Prescribing in Special Circumstances Flashcards
What is the definition of pharmacokinetics?
The science of the rate of movement of drugs within biological systems, as affected by the absorption, distribution, metabolism and elimination of medications
What your body does to the drug
What are pharmacodynamics?
Study of biochemical and physiologic processes underlying drug action - mechanism of drug action - drug receptor interaction - efficacy - safety profile What the drug does to your body
What is bioavailability?
Fraction of the administered dose of drug that reaches the systemic circulation (F)
Affected by many factors
What factors alter the bioavailability of a drug?
Molecular weigh/ionisation of the drug
Gastric pH/health of the GI tract (affects absorption)
First pass metabolism
Volume of distribution
- how much of the drug remains in the blood affects how much you should give
What is clearance?
Volume of plasma cleared of drug per unit time (e.g. ml/min or l/h)
What is the half-lie of a drug?
Time required for serum plasma concentration to decrease by half
What determines the half-life of a drug?
Clearance and volume of distribution
When are loading doses used?
When the drug has a long-half life
When does a drug reach a steady state?
After 4-5 half lives
What is the half life of a drug used to determine?
Time to eliminate the drug
Time to reach a steady state
Dosage interval
What is linear pharmacokinetics?
Concentration that results from a dose, is proportional to the dose
- double the dose, double the concentration
Rate of elimination is proportional to the concentration
- 50% of the drug will be eliminated in a given time
What is non-linear pharmacokinetics?
Concentration that results is not proportional to dose
- dosage increases can saturate binding sites and result in non-proportional increase in drug levels
Rate of elimination is constant regardless of the amount of drug in the system
What is the influence of age on pharmacokinetics?
Decrease in total body water (due to decrease in muscle mass) and increase in total body fat affects the volume of distribution
Reduced first pass metabolism due to variable decline in hepatic blood flow
Oxidative metabolism through cytochrome P450 decreases with ageing
- reduces clearance
GFR declines with age
Which drugs are affected by increasing age (less water and more fat)?
Water soluble drugs
- lithium, aminoglycosides, alcohol and digoxin
- serum levels go up due to decreased volume of distribution
Fat soluble drugs
- diazepam, thiopental and trazadone
- half life increases with increase in body fat
What is the influence of age on pharmacodynamics?
Effects of the following are increased - alcohol - opiates - sedatives - theophylline Effects of the following are decreased - HR response to isoproterenol and beta-blockers
Why are adverse drug reactions common in the elderly?
The more medications a person is on, the higher the risk of drug-drug interactions or adverse reactions
Risk of non-adherence is also higher
Name some drug-disease interactions.
Parkinson’s patients have increased risk of drug induced confusion
NSAIDs can exacerbate CHF
Decongestants and anticholinergics can cause urinary retention in BPH patients
Calcium, anticholinergics and calcium channel blockers worsen constipation
Neuroleptics and quinolones lower seizure thresholds
What are some common causes of adverse drug reactions in the elderly?
Statins and erythromycin and other antibiotics
Verapamil and beta-blockers
Warfarin and many drugs (e.g. aspirin)
ACE inhibitors increase hypoglycaemic effect of sulonylureas
What is commonly undertreated in the elderly?
Coronary artery disease - beta-blockers - aspirin Anticoagulation in AF Hypertension (especially systolic hypertension) Pain
How does renal disease affect pharmacokinetics?
Decrease elimination
Decreased protein binding
Decreased hepatic metabolism
How does renal disease affect pharmacodynamics?
Alters the sensitivity to the effect of the drug
- increased sensitivity to sedatives (by increasing BB permeability)
Adverse effects
Which drugs have decreased elimination in renal disease?
Aminoglycosides Lithium Digoxin Methotrexate Penicillins
What must you (the doctor) do if someone has decreased drug elimination in renal disease?
Determine the renal function of the patient
Alter the dosing schedule (increase)
Monitor the drug concentration
What effect does reduced protein binding due to renal disease have on the body?
Renal failure leads to acid retention
Acidic drugs are less bound to albumin
- conformational change in albumin leads to a less ionised drug binding instead
Increased free (active) drug in the plasma
How does renal failure affect hepatic metabolism?
Hepatic metabolism of some drugs is slower in renal failure
- endogenous inhibitor in uraemic plasma
Normalised by HD
What other considerations are there when prescribing to a patient with renal disease?
Nephrotoxins - amphoteracin and gentamicin Fluid retention - NSAIDs Increasing uraemia - tetracyclines Electrolyte disturbance - amiloride, digoxin
What should you do with the following drugs in a patient with renal disease?
- antibiotics
- LMWH
- metformin
- NSAIDs
- digoxin
- phenytoin
- ACE inhibitor
Antibiotics - reduce dose LMWH - reduce dose Metformin - avoid NSAIDs - avoid Digoxin - reduce dose Phenytoin - reduce dose ACE inhibitor - caution
How should you adjust drugs in general when someone has renal disease?
Same or increased dose
Increased dosing interval
-prolonged elimination
How does hepatic impairment affect pharmacokinetics?
First pass metabolism
Activation of prodrugs
Decreased protein binding
Decreased elimination
How does hepatic impairment affect pharmacodynamics?
Altered sensitivity to drugs - sensitivity to sedatives and oral anticoagulants Fluid retention Precipitation of encephalopathy Hepatorenal syndrome
How does hepatic disease affect first pass metabolsim?
Changes in bioavailability - chlormethiazole (1000% increase) - verapamil (140% increase) - paracetamol (50% increase) First pass activation is reduced - enalapril - perindopril
What is a high extraction drug?
Metabolised at a high rate by the liver
Rate varies with delivery
Affected by changes in blood flow
Morphine, verapamil and lignocaine
What is a low extraction drug?
Metabolised at a low rate by the liver
Independent of blood flow
Sensitive to changes in liver enzyme activity
Cholamphenicol, theophylline
In general, how do you prescribe
Decrease the dose
Increase the dosing interval
