects / Toxicity	1. Hypokalaemia (lower sodium concentration so hypernatraemia less likely) 2. Piptaz + vancomycin associated with increased AKI 3. LFT derangement Neutropenia	1. CNS Toxicity- GABA antagonists and may precipitate seizures in epileptic patients, particularly in presence of NSAIDs 2. Tendonitis and tendon rupture 3. QT prolongation- Low risk of Torsade’s in absence of other predisposing factors 4. Hemolysis in G6PD 5. Photosensitivity 6. Arthralgias and cartilage toxicity (generally avoided in children) 7. Dysglycaemia (hyper and hypoglycaemia)
PHARMACOKINETICS (PK)
PK: Absorption	Poorly absorbed orally Peak plasma concentrations occur immediately after the completion of intravenous infusion. Following several doses of piperacillin-tazobactam infusions every 6 hours, peak concentrations were similar to those that were measured after the initial dose.	Good oral absorption (80%) Undergoes first pass Coadministration of calcium or magnesium reduces absorption
PK: Distribution	Widely distributed in body tissues and fluids. Meningeal distribution of piperacillin-tazobactam increases with inflammation, but is otherwise low	High CSF and tissue penetration
Protein binding (PK: Distribution)	30% PB	30% PB
Volume of distribution (PK: Distribution)	Vd <1L/kg	Vd 2-3L/kg
PK: Metabolism	Piperacillin is not metabolized in man. Tazobactam is mainly metabolized to M1, an inactive metabolite.	Little hepatic metabolism
PK: Excretion	Renal: 80% unchanged + metabolite	Active tubular secretion
- Clearance (PK: Excretion)
- Half Life (PK: Excretion)	Half-life of Piperacillin-tazobactam: 0.7 to 1.2 hours	T1/2= 3 hours (renal dose adjustment required)
SPECIAL POINTS	Removed by haemodialysis

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---

Fluconazole | Amphotericin

Pharmacopeia - Antivirals and Antifungals (Level 3)

	AZOLES	AMPHOTERICIN B
GROUP	Antifungal	Antifungal
CICM Level of Understanding	Level 3	Level 3
INTRODUCTION	Triazoles: Fluconazole, Itraconazole, Voriconazole, Posaconazole Imidazoles: Clotrimazole, Ketoconazole	Polyene
USES
PHARMACEUTICS (PC)
PC: Chemical
PC: Presentation
PHARMACODYNAMICS (PD)
PD: Main Action
PD: Mode of Action	Azoles disrupt ergosterol production by interacting with 14-alpha demthylase, a cytochrome P450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of fungal cell membranes, inhibition of its synthesis leads to increased cell permeability causing leakage of contents.	Polyenes specifically target fungal membranes. They bind ergosterol, which is the principal sterol in fungal membranes as opposed to cholesterol found in host membranes. This interference creates a transmembrane channel and the resultant change in permeability allows leakage of intracellular components
PD: Route & Doses
PD: Metrics (Onset/ Peak/ Duration)
PD: Effects
PD: Spectrum of Activity	Fluc: Candida Cryptococcus Coccidia (No activity against histoplasma, blasto, sporotrichosis, Aspergillus, mucormycosis)	Broad antifungal cover including candida, Cryptococcus, aspergillus and zygomyces
PD: Resistance Mechanism	Fluc: Some candida species, Decreased drug concentration Target site alteration Up-regulation of target enzyme Development of bypass pathways
PD: Side Effects / Toxicity	Fluc: N/V/D, Abdominal pain Headache Skin rash Reversible alopecia Rare: Hepatic failure, SJS Should be avoided in Pregnancy Drug interactions: (inhibitor of CYP3A4, CYP2C9)	Dose related nephrotoxicity Infusion related reactions (hypotension, fever, rigors)
PHARMACOKINETICS (PK)
PK: Absorption	Well absorbed orally (except miconazole)	only administered IV
PK: Distribution	Fluc – good CSF penetration Itra, Keto – no CSF penetration	Poor tissue penetration. Negligable CSF or urine penetration.
Protein binding (PK: Distribution)	Itra, Keto – 99% PB	Highly protein bound
Volume of distribution (PK: Distribution)
PK: Metabolism	Fluc not metabolized well Itra, Keto – metabolized by liver	Metabolised by the liver
PK: Excretion	Fluc – Urine unchanged Itra, Keto – Excreted bile	poorly characterized but does not accumulate in renal failure
- Clearance (PK: Excretion)
- Half Life (PK: Excretion)
SPECIAL POINTS	potent CYP inhibitors with a wide range of drug interactions (including warfarin)

Column Visibility button: To choose the drugs you want to compare
Search bar: To search for something particular within the table.

---