Prescribing in special populations Flashcards
Approach to rational prescribing
Step 1: Define the patient’s problem
Step 2: Specify the therapeutic objective
Step 3: Verify whether your P-treatment is suitable for this patient
Step 4: Start the treatment
Step 5: Give information, instructions and warnings
Step 6: Monitor (stop) the treatment
Special risk groups
- Kidney disease
- Liver disease
- Elderly
- Pregnancy
- Lactation
- Very young
- Obesity
- Porphyria
- Palliative care
- Competitive sports
Prescribing in renal failure
•Drug/active metabolite may accumulate in renal failure, causing toxicity
–e.g. aminoglycosides largely excreted unchanged in urine
•Reduced dose and/or increased dosage interval often necessary
Exception ® need higher doses of loop diuretics
Prescribing in liver disease
- Drugs metabolised by the liver may have prolongation of half-lives/elimination times resulting in toxicity
- If possible, select drug with no hepatic metabolism, or metabolised by conjugation rather than cytochrome P450 (conjugation is less affected by liver disease)
- Reduce the dose of drugs that undergo extensive first pass elimination (e.g. propranolol) as portal hypertension reduces pre-systemic elimination by bypassing the liver with vascular shunting
- Higher risk of drug-induced hepatotoxic reactions
How is absorption changed in elderly
Relatively unchanged
How distribution changes in elderly
•decrease in total body water and lean body mass, with increase in fat mass
–Water soluble drugs, e.g. aminoglycosides, can cause toxicity
–Lipid soluble drugs e.g. benzodiazepines, can have a prolonged elimination half life
How metabolsim changes in elderly
•oxidative metabolism reduced, conjugation unchanged
–Administer drugs with high hepatic extraction, e.g. morphine, with caution
How excretion changes in elderly
•decline in glomerular filtration rate with advance age
–Always determine eGFR, even if the serum creatinine is within normal range
Effects of drug on pregnancy
Teratogenicity
Low birth weight
preterm labour
postnatal effects
miscarriage
How absorption changes in pregnancy
Change in rate and extent
How distribution changes in pregnancy
–Increase plasma volume in later stage leading to increased Vd of some drugs
•E.g. Sub-therapeutic concentrations of antiepilectic drugs
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–Changes in protein and free fatty acids affecting drug binding
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–Increase in fat
How metabolism changes in pregnancy
–Variable hepatic metabolism/elimination
Excretion in pregnancy
–increase in glomerular filtration rate
•Renally eliminated drugs may be reduced
PK changes in children: aboprtion
•Oral Absorption
–Neutral -> acidic pH (2 years)
–Gastric Emptying delayed in infants under 6-8 months and shorter in older infants.
–Intestinal mucosa immature
–Frequent feeding
- Intramuscular: Variable blood flow to muscles in neonates
- Percutaneous absorption faster and more extensive
- Rectal absorption not changed much by maturation (but alters with position of suppository)
PK chnges in childrren and adults:
–Increased body water : fat ratio highest in neonates (80-90% vs 55-60% in adults)
•infants have higher Vd for water soluble drugs (e.g aminoglycosides) than adults -> so need a higher loading dose
–Plasma protein binding lower in neonates
–Membrane permeability:
- BBB immature, larger CNS volume
- Apparent Volume of distribution increases approximately linearly with weight
Young children (aged 1-2 years) have a shorter half-life than adults and infants
PK changes in metabolsm between adults and children
–Phase 1 (oxidation / reduction / hydrolysis)-> active / inactive metabolites
–Phase 2 (glucoronidation / sulphation / methylation) -> more readily excretable polar metabolites
- Reduced hepatic metabolism in neonates, reaching adult levels by 6-12 months, then exceed adult levels for 1-4 years, returning to adult levels by adolescence
- Liver volume, blood flow and biliary function correlate well with Body Surface Area (BSA)
PK changes in children: excretion
- Clearance increases non-linearly with weight so the maintenance dose per kg is highest around 2 years of age
- Renal function reaches maturity ~ age 1-2 years, when the GFR correlates well with the BSA
PK/PD of antihistamines in children
paradoxical excitation even at low doses
Chloramphenicol- PK/PD in children
grey baby syndrome
Phenothiazine anti-emetics PK/PD in children
•extrapyramidal side effects even at low doses
Aspirin PK/PD problems in children
associated with Reyes syndrome (rash, vomiting, and liver damage
Sulphonmide PK/PD problems in children
risk of kernicterus if under 2 months
Tetracyclines PK/PD problems in children
teeth discoloration, impaired bone growth if under 8 years
Why is it important to calculate correct dose in children
Challenges
PK chnage in children affects ADME
–Variability in weight for age
–Variability in lean body mass
–Underweight
–Overweight / obese
•By Body surface area
