BNF - Chapter 9 - Blood and nutrition Flashcards
Before initiating treatment for anaemia it is essential to determine what?
To determine which type of anaemia is present - iron salts may be harmful if given to patients with anaemias other than those due to iron deficiency
What is sickle-cell disease?
Sickle-cell disease is caused by a structural abnormality of haemoglobin resulting in deformed, less flexible red blood cells
What is sickle-cell crisis?
where infarction of the microvasculature and restricted blood supply to organs results in severe pain.
What does sickle-cell crisis usually require?
Sickle-cell crisis usually requires hospitalisation, fluid replacement, analgesia, and treatment of any concurrent infection
What does haemolytic anaemia require?
Folate supplementation
What does folate supplementation help in sickle cell anaemia?
Helps to make new red blood cells as haemolytic anaemia increases erythropoiesis; this may increase folate requirements and supplementation with folic acid is recommended
Which drug can reduce the frequency of sickle cell crisis?
Hydroxycarbamide can reduce the frequency of crises and the need for blood transfusions in sickle cell disease
However the beneficial effects may not be evident for several months
What is G6PD deficiency?
Glucose 6-phosphate dehydrogenase (G6PD) deficiency is common in individuals originating from Africa, Asia, the Mediterranean region, and the Middle East; it can also occur less frequently in all other individuals.
Is G6PD deficiency more common in male or female?
In Males
What is haemolytic anaemia?
Hemolytic anemia is a disorder in which red blood cells are destroyed faster than they can be made. The destruction of red blood cells is called hemolysis
Individuals with G6PD deficiency are susceptible to developing what if they take a number of common drugs or when they have an infection?
acute haemolytic anaemia
They are also susceptible to developing acute haemolytic anaemia when they eat fava beans (broad beans); this is termed favism.
When prescribing drugs for patients with G6PD deficiency what three points should be kept in mind?
G6PD deficiency is genetically heterogeneous; susceptibility to the haemolytic risk from drugs varies; thus, a drug found to be safe in some G6PD-deficient individuals may not be equally safe in others;
manufacturers do not routinely test drugs for their effects in G6PD-deficient individuals;
the risk and severity of haemolysis is almost always dose-related.
Which drugs have a definitive risk of haemolysis in most G6PD-deficient individuals?
Dapsone and other sulfones Fluoroquinolones (including ciprofloxacin, moxifloxacin, norfloxacin, and ofloxacin) Methylthioninium chloride Nitrofurantoin Primaquine Quinolones Rasburicase Sulfonamides (including co-trimoxazole)
Which drugs have a possible risk of haemolysis in some G6PD-deficient individuals?
Aspirin
Chloroquine
Menadione, water-soluble derivatives (e.g. menadiol sodium phosphate)
Quinine (may be acceptable in acute malaria)
Sulfonylureas
What may be used as a immunosuppressive treatment for aplastic anaemia?
Intravenous horse antithymocyte globulin in combination with ciclosporin
Why is prednisolone used?
Prednisolone is used for the prevention of adverse effects associated with antithymocyte globulin treatment.
When are epoetins (recombinant human erythropoeitins used)
Epoetins (recombinant human erythropoietins) are used to treat anaemia associated with erythropoietin deficiency in chronic renal failure, to increase the yield of autologous blood in normal individuals and to shorten the period of symptomatic anaemia in patients receiving cytotoxic chemotherapy.
Which Epoetin is licensed for the prevention of anaemia in preterm neonates of low-birth weigh?
Epoetin - a therapeutic response may take several weeks
Compare Darbepoetin alfa to epoetin beta?
Darbepoetin alfa is a hyperglycosylated derivative of epoetin; it has a longer half-life and can be administered less frequently than epoetin.
What is Stevens’-Johnson syndrome (SJS)?
is a rare, serious disorder of the skin and mucous membranes. It’s usually a reaction to medication that starts with flu-like symptoms, followed by a painful rash that spreads and blisters. Then the top layer of affected skin dies, sheds and begins to heal after several days
What has been associated in patients treated with erythropoietins?
- rare cases of Steven’s-Johnson syndrome
What should patients be counselled on when on erthropoetin treatment?
Patients and their carers should be advised of the signs and symptoms of severe skin reactions when starting treatment and instructed to stop treatment and seek immediate medical attention if they develop widespread rash and blistering; these rashes often follow fever or flu-like symptoms—discontinue treatment permanently if such reactions occur.
What should the haemoglobin concentration be maintained within when on erythropoietin treatment?
10-12g/100ml
Haemoglobin concentrations higher than 12g/100ml should be avoided
What route should iron salts be given for iron deficiency anaemia?
By mouth unless there are good reasons for using another route
Is haemoglobin regeneration rate affected by the type of iron salt used?
It is little affected by the type of salt used provided sufficient iron is given, and in most patients the speed of response is not critical
what is the choice of preparations of iron salts decided by?
- side effects and cost
List the different iron salts and their content of ferrous iron?
Iron salt/amount Content of ferrous iron
ferrous fumarate 200 mg 65 mg
ferrous gluconate 300 mg 35 mg
ferrous sulfate 300 mg 60 mg
ferrous sulfate, dried 200 mg 65 mg
What should be noted about the folic acid content in iron preparations listed above?
It is important to note that the small doses of folic acid contained in these preparations are inadequate for the treatment of megaloblastic anaemias.
How daily administration are modified release preparations of iron tablets licensed for?
One-daily administration
What may the lower side effects with modified release preparations be associated with?
the low incidence of side-effects may reflect the small amounts of iron available for absorption as the iron is carried past the first part of the duodenum into an area of the gut where absorption may be poor.
What can iron be administered parentally as?
Iron can be administered parenterally as iron dextran, iron sucrose, ferric carboxymaltose, or ferric derisomaltose.
Does parenteral iron produce a faster haemoglobin response than oral iron?
With the exception of patients with severe renal failure receiving haemodialysis, parenteral iron does not produce a faster haemoglobin response than oral iron provided that the oral iron preparation is taken reliably and is absorbed adequately
Is parenteral iron given as a total dose or in divided doses?
Depending on the preparation used, parenteral iron is given as a total dose or in divided doses.
What should further treatment of parenteral iron be guided by?
Further treatment should be guided by monitoring haemoglobin and serum iron concentrations
What have been reported (serious side effects) with parenteral iron use?
Serious hypersensitivity reactions, including life-threatening and fatal anaphylactic reactions
These reactions can occur even when a previous administration has been tolerated (including a negative test dose).
Are test doses of parenteral iron recommended?
No longer recommended and caution is needed with every dose of IV iron
Can intravenous iron be used in pregnancy?
Intravenous iron should be avoided in the first trimester of pregnancy and used in the second or third trimesters only if the benefit outweighs the potential risks for both mother and fetus.
What has ferric carboxymaltose (IV iron) been associated with
The risk of persistent hypophosphatemia
For elderly, oral iron doses above what mg has no evidence of enhanced iron absorption?
Prescription potentially inappropriate (STOPP criteria) at oral doses greater than 200 mg elemental iron daily (no evidence of enhanced iron absorption above these doses).
What are some common side effects of oral iron?
Constipation; diarrhoea; gastrointestinal discomfort; nausea
What therapeutic levels should be aimed for with oral iron use?
The haemoglobin concentration should rise by about 100–200 mg/ 100 mL (1–2 g/litre) per day or 2 g/100 mL (20 g/litre) over 3–4 weeks.
When the haemoglobin is within the normal range, treatment should be continued for how many more months?
A further 3 months to replenish the iron stores
Can iron supplements change the colour of your stools?
yes - to a greenish or grayish black colour - this is normal
What is megaloblastic anaemia?
Megaloblastic anemia is a condition in which the bone marrow produces unusually large, structurally abnormal, immature red blood cells (megaloblasts).
what do most megaloblastic anaemia result from?
From a lack of vitamin B12 or folate and it is essential to establish in every case which deficiency is present and the underlying cause
what may you do in emergencies in megaloblastic anaemia?
In emergencies, when delay might be dangerous, it is sometimes necessary to administer both substances after the bone marrow test while plasma assay results are awaited.
What is one cause of megaloblastic anaemia in the UK?
One cause of megaloblastic anaemia in the UK is pernicious anaemia in which lack of gastric intrinsic factor resulting from an autoimmune gastritis causes malabsorption of vitamin B12.
When else is vitamin B12 also needed in the treatment of megaloblastosis?
in the treatment of megaloblastosis caused by prolonged nitrous oxide anaesthesia, which inactivates the vitamin, and in the rare syndrome of congenital transcobalamin II deficiency.
Which B12 therapy is used more commonly now?
Hydroxocobalamin has completely replaced cyanocobalamin as the form of vitamin B12 of choice for therapy;
Which is retained in the body for longer - hydroxocobalamin or cyanocobalamin?
Hydroxycobalamin is is retained in the body longer than cyanocobalamin and thus for maintenance therapy can be given at intervals of up to 3 months.
How is treatment with hydroxocobalamin initiated?
reatment is generally initiated with frequent administration of intramuscular injections to replenish the depleted body stores. Thereafter, maintenance treatment, which is usually for life, can be instituted. There is no evidence that doses larger than those recommended provide any additional benefit in vitamin B12 neuropathy.
For megaloblastic anaemia is folic acid given long term?
Folic acid has few indications for long-term therapy since most causes of folate deficiency are self-limiting or will yield to a short course of treatment.
It should not be used in undiagnosed megaloblastic anaemia unless vitamin B12 is administered concurrently otherwise neuropathy may be precipitated.
In folate-deficient megaloblastic anaemia (e.g. because of poor nutrition, pregnancy, or antiepileptic drugs), daily folic acid supplementation for how many months replenishes body stores?
daily folic acid supplementation for 4 months brings about haematological remission and replenishes body stores.
What is aplastic aneamia?
it is a condition which occurs when your body stops producing enough new blood cells. The condition leaves you fatigued and more prone to infections and uncontrolled bleeding. A rare and serious condition, aplastic anemia can develop at any age.
in which types of anaemias may tissue iron overload occur in?
in aplastic and other refractory anaemias, mainly as the result of repeated blood transfusions
What can iron overload associated with haemochromatosis be treated with?
Haemochromatosis - Haemochromatosis is an inherited condition where iron levels in the body slowly build up over many years.
Venesection
Venesection may also be used for patients who have received multiple transfusions and whose bone marrow has recovered
Venesection is a procedure where a trained nurse or doctor removes approximately 450mls of blood from your circulation
What if venesection is contra-indicated?
the long-term administration of the iron chelating compound desferrioxamine mesilate is useful
How much desferrioxamine mesilate may also be given at the time of blood transfusion?
Desferrioxamine mesilate (up to 2 g per unit of blood) may also be given at the time of blood transfusion, provided that the desferrioxamine mesilate is not added to the blood and is not given through the same line as the blood (but the two may be given through the same cannula).
Iron excretion induced by desferrioxamine mesilate is enhanced by daily administration of which compound?
Enhanced by administration of ascorbic acid (vitamin C) daily by mouth
Why should ascorbic acid be given separately from food?
Because it also enhances iron absoprtion
In which patients should ascorbic acid not be given to?
Ascorbic acid should not be given to patients with cardiac dysfunction; in patients with normal cardiac function ascorbic acid should be introduced 1 month after starting desferrioxamine mesilate.
What can desferrioxamine mesilate infusion be used to treated in dialysis patients?
can be used to treat aluminium overload in dialysis patients; theoretically 100 mg of desferrioxamine binds with 4.1 mg of aluminium.
What is neutropenia characterised by?
Neutropenia is characterised by a low neutrophil count (absolute neutrophil count less than 1.5 x 109/litre).
What can be sued to stimulate production of neutrophils and may reduce the duration of chemotherapy-induced neutropenia?
Recombinant human granulocyte-colony stimulating factor (rhG-CSF)
List some examples of granulocyte-colony stimulating factors?
‘grastim’
filgrastim, lenograstim, pegfilgrastim and lipegfilgrastim.
Which are longer acting?
Pegfilgrastim and lipegfilgrastim are polyethylene glycol-conjugated (‘pegylated’) derivatives of filgrastim, which are longer-acting forms of filgrastim due to decreased renal clearance.
What is immune thrombocytopenia purpura (ITP)?
Immune thrombocytopenic purpura (ITP) is a blood disorder characterized by a decrease in the number of platelets in the blood. Platelets are cells in the blood that help stop bleeding. A decrease in platelets can cause easy bruising, bleeding gums, and internal bleeding.
In adults with immune thrombocytopenia purpura, what is the initial treatment with?
A corticosteroid (such as prednisolone)
In patients with immune thrombocytopenic purpura who are bleeding or at high-risk of bleeding, who require a surgical procedure, or who are unresponsive to corticosteroids. what may be used?
Intravenous normal immunoglobulin
Immunoglobulin preparations may also be considered where a temporary rapid rise in platelets is needed, for example in pregnancy.
When can splenectomy be considered?
Splenectomy can be considered as a treatment option only if drug therapy has failed; the patients age and co-morbidities should also be taken into account
What is a good dietary source of folic acid?
Broccoli
Which drugs can cause agranulocytosis, neutropenia, other bone-marrow suppression or dyscrasis?
- Carbimazole
- Clozapine
- Co-trimoxazole
- Sulfasalazine
What are the normal levels sodium in the body?
142mmol/L
What is the normal plasma level of potassium?
4.5mmol/L
What is the normal plasma level of bicarbonate?
26mmol/L
What is the normal plasma level of chloride?
103mmol/L
What is the normal plasma level of calcium?
2.5mmol/L
When is compensation for potassium loss especially necessary?
- in those taking digoxin or anti-arryhthmic drugs, where potassium depletion may induce arrhythmias
- in patients in whom secondary hyperaldosteronism occurs, e.g. renal artery stenosis, cirrhosis of the liver, the nephrotic syndrome, and severe heart failure;
- in patients with excessive losses of potassium in the faeces, e.g. chronic diarrhoea associated with intestinal malabsorption or laxative abuse.
Measures may also be required during long-term administration of drugs known to induce potassium loss - give an example of a drug that causes hypokalaemia?
Corticosteroids
When small doses of diuretics are used to treat hypertension what is used to replace potassium?
Potassium supplements
to prevent hypokalaemia due to diuretics such as furosemide or the thiazides when these are given to eliminate oedema, what is preferred to be used for replacing potassium?
Potassium-sparing diuretics (rather than potassium supplements)
If potassium salts are used for the prevention of hypokalaemia then how are the doses given?
- doses of potassium chloride daily (in divided doses) by mouth are suitable in patients taking a normal diet.
Smaller doses must be used if there is renal insufficiency (common in the elderly) to reduce the risk of hyperkalaemia
What limits the use of potassium salts?
They cause nausea and vomiting and poor compliance is a major limitation to their effectiveness; when appropriate, potassium-sparing diuretics are preferable
The depletion of potassium is frequently associated with depletion of which other electrolyte?
Associated with chloride depletion and with metabolic alkalosis, and these disorders require correction
What potassium concentration is classed as acute severe hyperkalaemia?
Plasma potassium concentration 6.5mmol/L or greater or in the presence of ECG changes
What is the urgent treatment for acute severe hyperkalaemia?
- Calcium chloride 10% (unlicensed)
or - Calcium gluconate 10% (unlicensed)
to temporarily protect against myocardial excitability
What’s is a licensed treatment of acute severe hyperkalaemia?
An intravenous injection of soluble insulin (5–10 units) with 50 mL glucose 50% given over 5-15 minutes, reduces serum-potassium concentration; this is repeated if necessary or a continuous infusion instituted.
Can salbutamol be used to treat hyperkalaemia?
Salbutamol [unlicensed indication], by nebulisation or slow intravenous injection may also reduce plasma-potassium concentration; it should be used with caution in patients with cardiovascular disease.
The correction of casual or compounding acidosis should be corrected with what?
Sodium bicarbonate
What must be noted about preparation of sodium bicarbonate and calcium salts?
Sodium bicarbonate and calcium salts should not be administered in the same line - risk of precipitation
What is indicated in states of sodium depletion (hyponatraemia) and usually need to be given intravenously?
Sodium chloride
In chronic conditions associated with mild or moderate degrees of sodium depletion, e.g. in salt-losing bowel or renal disease, oral supplements of sodium chloride or sodium bicarbonate, according to the acid-base status of the patient, may be sufficient.
As a worldwide problem what is by far the most important indication for fluid and electrolyte replacement?
Diarrhoea
Intestinal absorption of sodium and water is enhanced by what?
Enhanced by glucose (and other carbohydrates)
Therefore replacement of fluid and electrolytes lost through diarrhoea can therefore be achieved by giving solutions containing what?
Containing sodium, potassium, and glucose or another carbohydrate such as rice starch
What key concepts should oral rehydration solutions have to be succesfull?
Oral rehydration solutions should:
enhance the absorption of water and electrolytes;
replace the electrolyte deficit adequately and safely;
contain an alkalinising agent to counter acidosis;
be slightly hypo-osmolar (about 250 mmol/litre) to prevent the possible induction of osmotic diarrhoea;
be simple to use in hospital and at home;
be palatable and acceptable, especially to children;
be readily available
What is the difference between WHO’s recommendation of oral rehydration solution contents and of that used in the UK?
The formulation recommended by the WHO and the United Nations Children’s fund is not commonly used in the UK.
Oral rehydration solutions used in the UK are lower in sodium (50–60 mmol/litre) than the WHO formulation since, in general, patients suffer less severe sodium loss.
Should rehydration occur rapidly or slowly?
Rehydration should be rapid over 3 to 4 hours (except in hypernatraemic dehydration in which case rehydration should occur more slowly over 12 hours).
When is sodium bicarbonate used?
It is given by mouth for chronic acidotic states such as uraemic acidosis or renal tubular acidosis
Is the dose correction of metabolic acidosis predicatable?
No and the the response must be assessed
For severe metabolic acidosis, how can sodium bicarbonate be given?
Intravenously
What other reason may sodium bicarbonate be used (to increase what)?
To increase the pH of the urine; it is also used in dyspepsia
What may sodium supplements increase?
Increase the blood pressure or cause fluid retention and pulmonary oedema in those at risk;
Hypokalaemia may be exacerbated
Where hyperchloraemic acidosis is associated with potassium deficiency, as in some renal tubular and gastrointestinal disorders, it may be appropriate to give which drug orally?
Potassium bicarbonate
Hyperchloraemic acidosis is associated with Hyperchloremic acidosis is a form of metabolic acidosis associated with a normal anion gap, a decrease in plasma bicarbonate concentration, and an increase in plasma chloride concentration
To replace electrolytes and water if intravenous administration is not possible, what can be given by subcutaneous infusion (hypodermoclysis)?
Fluid - Sodium chloride 0.9% or glucose 5%
Which solutions can be given safely into a peripheral vein?
Isotonic solutions may be infused safely into a peripheral vein. Solutions more concentrated than plasma, e.g. 20% glucose, are best given through an indwelling catheter positioned in a large vein.
If sodium chloride is required for acute or chronic hyponatraemia how fast or slow should this be given?
Regardless of the cause - the deficit should eb corrected slowly to avoid the risk of osmotic demyelination syndrome and the risk in plasma-sodium concentration should not exceed 10mmol/L in 24 hours.
In severe hyponatraemia what sodium chloride concentration may be used cautiously?
sodium chloride 1.8% may be used cautiously
What compound may be used instead of sodium chloride solution during or after surgery or in the initial management of the injured or wounded which may reduce the the risk of hyperchloraemic acidosis?
- Compound sodium lactate (Hartman’s solution)
When is sodium chloride with glucose solutions indicated?
When there is combined water and sodium depletion
What are glucose solutions (5%) mainly used to replace?
To replace water deficit
What is the average water requirements in an healthy adult?
1.5 to 2.5litres
Excessive loss of water without loss of electrolytes is uncommon but which situations or conditions can this occur in?
occurring in fevers, hyperthyroidism, and in uncommon water-losing renal states such as diabetes insipidus or hypercalcaemia.
What volume of glucose solution is required to replace deficits of water?
The volume of glucose solution needed to replace deficits varies with the severity of the disorder, but usually lies within the range of 2 to 6 litres.
Other than water, glucose solutions are also used to correct and prevent what?
Hypoglycaemia and to provide a source of energy in those too ill to be fed adequately by mouth; glucose solutions are a key component of parenteral nutrition
What is the initial management for the correction of severe hypokalaemia?
Potassium chloride with sodium chloride intravenous infusion - also when sufficient potassium cannot be taken by mouth
Should the initial potassium replacement therapy involve glucose?
No because glucose may cause a further decrease in the plasma-potassium concentration
Sodium bicarbonate is used to control severe metabolic acidosis for pH less than what??
pH<7.1
particularly that caused by loss of bicarbonate (as in renal tubular acidosis or from excessive gastro-intestinal losses)
Mild metabolic acidosis associated with volume depletion should be first managed by what?
managed by appropriate fluid replacement because acidosis usually resolves as tissue and renal perfusion are restored
Why is sodium lactate intravenous infusion no longer used in metabolic acidosis?
because of the risk of producing lactic acidosis, particularly in seriously ill patients with poor tissue perfusion or impaired hepatic function.
For chronic acidotic states, sodium bicarbonate can be given by which route?
By mouth
What is another name for plasma substitutes?
colloids
what is sodium chloride and glucose known as (Hint - plasma substitute is colloids)
Crystalloids
Compared to fluids containing electrolytes such as sodium chloride and glucose (‘crystalloids’), is a smaller or larger volume of colloid required to produce the same expansion of blood volume?
A smaller volume is required
What does albumin solution prepared from whole blood contain?
contain soluble proteins and electrolytes but no clotting factors, blood group antibodies, or plasma cholinesterases; they may be given without regard to the recipient’s blood group.
When is albumin usually used and can it be used for hypoalbuminaemia?
Albumin is usually used after the acute phase of illness, to correct a plasma-volume deficit; hypoalbuminaemia itself is not an appropriate indication.
When should plasma substitutes not be used?
Plasma substitutes should not be used to maintain plasma volume in conditions such as burns or peritonitis where there is loss of plasma protein, water, and electrolytes over periods of several days or weeks. In these situations, plasma or plasma protein fractions containing large amounts of albumin should be given.
Large volumes of soma plasma substitutes can increase the risk of bleeding through depletion of what?
Depletion of coagulation factors
List the normal plasma values of electrolytes?
Sodium 142 mmol/litre Potassium 4.5 mmol/litre Bicarbonate 26 mmol/litre Chloride 103 mmol/litre Calcium 2.5 mmol/litre
When are calcium supplements usually only required?
Where dietary intake is deficient
When is this dietary requirement relatively greater?
relatively greater in childhood, pregnancy, and lactation, due to an increased demand, and in old age, due to impaired absorption
In osteoporosis, a calcium intake which is double the recommended amount reduces the rate of what?
Reduces the rate of bone loss
In severe acute hypocalcaemia or hypocalcaemic tetany what should be given?
n initial slow intravenous injection of calcium gluconate injection 10% should be given, with plasma-calcium and ECG monitoring (risk of arrhythmias if given too rapidly), and either repeated as required or, if only temporary improvement, followed by a continuous intravenous infusion to prevent recurrence
Can calcium chloride injection be used?
Calcium chloride injection is also available, but is more irritant; care should be taken to prevent extravasation.
What may be required in persistent hypocalcaemia?
Oral supplements of calcium and vitamin D may also be required in persistent hypocalcaemia .
What should concurrent hypomagnesaemia be corrected with?
With magnesium sulfate
What should be corrected first in severe hypercalcaemia?
Dehydration should be corrected first with intravenous infusion of sodium chloride 0.9%
Drugs (such as thiazides and vitamin D compounds) which promote hypercalcaemia, should be discontinued and dietary calcium should be restricted.
If severe hypercalcaemia persists drugs which inhibit mobilisation of calcium from the skeleton may be required. The bisphosphonates are useful, which one is the most effective?
pamidronate disodium is probably the most effective.
Which other class of drug is widely used but may only be useful where hypercalcaemia is due to sarcoidosis or vitamin D intoxication?
Corticosteroids - they often take several days to achieve the desired effect
What can be used for the treatment of hypercalcaemia due to malignancy?
Calcitonin (salmon);
It is rarely effective where bisphosphonates have failed to reduce serum calcium adequately
What is the treatment for hypercalciuria?
- first investigate for an underlying cause, which should be treated
For idiopathic hypercalciuria - where a cause is not identified - the condition is managed by increasing fluid intake and giving bendroflumethiazide
Reducing dietary calcium intake may be beneficial but severe restriction of calcium intake has not proved beneficial and may even be harmful.
Primary hyperparathyroidism is a disorder of what gland?
Disorder of the parathyroid glands - most commonly caused by a non-cancerous tumour (adenoma) in one of the glands.
What does the resulting excess secretion of parathyroid hormone lead to?
Leads to hypercalcaemia, hypophosphataemia and hypercalciuria
What are the main symptoms?
Main symptoms are a result of hypercalcaemia and include thirst, increased urine output, constipation, fatigue and memory impairment.
What are the long term effects of hyperparathyroidism?
Long term effects include cardiovascular disease, kidney stones, osteoporosis, and fractures.
Does primary hyperparathyroidism affect more men or women?
It affects twice as many women than men and can develop at any age—with diagnosis most common in women aged 50 to 60 years.
What is the treatment of hyperparathyroidism focused on?
Treatment is focused on cure through surgery; other treatment options aim to reduce long-term complications and improve quality of life.
What is the first line treatment for hyperparathyroidism?
Parathyroidectomy surgery is the recommended first‐line treatment of primary hyperparathyroidism, with unsuccessful surgery requiring multidisciplinary team review at a specialist centre
For all patients with primary hyperparathyrodism what assessment should be carried out
Cardiovascular disease risk assessment and prevention, and assessment of Osteoporosis and fracture risk should be carried out.
For women with primary hyperparathyroidism who are considering pregnancy what should be offered?
Parathyroid surgery
Women with primary hyperparathyroidism are at an increased risk of what in pregnancy?
Increased risk of hypertensive disease
Treatment with which drug may be considered for patients with primary hyperparathyroidism if surgery has been unsuccessful (unlincesed indication), is unsuitable, or has been declined; and they have an elevated albumin‐adjusted serum calcium level with or without symptoms of hypercalcaemia.?
Cinacalcet
Can bisphosphonate be used in primary hyperparathyroidism
To reduce fracture risk for people with primary hyperparathyroidism who have an increased fracture risk, a bisphosphonate can be considered. Do not offer bisphosphonates for chronic hypercalcaemia of primary hyperparathyroidism.
What is the MAO of cincalcet?
Cincalcet reduces parathyroid hormone which leads to decrease in serum calcium concentrations
Where are the largest stores of magnesium in the body?
In the skeleton
Are magnesium salts well absorbed in the GI tract?
No - which explains the use of magnesium sulfate as an osmotic laxative
How is magnesium mainly excreted?
By the kidneys and is therefore retained in renal failure, which can result in hypermagnesemia
What can hypermagnesemia cause?
Cause muscle weakness and arrhythmias
What is used for the management of magnesium toxicity?
Calcium gluconate injection
What does hypomagnesaemia cause (secondary what) which electrolytes?
Hypomagnesaemia often causes secondary hypocalcaemia, and also hypokalaemia.
What routes can magnesium be given for hypomagnesaemia?
Magnesium can be given by intravenous infusion or by intramuscular injection of magnesium sulfate; the intramuscular injection is painful.
Do patients with mild magnesium depletion show symptoms?
Patients with mild magnesium depletion are usually asymptomatic.
Symptomatic hypomagnesaemia is usually associated with severe magnesium depletion.
Which oral magnesium salt is licensed for hypomagnesaemia?
Oral magnesium glycerophosphate is licensed for hypomagnesaemia.
Which oral magnesium salt is licensed for the treatment and prevention of magnesium deficiency?
Magnesium aspartate
Who is oral phosphate supplements licensed for?
Oral phosphate supplements are licensed for the treatment of patients with vitamin D-resistant hypophosphataemic osteomalacia.
Phosphate deficiency may arise in patients with what dependence?
Alcohol dependence
Phosphate depletion may also occur in patients with?
Diabetic ketoacidosis,
however phosphate replacement is not routinely recommended
Phosphate depletion in patients on total parenteral nutrition is common
For the management of hyperphosphataemia in patients with stage 4 or 5 chronic kidney disease (CKD), prior to starting phosphate-binding agents what should be optimised?
dietary management and dialysis (for patients who are having this) should be optimised
What should be offered as the first-line phosphate binder for hyperphosphataemia?
Calcium acetate
What if calcium acetate is not tolerated or unsuitable (e.g. because of hypercalcemia or low parathyroid hormone levels)?
Sevelamer (a non-calcium-based phosphate binder) should be offered
or patients in whom sevelamer is unsuitable, what can be used?
consider calcium carbonate as an alternative if a calcium-based phosphate binder is needed, or sucroferric oxyhydroxide for patients who are on dialysis and do not need a calcium-based phosphate binder.
When can Lanthanum be used?
Lanthanum (a non-calcium-based phosphate binder) should only be considered if other phosphate binders cannot be used
For patients with stage 4 or 5 CKD who are on the maximum tolerated dose of a calcium-based phosphate binder but remain hyperphosphataemic. what should you consider?
consider combining treatment with a non-calcium-based phosphate binder.
Whats the brand name of sevelamer tablets?
Ranagel
What is porphyrias?
Porphyrias are a group of rare inherited blood disorders. People with these disorders have problems making a substance called heme in their bodies. Heme is made of body chemicals called porphyrin, which are bound to iron. Heme is a component of hemoglobin, a protein in red blood cells that carries oxygen.
What is acute porphyrias?
Acute porphyrias include forms of the disease that typically cause nervous system symptoms, which appear quickly and can be severe. Symptoms may last days to weeks and usually improve slowly after the attack. Acute intermittent porphyria is the common form of acute porphyria
What is the prevalence of acute porphyrias?
about 1 in 75 000 of the population
Why is care needed when prescribing for patients with acute porphyria?
since certain drugs can induce acute porphyric crises. Since acute porphyrias are hereditary, relatives of affected individuals should be screened and advised about the potential danger of certain drugs.
What is administered by short intravenous infusion as haem replacement in moderate, severe or unremitting acute porphyria crises?
Haem arginate is administered by short intravenous infusion
Which drugs are unsafe for patients with porphyria?
Unsafe Drug Groups (check first)
Anabolic steroids
Antidepressants, MAOIs (contact UKPMIS for advice)
Antidepressants, Tricyclic and related (contact UKPMIS for advice)
Barbiturates (includes primidone and thiopental)
Contraceptives, hormonal (for detailed advice contact UKPMIS or a porphyria specialist)
Hormone replacement therapy (for detailed advice contact UKPMIS or a porphyria specialist)
Imidazole antifungals (applies to oral and intravenous use; topical antifungals are thought to be safe due to low systemic exposure)
Non-nucleoside reverse transcriptase inhibitors (contact UKPMIS for advice)
Progestogens (for detailed advice contact UKPMIS or a porphyria specialist)
Protease inhibitors (contact UKPMIS for advice)
Sulfonamides (includes co-trimoxazole and sulfasalazine)
Sulfonylureas (glipizide and glimepiride are thought to be safe)
Taxanes (contact UKPMIS for advice)
Triazole antifungals (applies to oral and intravenous use; topical antifungals are thought to be safe due to low systemic exposure)
Unsafe Drugs (check groups above first)
Aceclofenac Alcohol Amiodarone Aprepitant Artemether with lumefantrine Bexarotene Bosentan Busulfan Carbamazepine Chloral hydrate (although evidence of hazard is uncertain, manufacturer advises avoid) Chloramphenicol Chloroform (small amounts in medicines probably safe) Clemastine Clindamycin Cocaine Danazol Dapsone Diltiazem Disopyramide Disulfiram Ergometrine Ergotamine Erythromycin Etamsylate Ethosuximide Etomidate Flutamide Fosaprepitant Fosphenytoin Griseofulvin Hydralazine Ifosfamide Indapamide Isometheptene mucate Isoniazid (safety uncertain, contact UKPMIS for advice) Ketamine Mefenamic acid (safety uncertain, contact UKPMIS for advice) Meprobamate Methyldopa Metolazone Metyrapone Mifepristone Minoxidil (safety uncertain, contact UKPMIS for advice) Mitotane Nalidixic acid Nitrazepam Nitrofurantoin Orphenadrine Oxcarbazepine Oxybutynin Pentazocine Pentoxifylline Pergolide Phenoxybenzamine Phenytoin Pivmecillinam Pizotifen Porfimer Raloxifene Rifabutin (safety uncertain, contact UKPMIS for advice) Rifampicin Riluzole Risperidone Spironolactone Sulfinpyrazone Tamoxifen Temoporfin Thiotepa Tiagabine Tibolone Topiramate Toremifene Trimethoprim Valproate Verapamil Xipamide
What can selenium deficiency occur as a result of?
inadequate diet or prolonged parenteral nutrition.
What can be used for selenium deficiency?
Selenium supplement - but should not be given unless there is good evidence of deficiency
Is continuous zinc supplementation safe?
Yes however higher doses should be limited to short-term use due to an increased risk of gastro-intestinal adverse effects. copper deficiency, reduced immunity, anaemia, and genitourinary complications with long term use
When else is zinc used as a treatment for?
Zinc is used in the treatment of Wilson’s disease, and in acrodermatitis enteropathica—a rare inherited disorder characterised by impaired zinc absorption.
What are the names give to full parenteral nutrition or partial?
This may be in addition to ordinary oral or tube feeding—supplemental parenteral nutrition, or may be the sole source of nutrition—total parenteral nutrition (TPN)
What does parenteral nutrition require in the solution?
a solution containing amino acids, glucose, fat, electrolytes, trace elements, and vitamins
A single dose of what intramuscular injection is given?
A single dose of vitamin B12, as hydroxocobalamin, is given by intramuscular injection;
Are regular B12 injections usually required?
No unless total parenteral nutrition continues for many months
What dose is folic acid given usually in the nutrition solution?
Folic acid 15mg once or twice a week
What about other vitmains - how often are they given in parenteral nutrition?
Daily; they are generally introduced in the parenteral nutrition
Alternatively, if the patient is able to take small amounts by mouth, vitamins may be given orally.
How is the nutrition solution given parenterally?
The nutrition solution is infused through a central venous catheter inserted under full surgical precautions. Alternatively, infusion through a peripheral vein may be used for supplementary as well as total parenteral nutrition for periods of up to a month, depending on the availability of peripheral veins;
What factors prolong cannula life and prevent thrombophlebitis?
- the use of soft polyurethane paediatric cannulas
- use of feeds of low osmolality
- Neutral pH
- Only nutritional fluids should be given by the dedicated intravenous line
What are some complications of long-term parenteral nutrition?
gall bladder sludging, gall stones, cholestasis and abnormal liver function tests.
What ratio is energy provided in parenteral nutrition
Energy is provided in a ratio of 0.6 to 1.1 megajoules (150-250kcals) per gram of protein nitrogen.
Energy requirements must be et if amino acids are to be utilised for tissue maintenance
What percentage mixture of carbohydrate and fat energy sources gives better utilisation of amino acids than glucose alone?
(usually 30-50% as fat)
What is the preferred source of carbohydrate?
Glucose
When is frequent monitoring of glucose requried?
If more than 180g is given per day, and insulin may be necessary
To avoid thrombosis how should glucose be infused?
. Glucose in various strengths from 10 to 50% must be infused through a central venous catheter to avoid thrombosis.
In parenteral regimens - what is necessary to provide to allow phosphorylation of glucose?
it is necessary to provide adequate phosphate in order to allow phosphorylation of glucose and to prevent hypophosphataemia
What daily amount (mmol) of phosphate is required daily?
between 20-30mmol of phosphate daily
What do most enteral feed (oral nutrition) contain protein derived from what?
From cow’s milk or soya
What can be used in patients who have diminished ability to break down protein?
Elemental feeds containing protein hydrolysates or free amino acids can be used for patients who have diminished ability to break down protein, for example in inflammatory bowel disease or pancreatic insufficiency.
What is another name for vitamin A?
Retinol
What is deficiency of vitamin A associated with?
is associated with ocular defects (particularly xerophthalmia) and an increased susceptibility to infections, but deficiency is rare in the UK (even in disorders of fat absorption).
What B vitamin is thiamine?
Vitamin B1
Which B vitamin is riboflavin?
Vitamin B2
Why is nicotinamide used in preference to nicotinic acid?
As it does not cause vasodilation
Which severe B vitamin deficiency states are seen especially in chronic alcoholism?
- Wenicke’s encephalopathy and Korsakoff’s psychosis
How are the best treated?
Initially by the parenteral administration of B vitamins (Pabrinex), followed by oral administration of thiamine in the longer term
What has been reported with parenteral B vitamins use?
Anaphylaxis
What B vitamin is pyridoxine?
B6
Is B6 defficency common or rare?
(B6) deficiency is rare, but it may occur during isoniazid therapy or penicillamine treatment in Wilson’s disease and is characterised by peripheral neuritis.
There is some evidence to suggest that pyridoxine may provide some benefit in what condition?
In premenstrual syndrome
What does nicotinic acid inhibit the synthesis of?
Inhibits the synthesis of cholesterol and triglyceride
Folic acid and vitamin B12 are used in the treatment of which anaemia?
Megaloblastic anaemia
What is another name for vitamin C?
Ascorbic acid
What is vitamin C therapy essential in?
in the treatment of scurvy
What does severe scurvy ( a vitamin C deficiency) cause?
Gingival swelling and bleeding margins as well as petachiae on the skin.
This is, however, exceedingly rare and a patient with these signs is more likely to have leukaemia. Investigation should not be delayed by a trial period of vitamin treatment.
What condition can vitamin D deficiency lead to?
Rickets
Which vitamin D is ergocalciferol?
Calciferol, vitamin D2
Which vitamin D is colecalciferol?
Vitamin D3
Is alfacalcidol a vitamin D?
Yes
Which patients are at risk of vitamin D deficiency?
- Less exposure to sunlight
- low vitamin D in diet
- individuals with dark skin (such as those of African, African-Caribbean or South Asian origin) as their skin is less efficient at synthesising vitamin D
- individuals over 65 years
- Pregnant and breastfeeding women (particularly teenagers and young women)
- children aged 4 years
Which Vitamin D should patients with severe renal impairment be prescribed?
Vitamin D requires hydroxylation by the kidney to its active form, therefore the hydroxylated derivatives alfacalcidol or calcitriol should be prescribed if patients with severe renal impairment require vitamin D therapy
What is calcitriol also licensed for the management of?
Postmenopausal osteoporosis
What is paricalcitol (a synthetic vitamin D analgoue) licensed for?
for the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease.
What is another name for vitamin E?
Tocopherol
In young children with congenital cholestasis, abnormally low vitamin E concentration may be found in association with what?
With neuromuscular abnormalities, which usually respond only to the parenteral administration of vitamin E
What is vitamin K necessary for?
for the production of blood clotting factors and proteins necessary for the normal calcification of bone.
Is vitamin K fat soluble?
Yes
What does this mean for patient with fat malabsorption?
patients with fat malabsorption, especially in biliary obstruction or hepatic disease, may become deficient of vitamin K
Which water soluble synthetic vitamin K derivative can be given orally to prevent vitamin K deficiency in malabsorption syndromes?
Menadiol sodium phosphate
Which vitamins are fat soluble?
Vitamin A, D, E and K
What does neural tube defects represent?
Neural tube defects represent a group of congenital defects, caused by incomplete closure of the neural tube within 28 days of conception
What are the most common forms of neural tube defects?
The most common forms are anencephaly, spina bifida and encephalocele.
What are the main risk factors of neural tube defects?
- Maternal folate deficiency
- Maternal vitamin B12 deficiency
- Previous history of having an infant with a neural tube defect
- smoking
- diabetes
- Obesity
- use of antiepileptic drugs
When and how long should folic acid supplementation be recommended for pregnant women or those who plan to become pregnant?
Before conception and until week 12 of pregnancy
In which patients is a higher dose of folic acid recommended?
In women at high risk of conceiving a child with a neural tube defect, including women who have previously had an infant with a neural tube defect, who are receiving antiepileptic medication, or who have diabetes or sickle-cell disease
What is hyperkalaemia treated with?
Calcium gluconate 10% by slow IV injection to protect the heart
An I.V. injection of soluble insulin (5-10 units) with 50mL of glucose 50% given over 5-15 minutes also reduces serum-potassium concentration.
In severe hypocalcaemia an initial slow IV injection of what should be given?
Calcium gluconate 10%
What is corrected first in hypercalcaemia?
- ## Dehydration is corrected first with an IV infusion of sodium chloride
For hypercalcaemia which drugs should be restricted?
- Drugs (such as thiazides + vitamin D compounds) which promote hypercalcaemia should be discontinued and dietary calcium restricted.
If severe hypercalcaemia persists then what is used?
drugs which inhibit mobilisation of calcium from the skeleton are used. Bisphosphonates are useful and Pamidronate sodium is the most effective.
Corticosteroids are widely given but often take several days to achieve the desired effect.
What can magnesium sulfate injection also be used for emergency treatment of?
Treatment of serious arrhythmias
What is acute porphyrias?
Acute porphyria’s are a group of disorders affecting the synthesis of HAEM, it is hereditary (inherited).
what can be given for haem replacement if deficiency is severe?
Haem arginate
Vitamin A is mainly involved in the maintenance of what?
maintenance of healthy skin and eyes
Is long term use of pyridoxine safe?
Prolonged use of pyridoxine 10mg daily is considered safe… but long-term use of pyridoxine in a dose of 200mg or more daily has been associated with neuropathy
What counselling can you give for patients taking oral iron?
- Take with or after food (reduce GI side effects, constipation, diarrhoea)
- Take with a glass of orange juice (vitamin C aids absorption of iron)
- Continue for 3 months after blood levels return to normal
Which patients should only be using compound preparations of folic acid and iron?
Only for pregnant women at high risk of Iron AND folic acid deficiency
With parenteral iron preparations - how long should you monitor for after each injection?
Monitor for 30 minutes after each injection
Can parenteral iron be usd in pregnancy?
Avoid in pregnancy, especially in the first trimester
What are some symptoms of megaloblastic anaemia?
- numbness
- tingling hands/feet
- muscle weakness
- depression
For folate deficient megaloblastic anaemia is folic acid taken life long?
No - is it is taken dialy for 4 months
Why should you never give folic acid alone for undiagnosed megaloblastic anaemia or vitamin B12 deficiency megaloblastic anaemia?
Risk of neuropathy of the spinal cord
What is the antidote to iron overload?
Desferrioxamine
What is the treatment for low neutrophil count (a white blood cell type) - neutropenia?
- Filgrastim
Recombinant human granulocyte colony-stimulating factor (can reduce the duration of chemotherapy-induced neutropenia)
What are the symptoms of hypernatraemia?
- Convulsions
- Hypovolaemia
- Thirst
- Dehydration
- Oliguria
- Postural hypotension
- Tachycardia
Which drugs may cause hypernatraemia?
- Oral contraceptives
- Corticosteroids
- Sodium bicarbonate
- Sodium content in intravenous antibiotics
- Lithium
Given an example of a medical condition in which hypernatremia can be caused by volume depletion?
Diabetes insipidus
- Treatment is IV glucose
What are the symptoms of hyponatraemia?
- Drowsiness
- Confusion
- Convulsions
- Nausea
- Vomiting
- Headaches and cramps
Which drugs may cause hyponatraemia?
- Antidepressants
- Loop diuretics
- Carbamazepine
- Desmopressin
What is the treatment for mild-moderate hyponatraemia?
oral sodium chloride/ sodium bicarbonate (add glucose if there is water depletion)
What is the treatment for severe hyponatraemia?
IV saline (isotonic: via peripheral vein or concentrated: via central vein)
Why should IV saline for the treatment of hyponatraemia be given slowly?
Risk of osmotic demyelination syndrome
What is the medical name for metabolic acidosis?
Hyperchloraemia
What is used in metabolic acidosis?
Sodium bicarbonate
or
potassium bicarbonate - if caused by low potassium
What is used for the treatment of hypercalcaemia?
First correct dehydration with sodium chloride IV
Bisphosphonates or corticosteroids
What is used for hypercalcaemia of malignancy?
Calcitonin
Which drugs are used in treating hypercalcaemia caused by hyperparathyroidism?
- Cinalcet (reduces prathyroid hormone therefore calcium)
- Paracalcitol (in chronic renal faliure) (secondary hyperparathyroidism due to chronic renal failure)
What is the treatment for hypercalciuria?
Increase fluid intake and reduce calcium
Drug - Bendroflumethiazide (causes calcium reabsorption)
What condition does hypocalcaemia cause?
Osteoprosis
What is the treatment for mild-moderate hypocalcaemia (chronic)?
Vitamin D and calcium supplements
What is the treatment for severe acute hypocalcaemia or hypocalcaemic tetany?
Slow IV calcium gluconate (giving it too rapid = arrhythmias)
What can hypomagnesaemia also lead to?
Leads to hypocalcaemia, hypokalaemia and hyponatraemia
Which drug class is used to treat hyperphosphotaemia?
Calcium containing preparations
or
Phosphate binding agents
What are the symptoms of hyperkalaemia?
- Ventricular fibrillation
- Cardiac arrest
Which drugs can cause hyperkalaemia?
‘HADBEANS’
Heparins Ace inhibitors Digoxin Beta blockers Eplerenone Amiloride NSAIDs Spironolactone
What is the treatment for severe acute hyperkalaemia > (6.5mmol/L)
Slow IV calcium gluconate
IV insulin, glucose and salbutamol can be given in addition
In hyperkalaemia what can you add to correct compounding acidosis?
Sodium bicarbonate
What should you not do when adding sodium bicarbonate to correct compounding acidosis in severe hyperkalaemia treatment?
Do not give it via the same line;
causes precipitation = thrombosis
What are the symptoms of hypokalaemia?
Muscle hypotonia,
Arrhythmias
Which drugs can cause hypokalaemia?
I Don’t cut bananas
Insulin
Diuretics
Corticosteroids
Beta 2 agonist (salbutamol, theophylline)
What is the treatment for mild hypokalaemia?
Oral slow potassium chloride
- nausea and vomiting cause poor compliance
- Smaller doses in renal impairment
- If caused by diuretic = potassium=sparing diuretic preferred
What is the treatment for severe hypokalaemia?
IV potassium chloride
- do not add glucose for initial potassium replacement as glucose causes hypokalaemia
- KCL injection overdose is fatal = use ready-mixed solutions or thoroughly mic concentrate
In total parenteral nutrition how is glucose given to avoid thrombosis?
Via central vein
- Give enough phosphate to allow the phosphorylation of glucose
Which vitamins are fat soluble?
ADEK
Which vitamins are water soluble?
B and C
Is retinol (vitamin A) teratogenic?
Yes
What are good sources of vitamin A?
Liver pates, fish liver oil, raw eggs
What are good sources of vitamin c?
Oranges, peppers, tomatoes and blackcurrants
What does deficiency of vitamin D (calciferol) lead to?
Rickets and osteomalacia
What is D2 and D3 vitamin names?
D2 = ergocalciferol D3 = Colecalciferol
Which versions of vitamin D would you give in severe renal impairment?
Hydroxylated versions
Alfacalcidol
Calcitriol
What is the name for vitamin E?
Tocopherol
What does vitamin E inhibit?
Inhibits platelet aggregation, increased risk of bleeding with Warfarin
What is the name for vitamin K?
Phytomenadione
Is phytomenadione lipid or water soluble?
it is lipid soluble vitamin K
Which vitamin K derivative is used in liver impairment?
Water soluble = menadiol
Vitamin K is given to all new born babies to prevent what?
Prevent neonatal haemorrhage
What are good sources of vitamin K?
Green, leafy vegetables
What are the names for B1, B2, B3, B6, B7 and B12?
B1 - thiamine B2 - Riboflavin B3 - Niacin B6 - pyridoxine B7 - Biotin B12- cobalamin/hydroxycobalamin
What is Niacin (B3) availble as?
Nicotinamide (preferred) and Nicotinic acid (vasodilation side effects)
What does pyridoxine prevent when given with isoniazid/ Pencilliamine?
Prevents peripheral neuropathy
What is biotin used for?
Used to strengthen hair and nails
B12 deficiency is common in people with which diet?
Vegans
If a woman has sickle cell disease and is becoming pregnant what advice regarding folic acid would you give?
Take the high risk dose (5mg daily) and instead of taking it jus before then up to 12 weeks of pregnancy,
give throughout whole pregnancy
