Clinical Pharmacology Flashcards
What is the quantal dose response relationship?
plotting the fraction of the population that responds to a given dose of drug against the drug dose which generalises the effect of a drug to a population rather than an individual
What are the different 50% responses of significance in the quantal dose response?
ED50
TD50
LD50
What is the ED50?
the median effective dose in 50% of the population
What is the TD50?
the median toxic dose in 50% of the population
What is the LD50?
the median lethal dose in 50% of the population, often not recorded in humans
Give an example of drug interactions that can be beneficial
b-blockers + ACE inhibitors = decreased BP and hypertension
What kinds of interactions can result in adverse effects?
pharmacokinetic
pharmacodynamic
When does the risk of adverse reaction go significantly up?
when taking 12 drugs or more - 20% chance and up
What are pharmacodynamic interactions?
Drug A modifies the pharmacological effect of Drug B without affecting its concentration in tissues
What are pharmacokinetic interactions?
Drug A modifies the concentration of Drug B that reaches its site of action
How might pharmacokinetic interactions occur?
through ADME
How might pharmacokinetic interactions affect absorption?
increasing or decreasing the rate of emptying the stomach
enterohepatic recycling such as with the pill
Give an example of a drug that increases stomach emptying
metoclopramide
Give an example of a drug that decreases stomach emptying
atropine
How do antibiotics affect the absorption of the pill?
gut bacteria normally release the pill from the conjugated form released in the bile and allow reabsorption. Antibiotics prevent this
How might pharmacokinetic interactions affect distribution?
drugs bound to plasma proteins may be displaces by a second drug increasing their free concentration
When does plasma protein binding matter with drug interactions?
with drugs that are extensively protein bound or have a low therapeutic ratio
Why does plasma protein binding only have little significance?
Cp drives elimination
Give an example of a drug with low therapeutic ratio
phenytoin
How might pharmacokinetic interactions affect metabolism?
may induce hepatic enzymes decreasing the efficacy of another drug
may inhibit enzyme that metabolises another drug
How might pharmacokinetic interactions affect excretion?
drugs may share a common transporter e.g. in the proximal tubule of the nephron
Why does taking viagra and organic nitrates result in collapse?
organic nitrates cause vasodilation via NO and viagra potentiates this response by inhibiting PDEs causing severe hypotension
Why does taking warfarin and flucanazol cause blood in the urine?
flucanazol inhibits CYP3A4 which metabolises warfarin
hence anti-coagulant effect is enhanced and causes blood in urine
What may cause a Cp to be higher than desired?
excessive dosage and/or decreased clearance
What factors may cause a Cp to be higher?
normal variation saturable metabolism genetic enzyme deficiency renal/liver failure old age/young age enzyme inhibition
What may cause a Cp to be lower than desired?
dose too low and/or increased clearance
What factors may cause Cp to be lower?
normal variation poor absorption high first pass metabolism genetic hyper-metabolism enzyme induction non-compliance
How may enzymes be inhibited?
competitively - higher Km
non-competitively - lower Vmax
What are some example enzyme inhibitors?
cimetidine
erythromycin
fluoextine
What are some example enzyme inducers?
alcohol
phenobarbiton
phenytoin
What causes impaired drug metabolism in liver disease?
decreased enzyme metabolising capacity
decreased liver blood flow
How is drug dosage adjusted in liver disease?
for high Cl drugs
for low Cl drugs
What is hypoproteinemia?
reduced synthesis of blood plasma proteins
What is significant about hypoproteinemia in liver disease?
increases toxicity of highly bound drugs such as phenytoin
What effect does reduced clotting factor synthesis have in liver disease?
increases sensitivity to oral anti-coagulants i.e. warfarin
What is cholestasis?
flow of bile to the duodenum is compromised
what may occur as a result of hepatic encephalopathy?
deterioration of brain function which may be precipitated by several drug class i.e. sedatives and opioids
What may occur as a result of ascities?
accumulation of fluid in the peritoneal cavity associated with severe liver disease
may be worsened by drugs that cause fluid retention i.e. NSAIDs
What is used to measure renal impairment?
clearance of creatinine as a measure of GFR
How are drugs adjusted for in renal impairment?
reducing the size of individual dose or increasing the time interval between doses
Why may a loading dose be necessary in renal impairment?
T1/2 is increased for drugs cleared by the kidney which prolongs the time to Cpss
What are the grades of renal impairment?
mild - 20-50 ml.min
moderate - 10-20 ml.min
severe
How is dosing carried out in children?
by body weight and surface area
What is particularly problematic in neonates?
inefficient renal filtration
relative enzyme deficiencies
inadequate detoxifying systems
What are important considerations when prescribing for the elderly?
renal elimination tends to be impaired
metabolism is usually impaired
both lower overall clearance
What are the main issues in prescribing for pregnancy?
teratogenicity
if drug is absorbed orally, assume it crosses the placenta
benefits have to outweigh risks
