RENAL - Therapeutic Drug Monitoring Flashcards
(20 cards)
What factors should be considered in patients which increase the likelihood of an abnormal response to the drug?
Age
Sex
Renal Function
Concurrent administration of other drugs
What questions should you be asking yourself to determine whether a drug requires monitoring?
- Do we need to monitor plasma concentrations of the drug to check that the dose is therapeutic?
- Do we need to monitor plasma concentrations of the drug to check that the dose is not toxic?
- Do we need to monitor any other organ systems to check that the drug is not having an adverse effect on those?
- Do we need to monitor any other organ systems to know whether we need to alter the dose of the drug?
What does it mean for a drug to have a broad therapeutic index?
Give examples.
Difference between sub-therapeutic and toxic dose is large
- Optimum dose can be arrived at by commencing treatment with a standard dose and modifying this as necessary in the light of the observed response
Hypotensive agents, DOACs, insulin, oral hypoglycaemics
What does it mean for a drug to have a narrow therapeutic index?
Give examples.
Small changes in plasma concentration can be difference between sub-therapeutic and toxic dose
- Plasma concentration can be measured as an indicator of outcome to show, sub-therapeutic, therapeutic or toxic dose
Theophylline, lithium, phenytoin, aminoglycosides, digoxin
Describe half life and steady state of a drug.
- Half life - how long it takes for 50% of drug to be eliminated from the body
- Steady state is defined as the rate of drug input being equal to the rate at which the drug is eliminated from the body
- Time to steady state is approximately 5 x the half-life of the drug
- If you have a drug with a long half-life you can achieve steady
state more quickly by using a loading dose
The relationship between plasma concentration and clinical effect is not always linear.
Suggest why.
- Protein binding
- Metabolic rate
- Other drugs
- Genetic differences
Describe digoxin. PART 1
- Management of atrial fibrillation and rate control in cardiac failure
- Therapeutic range for plasma digoxin concentration 1.0-2.6nmol/L
- Toxicity almost invariable if >3.8nmol/L
- Some patients experience toxicity at <2.6nmol/L
Describe digoxin. PART 2
- Digoxin toxicity enhanced by hypokalaemia – many patients on digoxin also take diuretics
- Impaired renal function can impair digoxin excretion (think about elderly patients on multiple medications)
- Toxicity – nausea, vomiting, diarrhoea, visual disturbance, hallucination
Describe lithium. PART 1
- Management of Acute Mania and prophylaxis of manic- depressive psychosis
- Therapeutic range of 0.3-1.3mmol/L 12h after the last dose
- Time to steady state 4-7 days
- Significant interindividual differences in dose requirements
Describe lithium. PART 2
- Nephrotoxic and excreted by the kidneys
- Plasma concentrations >1.5mmol/L should be avoided
- In lithium toxicity, dialysis may be required to remove the drug if
the concentration exceeds 3.5mmol/L
Describe gentamicin. PART 1
- Very water soluble – very little moves into fatty tissues so increased risk of toxicity; weight based dosing and careful monitoring of serum concentrations
- Nephro and Ototoxic, but relatively high concentrations are needed for bactericidal effects
- Short plasma half- life (time to steady state, 12-24 hours depending on renal function)
Describe gentamicin. PART 2
- Toxicity appears to relate to the trough concentration (the concentration immediately before the next dose is due)
- Bactericidal action requires a sufficient peak concentration
Describe theophylline. PART 1
- Bronchodilator used in Asthma
- Response in different patients varies
considerably in relation to dosage but correlates well with plasma concentration - Therapeutic range is 10-15 mcg/ml (>20mcg/ml increases frequency and severity of adverse reactions)
Describe theophylline. PART 2
- Toxicity – primarily cardiac dysrhythmias
- Patients requiring IV theophylline for severe exacerbation of asthma have often already had an oral dose (may be requirement to measure concentrations rapidly)
Describe phenytoin. PART 1
- Used in Epilepsy, tonic-clonic and focal seizures
- Time to steady state; 5-10 days
- Take a trough sample (immediately before next dose), time since last dose should be recorded
Describe phenytoin. PART 2
Therapeutic range: 8-15mg/L
* Can be used to monitor compliance
* Toxic effects include nystagmus, blurred vision, ataxia, drowsiness and ECG changes
Why would some drugs require monitoring in relation to other body systems? Give examples.
- Some drugs require monitoring due to the possible adverse effect on other systems or because a change in renal function may require a different dose
- ACE-inhibitors and Angiotensin receptor blockers – U&E needs to be checked prior to starting and with every increase in dose
- Statins – Liver function needs to be checked within 3 months of starting
- Levothyroxine – Requires annual monitoring of TSH levels and 4-6 weeks after a dose change
Describe metformin. PART 1
First line treatment for Type 2 Diabetes
* Should not be prescribed in eGFR is <30 due to risk of lactic acidosis
* Renal function should be monitored annually on metformin and more frequently if eGFR decreases
Describe metformin. PART 2
Many patients on metformin are also on other medication that can affect their kidneys
* Diabetes is a risk factor for CKD
Why would lithium require monitoring? When prescribed what should also be monitored?
Requires regular monitoring of concentration of drug due to NTI
* Also requires regular monitoring of Thyroid Function, FBC and U&E every 3 to 6 months
* Also Calcium, HbA1c, Lipid profile and BP if >40 years
