Pharmacopoeia ICU Flashcards
ACETAZOLAMIDE / DIURETIC
Acetazolamide, whilst considered a class of diuretics is rarely used for this purpose
because excess carbonic anhydrase it requires very high doses to be effective and
due to the loss of HCO3
- associated with its use causes a metabolic acidosis and urinary alkanisation. It is mainly used for the treatment of glaucoma and altitude
sickness and may be used as an adjunct in epilepsy (increased CO2 decreases
seizure spread).
It is presented as a white tablet with a dose of 250mg.
Inhibits carbonic anhydrase in the proximal tubule cells which therefore reduces the production of H+ and HCO3- from H2O and CO2 which CA normally catalyses.
This theoretically leads to a decrease in sodium excretion via the sodium-H antiporter, and thus increased water excretion. In the eye it blocks the same reaction but the decreased is the most important aspect leading to less aqueous humour secretion and therefore lowers intraocular pressures.
ABSORPTION bioavailabilty ~100% routes of administration oral (IV also possible)
doses glaucoma 250mg q6hr
onset / duration
DISTRIBUTION lipid solubility crosses BBB protein binding highly protein bound
METABOLISM mechanism not metabolised
ELIMINATION half life 6–9 hours excretion Urine (70% to 100% as unchanged drug)
Up to 50% of patients prescribed acetazolamide do not tolerate its side effects.
Most side effects related to the metabolic acidosis and urinary alkanisation.
Contraindicated in patients with acidosis, may worsen sodium and potassium
depletion. Can cause parathesias, fatigue, drowsiness, depression, n+v, abdo pain.
ADENOSINE / OTHER ANTIARRHYTHMIC
Adenosine is a natural purine nucleoside. It slows conduction through the
atrioventricular node which makes it an effective treatment for the termination of
paroxsmal SVT. It is also used sometimes for slowing rapid atrial arrhythmias to aid
diganosis.
Adenosine is only available as a clear liquid with 6mg in 2mL.
It acts on the A1 adenosine receptors found in the SA and AV. It markedly slows or
completely blocks conduction in the atrioventricular node, probably by hyperpolarizing
this tissue (through increased IK1) and by reducing calcium current. This causes a temporary heart block and/or asystolic pause which acts to terminate the supra ventricular rhythm.
ABSORPTION bioavailabilty 100% routes of administration IV only doses 3-6mg as a bolus onset / duration seconds / seconds DISTRIBUTION volume of distribution not applicable
METABOLISM mechanism Rapidly deaminated in plasma and taken up by red blood cells
ELIMINATION half life ffects are transient but can be distressing for
patients (sense of impending doom). It may induce AF or flutter due to the reduced refractory period. It is contraindicated in sick sinus syndrome. It is avoided in asthmatics and pts with COPD as it may cause bronchospasm
ADRENALINE/ CATECHOLAMINE
Is a naturally occurring catecholamine that is released the adrenal medulla. It is used in a critical care setting for maintenance of haemodynamic parameters via increase in total peripheral resistance, in arrest situations as part of the ACLS protocols and in the setting of bronchoconstriction and anaphylaxis as a mast cell stabiliser.
It is an additive in local anesthetics to lower dosage by causing local vasoconstriction.
It is presented in clear solution only, usually 1mg/mL in 5 and 50 mL vials and in minijets with 1mg in 10mL (1:10000).
It also comes in combination with lignocaine for local anaesthesia with a concentration of 1:80000-200000.
It may also be nebulised. It is not stable in an alkaline solution as it oxidises to
adrenochrome and turns pink, therefore it is usually in an acidic solution.
It is a non selective adrengeric agonist. At lower doses it has vasodilatory effects and bronchial dilation via beta2 receptors. At higher doses beta1 agonism leads to
increased inotropy and chronotropy. At the highest doses it is primarily a
vasoconstrictor. It also stabilses mast cells which is why it is used in acute anaphylaxis.
ABSORPTION bioavailabilty 100%
routes of administration IV, IM, SC, Inhaled, ETT
doses 1mg in arrest, 0.1mg in anaplaxis,
infusion dose is 0.1 -0.3 mcg/kg/min beta effects
>0.3mcg/kg/min for alpha (vasoconstrictive effects)
onset / duration: immediate / 1-2 minutes
DISTRIBUTION lipid solubility doesn’t cross the BBB
METABOLISM mechanism Taken up into the adrenergic neuron and metabolized by monoamine oxidase and catechol-o-methyltransferase; circulating drug hepatically metabolized
ELIMINATION half life 2 minutes
excretion Urine as inactive metabolites,
High doses cause severe hypertension, tachyarrhythmias, and deranged metabolic states with increased glucogenolysis, lipolysis and gluconogenesis. Insulin production is initially increased (beta2) but later decreased (alpha) limiting use in DM. Can worsen PHTN. Avoid in glaucoma. Peripheral necrosis may occur.
ALFENTANIL / SYNTHETIC OPIOID
Is a synthetic phenylpiperidine. It is a μ receptor agonist and therefore has a mode
of action similar to morphine. Pharmacokinetic features, in particular the pKa
ensure however signicant differences to the related opioids such as fentanyl. It is
marketed as an induction agent but is usually used for its analgesic properties.
COMPARED TO FENTANYL
Both synthetic phenylpiperidine derivatives, Alfentanil 1/5th as potent, Eect-site
equilibration time =1.4 min, pKa = 6.5, 10x as much alfentanil present in unionised
form at pH 7.4, More rapid transfer across blood brain barrier, Only 10% 1st pass
pulmonary uptake for alfentanil, Alfentanil lower clearance rate but shorter t1/2
10x variability in alfentanil clearance because of interpersonal variability of CYP3A4
Lower Vd (4-6x smaller than fentanyl), Less lipid soluble, Both 85-90% protein bound
Alpha 1 acid glycoprotein, Alfentanil has sorter context sensitive half time following
prolonged infusions
PHARMACEUTICAL ASPECTS
Alfentanil is presented as a colourless solution containing 500mcg/ml in 2 of 5ml
vials.
PHARMACODYNAMIC ASPECTS
It has the same mode of action and generally similar eects to morphine
PHARMACOKINETIC ASPECTS
MAJOR ISSUES OR SIDE EFFECTS
ABSORPTION bioavailabilty 100%
routes of administration IV
doses 7mcg/kg up to 50 mcg/kg if ventilated
onset / duration rapid / 30-60 minutes
DISTRIBUTION volume of distribution 0.5 L/kg (much lower than fentanyl)
protien binding 85-90%
lipid solubility less than fentanyl (more than morphine)
pKa 6.5, mostly non ionised therefore crosses the BBB
rapidly
METABOLISM mechanism Liver by N - demethylation
ELIMINATION half life 1.5 hours (shorter context sensitive compared fent
excretion urine
as per other opiates
GENTAMICIN / AMINOGLYCOSIDE
Gentamicin is the aminoglycoside of choice because of its lower cost and reliable activity against gram negative bacillary infections. 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.
PHARMACEUTICAL ASPECTS:
Presented as clear solution for injection. Requires monitoring of levels especially
if there is any renal impairment, to prevent complications.
PHARMACODYNAMIC ASPECTS:
Aminoglycosides are bactericidal antimicrobials that block protien synthesis by
binding to the bacterial 30S ribosomal subunit.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty no oral absorption, rapid and complete IM
routes of administration IV (poor lipid solubility)
doses 3-10mcg/kg depending on severity
onset / duration 30mins
DISTRIBUTION volume of distribution 0.2-0.3 L/kg
protien binding ammed meniges (30%)
METABOLISM mechanism not metabolised
ELIMINATION half life 1.5-3 hrs, +++ in renal impairment (up to 70hrs)
excretion urine as unchanged drug
Dose dependent nephrotoxicity and otoxicity. May cause C.Di overgrowth. They
decrease the prejunctional release of acteylcholine, which reduces post junctional
sensitivity to acetlycholine and therefore increases NDMR activity and cause muscle weakness.
AMIODARONE / CLASS III (ALL CLASS ACTIONS)
Amiodarone is a benzofuran derivative which contains 37% iodine by weight and
structurally resembles thyroxine. Although usually considered a class III antiarrhythmic is displays actions of all four classes. It is now preferred over procainamide and
lignocaine for the treatment of unstable VT and VF. It is also used for SVT, VT and
WPW and o label for most arrhythmias in a critical care setting.
PHARMACEUTICAL ASPECTS
It is presented in 100mg and 200mg tablets and as a clear uid with a concentration of 50mg/mL. It has a therapeutic concentration range of 1-2.5mg/L but
monitoring is rarely necessary.
PHARMACODYNAMIC ASPECTS
As noted it has all class actions, It blocks sodium, calcium, and potassium channels
and adrenoceptors. The result is a prolonging of the eective refractory period of
all cardiac tissues, including the sinoatrial node, atrium, atrioventricular node,
His-Purkinje system, and ventricle.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty poorly absorbed, bioavailability 40-70%
routes of administration PO/IV
doses PO 200mg TDS 1/52, BD 1/52, then OD, 5mg/kg over
one hour then 15mg/kg over 24 hours IV
onset / duration 2 days to 3 weeks / 1 week to 5 months
DISTRIBUTION volume of distribution 66 L/kg (range: 18-148 L/kg)
protien binding 96%
METABOLISM mechanism Hepatic via CYP2C8 and 3A4 to active
N-desethylamiodarone metabolite
ELIMINATION half life Terminal: 40-55 days
excretion Faeces, urine, skin and lachrymal glands
MAJOR ISSUES OR SIDE EFFECTS
Amiodarone has major side effects that worsen over time and affect most patients.
Respiratory - it may cause pneumonitis, brosis or pleuritis. Endocrine - it may cause
hypothyroidism (6%) or hyperthroidism (1%). Hepatic - it is associated with cirrhosis,
hepatitis and jaundice. LFT monitoring is recommended. Ophthalmic - corneal
microdeposits occur commonly but usually resolve of cessation. Cardiac - it is not
particularly arrhythmogenic despite QT prolongation (likely because of it multiple
actions) but can cause bradycardia and hypotension.
AMPICILLIN / BETALACTAM ANTIBIOTIC
PHARMACEUTICAL ASPECTS
PHARMACODYNAMIC ASPECTS
PHARMACOKINETIC ASPECTS
MAJOR ISSUES OR SIDE EFFECTS
Ampicillin is an aminopenicillin and is also known as a broad spectrum penicillin. It
is eective against the same range of organisms as benpen but because it is more
hydrophilic it penetrates the pores of the outer phospholipid membrane of gram
negatives thus giving it some activity against some H. inuenza, Salmonella, E. coli
and E. faecalis. It is inactivated by beta-lactamases and are may be given with
clauvanic acid.
May be given orally or parenterally, however amoxycillin is preferred orally due to
its improved oral bioavailability. It is marketted under several trade names in
Australia.
Beta-lactam antibiotics inhibit the growth of sensitive bacteria by inactivating
enzymes located in the bacterial cell membrane, which are involved in the third
stage of cell wall synthesis. It is during this stage that linear strands of peptidogly
can are cross-linked, beta lactams prevent this linking occuring.
ABSORPTION bioavailabilty 50%
routes of administration PO, IV or IM
doses Usually given QID or TDS in up to 70mg/kg/day
DISTRIBUTION volume of distribution ~0.38 L/kg
protien binding 15% to 25%
lipid solubility penetration into CSF occurs with inamed
meninges only
METABOLISM mechanism Minimal metabolism
ELIMINATION half life 1-1.8 hours, prolonged in anuria/renal impair
excretion Urine (90% as unchanged drug) within 24 hours
Up to 10% of the population have allergies to penicllins. Due to the high percent
age excreted renally unchanged dose adjustment is required in low urine output
ASPIRIN / IRREVERSIBLE NONSELECTIVE NSAID
PHARMACEUTICAL ASPECTS
PHARMACODYNAMIC ASPECTS
PHARMACOKINETIC ASPECTS
MAJOR ISSUES OR SIDE EFFECTS
Aspirin (acetylsalicylic acid) is a non selective non steroidal antinammatory drug
which is used for its analgesic, anti inammatory and its irrevesible binding to
platelets and subsequent reduction of thromboembolic events such as acute
myocardial infarction and stroke.
Aspirin is usually presented as 300mg or 100mg tablets.
Irreversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, via acetyla
tion, which results in decreased formation of prostaglandin precursors; irreversibly
inhibits formation of prostaglandin derivative, thromboxane A2, via acetylation of
platelet cyclooxygenase, thus inhibiting platelet aggregation; has antipyretic,
analgesic, and anti-inammatory properties
ABSORPTION bioavailabilty Rapid, 50%-75% reaches systemic circulation
routes of administration oral
doses 100mg for antiplatelet, 300-900mg other
onset / duration 4-6 hours
DISTRIBUTION volume of distribution Vd: 10 L;
protien binding 85% mostly albumin
pKa 3 weak acid, mostly non ionised, therefore good gastric
absorption, although may become trapped in mucosal cells.
most absorption is therefore in the small bowel)
METABOLISM mechanism Hydrolyzed to salicylate (active) by esterases in
GI mucosa, red blood cells, synovial uid, metabolism of
salicylate occurs primarily by hepatic conjugation; metabolic
pathways are saturable
ELIMINATION half life Parent drug: 15-20 minutes; Salicylates (dose
dependent): 3 hours at lower doses (300-600 mg), 5-6 hours
(after 1 g), 10 hours with higher doses
excretion Urine (75% as salicyluric acid, 10% as salicylic
acid)
Normal NSAID side eects. See AI summary regarding toxicity.
Christopher Andersen 2012
ATROPINE / ANTICHOLINERGIC
PHARMACEUTICAL ASPECTS
PHARMACODYNAMIC ASPECTS
PHARMACOKINETIC ASPECTS
MAJOR ISSUES OR SIDE EFFECTS
Atropine is a naturally occuring tertiary amine derived from the belladona plant. It’s
anticholinergic activity is used to antagonize the muscarinic eects produced by
anticholinesterase drugs, in the management of intraoperative bradycardia during
general anaesthesia, or in the treatment and diagnosis of organophosphate
poisoning. In ophthalmology it is used to induce mydriasis and cycloplegia to aid
examination.
Atropine’s anticholinergic activity is primarily due to the L enantiomer although it
is presented as a racemic mixture. Although previously available in oral formula
tions it is only available or for topical application to the eye.
Low doses of atropine (2mcg/kg) act centrally and may augment vagal outow,
decreasing heart rate. At normal clinical doses (15-70mcg/kg) atropine also acts on
peripheral muscarinic receptors blocking the action of the vagal nerve and
increasing the heart rate and pupil size whilst decreasing secretory gland activity.
The latter is particularly important in cholinergic poisoning to reduce bronchor
rhoea and bronchoconstriction. Other eects include reduced tone in the gut, bile
ducts, and contractions in the ureter and bladder.
ABSORPTION bioavailabilty 100% (Oral
routes of administration IV
doses 15-70 mcg/kg
onset / duration rapid / 1-2 hours
DISTRIBUTION volume of distribution 1-2 l/kg rapidly distributed from
central compartment on administration
protien binding 50% plasma bound
METABOLISM mechanism extensively metabolised by liver esterases
ELIMINATION half life 2-3 hours
excretion urine (fraction unchanged)
Although less pronounced than scopolamine (hyoscine) high doses and overdos
age of atropine may cause a central anticholinergic syndrome characterised by
excitement, hallucinations and hyperpyrexia. In overdosage this leads to coma,
respiratory depression and death.
BENZYLPENICILLIN / BETALACTAM ANTIBIOTIC
PHARMACEUTICAL ASPECTS
PHARMACODYNAMIC ASPECTS
PHARMACOKINETIC ASPECTS
MAJOR ISSUES OR SIDE EFFECTS
Benzyl penicillin was the rst penicillin and remains an important antibiotic toda
It is also known as penicllin G. It’s specturm of coverage includes gram positive
pathogens, gram negative cocci and some gram negative bacilli. Its most commo
use is for treating streptococci, syphyllis and nesseria.
It is inactivated by the acid in the stomach so is therefore normally delivered
parenterally either IM or IV. In Australia its trade name is BenPen. It is presented a
a powder for reconstitution.
Beta-lactam antibiotics inhibit the growth of sensitive bacteria by inactivating
enzymes located in the bacterial cell membrane, which are involved in the third
stage of cell wall synthesis. It is during this stage that linear strands of peptidogly
can are cross-linked, beta lactams prevent this linking occuring.
ABSORPTION bioavailabilty Poorly available orally due to low gut pH.
routes of administration IV or IM
doses Usually given QID in up to 24g/day
DISTRIBUTION volume of distribution ~0.35 L/kg
protien binding 65%
lipid solubility Poor penetration across blood
brain barrier, slight improvement with inamed meninges
METABOLISM mechanism Hepatic (30%) to penicilloic acid
ELIMINATION half life Normal renal function: 30-50 minutes
excretion Urine (58% to 85% as unchanged drug)
Up to 10% of the population have allergies to penicllins. Due to the high percent
age excreted renally unchanged dose adjustment is required in low urine output
states. High doses used in critical care settings lower seizure thresholds. Benpen
has a high sodium content.
BUPIVACAINE / LOCAL ANAESTHETIC
including LEVOBUPIVACAINE and ROPIVACAINE
PHARMACEUTICAL ASPECTS
PHARMACODYNAMIC ASPECTS
PHARMACOKINETIC ASPECTS
MAJOR ISSUES OR SIDE EFFECTS
Is an amide local anaesthetic. It is used primarily in spinal and epidural anaesthesia.
It may be prepared in a concentrated glucose solution (80mg/mL), this is marketed
as ‘heavy’ marcain.
It is presented as a racemic mixture. An alternative presentation is levobupiva
caine which is as the name suggests only the S (-) enantiometer which is less
cardiotoxic. Ropivacaine is a very similar drug it is also only the S (-) enantiom
eter with marginally dierent amide side chain, this confers reduced toxicity and
slightly decreased potency (lipid solubiltiy)
Similar to lignocaine they block nerve conduction by inhibiting voltage gated
sodium channels at an intracellular site probably within the pore of the channel.
Local anaesthetics once bound to the channel stabilise and prolong the duration
of the inactivated state, thus preventing sodium channel opening during further
depolarisations. Sensory function is more sensitive to local anaesthetic block than
motor function possibly due to greater sensitivity of the small myelinated bres.
ABSORPTION routes of administration SC, IM, Intrathecal
dose 15-20mg intrathecally
Max dose 2mg/kg with or without adrenaline
onset / duration route and dose dependent 1-15min/ 2-9 hrs
DISTRIBUTION protien binding (duration) ~95% higher than lignocaine
lipid solubility (potency) higher than lignocaine
pKa (onset) 8.1 higher than lignocaine = slower onset
METABOLISM mechanism Hepatic;
ELIMINATION half life 2.7 hours
excretion Urine (~6% unchanged)
Has the same issues as lignocaine but at lower doses. The R enantiomer seems to
cause cardaic issues earlier than the S enantiomer hence the development of
levobupivacaine and the S enantiomer ropivacaine.
CAPTOPRIL / ACE INHIBITOR
PHARMACEUTICAL ASPECTS
PHARMACODYNAMIC ASPECTS
PHARMACOKINETIC ASPECTS
MAJOR ISSUES OR SIDE EFFECTS
Captopril is an active drug converted to active metabolites. It is a competitive ACE
inhibitor that is used for management of hypertension, LV dysfunction post
myocardial infarction and in the setting of heart failure. It’s use has been shown to
decrease progression of heart failure (disease modifying).
It is an oral formulation presented as white tablets in dosage ranging from
12.5mg to 50mg.
Cardiovascular - Competitive inhibition of angiotensin coverting enzyme leads to
decreased angiotensin II production and its eects. TPR and Afterload is decreased
to a greater extent than preload, and this may result in improved CO in heart
failure patients. HR is usually unchanged and baroreceptor reexes also
unchanged. Renal- the impairment of AngII means that the body is less able to
respond to a drop in renal perfusion and this may precipitate failure. Metabolic -
Accumulation of K+ may occur due to decreased aldosterone.
ABSORPTION bioavailabilty rapidly absorbed, bioavailability of 60-70%
routes of administration oral
doses commenced at 6.25mg TDS and uptitrated
potency moderately potent
DISTRIBUTION protien binding 25% protien bound
METABOLISM mechanism oxidised in the liver and coverted to sulphides
ELIMINATION half life 2-4 hours
excretion urine both as active metabolites and unchanged
A dry cough may occur especially in patients with pre-exisiting lung disease.
Caution should be exercised in patients on potassium sparing medications. NSAIDs
may precipitate renal failure.
CARVEDILOL / BETA & ALPHA BLOCKER
PHARMACEUTICAL ASPECTS
PHARMACODYNAMIC ASPECTS
PHARMACOKINETIC ASPECTS
MAJOR ISSUES OR SIDE EFFECTS
Carvedilol is a third generation non selective beta blocker with alpha 1 antagonist
properties. It is used to reduce the excessive adrenergic activity that occurs in
response to heart failure. It may be also used in the treatment of hypertension.
It is only available in oral form in both immediate and sustained release
formulations.
Beta blockage leads to decreased G
s
activity in receptor associated organs and
associated decrease in adenylyl cyclase and intracellular Ca2+. It produces
decreases in heart rate and cardiac output and myocardial oxygen consumption.
Alpha blockage leads to decrease G
q
activation and subsequent decrease in IP3 and
intracellular Ca2+.
ABSORPTION bioavailabilty rapid and extenisve absorption but high rst
pass metabolism leading to bioavailability of 25-35%
routes of administration oral
doses start at 6.25 BD and doubled 1/52 until not tolerated
DISTRIBUTION volume of distribution 105 L/kg
protien binding 98% to albumin
lipid solubility moderate lipid solubility
METABOLISM method Extensively hepatic, via CYP2C9, 2D6, 3A4, three
active metabolites
ELIMINATION half life 7-8 hours
excretion in faeces
Similar to other betablockers with respect to the withdrawal aspects, use in the
setting of COPD and with Ca Channel blockers and Halothane. Due to its
metabolism it should be used in caution in liver failure patients and elderly.
CEFTRIAXONE / CEPHALOSPORIN
PHARMACEUTICAL ASPECTS
PHARMACODYNAMIC ASPECTS
PHARMACOKINETIC ASPECTS
MAJOR ISSUES OR SIDE EFFECTS
“Ceftriaxone” is a third-generation cephalosporin antibacterial 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, gynaeco
logical infections, and early Lyme disease.
Clear solution for injection
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin
binding proteins (PBPs) which in turn inhibits the nal transpeptidation step of
peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthe
sis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes
(autolysins and murein hydrolases) while cell wall assembly is arrested.
ABSORPTION bioavailabilty Well absorbed when given IM
routes of administration IV/IM
doses 1-2 g daily
onset / duration serum peak in 2-3 hrs (following IM inj)
DISTRIBUTION volume of distribution 6-14L
protien binding 85-95%, may lead to non linear dose
dependent responses
lipid solubility crosses the BBB regardless of meingeal in
METABOLISM mechanism only partial
ELIMINATION half life up to 8 hours enabling daily dosing
excretion urine 33-66% unchanged and in the bile
highly protein bound and is able to displace bilirubin from albumin binding sites,
causing hyperbilirubinaemia; its use should be avoided in jaundiced neonates.
Biliary sludge or pseudolithiasis due to a precipitate of calcium “ceftriaxone” has
been seen occasionally in patients given “ceftriaxone”.
CIPROFLOXACIN / FLUOROQUINOLONE
Ciprooxacin is a uoroquinolone which inhibits nucleic acid synthesis. It is activeagainst a wide range of gram negative and some gram positive bacteria (streptococcus and enterococcus have moderate sensitivity).
PHARMACEUTICAL ASPECTS
Is available in both oral and IV formulations (clear solution). Marketed under several trade names including ciproxin.
The quinolones are bactericidal antimicrobials that inhibit the alpha subunit of the
DNA gyrase enzyme. This enzyme is responsible for the negative supercoiling of
bacterial and when activated rapidly results in cell death.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty Oral: Rapid (~50% to 85%)
routes of administration IV and PO
doses 250-750mg PO BD or 200-300mg IV BD
onset / duration peak concentration in 2hrs PO
DISTRIBUTION volume of distribution 2.1-2.7 L/kg, tissue concentrations
may exceed serum concentrations
protien binding 20% to 40%
lipid solubility 10% CSF penetration (up to 40%
with inflammed meninges)
METABOLISM mechanism Partially hepatic; metabolites (limited activity)
ELIMINATION half life 3-5 hrs, extended in renal failure
excretion Urine (30% to 50% as unchanged drug); feces
(15% to 43%)
MAJOR ISSUES OR SIDE EFFECTS
Can cause issues with G6PD patients, may cause nausea, vomitting and abdominal
pain. Caution in epileptic patients as it may cause seizures, confusion and
restlessness. Some issues with anaphylaxis.
CLONIDINE / CENTRAL ALPHA
2 AGONIST
Clonidine is a partial alpha agonist with an affinity for alpha2 receptors 200 times
that for alpha1 receptors. In addition to its use in refractory hypertension it is also
used as an adjunct in pain management and during anaesthesia. It has been used
in patients withdrawing from opioids and for the diagnosis of phaechromocytoma.
PHARMACEUTICAL ASPECTS
It is available both in oral form as a white tablet in dosages of 100-150mcg and IV/IM forms as a colourless solution with 150mcg/ml.
PHARMACODYNAMICS
The useful effects of clonidine rest on its ability to stimulate alpha2 receptors in the lateral reticular nucleus resulting in decreased central sympathetic outow by a positive feedback mechanism, and in the spinal cord where it augments
endogenous opiate release and modulates descending noradrenergic pathways.
Cardio - transient increase in BP due to alpha2 agonism peripherally but this is followed by a more prolonged fall in BP. CO is usually maintained despite
bradycardia. CNS - sedation and anxiolysis at low doses but anxigenic at higher doses. Provides analgesia without respiratory centre depression and is synergistic with opiods. Renal - inhibition of ADH may be the cause of diuresis. Endocrinestress response to surgery inhibited. Insulin release in reduced, usually BSL ok.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty Immediate release: 75% to 85%
routes of administration Oral, IV and IM
doses usually 150-300mcg twice daily
DISTRIBUTION volume of distribution 2.1 L/kg
protien binding 20% to 40%
lipid solubility highly lipid soluble in order to cross the BBB
METABOLISM mechanism Extensively hepatic to inactive metabolites
ELIMINATION half life 12-16 hours (increased in pts with renal disease)
excretion Urine (40% to 60% as unchanged drug)
MAJOR ISSUES OR SIDE EFFECTS
The multiple effects of this drug make it intolerable to many patients, with
somnolence and dry mouth being a frequent concern. It may cause profound
bradycardia if used with beta blockers. If withdrawn suddenly it may cause a rebound hypertension.
CLOPIDOGREL / PLATELET ADP ANTAGONIST
Clopidogrel is a thienopyridine derivative which acts as a non competitive antagonist of platelet surface ADP, which is responsible for platelet aggregation. It is used for prevention of vascular ischaemic events, as an adjuvant in the treatment of NSTEMI (when grafting is not indicated) and in the management of patients post
stenting.
PHARMACEUTICAL ASPECTS
It is presented as 75mg tablets. A loading dose of 300mg should be used when
instigating treatment. It’s trade name is Plavix.
PHARMACODYNAMIC ASPECTS
Clopidogrel irreversibly prevent ADP from binding to its receptor on the platelet surface, thereby preventing the glycoprotien IIb/IIIa receptor transforming into its active form.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty Well absorbed
routes of administration oral
doses 300mg loading, 75mg daily
onset / duration 2hrs / 5 days
DISTRIBUTION volume of distribution
protien binding Parent drug: 98%; Inactive metabolite: 94%
METABOLISM mechanism Extensively hepatic via esterase-mediated
hydrolysis, active metabolite and inactive metabolite
ELIMINATION half life Parent drug: ~6 hours; Active metabolite: ~30 mins
excretion Urine (50%); feces (46%)
MAJOR ISSUES OR SIDE EFFECTS
Commonly causes GI irritation. Issues with haemorrhage. Rarely causes neutropaenia.
DEXMEDETOMIDINE / CENTRAL ALPHA 2 AGONIST
Is a central alpha2 agonist which is primarily used for its sedating properties for the
short term management of intubated patients. It has greater selectivity and
potency than clonidine with an alpha1:alpha2 ratio of 1:1600.
PHARMACEUTICAL ASPECTS
Medetomidine is a racemic misture but only the D-Stereoisomer is active, so it has been developed as dexmedetomidine. Although textbooks indicate that oral
preparations exist in Australia its usage is IV only.
PHARMACODYNAMIC ASPECTS
Broadly similar to clonidine although sedative and analgesic aspects predominate.
It is believed that this is due to central activation of alpha2 adrenoceptors in the
locus cerrulus. Peripheral alpha2b-adrenoceptors are activated at high doses or
with rapid I.V. administration resulting in vasoconstriction. Its lack of respiratory
depression increases its utility in the ICU setting.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty IV therefore 100%
routes of administration IV
doses Usually 1mcg/kg over 20 minutes, then a mainte
nence dose of 0.2-0.7 mcg/kg per hour titrated
onset of action I.V. Bolus: 5-10 minutes
DISTRIBUTION volume of distribution Vss: ~118 L
protien binding ~94%
lipid solubility
METABOLISM mechanism Hepatic via N-glucuronidation, N-methylation,
and CYP2A6
ELIMINATION half life ~6 minutes;
excretion Urine (95%); feces (4%)
MAJOR ISSUES OR SIDE EFFECTS
There may be a transient hypertension on commencement followed by hypotension and bradycardia. Other side eFFects include dry mouth, hypotension,
bradycardia and the risk of a rebound hypertension on withdrawal.
DIAZEPAM / BENZODIAZEPINE
Is a benzodiazepine used for the management of anxiety disorders, ethanol
withdrawal symptoms; skeletal muscle relaxant; treatment of convulsive disorders;
preoperative or preprocedural sedation and amnesia.
PHARMACEUTICAL ASPECTS
Available in a range of different formulations, tablets, oral suspension, rectal gel,
IV. Trade name valium.
PHARMACODYNAMIC ASPECTS
Benzodiazepines appear to produce all their pharmacologic eects by facilitating
the actions of gamma-aminobutyric acid (GABA), the principal inhibitory
neurotransmitter in the CNS. Benzodiazepines do not activate GABAA receptors
but rather enhance the anity of the receptors for GABA. As a result of this
drug-induced increased anity of GABA receptors for the inhibitory neurotrans
mitter, an enhanced opening of chloride gating channels results in increased
chloride conductance, thus producing hyperpolarization of the postsynaptic cell
membrane
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty Oral: 85% to 100%
routes of administration PO, IV, IM
doses 5-20mg PO
onset / duration IV rapid onset / prolonged action
DISTRIBUTION volume of distribution 1-1.5 L/kg (same as midazolam)
protien binding 98%
lipid solubility v. high
METABOLISM mechanism Hepatic oxidation, slow clearance and +++
context sensitive half time if delivered as infusion. Reduce
dose in liver failure. clearance is much slower than midaz
ELIMINATION half life Parent drug: 20-50 hours Active major metabolite
(desmethyldiazepam): 50-100 hours
excretion
MAJOR ISSUES OR SIDE EFFECTS
Main issues are from overdosage and excessive sedation and depression of
respiratory drive. Causes tolerance and dependence and may precipitate
withdrawals if ceased following long term use.
DIGOXIN / OTHER ANTIARRHYTHMIC, INOTROPE
Digoxin is a glycoside derived from the dried leaves of the foxglove. It is used in AF
and atrial utter, SVT and in heart failure
PHARMACEUTICAL ASPECTS
Digoxin in available in oral tablets 62.5mcg or 250mcg and injectable for with a
concentration of 25-250mcg/ml. There is a narrow therapeutic window and
monitoring is necessary, with most aiming for the lower range of 0.5-2mcg/L
concentrations (often around 1mcg/L)
PHARMACODYNAMIC ASPECTS
The direct effect of digoxin is via Inhibition of Na+/K+ ATPase is considered to be
the primary biochemical mechanism of action. Then higher intracellular Na
reduces action of the Na-Ca pump leading to decreased calcium extrusion and
therefore increased intracellular Ca therefore increased inotropy. Other direct
eects include an increased AV node refractory node period but decreased
ventricle refractory period. Indirect eects are mediated by the vagus nerve and
include bradycardia, reduced refractory period in the atrial muscle and an
augmentation of the direct increase in AV node refractory period. It is the AV node
actions and bradycardia which are eective treating AF and Flutter.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty 60% to 80%
routes of administration PO / IV
doses loading 250-500mcg QID then 62.5-125mcg daily
onset / duration Oral: 1-2 hours; I.V.: 5-60 mins / 3-4 days
DISTRIBUTION volume of distribution 6-7 L/kg thyroid status important
protien binding ~25%; in uremic patients, digoxin is
displaced from plasma protein binding sites
METABOLISM mechanism Via sequential sugar hydrolysis in the stomach
or by reduction of lactone ring by intestinal bacteria ,
minimal hepatic metabolism, most excereted unchanged
ELIMINATION half life 36-48 hours
excretion Urine (50% to 70% as unchanged drug)
MAJOR ISSUES OR SIDE EFFECTS
Thyroid function has signicant effects on VD increasing in hyper and decreasing in
hypothyroidism. It is toxic above concentrations of 2.5mcg/L causing arrhythmias,
and AV block. It also causes anorexia, nausea and vomitting, diarrhoea and lethargy.
Red green colour perception may be altered. ECG changes include prolonged PR, ST
depression, T wave flattening and QT shortening (may not indicate toxicity).
DILTIAZEM / Ca2+ CHANNEL BLOCKER
Diltiazem is a nondihydropyridine calcium channel blocker. It is used for angina and hypertension.
PHARMACEUTICAL ASPECTS
Is available in sustained and immediate release oral formulations, 60-360mg
PHARMACODYNAMIC ASPECTS
Similar to the other Ca Channel blockers in terms of blood pressure. Produces
more peripheral vasodilation than verapamil and more conduction delay than the
dihydropyridines such as nifedipine.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty Well absorbed high rst pass metabolism
leading to bioavailability of 40%
routes of administration oral or IV
doses 30-80mg TDS
onset / duration tablet: 30-60 minutes; I.V.: 3 minutes
DISTRIBUTION volume of distribution 3-13 L/kg
protien binding 70% to 80%
METABOLISM mechanism Hepatic active metabolites desacetyldiltiazem
ELIMINATION half life 3-4.5 hours (prolonged in renal failure)
excretion Urine ( 4% as unchanged, 7% as metabolites);
feces
MAJOR ISSUES OR SIDE EFFECTS
Peripheral oedema is a common side eect, 2-3 weeks post initiation of therapy.
Other side eects include ushing, vertigo, headaches, hypotension and
parathesias.
DIPYRIDAMOLE / PLATELET PDE INHIBITOR
Dipyridamole acts by inhibiting phophodiesterase, which increases platelet cAMP
and inhibits platelet aggregation. It’s main use is in the prevention of stroke when
in combination with aspirin. It may have a marginal additive benefit in patients
with prosthetic heart valves when used in combination with warfarin. It is a potent
vasodilator and is sometime used in cardiac function testing.
PHARMACEUTICAL ASPECTS
It is available in both oral and IV formulations and is known as persantin. In combination with aspirin it is traded as asasantin. If take orally it should be taken
away from meals as this leads to variable absorption.
PHARMACODYNAMIC ASPECTS
Dipyridamole inhibits platelet adhesion to damaged vessel walls (by inhibiting
adenosine uptake), potentiates the effects of prostacyclin and at high doses
inhibits platelet phophodiesterase activity resulting in increased cAMP levels and lower intraplatelet calcium levels. Compared to aspirin it inhibits platelet adhesion to vessel walls more than aggregation. It is a potent coronary artery dilator via the
phosphodiesterase inhibition mechanism.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty variable depending on concurrent oral intake
routes of administration IV and oral
doses 200mg BD for CVA prevention
onset / duration onset is within 1hr, peak 2hrs
DISTRIBUTION volume of distribution 2-3 L/kg
protien binding 90-99%
METABOLISM mechanism hepatic glucoridation, incomplete
ELIMINATION half life 10-12 hours
excretion faeces as glucoronides and unchanged
MAJOR ISSUES OR SIDE EFFECTS
Major side effects relate to its vasodilatory properties making it unsafe in patients
with recent MIs and aortic stenosis. Other issues relate to its anti thrombotic
behaviours and the risk of haemorrhage.
DOBUTAMINE / CATECHOLAMINE
Dobutamine is a direct acting synthetic catecholamine derivative of isoprenaline. It
has primarily beta1 agonising activity although there remains some beta2 activity.
It is used for inotropic support in acute heart failure and cardiogenic shock due to
MI. It is also used as a pharmacological alternative to exercise during stress testing
of the heart.
PHARMACEUTICALS
It is available as a white powder for reconsititution (250mg) or as a clear uid for injection with 12.5mg/mL in 20ml vials. It should not be mixed with alkaline solutions due or sodium bicarbonate.
PHARMACODYNAMICS
Its main actions are via direct agonism of beta1 receptors leading to increased contractility, chronotropy and myocardial oxygen demand. Blood pressure is usually increased despite some peripheral vasodilatation due to weak beta2 effects. It may precipitate tachyarrythmias in patients with AF or AFlut due to
increased AV conduction. It does not eect the splanchnic or renal circulation
although there may be a slight increase in urine output secondary to CO increase.
PHARMACOKINETICS
ABSORPTION bioavailabilty 100%
routes of administration IV
doses 2.5-5mcg/kg/min uptitrate to 40mcg/kg/min max
onset / duration 1-10 minute /10-20 minutes
DISTRIBUTION no data
METABOLISM mechanis In tissues and hepatically to inactive metabolites
ELIMINATION half life 2 minutes
excretion Urine (as metabolites)
MAJOR ISSUES OR SIDE EFFECTS
Hypertensive patients may exhibit such an exaggerated pressor response more
frequently. Caution in pts with AF/AFlut due to risk of tachcardias (digoxin may be
needed). May cause ventricular ectopic activity. Increasing myocardial O2 demand
may worsen ischaemia especially in setting of MI. Evidence of the development of
tolerance.
DOPAMINE / NATURAL CATECHOLAMINE
Dopamine is a natural catecholamine which acts centrally as a neurotransmitter
and peripherally it has naturetic and diuretic properties. When given at signiFIcantly higher than physiological doses it has beta and eventually alpha adrenergic eects
including increased inotropy. It is used primarily for improving haemodynamic
parameters and increasing urine output.
PHARMACEUTICAL ASPECTS
Dopamine is presented as clear liquid for injection in concentration of 40mg/mL
in 5 mL vials. It should ideally be administered via a central line as extravasation
may lead to necrosis. It should not be administered with alkaline solutions such
as sodium bicarbonate.
PHARMACODYNAMIC ASPECTS
In addition to its eects on alpha and beta receptors, dopamine also acts via
dopamine (D1 and D2) receptors via Gs and Gi coupled adenylyl cyclase leading to
increased or decreased levels of cAMP. At low doses it is a vasodilator (due to D
1
activation) and at high doses it demonstrates increased chronotropy, vasoconstric
tion then inotropy (beta then alpha adrenergic activation).
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty 100%
routes of administration IV only
doses commence @ 2.5 mcg/kg/min up to max 60 mcg/kg/min
onset / duration 5 minutes / 10 minutes
DISTRIBUTION lipid solubility does not cross the BBB
METABOLISM mechanism Renal, hepatic, plasma by COMT and MAO
; 75% to inactive metabolites and
25% to noradrenaline
ELIMINATION half life 2 minutes
excretion Urine (as metabolites)
MAJOR ISSUES OR SIDE EFFECTS
It is important to ensure adequate lling prior to initiation of therapy. At very high
doses it may cause peripheral tissue necrosis due to vasoconstriction. May cause
vomitting due to chemoreceptor zone activation. Caution should be exhibited
when patient is using MAO inhibitors.
ENOXAPARIN (LMWH) / ANTICOAGULANT
Consisting of smaller fragments of heparin, LMWH is prepared from unfractionated
heparin by controlled enzymatic or chemical depolymerization. The mean
molecular weight of LMWH is 5000, one-third the mean molecular weight of
unfractionated heparin. It has similar indications to unfractionated heparin.
PHARMACEUTICAL ASPECTS
Usually given SC, but can be given IV for a more rapid response.
PHARMACODYNAMICS
Like heparin, LMWH exerts its anticoagulant activity by activating antithrombin.
With a mean molecular weight of 5000, which corresponds to about 17 saccharide
units, at least half of the pentasaccharide-containing chains of LMWH are too short
to bridge thrombin to antithrombin. Consequently, LMWH catalyzes factor Xa
inhibition by antithrombin more than thrombin inhibition
PHARMACOKINETICS
ABSORPTION bioavailabilty 90% after SC injection (more than heparin)
routes of administration SC (occasionaly IV)
doses 1mg/kg BD therapeutic, 20 or 40mg OD Prophylactic
onset / duration Antifactor Xa activity: ~12 hours
DISTRIBUTION volume of distribution 4.3 L (based on antifactor Xa activity)
protien binding Does not bind to heparin binding proteins
METABOLISM mechanism Hepatic, to lower molecular weight fragments
(little activity)
ELIMINATION half life 2-4 times longer than standard heparin,
independent of dose;
excretion Urine (40% of dose; 10% as active fragments)
MAJOR ISSUES OR SIDE EFFECTS
Unlike heparin, enoxaparin is excreted renally and as such it requires dose
adjustment in the setting of renal impairment. It has an improved side eect
prole however with signicantly less thrombocytopaenia and osteoporosis,
enabling long term treatment.
ERYTHROMYCIN / MACROLIDE ANTIBIOTIC
Erythromycin is the parent drug of the macrolides, but newer drugs such as
clarythromicin and roxithromycin are also available. They have a similar range of activity to penicillins and may be used as an alternative in patients with allergy.
They cover most gram positive organisms, Neisseria and haemophilis, with activity
against gram positive and gram negative aneorobes. They may also be used as a
prokinetic in critical care.
PHARMACEUTICAL ASPECTS
Available in both oral and IV
PHARMACODYNAMIC ASPECTS
Macrolides are baceteridal or bacteriostatic bepending on plasma concentration.
They halt bacterial protien synthesis by binding to the 50S ribosomal subunit.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty 18% to 45%
routes of administration PO/IV
doses up to 4g per day in divided doses
onset / duration 2-4 hrs to peak, food dependent
DISTRIBUTION volume of distribution
protien binding 73% to 81%
lipid solubility minimal CSF penetration some improve
ment with inammed meninges
METABOLISM mechanism Demethylation primarily via hepatic CYP3A4
ELIMINATION half life 1.5-2 hours
excretion Primarily feces; urine (2% to 15% as unchanged
drug)
MAJOR ISSUES OR SIDE EFFECTS
Nausea, vomitting and diarrhoea occur especially following IV delivery due to the
prokinetic eect. Associated with a prolonged QT with attendant risk of arryth
mias. Actions of warfarin, theophylline and digoxin may all be increased with
coadministration of macrolides.
ESMOLOL / BETA BLOCKER
Is a cardioselective beta blocker with rapid onset and oset. It is used for the short
term management tachycardia and hypertension in a monitored patient and for
SVT termination. It has no intrinsic sympathomimetic activity or membrane
stabilising properties.
PHARMACEUTICAL ASPECTS
It is only available as an IV formulation. It is presented as a clear liquid usually at a
concentration of 10mg/ml.
PHARMACODYNAMIC ASPECTS
Beta blockage leads to decreased Gs activity in receptor associated organs and
associated decrease in adenylyl cyclase and intracellular Ca2+. It produces
decreases in heart rate and cardiac output and myocardial oxygen consumption.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty Only available as IV therefore 100%
routes of admin IV
dose In 10mg increments titrate to eect
DISTRIBUTION volume of distrib 3.5 L/Kg
protien binding 60% to albumin
lipid solubility is high so it crosses the BBB
METABOLISM neither hepatic or renal! by red blood cell esterases to a
mostly inactive metabolite
ELIMINATION half life 10 minutes
excretetion In urine
MAJOR ISSUES OR SIDE EFFECTS
Care should be taken when used in conjuction with opiods and halothane and in
patients with obstructive airway disease. Use with Ca Channel blockers may result
in complete heart block. It is an irritant to veins and may lead to tissue necrosis
with extravasation
FENTANYL / SYNTHETIC OPIOID
Fentanyl is a synthetic phenylpiperidine derivative with a rapid onset of action. It is
a μ receptor agonist and as such it shares morphines eects. It’s main dierences
are due to it’s lipid solubility, rapid redistribution and prolonged context sensitive
half time.
PHARMACEUTICAL ASPECTS
Fentanyl is presented as a colourless solution for injection containing 50 mcg/ml,
as transdermal patches (25mcg-100mcg per hour) and as lozenges.
PHARMACODYNAMIC ASPECTS
It has the same mode of action and generally similar eects to morphine although
it is less likely to precipitate histamine release.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty 50-70% when taken buccal/sublingual route
routes of administration IM, IV, buccal, topical
doses Bolus: 1-2 mcg/kg or 25-100 mcg/dose; continuous
infusion rate: 1-2 mcg/kg/hour or 25-200 mcg/hour
onset I.M.: 7-8 mins; I.V immediate; Transdermal 6 hours
duration I.M.: 1-2 hours; I.V.: 0.5-1 hour; Transdermal 12 hrs
DISTRIBUTION volume of distribution 4-6 L/kg
protien binding 80% to 85%
lipid solubility Highly lipophilic (600 times morphine)
pKa 8.4 (10% ionised)
METABOLISM mechanism Hepatic, primarily via CYP3A4
ELIMINATION half life I.V.: 2-4 hours, prolonged context sensitive half time
excretion Urine 75%
MAJOR ISSUES OR SIDE EFFECTS
The side effect profile is similar to morphine. Differences are due to the lipid solubility. Unlike morphine it does not cause delayed respiratory depression
because it rapidly diuses into and out of the CSF. Because of the raised context
sensitive half time prolonged infusion may lead to increased duration of action
and subsequent side eects.
FLECAINIDE / CLASS IC ANTIARRHYTHMIC
Flecainide is a fluorinated derivative of procainamide. Flecainide is used in the
prophylaxis and treatment of paroxysmal atrial brillation or utter, SVT and serious ventricular arrhythmias not responsive to other therapies including DC
shock.
PHARMACEUTICAL ASPECTS
It is presented as an IV presentation in 10mg/ml or in an oral preparation in 50 or
100mg tablets. Concentration monitoring aims for a therapeutic range of 0.-0.9
mg/L
PHARMACODYNAMIC ASPECTS
Flecainide prevents the fast sodium f;ux into cardiac tissue and prolongs phase 0
of the action potential. It has no eect on the action potential duration or the
refractory period. Its eects are more pronounced in the conduction pathways. It
has moderate negative inotropic eects.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty rapidly absorbed, 90% bioavailability
routes of administration IV/ PO
doses IV 2mg/Kg over 10 minutes, PO 50-100mg BD
DISTRIBUTION volume of distribution 6-10kg/L
protien binding 50%
METABOLISM mechanism hepatic with active metabolites
ELIMINATION half life 7-22 hours, increased with congestive heart
failure or renal dysfunction; End-stage renal disease:
excretion Urine (80% to 90%, 10% to 50% as unchanged
drug and metabolites)
MAJOR ISSUES OR SIDE EFFECTS
Dizziness, parathesia and headaches complicate use. The major drawback of
ecainide however is the proarrhythmogenic aspects, especially in the setting of
LV dysfunction or recent MI. has signicant pharmacokinetic interactions with many other drugs, including digoxin, propranolol and amiodarone.
FLUCLOXACILLIN/BETA LACTAM ANTIBIOTIC
Flucloxacillin is a semi synthetic penicillin which has a narrow spectrum but is
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.
PHARMACEUTICAL ASPECTS
May be given orally or parenterally. It is marketed under several trade names in
Australia including Flopen. It is available in tablet form or powder for reconstitution.
PHARMACODYNAMIC ASPECTS
Beta-lactam antibiotics inhibit the growth of sensitive bacteria by inactivating
enzymes located in the bacterial cell membrane, which are involved in the third
stage of cell wall synthesis. It is during this stage that linear strands of peptidoglycan are cross-linked, beta lactams prevent this linking occuring.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty 50–70%
routes of administration PO, IV or IM
doses Usually given QID or TDS in up to 2g/day
DISTRIBUTION volume of distribution ~0.28 L/kg
protien binding up to 95%
lipid solubility penetration into CSF occurs with inamed
meninges only
METABOLISM mechanism Hepatic with active metabolites
ELIMINATION half life 0.75–1 hours, prolonged in anuria/renal impair
excretion Urine (50-65% as unchanged drug)
MAJOR ISSUES OR SIDE EFFECTS
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.
FLUMAZENIL / BENZODIAZEPINE ANTAGONIST
Flumazenil is an imidazobenzodizepine. It is a competitive antagonist at benzodiazepine and is used for the reversal of BDZ sedation used for anaesthesia. It may be
used for BDZ overdose or intoxication but it is rarely indicated for this use due to
the associated risks of precipitating a withdrawal syndrome.
PHARMACEUTICAL ASPECTS
It is available in injectable form, 0.1mg/ml in 5ml vials.
PHARMACODYNAMICS
Competes with benzodiazepines at GABAA receptors and reduces the potentiation
eect of BDZ at this receptors. Flumazenil does not antagonize the CNS eect of
drugs aecting GABA-ergic neurons by means other than the benzodiazepine
receptor (such as ethanol, barbiturates, general anesthetics) and does not reverse
the eects of opioids.
PHARMACOKINETICS
ABSORPTION bioavailabilty 100%
routes of administration IV
doses 0.1-0.3mg initially, titrate to eect up to 2mg
onset / duration 1-3 mins / ~1 hour (nb may wear o prior
to metabolism of the BDZ thus a return to sedation is a
concern).
DISTRIBUTION volume of distribution Initial Vd: 0.5 L/kg
protien binding 40% to 50%
METABOLISM mechanism Hepatic; dependent upon hepatic blood ow
(therefore prolonged in liver failure)
ELIMINATION half life biphasic, initial 10 mins, terminal 40-80mins
excretion urine
MAJOR ISSUES OR SIDE EFFECTS
Side eects include nausea and vomitting. It may precipitate anxiety and agitation.
Major concern is precipitating a withdrawal syndrome in a BDZ dependent patient,
therefore caution should be exercised when considering its use.
FRUSEMIDE / LOOP DIURETIC
Frusemide is an organis ion that enter the tubular lumen primarily through
secretion into the proximal tubule. Frusemide is a carboxylic acid derivative and
represents the most potent diuretic available, are responsible for an 25% increase
in the excretion of sodium ltered load. It is used in severe heart failure to reduce
peripheral and pulmonary oedema. It may also be used in chronci and acute renal
failure.
PHARMACEUTICAL ASPECTS
It is available as both a tablet form in 20 and 40mg quantities and for IV injection
PHARMACODYNAMIC ASPECTS
Frusemide acts in the thick ascending limb of the loop of Henle where it inhibits
Na+ reabsorption by blocking the Na+.K+.2Cl- symporter located in the apical
membrane of these cells and causing a signicant diuresis. It produces arteriolar
vasodilation which reduces TPR. Preload is also reduced ahead of any diuresis. In
contrast to thiazides there is a decrease in renal blood ow. The main electrolyte
disturbances are hypokalaemia, hyponatraemia, hypomagnesmaemia and a
hypochloraemic alkalosis.
PHARMACOKINETIC ASPECTS
ABSORPTION bioavailabilty Orally - 50% (20mg PO = 10mg IV)
routes of administration PO, IV, SL, IM
doses ranging from 10-20mg stat to 2-3g grams per day
onset Diuresis: Oral, S.L: 30-60 minutes; I.V.: ~5 minutes
duration Oral, S.L.: 6-8 hours; I.V.: 2 hours
DISTRIBUTION protien binding 91% to 99%; primarily to albumin
METABOLISM mechanism Minimally hepatic
ELIMINATION half life Normal renal function: 0.5-2 hours; End-stage
renal disease: 9 hours
excretion Urine (Oral: 50%, I.V.: 80% as unchanged drug)
MAJOR ISSUES OR SIDE EFFECTS
It may cause ototoxicity, especially if delivered in high doses rapidly, this is
compounded by impaired renal function and the use of aminoglycosides.
Electrolyte disturbances as liste above, often given with potassium replacement or
potassium sparing drugs.
