Metabolic Flashcards
What is the immediate management of AKI?
- IV fluid therapy
- Withdrawal of nephrotoxins
- Withholding of hypotensive agents and diuretics
- Withhold atorvastatin
What is spirolactone’s mechanism of action?
Aldosterone antagonist in distal renal tubules
Increasing NaCl and water excretion while conserving K+ and H+ ions; may have effect on arteriolar smooth muscle as well
What are the indications for use of spirolactone?
- Systolic heart failure
- Resistant hypertension
- Temporary treatment of Conn’s syndrome
- Liver failure (oedema)
- Management of oedema associated with excessive aldosterone excretion/ congestive heart failure.
What are the cardiovascular and neurological side-effects of Spirolactone?
CV: vasculitis
CNS: ataxia, confusion, lethargy
What are the dermatological side effects of Spirolactone?
- DRESS syndrome
- Erythematous maculopapular rash
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Urticaria
What are the GI side effects of Spirolactone?
- Abdo cramps
- Diarrhoea
- Gastritis
- GI haemorrhage
- GI ulcer
- Nausea
- Vomiting
What are the renal side effects of Spirolactone?
- Increased blood urea nitrogen
- Renal failure
- Renal insufficiency
What is Furosemide’s mechanism of action?
Inhibits reabsorption of Na+ and Cl- in the ascending loop of Henle and distal renal tubule -> increased water, Na+, Cl-, Mg2+ and Ca2+ excretion
What are the indications for use of loop diuretics?
- Management of oedema associated with heart failure and hepatic/ renal disease
- Acute pulmonary oedema
- Resistant hypertension
What are the the indications for Ramipril’s use?
- Hypertension
- Symptomatic heart failure
- Prophylaxis after MI
- Prevention of CV events in patients with atherosclerotic CVD, diabetes and at least one additional risk factor
- Nephropathy
What are the most common side effects of Ramipril?
- Increased cough (7-12%)
- Hypotension (11%)
- Hyperkalaemia (1-10%)
- Headache
- Dizziness
What is the difference between pharmacokinetics and pharmacodynamics?
Pharmacokinetics - what the body does to the drug
Pharmacodynamics - what the drug does to the body
What are pharmacodynamic drug-drug interactions?
Interacting drugs have additive effects (increasing overall effect) or opposing effects (decreased overall effect/ cancelled out)
What are pharmacokinetic drug-drug interactions?
One drug changes the systemic concentration of another drug (can reflect amount at site of action or period of time for which the whole concentration exists there)
What are examples of pharmacodynamic drug interactions of ACE inhibitors?
BP lowering with diuretics/ other antihypertensives = hypotension
Increase in plasma K+ with potassium sparing diuretics/ ARBs = hyperkalaemia
How are NSAIDs thought to contribute to the development of AKI?
Directly inducing different forms of kidney injury
NSAID induced attenuation of (PG mediated) renal vasodilation
How could you measure GFR?
Measure urine clearance of an ideal filtration marker (gold standard = inulin)
Why is inulin the gold standard exogenous filtration marker?
- Physiologically inert
- Not secreted, reabsorbed, synthesised or metabolised by the kidney
- Amount of inulin filtered at glomerulus matches the amount excreted in urine
Why is inulin not a commonly used method for estimation of GFR?
- Expensive
- Limited
- Difficult to assay
- Requires continuous IV infusion, multiple blood samples and bladder catheterisation
What are the most common methods used to estimate GFR?
- Creatinine clearance
- Estimation equations:
Cockcroft-Gault
MDRD
CKD-EPI
Why is CrCl from Cockcroft and Gault more accurate than an eGFR from a BCP?
It uses weight to add further information (may overestimate)
Allows creatinine clearance to be estimated from serum creatinine (only good in patients with stable values)
Why is it important to know a patient’s eGFR/ CrCl?
- To safely prescribe drugs that could affect/ be affected by renal function
- Good to monitor changes in renal function
How could you make eGFR more accurate?
Adjust it to the patient’s actual body weight
When would you use absolute eGFR / Cockcroft & Gault’s CrCl when prescribing drugs?
- Patients at the extreme of body mass
- Any Hx of renal disease
- Prescribing certain drugs
What effect will renal impairment have on the half life of a drug that is cleared by the kidney?
Increased half-life-> takes longer to reach steady state
More likely to be toxic dose
How might you alter the prescription of a drug that’s excreted through the kidney in a patient with significant renal impairment
- Give smaller dose initially and then titrate it up to a therapeutic level
- Give loading dose if needed to reach steady state quickly (lower at more frequent intervals in impairment)
What is the most frequently prescribed oral treatment for iron deficiency anaemia?
- Ferrous sulfate
- Ferrous fumarate
- Ferrous gluconate
What is the most frequently prescribed parenteral treatment for iron deficiency anaemia?
- Parenteral iron
- Iron dextran
- Iron sucrose
- Ferric carboxymaltose
- Iron isomaltoside 1000
What is the difference between the iron taken from omnivorous and herbivorous diets?
Omnivorous - iron absorbed from meat in the ferrous form of haem (Fe2+)
Herbivorous - non-haem iron is in the ferric state (Fe3+)
What are important adverse effects of iron?
- GI disturbances
- Oral iron turns stools black -> may obscure view in endoscopy
What dose of iron should be prescribed in iron deficiency anaemia and why?
100-200mg of elemental iron
To correct the anaemia and replace the depleted stores
How long should iron be given in iron deficiency anaemia?
3-4 weeks after Hb concentration is stable
What other measures could be considered in iron deficiency anaemia for a patient who experiences heavy periods?
- Combined contraceptive pill
- Endometrial ablation
- Hormonal therapy
Why is folic acid used in pregnancy?
Reduced risk of neural tube defects
What dose of folic acid would be appropriate for pregnant women?
Women with a previous child with neural tube defects/ taking anticonvulsants associated with neural tube defects should take 5mg
What is the recommended duration of folic acid treatment in pregnant women?
From conception until the 12th week of pregnancy (end of organogenesis)
What drug is offered to BPH patients?
Tamsulosin
How does Tamsulosin work?
Alpha blocker
Causes smooth muscle dialtion
What drugs are given in urinary obstruction linked to the bladder?
Finasteride (5-alpha reductase inhibitor)
What is anastrozole?
Aromatase inhibitor
What is tamoxifen?
Selective oestrogen receptor modulator
Inhibits breast cancer cell growth by antagonising the oestrogen receptor
What is tamoxifen indicated for?
- Adjuvant treatment of premenopausal women with breast cancer
- Postmenopausal women who are not candidates for an aromatase inhibitor
What is the initial drug treatment for adults with type 2 diabetes?
Standard-release metformin
What do you need to consider before prescribing metformin?
Renal function - increased risk of lactic acidosis
- Review metformin dose if eGFR is <45ml/min/1.73m2
- Stop it if eGFR is <30
- Use with caution if the patient is at risk of sudden deterioration in kidney function
How would you introduce metformin?
Gradually increase the dose over several weeks to minimise risks of GI side effects
What are the common side effects of metformin?
Abdo pain, anorexia, diarrhoea, nausea & vomiting, taste disturbance
If metformin does not control HbA1c levels, what should the next steps in treatment be?
Dual therapy of metformin with either:
- DPP-4 inhibitor
- Pioglitazone
- Sulfonylurea
What are the main side effects of sulfonylureas?
Hypoglycaemia (usually indicates excessive dosage)
What drugs are available for triple therapy of diabetes?
- Metformin + DPP-4 inhibitor + sulfonylurea
- Metformin + pioglitazone + sulfonylurea
- Insulin-based treatment
What features are necessary for you to diagnose a DKA?
- Ketonaemia > 3.0mmol/ L
- Blood glucose > 11.0mmol/L
- Bicarbonate <15.0mmol/L OR venous pH <7.3
What is the immediate management for DKA?
- ABCDE
- IV Fluids - 0.9% NaCl 500mL over 15 mins
T= 0 at time IV fluids are started - Fixed rate intravenous insulin infusion after starting IV fluids
What is important to communicate to the patient with respect to monitoring?
- Hourly blood glucose
- Hourly ketone measurement
- At least 2 hourly serum potassium & bicarbonate for the first 6 hours
- Clinical & biochemical assessment of the patient
How does intravenous insulin work?
- Reduction in blood glucose
- Suppression of lipolysis to resolve ketonaemia
How is insulin produced for the management of diabetes?
Genetic engineering: implant insulin gene in bacteria grown in vats, then remove insulin
What are examples of short acting human insulins?
Humulin S
Actrapid
What are examples of ultra-short acting human insulins?
Humalog
Novorapid
Why are Humalog and Novorapid faster in clinical effect than Humulin S and Actrapid?
The former two have been altered in molecular structure.
They more easily separate into insulin dimers and monomers which speeds up absorption from the injection site.
What are examples of NPH (isophane) intermediate acting insulins?
Insulatard
Humulin I
What are examples of analogue long acting insulins?
Lantus
Levemir
How are long acting analogue insulins different from isophane insulins?
Lantus has been genetically altered to make it more soluble in its cartridge (higher pH) than in the blood, slowing absorption.
Levemir has a fatty acid moiety sick to it, delaying absorption.
What are biphasic insulins?
Mix of analogue ultra short acting insulin with an NPH/ isophane form of insulin
What are biphasic insulins indicated for?
- Used in adults with learning difficulties and T1DM
- Patients with poor compliance
What does the number in ‘mix’/ biphasic insulins refer to?
Percentage of quick acting insulin in the mixture
What does U100 mean in the context of insulins?
100 units of insulin per mL.
Most insulins are described as this.
What are potential disadvantages of introducing insulin Degludec which comes as U100 and U200?
Could lead to dosing errors.
The manufacturer only supplied Degludec in pre-filled pens which reduces the risk of this error.
What is the initial therapy for management of hyperthyroid symptoms?
Beta blocker - can be started once the diagnosis is made, irrespective of whether Graves’ is confirmed
Besides direct beta receptor antagonism, how do beta blockers help with hypothyroidism?
Slowly decreasing T3 concentrations by inhibiting 5’-monodeiodinase (converter of T4 to T3)
How long does it take to see the T3 reducing effect of beta blockers?
7-10 days
What is carbimazole?
Thionamide
How does carbimazole work?
Inhibits thyroid peroxidase and therefore thyroid hormone synthesis
How long does it take to see the T4 and T3 lowering effect of carbimazole?
4-6 weeks
How does propylthiouracil (PTU) work in hyperthyroidism?
Inhibits 5’ monodeiodinase that converts T4 to T3 in extra thyroidal tissue
What is methimazole (MMI)?
An active metabolite of carbimazole
What is the difference between MMI and PTU?
MMI’s better
Half-life of MMI = 4-6 hours
Half-life of PTU = 75 mins
Intrathyroidal MMI concentration remains high for up to 20 hours which is considerably longer than PTU.
Why might PTU be the preferential thionamide in early pregnancy?
All the antithyroid drugs have been associated with teratogenic effects but they’re less common and less severe in PTU.
Why isn’t PTU used as the first-line therapy in non-pregnant adults?
Severe hepatic reactions have been reported including patients requiring liver transplant and death
How do you advise pregnant patients of potential PTU hepatic effects?
Teach them how to recognise signs of liver disorder
Discontinue drug if significant liver-enzyme abnormalities develop
When commencing a patient on carbimazole, what do you warn them of?
Agranulocytosis - 0.1 - 0.5%, usually within first 2 months of treatment
Any sign of illness e.g. fever/ sore throat, discontinue drug and get WCC done.
What are the two ways of treating thyrotoxicosis with carbimazole?
Titration therapy
Block and replace therapy
Why do doctors generally pre-treat with carbimazole before giving radioiodine?
Small risk of inducing thyroid storm after radioiodine
Contraindications of radiotherapy:
- Pregnancy
- Significant thyroid eye disease
What hormones would you use to replace anterior pituitary function?
Hydrocortisone
Growth hormone analogue
Levothyroxine
Testosterone/ Oestrogen
How would you give glucocorticoid replacement therapy?
Hydrocortisone 15-30mg daily in 2-3 divided dose in the morning later in the day
What are the risks of under over replacement with glucocorticoids
Under = Addison's Over = Cushing's
Do you need to give fludrocortisone in a patient with secondary adrenal insufficiency?
Not usually because if the adrenal gland’s fine, aldosterone function is preserved
How do you treat and monitor TSH deficiency?
T4 and T3
T4 shouldn’t be administered until adrenal function has been evaluated and found to be normal/ treated
Why is it important to manage a patient with coexisting hypothyroidism and hypoadrenalism appropriately?
Treating the hypothyroidism alone may increase the clearance of the little cortisol that is produced -> makes Addison’s worse
How do you measure treatment of FSH and LH deficiency?
Measurements of serum testosterone/ oestrogen
Is it necessary to treat GH deficiency?
No but you could monitor levels via centripetal (abdominal) obesity
