1/25/14

Zinc

Zinc is an essential constituent of many enzymes. Deficiencies in zinc may result in poor wound healing. Zinc deficiency can occur in patients on inadequate diets, in malabsorption, with increased catabolism due to trauma, burns and protein-losing conditions, and during TPN. Hypoproteinaemia spuriously lowers plasma zinc levels.
Normal range: 12–23 μmol/l

Uses
Zinc deficiency
As an antioxidant

Administration
• Orally: zinc sulphate effervescent tablet 125 mg dissolved in water, 1–3 times daily after food

Adverse effects
Abdominal pains
Dyspepsia

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Vitamin K (Phytomenadione)

Vitamin K is necessary for the production of prothrombin, factors VII, IX and X. It is found primarily in leafy green vegetables and is additionally synthesised by bacteria that colonise the gut. Because it is fatsoluble, it requires bile salts for absorption from the gut. Patients with biliary obstruction or hepatic disease may become deficient.Vitamin K deficiency is not uncommon in hospitalised patients because of poor diet, parenteral nutrition, recent surgery, antibiotic therapy or uraemia.

Uses
Liver disease
Reversal of warfarin

Contraindications
Hypersensitivity
Reversal of warfarin when need for re-warfarinisation likely (use FFP)

Administration
• Konakion® (0.5-ml ampoule containing 1 mg phytomenadione)

IV bolus: 1–10 mg, give over 3–5 min Contains polyethoxylated castor oil which has been associated with anaphylaxis; should not be diluted

• Konakion® MM (1-ml ampoule containing 10 mg phytomenadione in a colloidal formulation)
IV bolus: 1–10 mg, give over 3–5 min
IV infusion: dilute with 55 ml glucose 5%; give over 60 min. Solution should be freshly prepared and protected from light
Not for IM injection

Maximum dose: 40 mg in 24 h

How not to use vitamin K
Do not give by rapid IV bolus
Do not give IM injections in patients with abnormal clotting
Not for the reversal of heparin

Adverse effects
Hypersensitivity

Cautions
Onset of action slow (use FFP if rapid effect needed)
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Verapamil

Verapamil - a calcium-channel blocker that prolongs the refractory period of the AV node.

Uses
SVT
AF
Atrial flutter

Contraindications
Sinus bradycardia
Heart block
Congestive cardiac failure
VT/VF – may produce severe hypotension or cardiac arrest
WPW syndrome

Administration
• IV bolus: 5–10 mg over 2 min, may repeat with 5 mg after 10 min if required

Continuous ECG and BP monitoring
Decrease dose in liver disease and in the elderly

How not to use verapamil
Do not use in combination with B-blockers (bradycardia, heart failure, heart block, asystole)

Adverse effects
Bradycardia
Hypotension
Heart block
Asystole

Cautions
Sick sinus syndrome
Hypertrophic obstructive cardiomyopathy
Increased risk of toxicity from theophylline and digoxin

Organ failure
Hepatic: reduce dose
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Vecuronium

Vecuronium - a non-depolarising neuromuscular blocker with minimal cardiovascular effects. It is metabolised in the liver to inactive products and has a duration of action of 20–30 min. Dose may have to be reduced in hepatic/ renal failure.

Uses
Muscle paralysis

Contraindications
Airway obstruction
To facilitate tracheal intubation in patients at risk of regurgitation

Administration
• Initial dose: 100 μg/kg IV
• Incremental dose: 20–30 μg/kg according to response
Monitor with peripheral nerve stimulator

How not to use vecuronium
As part of a rapid sequence induction
In the conscious patient
By persons not trained to intubate the trachea

Cautions
Breathing circuit (disconnection)
Prolonged use (disuse muscle atrophy)

Organ failure
Hepatic: prolonged duration of action
Renal: prolonged duration of action
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Vasopressin

Vasopressin (antidiuretic hormone, ADH) controls water excretion in kidneys via V2 receptors and produces constriction of vascular smooth muscle via V1 receptors. In normal subjects vasopressin infusion has no effect on blood pressure but has been shown to significantly increase blood pressure in septic shock.The implication is that in septic shock there is a deficiency in endogenous vasopressin, and this has been confirmed by direct measurement of endogenous vasopressin in patients with septic shock requiring vasopressors. In vitro studies show that catecholamines and vasopressin work synergistically.

Anecdotally, use of 3 units per hour is usually very effective and not associated with a reduction in urine output.

As its pseudonym antidiuretic hormone implies, vasopressin infusion might be expected to decrease urine output, but the opposite is the case at doses required in septic shock.This may be due to an increase in blood pressure and therefore perfusion pressure. It is also worth noting that, whereas noradrenaline constricts the afferent renal arteriole, vasopressin does not, so may be beneficial in preserving renal function. It has been shown that doses as high as 0.1 units/min (6 units/h) do reduce renal blood flow, so should be avoided.A dose of 0.04 units/min (2.4 units/h) is often efficacious in septic shock and does not reduce renal blood flow. The VAAST study (N Engl J Med 2008; 358: 877–87) found that lowdose vasopressin (0.01–0.03 units/min) in addition to noradrenaline did not reduce mortality compared with noradrenaline alone.However,benefit was seen in less severe septic shock, where mortality was lower in the vasopressin group.The less severe group were identified as those stabilized on noradrenaline at doses of 5–15 μg/min

Vasopressin does not cause vasoconstriction in the pulmonary or cerebral vessels, presumably due to an absence of vasopressin receptors. It does cause vasoconstriction in the splanchnic circulation, hence the use of vasopressin in bleeding oesophageal varices.The dose required in septic shock is much lower than that required for variceal bleeding.

Uses
In septic shock: reserve its use in cases where the noradrenaline dose exceeds 0.3 μg/kg/min (unlicensed)

Contraindications
Vascular disease, especially coronary artery disease

Administration
IV infusion: 1–4 units/h
Dilute 20 units (1 ml ampoule of argipressin) in 20 ml glucose 5% (1 unit/ml) and start at 1 unit/h, increasing to a maximum of 4 units/h

Do not stop the noradrenaline, as it works synergistically with vasopressin. As the patient’s condition improves, the vasopressin should be weaned down and off before the noradrenaline is stopped

Available as argipressin (Pitressin)
Stored in fridge between 2 and 8°C

How not to use vasopressin
Doses in excess of 5 units/h

Adverse effects
Abdominal cramps
Myocardial ischaemia
Peripheral ischaemia

Cautions
Heart failure
Hypertension
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Vancomycin (Vancocin)

This glycopeptide antibiotic has bactericidal activity against aerobic and anaerobic Gram + ve bacteria, including MRSA. It is only bacteriostatic for most enterococci. It is used for therapy of Clostridium difficileassociated diarrhoea unresponsive to metronidazole, for which it has to be given by mouth. It is not significantly absorbed from the gut.

Serum level monitoring is required to ensure therapeutic levels are achieved and to limit toxicity. Successful treatment of MRSA infections requires levels above the traditionally recommended range. Underdosing and problems associated with the sampling and the timing of serum level monitoring are problems that may result in decreased efficacy of vancomycin in the treatment of infection.The efficacy of vancomycin depends on the time for which the serum level exceeds the MIC (minimum inhibitory concentration) for the micro-organism rather than the attainment of high peak levels. Administration of vancomycin as a continuous IV infusion is therefore an ideal method of administration for optimum efficacy. Once the infusion reaches a steady state, the timing for serum level monitoring is not crucial, and samples can be taken at any time.

Vancomycin-resistant strains of enterococcus (VRE) are well recognized in the UK. Resistance also occurs less commonly in coagulase-negative staphylococci and is starting to emerge in rare isolates of Staphylococcus aureus.

Uses
C. difficile-associated diarrhoea via the oral route
Serious Gram + ve infections:
• prophylaxis and treatment of infective endocarditis (usually combined with gentamicin)
• dialysis-associated peritonitis
• infection caused by MRSA
• prosthetic device infections due to coagulase-negative staphylococci
• alternative to penicillins and cephalosporins where patients are allergic

Contraindications
Hypersensitivity

Administration
• C. difficile-associated diarrhoea
Orally: 125 mg 6 hourly for 7–10 days
For NG administration, the 500-mg reconstituted vial can be used nasogastrically for the four daily doses, otherwise 125-mg capsules can be used.

• Infective endocarditis and other serious Gram + ve infections including those caused by MRSA

IV infusion: 1 g 12 hourly, given over at least 100 min or 500 mg 6 hourly, given over at least 60 min

Duration of therapy is determined by severity of infection and clinical response. In staphylococcal endocarditis, treatment for at least 4 weeks is recommended.If pre-dose (trough) level is consistently less than 10 mg/l, (or 15–20 mg/l for less sensitive strains of MRSA), decrease the dose interval to 8 hourly or 6 hourly. If the post-dose (peak) level is >30 mg/l, decrease the dose (see therapeutic drug monitoring).

Vancomycin must be initially reconstituted by adding WFI:
• 250-mg vial – add 5 ml WFI
• 500-mg vial – add 10 ml WFI
• 1-g vial – add 20 ml WFI

The liquid in each reconstituted vial will contain 50 mg/ml vancomycin. Further dilution is required:
• reconstituted 250-mg vial – dilute with at least 50 ml diluent
• reconstituted 500-mg vial – dilute with at least 100 ml diluent
• reconstituted 1-g vial – dilute with at least 200 ml diluent

Suitable diluent: sodium chloride 0.9% or glucose 5% Continuous IV infusion

Monitor: Renal function
Serum vancomycin levels

How not to use vancomycin
Rapid IV infusion (severe hypotension, thrombophlebitis)
Not for IM administration

Adverse effects
Following IV use:
• severe hypotension
• flushing of upper body (‘red man’ syndrome)
• ototoxic and nephrotoxic
• blood disorders
• hypersensitivity
• rashes

Cautions
Concurrent use of:
• aminoglycosides – ↑ototoxicity and nephrotoxicity
• loop diuretics – ↑ototoxicity

Organ failure
Renal: reduce dose

Renal replacement therapy
CVVH dialysed, dose as in CC 10–20 ml/min, i.e. 1 g IV dose then monitor plasma levels every 24 hours until 10–15 mg/l, then give another 1 g dose and repeat this process. For continuous vancomycin infusions, consult local guidance for dosing in CVVH. HD/PD not dialysable, dose as in CC <10 ml/min, i.e. 500 mg–1 g IV every 48–96 hours. For oral/enteral treatment, no dose adjustment is needed in renal replacement therapy as insignificant absorption occurs.
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Tranexamic Acid

Tranexamic acid is an antifibrinolytic employed in blood conservation. It acts by inhibiting plasminogen activation.

Uses
Uncontrolled haemorrhage following prostatectomy or dental extraction in haemophiliacs
Haemorrhage due to thrombolytic therapy
Haemorrhage associated with DIC with predominant activation of the fibrinolytic system

Contraindications
Thrombo-embolic disease
DIC with predominant activation of coagulation system

Administration
• Uncontrolled haemorrhage following prostatectomy or dental extraction in haemophiliacs
Slow IV: 500–1000 mg 8 hourly, given over 5–10 min (100 mg/min)

• Haemorrhage due to thrombolytic therapy
Slow IV: 10 mg/kg, given at 100 mg/min

• Haemorrhage associated with DIC with predominant activation
of the fibrinolytic system (prolonged PT, ↓ fibrinogen, ↑fibrinogen degradation products)

Slow IV: 1000 mg over 10 min, single dose usually sufficient Heparin should be instigated to prevent fibrin deposition

In renal impairment:

CC (ml/min)
Dose (mg/kg)
Interval
20–50
10
12 hourly
10–20
10
every 12–24 h
<10
5
every 12–24 h

How not to use tranexamic acid
Rapid IV bolus

Adverse effects
Dizziness on rapid IV injection
Hypotension on rapid IV injection
Cautions
Renal impairment (reduce dose)

Organ failure
Renal: reduce dose

Renal replacement therapy
CVVH unknown dialysability, dose as in CC 10–20 ml/min, i.e. 10 mg/kg every 12–24 hours. HD/PD unknown dialysability, CC <10 ml/min, i.e. 5 mg/kg every 12–24 hours.
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Tigecycline (Tygacil)

Tigecycline is a glycylcycline antibiotic (structurally similar to tetracyclines) with a broad-spectrum bactericidal activity against a wide range of Gram + ve and Gram - ve aerobic and anaerobic bacteria. It acts by inhibiting protein translocation in bacteria. Tigecycline is not active against Pseudomonas aeruginosa.The primary route of elimination is biliary excretion of unchanged tigecycline.

Uses
Intra-abdominal infections including peritonitis
Skin and soft tissue infections

Contraindications
Hypersensitivity to tetracycline
Pregnancy and lactating women (permanent tooth discoloration in foetuses)
Children and adolescents under the age of 18 years (permanent tooth discoloration)

Administration
• IV infusion: initial dose of 100 mg, followed by 50 mg 12 hourly, given over 30–60 min, for 5–14 days

Reconstitute the 50-mg vial with either 5 ml sodium chloride 0.9% or 5 ml glucose 5%. For a 100 mg dose, reconstitute using two vials.Then add the reconstituted solution to 100 ml sodium chloride 0.9% or 5 ml glucose 5% and give over 30–60 min
In severe hepatic impairment (Child–Pugh C): initial dose of 100 mg, followed by 25 mg 12 hourly

Adverse effects
Hypersensitivity
Acute pancreatitis
Elevated LFTs
Hyperphosphataemia
Prolonged APPT and PT
Clostridium difficile-associated diarrhoea

Cautions
Severe hepatic impairment (reduce dose)
Concurrent use of warfarin (increased INR)

Renal replacement therapy
No dosage adjustment required
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Ticarcillin + Clavulanic Acid (Timentin)

Timentin is a broad-spectrum antibiotic with bactericidal activity against a wide range of Gram + ve and Gram -ve aerobic and anaerobic bacteria. It contains ticarcillin and clavulanic acid.The presence of clavulanic acid extends the spectrum of activity of ticarcillin to include many β-lactamase-producing bacteria normally resistant to ticarcillin and other β-lactam antibiotics. Timentin acts synergistically with aminoglycosides against a number of organisms, including Pseudomonas.

Timentin is not active against MRSA.

Uses
Intra-abdominal infections including peritonitis
Pneumonia
Urinary tract infections
Skin and soft tissue infections

Contraindications
Hypersensitivity to β-lactam antibiotics (penicillins and cephalosporins)

Administration
• IV infusion: 3.2 g 6–8 hourly (maximum 3.2 g 4 hourly)
Reconstitute 3.2-g vial with 100 ml WFI or glucose 5%, given over 30 min

In renal impairment:

CC (ml/min)
Dose (g)
Interval (h)
<30
3.2
8
10–30
1.6
8
>10
1.6
12
How not use Timentin
Do not give IV infusion over longer than 40 min, as this may result in subtherapeutic concentrations

Adverse effects
Hypersensitivity
Hypokalaemia
False-positive Coombs’ test
Thrombocytopenia
Prolonged prothrombin time

Cautions
Renal impairment (reduce dose)
Each 3.2-g vial of Timentin contains 15.9 mmol of sodium. A typical
daily dose regime may contain over 60 mmol Na+

Renal replacement therapy
CVVH unknown dialysability, dose at 2.4 g every 6–8 hours. HD dialysed, dose 1.6 g every 12 hours. PD not dialysed, dose 1.6 g 12 hourly
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Thiopentone

Thiopentone is a barbiturate that is used widely as an IV anaesthetic agent. It also has cerebroprotective and anticonvulsant activities.Awakening from a bolus dose is rapid due to redistribution, but hepatic metabolism is slow and sedative effects may persist for 24 hours. Repeated doses or infusion has a cumulative effect. Available in 500-mg ampoules or 2.5-g vial,which is dissolved in 20 or 100 ml WFI respectively to make a 2.5% solution.

Uses
Induction of anaesthesia
Status epilepticus

Contraindications
Airway obstruction
Previous hypersensitivity
Status asthmaticus
Porphyria

Administration
• IV bolus: 2.5–4 mg/kg.After injecting a test dose of 2 ml, if no pain, give the rest over 20–30 s until loss of eyelash reflex. Give further
50–100 mg if necessary

Reduce dose and inject more slowly in the elderly, patients with severe hepatic and renal impairment, and in hypovolaemic and shocked patients. In obese patients, dosage should be based on lean body mass.

How not to use thiopentone
Do not inject into an artery (pain and ischaemic damage)
Do not inject solution >2.5% (thrombophlebitis)

Adverse effects
Hypersensitivity reactions (1:14 000–35 000)
Coughing, laryngospasm
Bronchospasm (histamine release)
Respiratory depression and apnoea
Hypotension,myocardial depression
Tachycardia, arrhythmias
Tissue necrosis from extravasation

Cautions
Hypovolaemia
Septic shock
Elderly (reduce dose)
Asthma

Organ failure
CNS: sedative effects increased
Cardiac: exaggerated hypotension and ↓ cardiac output
Respiratory: ↑ respiratory depression
Hepatic: enhanced and prolonged sedative effect. Can precipitate coma
Renal: increased cerebral sensitivity
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Terlipressin

Terlipressin - oesophageal varices are enlarged blood vessels that form in the stomach or oesophagus as a complication of liver disease. When administered in bleeding oesophageal varices, terlipressin (Glypressin) is broken down to release lysine vasopressin, which causes vasoconstriction of these vessels thereby reducing the bleeding. In addition, terlipressin may have a role in the treatment of hepatorenal syndrome, by increasing renal perfusion.Terlipressin can also be used in resistant septic shock, in addition to noradrenaline.

Uses
Bleeding oesophageal varices
Resistant high-output septic shock
Hepatorenal syndrome

Contraindications
Pregnancy

Administration
• Varicies
IV bolus: 2 mg, then 1–2 mg every 4–6 hourly, for up to 3 days

• Resistant high-output septic shock (unlicensed indication)
IV 0.25 mg bolus, repeated up to 4 times with 20-min intervals between doses or IV infusion (unlicensed) 0.1 mg/h (can increase to 0.3 mg/h).Will take 20 min for first effect.The infusion can be made up with 1 mg in 5 ml with the diluent provided

• Hepatorenal syndrome (unlicensed indication)
IV bolus: 0.5–1 mg 6 hourly

Reconstitute with the supplied solvent containing sodium chloride and hydrochloric acid.There is now a perparation that does not need
reconstituting but should be stored in the fridge.

Monitor: BP
Serum sodium and potassium
Fluid balance

Adverse effects
Abdominal cramps
Headache
Raised blood pressure

Cautions
Hypertension
Arrhythmias
Ischaemic heart disease

Organ failure
Renal: no dose reduction needed
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Teicoplanin

Teicoplanin - This glycopeptide antibiotic, like vancomycin, has bactericidal activity against both aerobic and anaerobic Gram + ve bacteria: Staphylococcus aureus, including MRSA, Streptococcus spp., Listeria spp. and Clostridium spp. It is only bacteriostatic for most Enterococcus spp. It does not cause red man syndrome through histamine release and is less nephrotoxic than vancomycin. However, due to the variation between patients, effective therapeutic levels for severe infections may not be reached for a number
of days using the most commonly recommended dosage schedules. Serum monitoring of pre-dose levels is recommended, particularly for severe infections.

In the UK resistance is well recognised in enterococci and coagulasenegative staphylococci and, more worryingly, is now emerging in
S. aureus.

Uses
Serious Gram + ve infections:
• prophylaxis and treatment of infective endocarditis (usually combined with gentamicin)
• dialysis-associated peritonitis
• infection caused by MRSA
• prosthetic device infections due to coagulase-negative staphylococci
• alternative to penicillins and cephalosporins where patients are allergic

Contraindications
Hypersensitivity

Administration
IV bolus: 400 mg 12 hourly for 3 doses, then 400 mg daily. Give over 3–5 min

In obesity, use 6 mg/kg per dose (rounded to the nearest 100 mg) rather than 400mg

Reconstitute with WFI supplied. Gently roll the vial between the hands until powder is completely dissolved. Shaking the solution will cause the formation of foam. If the solution becomes foamy allow to stand for 15 min

Monitor: FBC, U&E, LFT
Serum pre-dose teicoplanin level
Pre-dose (trough) serum concentration should not be <10 mg/l For severe infections, trough serum concentration >20 mg/l is recommended. Levels are not essential for treatment In renal impairment: dose reduction not necessary until day 4, then reduce dose as below:

CC (ml/min)
Dose (mg)
Interval
20–25
400
every day
10–20
400
every 24–48 h
<10
400
every 48–72 h

How not to use teicoplanin
Do not mix teicoplanin and aminoglycosides in the same syringe

Adverse effects
Raised LFTs
Hypersensitivity
Blood disorders
Ototoxic
Nephrotoxic

Cautions
Vancomycin sensitivity
Renal/hepatic impairment
Concurrent use of ototoxic and nephrotoxic drugs

Organ failure
Renal: reduce dose

Renal replacement therapy
CVVH unknown dialysability, dose as in CC 10–20 ml/min, i.e. 400mg 12 hourly for 3 doses then 400 mg every 24–48 hours. HD/PD not dialysable, dose 400 mg 12 hourly for 3 doses then 400 mg every 48–72 hours. Can measure levels for therapy optimisation but is not
essential.
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Suxamethonium

Suxamethonium - The only depolarising neuromuscular blocker available in the UK. It has a rapid onset of action (45–60 s) and a short duration of action (5 min). Breakdown is dependent on plasma pseudocholinesterase. It is best to keep the ampoule in the fridge to prevent a gradual loss of activity due to spontaneous hydrolysis.

Uses
Agent of choice for:
• rapid tracheal intubation as part of a rapid sequence induction
• for procedures requiring short periods of tracheal intubation, e.g. cardioversion
• management of severe post-extubation laryngospasm unresponsive to gentle positive pressure ventilation

Contraindications
History of malignant hyperpyrexia (potent trigger)
Hyperkalaemia (expect a further increase in K+ level by 0.5–1.0 mmol/l)
Patients where exaggerated increase in K+ (>1.0 mmol/l) are expected:
• severe burns
• extensive muscle damage
• disuse atrophy
• paraplegia and quadriplegia
• peripheral neuropathy, e.g. Guillain–Barre´

Administration
As a rapid sequence induction: 1.0–1.5 mg/kg IV bolus, after 3 min pre-oxygenation with 100% O2 and a sleep dose of induction agent Apply cricoid pressure until tracheal intubation confirmed. Intubation possible within 1 min. Effect normally lasting <5 min Repeat dose of 0.25–0.5 mg/kg may be given. Atropine or glycopyrollate should be given at the same time to avoid bradycardia/asystole

How not to use suxamethonium
In the conscious patient
By persons not trained to intubate the trachea

Adverse effects
Malignant hyperpyrexia
Hyperkalaemia
Transient increase in IOP and ICP
Muscle pain
Myotonia
Bradycardia, especially after repeated dose

Cautions
Digoxin (may cause arrhythmias)
Myasthenia gravis (resistant to usual dose)
Penetrating eye injury ( IOP may cause loss of globe contents)
Prolonged block in:
• patients taking aminoglycoside antibiotics, magnesium
• myasthenic syndrome
• pseudocholinesterase deficiency (inherited or acquired)

Organ failure
Hepatic: prolonged apnoea (reduced synthesis of pseudocholinesterase)
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Sucralfate

Sucralfate - a complex of aluminium hydroxide and sulphated sucrose. It acts by protecting the mucosa from acid-pepsin attack.

Uses
Prophylaxis of stress ulceration

Contraindications
Severe renal impairment (CC <10 ml/min)

Administration
• Orally: 1 g suspension 4 hourly
Stop sucralfate when enteral feed commences

How not to use sucralfate
Do not give with enteral feed (risk of bezoar formation)
Do not give ranitidine concurrently (may need acid environment to work)

Adverse effects
Constipation
Diarrhoea
Hypophosphataemia

Cautions
Renal impairment (neurological adverse effects due to aluminium toxicity)

Risk of bezoar formation and potential intestinal obstruction
Interferes with absorption of quinolone antibiotics, phenytoin and digoxin when given orally

Organ failure
Renal: aluminium may accumulate

Renal replacement therapy
CVVH not dialysable, dose as in CC 10–20 ml/min, i.e. half normal dose 2–4 g daily. HD/PD not dialysable CC < 10 ml/min, i.e. 2–4 g daily.
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Spironolactone

Spironolactone is a potassium-sparing diuretic, which acts by antagonizing aldosterone. Low doses of spironolactone have been shown to benefit patients with severe congestive heart failure who are already receiving an ACE inhibitor and a diuretic. It is also of value in the treatment of oedema and ascites in cirrhosis of the liver.

Uses
Congestive heart failure
Oedema and ascites in liver cirrhosis

Contraindications
Hyperkalaemia
Hyponatraemia
Severe renal failure
Addison’s disease

Administration
• Congestive heart failure
  Orally: 25–50 mg once daily
• Oedema and ascites in liver cirrhosis
  Orally: 100–400 mg once daily

If IV route is needed, use potassium canrenoate (unlicensed drug). Conversion: potassium canrenoate 140 mg is equivalent to spironolactone 100 mg.Administer by IV bolus via a large vein at a maximum rate of 100 mg/min, otherwise administer via IV infusion in 250 ml of glucose 5% over 90 min

Monitor: serum sodium, potassium and creatinine

Adverse effects
Confusion
Hyperkalaemia (unlikely to occur with congestive heart failure dose)
Hyponatraemia
Abnormal LFT
Gynaecomastia (usually reversible)
Rashes
Cautions
Porphyria
Renal impairment (risk of hyperkalaemia)
Concurrent use of:
• ACE inhibitor (risk of hyperkalaemia)
• angiotensin-II antagonist (risk of hyperkalaemia)
• digoxin ( plasma concentration of digoxin)
• ciclosporin (risk of hyperkalaemia)
• lithium ( plasma concentration of lithium)

Organ failure
Renal: risk of hyperkalaemia; use with caution in severe renal failure
Hepatic: may precipitate encephalopathy

Renal replacement therapy
CVVH not dialysable, dose as in CC 10–20 ml/min, i.e. half normal dose. HD/PD not dialysable, use with caution; 25 mg three times per
week appears safe.
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Sodium Valproate (Epilim)

Sodium valproate is used to treat epilepsy. The IV route is chosen only when the oral/nasogastric route is unavailable. The therapeutic range for trough plasma valproic acid levels is 40–100 mg/l (278–694 μmol/l), though there is a less reliable correlation between the level and efficacy. The oral form is available as a liquid (200 mg/5 ml), which is useful for nasogastric administration, and tablets, crushable tablets and in modified release formulations. Sodium valproate should not be confused with valproic acid (as semi-sodium valproate), which is licensed for acute mania.

Uses
All forms of epilepsy, including emergency management

Administration
For conversion of oral to IV doses, the same daily dose is used in divided doses administered over 3–5 min

Initiating IV valproate: 400–800 mg (up to 10 mg/kg), then IV infusion of up to 2.5 g maximum

To prepare, reconstitute 400-mg vial with 4 ml diluent provided and further dilute to a convenient volume with sodium chloride 0.9% or
glucose 5%. It may be administered as a bolus over 3–5 min or as a continuous infusion

Oral: usually 20–30 mg/kg/day in two divided doses

Adverse effects
Transient raised LFTs
Severe liver dysfunction, which can be fatal
Hyperammonaemia and hyponatraemia
Rarely exanthematous rash

Cautions
Pancreatitis
Liver toxicity
Sodium valproate is eliminated mainly through the kidneys, partly in the form of ketone bodies; this may give false positives in urine testing Sodium valproate concentrations are reduced by carbamazepine and phenytoin.Valproate increases or sometimes decreases phenytoin levels, and increases levels of lamotrigine

Organ failure
Renal: no dose adjustment required
Hepatic: avoid if possible; hepatotoxicity and hepatic failure may occasionally occur
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Sildenafil

Sildenafil (Viagra, Revatio), epoprostenol (Flolan), bosentan (Tracleer) and sitaxentan (Thelin) are licensed for the treatment of pulmonary hypertension.Epoprostenol is the only one available for intravenous use. Sildenafil is a potent and selective inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5), the enzyme that is responsible for degradation of cGMP. Apart from the presence of this enzyme in the corpus cavernosum of the penis, PDE5 is also present in the pulmonary vasculature. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells, resulting in relaxation. In patients with pulmonary arterial hypertension this can lead to vasodilatation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation.

Uses
Pulmonary hypertension

Contraindications
Recent stroke or MI
Severe hypotension (SBP < 90mmHg)
Severe hepatic impairment (Child-Pugh class C)
Avoid concomitant use of nitrates, ketoconazole, itraconazole and ritonavir

Administration
• Orally: 20 mg 8 hourly
   Renal impairment: 20 mg 12 hourly
   Hepatic impairment (Child-Pugh class A and B): 20 mg 12 hourly

Adverse effects
GI disturbances
Dry mouth
Flushing
Headaches
Back and limb pain
Visual disturbances
Hearing loss
Pyrexia

Cautions
Hypotension (avoid if SBP < 90mmHg)
Dehydration
Left ventricular outflow obstruction
IHD
Predisposition to priapism
Bleeding disorders
Active peptic ulceration
Hepatic impairment (avoid if severe)
Renal impairment (reduce dose)
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Salbutamol

Uses
Reverses bronchospasm

Administration
• Nebuliser: 2.5–5 mg 6 hourly, undiluted (if prolonged delivery time desirable then dilute with sodium chloride 0.9% only)

For patients with chronic bronchitis and hypercapnia, oxygen in high concentration can be dangerous, and nebulisers should be driven by air
• IV: 5 mg made up to 50 ml with glucose 5% (100 μg/ml)
Rate: 200–1200 μg/h (2–12 ml/h)

How not to use salbutamol
For nebuliser: do not dilute in anything other than sodium chloride 0.9% (hypotonic solution may cause bronchospasm)

Adverse effects
Tremor
Tachycardia
Paradoxical bronchospasm (stop giving if suspected)
Potentially serious hypokalaemia (potentiated by concomitant treatment with aminophylline, steroids, diuretics and hypoxia)

Cautions
Thyrotoxicosis
In patients already receiving large doses of other sympathomimetic drugs
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Rifampicin

Rifampicin is active against a wide range of Gram +ve and Gram -ve organisms, but resistance readily emerges during therapy due to preexisting mutants present in most bacterial populations. It must therefore be used with a second antibiotic active against the target pathogen. Its major use is for therapy of tuberculosis.

Uses
In combination with vancomycin for:
• penicillin-resistant pneumococcal infections including meningitis
• serious Gram + ve infections including those caused by MRSA
• prosthetic device-associated infections

Legionnaires’ disease (in combination with a macrolide antibiotic) Prophylaxis of meningococcal meningitis and Haemophilus influenza (type B) infection Combination therapy for infections due to Mycobacterium tuberculosis

Contraindications
Porphyria
Jaundice

Administration
• Serious Gram +ve infections (in combination with vancomycin)
• Legionnaires’ disease (in combination with a macrolide antibiotic)
  Oral or IV: 600 mg 12 hourly
• Prophylaxis of meningococcal meningitis infection
  Oral or IV: 600 mg 12 hourly for 2 days
  Child 10 mg/kg (under 1 year, 5 mg/kg) 12 hourly for 2 days
• Prophylaxis of Haemophilus influenzae (type b) infection
  Oral or IV: 600 mg once daily for 4 days
  Child 1–3 months 10 mg/kg once daily for 4 days, over 3 months
  20 mg/kg once daily for 4 days (maximum 600 mg daily)

IV formulations are available as Rifadin and Rimactane Reconstitute with the solvent provided, then dilute with 500 ml (for Rifadin) or 250 ml (for Rimactane) of glucose 5%, sodium chloride 0.9% or Hartmann’s solution, given over 2–3 hours
Monitor: FBC, U&E, LFT

Adverse effects
GI symptoms (nausea, vomiting, diarrhoea)
Bodily secretions (urine, saliva) coloured orange-red
Abnormal LFT
Haemolytic anaemia
Thrombocytopenic purpura
Renal failure

Cautions
Discolours soft contact lenses
Women on oral contraceptive pills will need other means of contraception

Organ failure
Hepatic: avoid or do not exceed 8 mg/kg daily (impaired elimination)
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Remifentanil (Ultiva)

Remifentanil (Ultiva) is a potent, short-acting, selective μ opioid receptor agonist. In critical care, it has been used for sedation and analgesia in mechanically ventilated adult patients.The concept of analgesia-based sedation represents a move away from traditional analgesic/hypnoticbased sedation, and with appropriate training this may be an easier regimen to manage. Remifentanil is also licensed for use in general anaesthesia. It has an onset of action of approximately 1 min and quickly achieves steady state. It is metabolised rapidly by non-specific blood and tissue esterases into clinically inactive metabolites.Thus the terminal half-life of 10–20 min is independent of infusion duration and renal and hepatic dysfunction.Though more expensive than traditional nanalgesic/hypnotic-based regimens, some units use remifentanil particularly in patients with renal or hepatic dysfunction, to avoid accumulation and prolonged sedation. Other possible indications for remifentanil include overnight ventilation, tracheostomy and ready to wean, difficult weans (e.g. COPD cardiovascular disease, obesity, problems of withdrawal following long-term sedation), head injuries or patients with low GCS requiring regular assessment, raised intracranial pressure (resistant to medical management) and to assess neurological function in mechanically ventilated patients.

Concerns around use of remifentanil include side-effects of hypotension and bradycardia, possible development of tolerance (common to all opioids) and the onset of pain on discontinuation of remifentanil.

Uses
Analgesia and sedation in mechanically ventilated adults. Trials have been conducted for up to 3 days of use.

Contraindications
Epidural and intrathecal use, as formulated with glycine
Hypersensitivity to fentanyl analogues

Administration
• IV: initially 0.1 μg/kg/min, evaluate after 5 min, if pain, anxiety or agitation or difficult to wake, then titrate infusion up or down with steps of 0.025 μg/kg/min (range 0.007–0.75 μg/kg/min).At a dose of 0.2 μg/kg/min, if the patient is in pain or ventilator intolerant, increase the infusion by additional steps of 0.025 μg/kg/min until adequate pain relief. At a dose of 0.2 μg/kg/min, if the patient is anxious or agitated then add a hypnotic agent, e.g. midazolam (bolus up to 0.03 mg/kg or initial infusion 0.03 mg/kg/h) or propofol (bolus up to 0.5 mg/kg or initial infusion 0.5 mg/kg/h)

• Additional analgesia will be required for ventilated patients undergoing stimulating procedures such as suctioning,wound dressing and physiotherapy. An infusion of 0.1 μg/kg/min should be maintained for at least 5 min prior to intervention. Further adjustments every 2–5 minutes in increments of 25–50% may be needed

• To extubate and discontinue remifentanil, titrate in stages to 0.1 μg/kg/min over 1 hour prior to extubation. After extubation, reduce infusion rate by 25% at least every 10 min till discontinuation. If residual pain is expected use alternative opioid

Reconstitute vial to 100 μg/ml, i.e. 5-mg vial with 50 ml, 2 mg with 20 ml, and 1 mg with 10 ml of diluent. Suitable diluents are WFI, glucose 5% or sodium chloride 0.9% In obesity, use ideal body weight rather than actual weight In the elderly, reduce initial dose by 50% Due to the short half-life, a new syringe should be ready for use at the end of each infusion.

How not to use remifentanil
Bolus doses are not recommended in the critical care setting. Not to be used as a sole induction agent

Adverse effects:
• hypomagnesaemia
• bradycardia
• hypotension
• respiratory depression
• muscle rigidity
• dependency

Cautions
Upon discontinuation, the IV line should be cleared or removed to prevent subsequent inadvertent administration

Organ failure
Renal: no dose adjustment necessary
Hepatic: no dose adjustment, but in severe disease respiratory depression more common

Organ replacement therapy
Not removed by dialysis, so no dose adjustment required in renal replacement therapy
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