Monitoring and drug therapy Flashcards
why is it important to monitor?
Why monitor? Aid diagnosis Assess severity of disease Effectiveness of treatment Review response to treatment Dose adjustments identified ADRs Renal/hepatic function TDM drugs
what are some example blood tests which can be monitored?
Urea and electrolytes – urea is a marker of kidney function but can be used as a marker for some disease states. Electrolyte disturbances can lead to a range of symptoms and are common side effects of some drug therapies.
Haematology – Used to diagnose causes of anaemia, diagnose and monitor response to infection, and identify coagulation status by monitoring prothrombin time as well as platelet function. Issues with bone marrow function may cause problems with all types of blood cell.
Renal and liver function – really important for us pharmacists as lots of meds require dosage adjustment in those with impaired function. Quantifying renal function is relatively easy to do and interpret into drug dose reductions but interpreting deranged liver enzymes and relating this into an appropriate drug dose reduction is less easy. As those with end stage liver disease sometimes produce near normal liver function tests.
Cardiac enzymes – important for diagnosing an acute cardiac event – these are becoming ever more specific so more and more people are getting diagnosed and treated for heart attacks.
Therapeutic drug monitoring – measurement of concentrations of medication within the blood. This is mainly done for narrow therapeutic window drugs, sometimes done to check compliance (e.g for TB eradication), or done in cases of overdose in order to choose the most appropriate treatment.
what are some clinical observations which can be monitored?
BP and pulse Oxygen saturations Respiratory rate Urine output, fluid balance, daily weights Pain score Blood glucose Temperature
what is the hyper and hypo levels of electrolytes - na ,k , cl , Ph
Sodium
Hypo: <133
Hyper: >146
Potassium
Hypo : <3.5
Hyper : >5.5
Calcium
Hypo: <2.12
Hyper: >2.65
Phosphate
Hypo: <0.7
Hyper: >1.4
Magnesium
Hypo: <0.6
Hyper: >1.1
what is the function of sodium - 133- 146 mmol/l
Major extracellular cation
Regulated by aldosterone (RAAS system)
Can indirectly affect blood pressure;
Low sodium level is associated with hypotension (as excess water lost from circulating volume)
Conversely a large intake of salt from the diet can cause hypertension (as excess water retained in circulating volume)
explain the RAAS system
liver - produces angiotensinogen
renin from juxtaglomerular enters and causes the conversion to angiotensin 1
ace causes conversion to angiotensin 2
adrenal gland causes the production of aldosterone
which causes increased na and h20 reabsorption in the distal tubule
which causes homeostasis - bp
causes low blood pressure
what is the cause of Hypernatraemia (Na+ >146mmol/L)
Insufficient fluid intake (elderly, babies, impaired swallow) or
Excessive water loss (from GI tract in D+V, from skin as sweat or from urine in diabetes insipidus or uncontrolled diabetes mellitus)
(ESSENTIALLY DEHYDRATION!)
Rarely caused by:
Sodium retention/too much sodium from diet
Excess adrenocorticoid hormones e.g. Cushing’s syndrome
Pharmacological agents e.g. corticosteroids, NSAIDs and Lithium toxicity
what are the consequences for Hypernatraemia (Na+ >146mmol/L)
CNS changes from lethargy/stupor to deep coma
Dependant on level >170mmol/l life-threatening
what are the symptoms of hypernatraemia
Symptoms may include: fever, tachycardia, hypertension, dizziness, increased thirst, oedema.
how can you treat hypernatraemia?
Rapid water replacement is very dangerous as can cause cerebral oedema, convulsions and possible brain injury.
Aim to replace fluid deficit slowly over 48-72 hours depending on severity of condition
Consider NG tube for enteral fluid replacement if possible (to avoid unnecessary IV administration)
If IV administration is necessary usually hypotonic fluids are given slowly with close monitoring.
Na level should fall no faster than 0.5mmol/L per hour.
what is the causes of Hyponatraemia (Na+ <133mmol/L)
- Sodium depletion from various disease states: - excessive sweating, vomiting diarrhea, infection, addisons disease, skin lesions
- Water retention- Water excess/Over-treatment with fluid, SIADH
Haemodilution caused by cardiac, hepatic, renal failure
3. Pharmacological - Diuretics Carbamazepine Antidepressants (more commonly SSRIs) ACE inhibitors Some antipsychotics PPI’s
symptoms of Hyponatraemia (Na+ <133mmol/L)
Symptoms: Headache Nausea Vomiting Cramps Circulatory failure Confusion Convulsions Postural hypotension Fatigue
treating hyponatremia
Will depend on the cause
Pharmacological: Stop/switch/reduce dose of causative drug
Euvolaemic (usually endorcrine cause): Treat the Addison’s disease/pituitary failure/hypothyroidism, SIADH
Hypovolaemic: Replacement with IV NaCl 0.9%
Hypervolaemic: Treatment of the underlying organ system disease (e.g. treat heart failure with fluid restriction, diuretics, ACEi, B-blocker)
where is Potassium (K+) 3.5 - 5.3mmol/L found and its causes
Largely intracellular
Needs usually met from dietary sources
Essential for maintaining muscle contractility, e.g. cardiac muscle
Maintains fluid balance, nerve impulse function and muscle function
Causes: Renal failure (acute or chronic) Redistribution of K+ between ICF and ECF Metabolic acidosis K+ sparing diuretics K+ supplements ACE inhibitors, Angiotensin II receptor blockers, NSAIDs Heparin Beta blockers (non-selective) Trimethoprim Azole antifungals
what are the consequences for hyperkalemia
Consequences (usually only when >6mmol/L): Arrhythmia Muscle weakness Tachycardia Ventricular fibrillation Asystole!
what is euvolaemic hyponatraemia and what is it caused by?
Euvolaemic hyponatraemia will usually be fluid restricted initially until treatment started for what is usually an endocrine cause (so inappropriate secretion of hormones). Sometimes this can be cause by people exercising for prolonged periods of time or some people who take ecstasy or I have seen a case where a patient with a complex mental health history repeatedly ingested excessive amounts of water, to the point where they ended up in ITU several times.
what is treatment for hypovolemic hyponatraemia
Hypovolaemic hyponatraemia Depletional hyponatraemia; the basic therapy is fluid replacement with normal saline, which will be continued until the person’s blood pressure is restored.
what are the treatment for hyperkalemia?
Treatment:
1) ) Calcium salts: reduce the risk arrhythmias by antagonising cardiac membrane excitability therefore stabilising the myocardium and hopefully preventing arrhythmia. IV CG (less irritant than CC) 10ml over 5 mins.
2) Insulin is the most effective and evidence based therapy to actually reduce K+ - it activates Na/K ATPase responsible for moving potassium into cells. Obviously if you give insulin you will need to give glucose –standard practice in the NHS currently is 10 units of Actrapid insulin in 50ml of 50% glucose given IV over 15 mins – then monitor CBG and BMs. Subsequent boluses or a continuous infusion can be set up if necessary.
3) Salbutamol – stimulate beta 2 receptors to enhance cellular uptake of potassium by muscle and liver cells via activation of NA/K ATPase. Combination with insulin is more effective than alone. Not best used alone as many patients are resistant to this treatment. Careful using this in ischaemic heart disease or if significant tachycardia as the risks may outweigh the benefits of this treatment.
4) Ion exchange – bind to potassium in GIT and increase faecal elimination. Delayed onset of action >4 hours (osmotic laxative concomitantly). 15g 3-4x daily. Wont actively reduce the current K+ level but will help stop and further PO absorption.
5) Haemodialysis/haemofiltration – last line.
what is the causes of Hypokalaemia (K+<3.5mmol/L)
Causes: Inadequate intake Loss from gastrointestinal secretions Re-feeding syndrome Redistribution between ECF and ICF Mineralocorticoid excess e.g. hyperaldosteronism Renal failure
Drugs: Diuretics Amphotericin Corticosteroids Gentamicin Theophylline Salbutamol
symptoms of Hypokalaemia (K+<3.5mmol/L)Hypokalaemia (K+<3.5mmol/L)
Symptoms (usually only if K+ falls below 2.5mmol/L)
Muscular weakness Tetany Respiratory failure Paralysis Constipation Cardiac arrhythmias Sudden death
what is the treatment for hypokaleamia
Treatment
Potassium effervescent tablets (sando-K®)
Intravenous potassium (usually mixed with glucose or sodium chloride) at 20 - 40mmol/Litre
Bananas!
what are the main hormones involved in calcium homeostatis
Main hormones involved in calcium homeostasis:
Parathyroid hormone
Vitamin D metabolites (calcifediol and calcitriol)
Calcitonin
Negative feedback in calcium homeostasis. A drop in blood Ca2+ causes the parathyroid gland to produce parathyroid hormone (PTH), which has several effects:
Ca2+ is released from bone.
Bone metabolism controlled by bone cells called osteoclasts and osteoblasts. Osteoclasts remove damaged bone and osteoblasts help building and repair bone. These cells have a direct impact on calcium as they release hormones which can cause increased or decreased levels.
Free calcium is bound to albumin
Ca2+ is reabsorbed in the kidney.
Kidney in turn activates Vitamin D, which promotes the uptake of Ca2+ in intestines.
Hydroxylated derivatives = calcifediol and calcitriol
common causes for hypercalcemia
Primary hyperparathyroidism (~50% of cases) – Excessive secretion of PTH, stimulating calcium uptake in the kidneys and intestines as well as promoting bone resorption to release bound calcium
Malignancy (20-30% of cases) – usually only in advanced cancer
Can occur without skeletal metastases due to excess secretion of PTH
Can occur with skeletal metastases which causes bone lysis and release of skeletal calcium
Less common causes:
Pharmacological (thiazide diuretics, lithium, vitamin D, vitamin A, co-prescription of calcium)
End stage CKD (secondary hyperparathyroidism)
Dehydration
Bone disease
Excess secretion of PTH can be due to several different diseases, including cancer, benign enlargement, genetic disorders, radiation treatment.
Can be caused by drugs, chronic kidney disease, dehydration, osteodystrophy or Paget’s disease – both of which have enhances osteoclast activity and reduced osteoblast activity – results in increased bone resorption. Immobility also doesn’t help as this can promote bone loss resulting in increased calcium levels.
what are the symptoms
Bone pain, fractures
Kidney stones, nephrocalcinosis
Neurological symptoms: fatigue, depression, drowsiness,
headaches and generalised muscle weakness
GI disturbances: Anorexia, Nausea/vomiting, Constipation
treatment for hypercalcaemia?
Treatment:
Review/discontinue drugs promoting hypercalcaemia (thiazides, vitamin D analogues, calcium supplements) and correct dehydration.
Surgery if caused by primary hyperparathyroidism
Bisphosphonates in bone metastases
Steroids
Cinacalcet (used for renal dialysis patients with parathyroid dysfunction or those ineligible/refuse for surgery)
Cinacalcet is a calcimimetic – so it mimics the effect of circulating calcium upon tissues therefore reducing the stimulus on parathyroid gland and subsequently reducing PTH release = decrease serum calcium.
