Pharmacokinetics and Pharmacodynamics Flashcards
Define pharmacokinetics vs pharmacodynamics
PK: study of how the organism affects the drug (ADME: absorption, distribution, metabolism, excretion)
PD: study of how the drug affects the organism (relationship of drug concentration and response)
(ADME) What affects the Absorption of drugs?
rate of absorption is affected by:
1. route of administration (IV bolus> IV infusion > intramuscular > oral > oral extended release)
2. properties of drug: molecular weight and structure (typical drug: 100-1000 Da, solubility (partition coefficient increases as lipid solubility increases), ionization (most drugs are weak acid/bases; uncharged form can diffuse across membrane)
3. underlying physiology of patient: adherence or compliance (elderly and psychiatric), GI function for oral drugs (pH, gastric emptying, malabsorption, variable expression of GI drug transporters), physiological factors (age, gender, pregnant, obese), environment (other medications, herbal products, food, etc.)
(ADME) Describe the distribution of drugs. What affects the distribution of drugs?
Drugs can be distributed from circulation to target tissue/rest of body. First goes to highly perfused organs (liver, kidney, brain) then to lesser ones (adipose, muscle, etc)
properties of the drug that affect distribution:
- protein* (acidic drugs bind to albumin, basic drugs bind to AAG; only free (unbound) drugs can produce pharmaco effect; high binding -> slower elimination, prolonged duration of action)
- molecular size and struct
- lipid solubility
- degree of ionization
- tissue perfusion
- movement across membranes
What are some considerations for effect of binding protein on free drug conc.
albumin levels can be decreased in liver diseases
AAG is acute phase reactant (elevated in inflammation)
co-administered drugs can compete for binding sites and result in higher free drug concentration; (increased free drug conc. = increased pharmacologic effect; may be over toxicity threshold)
Define volume of distribution and why is it helpful
Volume of distribution is the theoretical volume of total body fluid which all of the drugs is distributed.
Anatomic Vd = total amount of drug in body/ initial plasma drug conc.
Apparent Vd = Anatomic Vd/ body weight
Volume of distribution can be helpful for 3 reasons:
- predicting where drug might be distributed (plasma vs tissue)
- predicting plasma drug concentration when dose administered is known
- deciding whether to use hemodialysis in poisonings
(ADME) What is the result of metabolism on drugs (ie. how is it altered)? What are the responsible organs? how are the metabolisms categorized?
metabolism alters drugs to be more water soluble for excretion
- responsible organs: liver (main), kidneys, intestines, lungs, skin, eye
- categorized into: hepatic microsomal, non-microsomal, extra-hepatic
parent compounds are metabolized into metabolites (may or may not be active)
Define bioavailability
bioavailability is the measure of the extent of absorption NOT the rate.
- measures the percentage of drug that enters the circulation in an unchanged form
- bioavailability over 70% is considered useful for oral drugs
- affected by first pass effect
Define the first pass effect
The first pass effect is the biotransformation of a drug before it reaches its site of action
(affects bioavailability)
- predominately occurs in liver (but can also occur in small intestine)
- drugs are absorbed from small intestine -> liver via hepatic portal vein -> metabolized by liver enzymes -> blood with parent compound + metabolites enter circulation by hepatic vein
What are 4 factors that affect biotransformation? describe induction vs inhibition on drug concentration
genetic polymorphisms (can increase or decrease enzyme act.)
physiological factors: age, gender, etc.
environmental factors: diet, medication, etc.
Drug-drug interactions can lead to enzyme induction (increased enzyme synthesis, increased metabolism of drug, decreased drug concentration) or enzyme inhibition (decreased enzyme synthesis, decreased metabolism, increased drug concentration)
(ADME) What are the routes of elimination of drugs?
Elimination routes:
Kidneys -> urine
Liver -> secreted into bile -> feces
breath, breast milk, saliva, sweat, tears, hair
(ADME) What are some factors that affect renal and hepatic elimination of drugs
Perfusion and function of organs (renal function on glomerular filtration)
protein binding: free drugs get filtered by glomerulus; therefore bound drugs prolong half-life
urine pH and resorption in tubules: pH alters ionization and solubility of drug
What is the elimination half life? What is an assumption made? what does it determine?
elimination half life is the time it takes for the concentration to decrease by 50%
- assumes absorption and distribution phase are complete
- determines the length of drug effect
- sum of metabolism + excretion
Describe the difference between potency and efficacy
potency: minimum dose to see expected results (higher potency, less drug needed to give a desired effect); measured using ED50 (dose needed to see effects in 50% of pop)
efficacy: maximal effects achievable (reflects how the drug works in ideal situations)
Describe the difference between an agonist and an antagonist
Agonist binds to receptor to produce a biological response that mimics that of an endogenous ligand (can be a full agonist, partial agonist, or inverse agonist)
Antagonist binds to receptor but has no activity, can block endogenous ligand from binding (attenuates effect of agonists)
What is the therapeutic index? how is it calculated?
therapeutic index is the comparison of a drugs therapeutic effect vs toxic effect
TI =LD50/ED50
-higher the TI, the more separated the toxic effect and therapeutic effect are therefore safer
