Prescribing in Special Circumstances

Question 1

What is the definition of pharmacokinetics?

Answer 1

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

Question 2

What are pharmacodynamics?

Answer 2

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

Question 3

What is bioavailability?

Answer 3

Fraction of the administered dose of drug that reaches the systemic circulation (F)
Affected by many factors

Question 4

What factors alter the bioavailability of a drug?

Answer 4

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

Question 5

What is clearance?

Answer 5

Volume of plasma cleared of drug per unit time (e.g. ml/min or l/h)

Question 6

What is the half-lie of a drug?

Answer 6

Time required for serum plasma concentration to decrease by half

Question 7

What determines the half-life of a drug?

Answer 7

Clearance and volume of distribution

Question 8

When are loading doses used?

Answer 8

When the drug has a long-half life

Question 9

When does a drug reach a steady state?

Answer 9

After 4-5 half lives

Question 10

What is the half life of a drug used to determine?

Answer 10

Time to eliminate the drug
Time to reach a steady state
Dosage interval

Question 11

What is linear pharmacokinetics?

Answer 11

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

Question 12

What is non-linear pharmacokinetics?

Answer 12

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

Question 13

What is the influence of age on pharmacokinetics?

Answer 13

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

Question 14

Which drugs are affected by increasing age (less water and more fat)?

Answer 14

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

Question 15

What is the influence of age on pharmacodynamics?

Answer 15

Effects of the following are increased
- alcohol
- opiates
- sedatives
- theophylline
Effects of the following are decreased
- HR response to isoproterenol and beta-blockers

Question 16

Why are adverse drug reactions common in the elderly?

Answer 16

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

Question 17

Name some drug-disease interactions.

Answer 17

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

Question 18

What are some common causes of adverse drug reactions in the elderly?

Answer 18

Statins and erythromycin and other antibiotics
Verapamil and beta-blockers
Warfarin and many drugs (e.g. aspirin)
ACE inhibitors increase hypoglycaemic effect of sulonylureas

Question 19

What is commonly undertreated in the elderly?

Answer 19

Coronary artery disease
- beta-blockers
- aspirin 
Anticoagulation in AF
Hypertension (especially systolic hypertension)
Pain

Question 20

How does renal disease affect pharmacokinetics?

Answer 20

Decrease elimination
Decreased protein binding
Decreased hepatic metabolism

Question 21

How does renal disease affect pharmacodynamics?

Answer 21

Alters the sensitivity to the effect of the drug
- increased sensitivity to sedatives (by increasing BB permeability)
Adverse effects

Question 22

Which drugs have decreased elimination in renal disease?

Answer 22

Aminoglycosides
Lithium
Digoxin
Methotrexate 
Penicillins

Question 23

What must you (the doctor) do if someone has decreased drug elimination in renal disease?

Answer 23

Determine the renal function of the patient
Alter the dosing schedule (increase)
Monitor the drug concentration

Question 24

What effect does reduced protein binding due to renal disease have on the body?

Answer 24

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

Question 25

How does renal failure affect hepatic metabolism?

Answer 25

Hepatic metabolism of some drugs is slower in renal failure
- endogenous inhibitor in uraemic plasma
Normalised by HD

Question 26

What other considerations are there when prescribing to a patient with renal disease?

Answer 26

Nephrotoxins
- amphoteracin and gentamicin 
Fluid retention 
- NSAIDs
Increasing uraemia 
- tetracyclines
Electrolyte disturbance 
- amiloride, digoxin

Question 27

What should you do with the following drugs in a patient with renal disease?

• antibiotics
• LMWH
• metformin
• NSAIDs
• digoxin
• phenytoin
• ACE inhibitor

Answer 27

Antibiotics - reduce dose
LMWH - reduce dose
Metformin - avoid
NSAIDs - avoid
Digoxin - reduce dose
Phenytoin - reduce dose
ACE inhibitor - caution

Question 28

How should you adjust drugs in general when someone has renal disease?

Answer 28

Same or increased dose
Increased dosing interval
-prolonged elimination

Question 29

How does hepatic impairment affect pharmacokinetics?

Answer 29

First pass metabolism
Activation of prodrugs
Decreased protein binding
Decreased elimination

Question 30

How does hepatic impairment affect pharmacodynamics?

Answer 30

Altered sensitivity to drugs 
- sensitivity to sedatives and oral anticoagulants
Fluid retention
Precipitation of encephalopathy
Hepatorenal syndrome

Question 31

How does hepatic disease affect first pass metabolsim?

Answer 31

Changes in bioavailability
- chlormethiazole (1000% increase)
- verapamil (140% increase)
- paracetamol (50% increase)
First pass activation is reduced
- enalapril
- perindopril

Question 32

What is a high extraction drug?

Answer 32

Metabolised at a high rate by the liver
Rate varies with delivery
Affected by changes in blood flow
Morphine, verapamil and lignocaine

Question 33

What is a low extraction drug?

Answer 33

Metabolised at a low rate by the liver
Independent of blood flow
Sensitive to changes in liver enzyme activity
Cholamphenicol, theophylline

Question 34

In general, how do you prescribe

Answer 34

Decrease the dose

Increase the dosing interval