Clinical pharmacodynamcis. Changes in drug pharmacokinetics and pharmacodynamics in patients with liver and heart failure:

Question 1

dose response relationship

Answer 1

dosage is proportionsl to magnitude of desired effect until a max effect is reached

Question 2

dose response curve

Answer 2

derived from a number of pts to estimate the 1st dose in a pt w/o prior exposure to drug

after this obvs of pt response to dose is used

Question 3

conc response relationship

Answer 3

conc of drug is unque to indivuduals d/2 diff phK by the pt making it less predictable but more acc

Question 4

interpatient variation

Answer 4

drugs have a standard dose however pt’s vary in terms of their phD and phK

E.G.
acylation speed
renal / liver dysfunction
concomitant disease

Question 5

effect of acute liver failure on drug phK

Answer 5

impaired metabolism

impaired elimination

Question 6

effect of chronic liver failure on drug phK

Answer 6

impairment affects all parameters of pharmacokinetic.

Question 7

guidlines in suspected liver failure

Answer 7

check for signs of hepatotoxicity

• nausea
• hepatomegaly
• jaundice

avoid hepatotoxic drugs where possible

• alcohol
• aspirin
• methotrexate
• phenytoin
• statins

Question 8

oral drugs in cirrhosis

Answer 8

decreased first pass met
drug directly introduced into circ
require reduced dose

Question 9

Phase 1 liver metabolism

Answer 9

oxidation (most common, CYP ez’s,
reduction
hydrolysis.

Question 10

pharm activity of metabolites after first phase

Answer 10

• inactive metabolites
• less active metabolites than initial drug
• prodrug inactive but has active metabolites

Question 11

Phase 2 metabolism

Answer 11

chemically changes phase 1 metabolites into compounds that are soluble enough to be excreted in urine.

usually inactive

done via conjugation

Question 12

methods of conjugation

Answer 12

glucoronidisation

acetylation

Question 13

General inducers of CYP metabolism

Answer 13

anticonvulsants and antibiotics (Rifampin).

Question 14

General inhibitors of CYP metabolism:

Answer 14

acute alcohol
cimetidine
omeprazole

Question 15

factors determining the liver’s metabolic activity

Answer 15

⦁ Hepatic blood flow.
⦁ Liver enzyme activity.
⦁ Binding of a drug to plasma proteins.

Question 16

how does decreased hepatic flow impair drug met

Answer 16

-⦁ drug delivery to the hepatocytes decreases,
⦁ Drug metabolism decreases,
⦁ drug toxicity increases.

Question 17

effect of low protein binding on metabolism

Answer 17

⦁ impaired liver is unable to synthesize plasma proteins (albumin)
⦁ Liver impairment causes accumulation of substances (bilirubin) that displace drugs from protein-binding sites.
⦁ protein binding decreases so the free drug increases,
⦁ peak blood levels and adverse effects increase.

Question 18

principles of dose adjustment in liver impairment

Answer 18

⦁ Starting therapy with low doses and monitoring response or plasma levels

⦁ In case of a high-clearance drug: reduce the initial dose by 50%

⦁ In case of a low-clearance drug: reduce the maintenance dose by 35%

Question 19

why is dose adaptation harder in liver impairment than renal

Answer 19

no endogenous marker for hepatic clearance that can be used as a guide for drug dosing. Unlike creatinine clearance for the kidney

Question 20

phK effects of liver imparment

Answer 20

⦁ Absorption increased bioavailability.
⦁ Distribution decreased plasma binding and increased distribution.
⦁ Metabolism impaired.
⦁ Excretion impaired.

Question 21

define heart failure

Answer 21

inability of the heart to keep up with the demands on it and, specifically, failure of the heart to pump blood with normal efficiency.

Question 22

what is elimination half life

Answer 22

time it takes for the concentration of the drug in the plasma or the total amount in the body to be reduced by 50%

Question 23

changes to phK in CHF

Answer 23

reduced distrinution

impaired drug clearance

elimination half life depends on the first 2

Question 24

how does CHF affect drug plasma conc

Answer 24

increased compared to healthy pt

Question 25

which drugs are important to monitor in CHF phK

Answer 25

drugs w/ narrow therapeutic index (Anti arrythmics)

• digoxin
• lidocaine
• procainamide

Question 26

how to manage drugs w/ narraw therapeutic ratio in CHF

Answer 26

reduce loading and maintenance doses

measure plasma conc of drugs