Monitoring Drug Therapy 2 renal, Haematology, coagulation

Question 1

how is creatinine produced in the body and what does its plasma concentration depend on?

Answer 1

1) Produced continuously as a by-product of normal muscle metabolism, and is eliminated by the kidneys
2) Plasma concentration depends on muscle mass and breakdown, and the ability of the kidney. Changes in creatinine levels can give an estimate of renal function.

Question 2

what is are the causes of :

1) Pre-renal
2) Renal (intra-renal)
3) Post renal

Answer 2

1) Pre-renal: reduced blood flow to kidneys
- Damage aorta, dehydration causing hypovolaemia, low blood pressure, heart failure, liver cirrhosis
2) Intra-renal: Sources of damage to the kidney itself
- glomerulonephritis, acute tubular necrosis (ATN), and Kidney disease
3) Post-renal- obstruction of the urinary tract
- Kidney stone on urethra

Question 3

how would you calculate creatinel clearance and what is the formula?
- what are the normal ranges for a male and female

Answer 3

1) Involves collecting urine over 24 hours and measuring the quantity of creatinine in the sample.
2) CrCl = U x V / S
- U = urine creatinine concentration (mmol/L)
- V = urine flow rate (ml/min)
- S = serum creatinine concentration (mmol/L)
3) male: 90-140ml/min (M), female: 80-125ml/min (F)

Question 4

how would you estimate Creatinine Clearance (Cockcroft-Gault Equation)

Answer 4

1) CrCl = F(140-age) x weight/ SrCr
- F = 1.04 in females, F = 1.23 in males
- SrCr- serum creatinine

Question 5

what is the best measure of overall kidney function?

Answer 5

1) Measured glomerular filtration rate (GFR) is considered the best measure of overall kidney function
2) It involves injecting a contrast dye into the kidney and monitoring the rate of travel through the kidney

Question 6

Estimated GFR (eGFR) uses the MDRD equation, what does this equation take into account?

Answer 6

1) takes sex, age, weight and ethnicity into account
2) assumes a body surface area of 1.73m²
3) used to classify kidney function

Question 7

what is the difference in purpose of eGFR and CrCl

Answer 7

1) eGFR: Capacity of the kidney
- used by BNF
2) CrCl: Kidney function
- Used by manufacturer
3) Limitations: if patient is dehydrated levels do not represent a true reflection of renal dysfunction. Muscle mass not taken into account e.g. body builder!

Question 8

You are looking after a 35 year old male patient (who is 80kg; he works out a lot) and his serum creatinine has come back from the lab as 130micromol/litre. Calculate his creatinine clearance.

Answer 8

79ml/min

Question 9

what is the Importance of monitoring renal function

Answer 9

1) A rapid fall in creatinine clearance can be an indication of acute renal failure, which may be prevented.
- As renal function declines, it can impact on other organ systems
2) Pharmacological treatment can be tailored to the patients renal function appropriately.
- For example: nephrotoxic agents should be avoided, drugs that are renally metabolised/excreted may require dose reductions.

Question 10

name a nephrotoxic drug

Answer 10

aminoglycosides

Question 11

what is the normal level of Urea in the body?

Answer 11

Urea (2.5-7.8mmol/L)

Question 12

in what condition does the concentration of urea increase or decrease in the body?

Answer 12

1) Increases due to renal failure, increased catabolism, GI bleeding, dehydration
2) Decreases with low protein diet, water retention
3) Useful indicator of hydration when compared with creatinine

Question 13

what is the concentration of urea in the body a useful indicator of?

Answer 13

Useful indicator of hydration when compared with creatinine:

1) A serum creatinine ratio of 15 supports a picture of renal impairment
3) e.g. a patient with a serum creatinine of 250mmol/L and urea of 20, will potentially be dehydrated.

Question 14

what is Haematology? and name some blood tests

Answer 14

1) Examines the cellular composition of the blood
2) Tests:
- White blood cells (WBC)
- Red blood cells (RBC)
- C-reactive protein

Question 15

what can the level of WBC and RBC indicate and what is C-reactive protein a marker for?

Answer 15

1) White blood cells (WBC): Increased if an infection is suspected
2) Red blood cells (RBC): Low levels can indicate blood loss and or reduced production which can result in anaemia
3) C-reactive protein (CRP) : General marker for inflammation or infection
- should be considered alongside all blood test results to help reach a diagnosis

Question 16

what type of white blood cells increase when there is an infection?

Answer 16

1) Neutrophils- Increase in response to CRP seen in:
- bacterial infection, auto-immune disease, acute phase response, inflammation
2) Lymphocytes
- chemotherapy can result in low levels as production is decreased (bone marrow suppression

Question 17

what information can be ascertained from a RBC count?

Answer 17

1) Erythrocytes: Erythrocyte sedimentation rate (ESR)
2) Platelets
- Reduced count (thrombocytopenia) – immune thrombocytopenia purpura, drugs (penicillin, sulphonamides, diuretics, anti-inflammatories)
- Increased count – malignant disorders of bone, chronic inflammatory conditions, severe infectious illness, haemorrhage, surgery
3) Haemoglobin
4) Ferritin: Iron status

Question 18

list some coagulation tests

Answer 18

1) Prothrombin time (PT) 10-14 seconds
2) International normalised ratio (INR)
3) Activated partial thromboplastin time (APPT)

Question 19

what is Prothrombin time (PT) 10-14 seconds, and what is it used to measure?

Answer 19

?

1) clotting factor dependent on vitamin k, which is absorbed by the liver.
2) Vitamin K essential in activating clotting factors
3) Liver function impairment = absorption is reduced = prothrombin production PT will be increased.

Question 20

what is the International normalised ratio (INR) used to measure?

Answer 20

?

1) Used to monitor the anticoagulant effect of warfarin.
2) - The liver produces clotting factors, and impaired function can mean a deranged INR. Normal level = 1, target usually 2-3, higher in patients with valves/ hereditary diseases

Question 21

what is Activated partial thromboplastin time (APPT) used to measure?

Answer 21

?

Used for the monitoring of heparin

Question 22

describe the clotting cascade

Answer 22

e
1) injured vessel:
- exposure of collagen to blood
- damaged cells release phospholipids
2) platelet plug formed: clotting cascade activated Prothrombin ->Thrombin
3) Clot:
platelets, fibrinogen -> fibrin

Question 23

what is the purpose of a liver function test and what do they investigate ?

Answer 23

?

1) LFTs look at the expression of several enzymes in the liver, which may be raised due to damage.
2) Each enzyme should never be considered singularly
3) Patterns of increasing or decreasing levels are more valuable to assess liver function.

Question 24

list some liver function tests

Answer 24

s

1) ALT = alanine transaminase
- alongside AST markers of inflammation e.g. hepatitis
2) AST = aspartate transaminase
3) ALP = alkaline phosphatase
4) GGT = gamma glutamyltransferase (typically raised in alcoholism)
5) Bilirubin – results from breakdown of Hb
- Increased in jaundice, Cholestasis
6) Albumin – protein, made solely in liver
- In chronic liver cell disease, there is reduced production and levels fall
7) Coagulation (INR and PT)

Question 25

in liver disease Liver cell destruction and Cholestasis may both occur. outline the causes of cholestasis and liver cell destruction

Answer 25

n

1) liver cell destruction:
- Alcohol, hepatitis, drugs
- Biliary obstruction
2) cholestasis: Failure of bile to reach duodenum

Question 26

list the three different types of jaundice and outline the problems, causes and results of each one.

Answer 26

.
RBC breakdown-> Processed by liver-> Excreted bile
1) Pre-hepatic (haemolytic)- problem: Production exceeds capacity to process
- cause: Haemolysis, Gilbert’s syndrome
- Result: Unconjugated bilirubin in blood
2) Intra-hepatic (hepatocellular)- Problem: Liver unable to utilise bilirubin
- result : liver disease
- Result: Unconjugated and conjugated bilirubin in blood
3) Post-hepatic (obstructive): problem: Obstruction of bile duct
- causes: Gall stones, Drug induced
- result: Conjugated bilirubin in blood

Question 27

list and explain 3 types of liver damage

Answer 27

e

1) Acute hepatitis: Damage to liver cells leads to excretion of enzymes (usually ALT and AST). Clearance of bilirubin is reduced.
2) Chronic liver damage: Results in fibrous scar tissue building up in the liver, impairing the synthetic function so albumin and clotting factors are reduced.
3) Cholestasis: Can be considered as a ‘blockage’. Substances that are usually secreted by the liver accumulate due to impaired metabolism or excretion. ( ALP, GGT, bilirubin increase)

Question 28

eGFR is calculated using the Cockcroft-Gault equation? True/False

Answer 28

e

False

Question 29

Dose reductions in renal impairment are usually calculated using the eGFR? True/False

Answer 29

e

False

Question 30

CRP increases/decreases in response to infection/inflammation

Answer 30

n

Increases

Question 31

Bilirubin levels can decrease due to liver damage? True/False

Answer 31

e

False = Increases

Question 32

ALT is more highly concentrated and more specific to the liver than other liver enzymes? True/False

Answer 32

e

true

Question 33

Albumin has a short serum half life? True/False

Answer 33

e

false

Question 34

list some Clinical observation tests

Answer 34

s

1) Blood pressure (lying and standing)
2) Pulse
3) Temperature
4) Urine output
5) Respiratory rate
6) Oxygen saturations (pulse oximeter)
7) Blood glucose
8) Daily weights
- It is essential to use these parameters along with blood tests to support a potential diagnosis, monitor disease and identify possible adverse drug reactions.

Question 35

list the ideal blood pressure measurement

Answer 35

140/90mm hg

Question 36

outline the implications of hypertension and hypotension and also state what Postural hypotension is and what causes it.

Answer 36

.

1) Implications of hypertension include increased risk of stroke, MI and renal impairment
2) Implications of hypotension include dizziness, falls and collapse.
3) Postural hypotension describes a sudden drop in BP when patients change position from lying/sitting to standing
- Can be caused by medications (ACEi, diuretics, antipsychotics)
- Leading cause of falls in the elderly

Question 37

state what the ideal heart rate measurement is and outline when it may increase or decrease

Answer 37

1) Pulse: Heart rate (bpm): Normal pulse is approx 60-70bpm .
2) Can be elevated (tachycardia) for many reasons e.g. stress, medications, exercise, arrhythmias
3) Can be reduced (bradycardia) by medications, arrhythmias

Question 38

state the ideal body temperature and outline when it might increase or decrease.

Answer 38

1) Temperature 37℃.
2) Pyrexia ( raised body temp ) is usually caused by infection.
2) Hypothermia (below 35 ℃) is usually caused by exposure to cold temperatures, and can be extremely dangerous.
3) Temperature is usually monitored to look at presence of infection.

Question 39

what is Urine output (UO) an indication of?

- in what conditions does the quantity of urine increase or decrease?

Answer 39

1) Indicates renal function, but can also indicate fluid status (dehydration, overload with fluids).
2) Typical urine output would be approx 1.5 litres/day
- Can be higher in patients with oedema or ascites, where diuretics can be used to rid the body of fluid.
3) Low UO is a useful predictor of renal failure and may require the use of diuretics (furosemide) to encourage the kidneys to work harder.

Question 40

how is urine output measured?

Answer 40

UO can be measured using a comode or by a catheter bag if the patient is catheterised.

Question 41

what does Respiratory rate measure and when might it be higher?
- what class of drug reduces respiratory rate?

Answer 41

1) Number of breaths taken per minute (usually 12-16)
2) Respiratory rate may be higher in patients with acute exacerbations of asthma and COPD.
3) In severe cases the patient may accumulate CO2 as they fail to expel it. will affect the pH of the blood and cause acidosis, which left untreated, can lead to other organs failing
4) Low respiratory rate can be caused by opioid toxicity.

Question 42

what does Oxygen saturation measure and what is the ideal % in healthy patients?
- in which condition might the oxygen saturation of blood drop ?

Answer 42

1) Indicates the level of oxygen circulating in the blood. It is measured by an oximeter. should be 99-100%.
2) In patients with severe cases of COPD or acute exacerbations of asthma this can fall to below 90%
Patients at this level will be obviously breathless, with an increased respiratory rate and tachycardia. Most will require respiratory support using a ventilator.
3) Treating patients with high concentration oxygen (28%) can lead to CO2 retention so should be avoided.

Question 43

list some other specific tests which can be measured

Answer 43

1) Thyroid function: T4, TSH
2) Therapeutic Drug Monitoring (TDM)
For drugs with narrow therapeutic index eg phenytoin, digoxin, vancomycin, gentamicin
3) Lipids: LDL- Cholesterol, triglycerides
4) Cardiac enzymes (eg Troponin)
5) Blood glucose