pharmacokinetics and dynamics

concentration of substrate where enzyme is going at a 50% rate

the point at which increasing the substrate does not make the enzyme go faster because it is maxed out

• K_m = x axis at point on slope where y = ¹/₂V_max
• V_max = y value where it flattens out
• 

• K_m = -1/x_int
• V_max = +1/y_int
• increasing abs(x_int) reduces K_m
• increasing y_int reduces V_max
• 

• binds active site/resembles substrate
• V_max unchanged (just takes substrate)
• K_m increased (=takes more substrate)
• reduces potency
• no effect on efficacy

• binds active site/resembles substrate
• V_max reduced (some of enzyme is deactivated because it bound the wrong thing)
• K_m unchanged (the enzyme that still works is doing fine)
• reduces efficacy
• no effect on potency

• binds alternate site on enzyme to inhibit it
• V_max reduced (some of enzyme is deactivated)
• K_m unchanged (the enzyme that still works is doing fine)
• reduces efficacy
• no effect on potency

• depends on absorption
• hepatic destruction

100%

• lowest for large charged molecules/plasma protein bound
• small greatest for lipophilic esp if tissue protein bound
• 

• depends on cardiac, hepatic, renal function
• 

• time to reduce amount of drug in body by half
• 1st order kinetics takes 4-5 half lives to reach steady state
• 

• NOT affected by renal or liver disease
• 

• affected by renal/liver disease
• 
• C_p=target [drug]_plasma
• for a continuous does just move tau to the bottom of the maintenance dose side and you're calculating a rate instead

• sum of the two effects is the total effect
• aspirin and acetaminophen

• presence of A is required for full effect of B
• cortisol on catecholamine responsiveness

• effect of A and B is greater than the sum
• clopidogrel and aspirin

• acute decrease in response to drug after initial/repeated administration
• MDMA
• LSD

• phenytoin
• ethanol
• aspirin (high/toxic concentrations)
• constant elimination regardless of C_p

• phenobarbital
• methotrexate
• aspirin
• treat with bicarb (trapping it in ionized state)

• amphetamines
• TCAs
• treat with ammonium chloride (trapping in ionized state)

• reduction, oxidation, hydrolysis via P-450
• geriatric patients lose phase I first

• sulfation, acetylation, glucuronidation, glutathione conjugation, glycine conjugation, methylation
• slow acetylators have more side effects

• how much of a response a drug can cause
• regardless of how much drug you have to give to generate that response (potency)

• measure of potency
• not related to partial/full agonism
• how much drug you need to get half the max response
• low EC₅₀=high potency

• binds to receptor
• reduces potency not efficacy
• increase EC₅₀ (increase dose required to generate same effect)
• can also be overcome by increasing substrate
• dizepam (agonist) and flumazenil (comp antag)

• binds to receptor
• reduces efficacy not potency
• cannot be overcome by increased drug or substrate
• NE (agonist) and phenoxybenzamine (non comp antag)

• less effective
• potency could be higher or lower than full agonist

• TI (therapeutic index)
• measure of safety
• 
• safer drug has higher TI
• LD₅₀ replaces TD₅₀ in animal studies