6. Pharm

Question 1

A high Km means a high or low affinity between enzyme and substrate?

why?

Answer 1

High Km -> LOW affinity

-because Km is defined as the [substrate] at which the reaction velocity is 1/2 its possible maximum. if the reaction needs a lot of substrate (ie high Km) to reach 1/2 its possible max speed, that indicates low affinity between substrate and enzyme.

Question 2

Low Km means high or low affinity between substrate and enzyme?

Answer 2

Low Km -> high affinity

Question 3

what enzymatic reaction in the body doesn’t follow the typical hyperbolic curve (ie doesn’t exhibit Michaelis-Menten kinetics)?

Answer 3

hemoglobin – O2 binding

follows a sigmoid curve due to cooperative kinetics.

Question 4

Equation for reaction velocity?

V = ?

Answer 4

V = Vmax * ( [S]/(Km+[S]) )

Question 5

at what point does Km = [S]?

Answer 5

at 1/2 Vmax

Question 6

with the Lineweaver-Burke plot (double reciprocal of the Michaelis-Menten), describe where some form of Km intersects the x-axis

Answer 6

Tricky to describe…. but 1/-Km is the x-intercept. It will be belox zero obvi!

Question 7

As the y-intercept increases on the Lineweaver-Burk plot, what does that mean about the reaction’s Vmax?

Answer 7

as the y-intercept increases, the reactions Vmax decreases.

Because the y-intercept = 1/V

Question 8

As the x-intercept moves to the right on the L-B plot (ie closer to 0), what is happening to Km? what is happening to the enz-substrate affinity?

Answer 8

As the x-int moves to the right (closer to 0) Km is increasing and enz-substrate affinity is decreasing.

Question 9

A reversible competitive inhibitor…?

Resemble substrate?

Overcome by incr [S]?

Bind the active site?

Effect on Vmax?

Effect on Km?

effect on pharmacodynamics?

Answer 9

A reversible competitive inhibitor:

Resemble substrate? YES

Overcome by incr [S]? YES

Bind the active site? YES

Effect on Vmax? NO CHANGE

Effect on Km? INCR

effect on pharmacodynamics? DECR POTENCY. (KJ sez: be careful about a possible toxic overdose)

Question 10

A non-reversible competitive inhibitor…?

resemble substrate?

Overcome by incr [S]?

Bind the active site?

Effect on Vmax?

Effect on Km?

effect on pharmacodynamics?

Answer 10

A non-reversible competitive inhibitor…?

resemble substrate? YES

Overcome by incr [S]? NO

Bind the active site? YES

Effect on Vmax? DECR

Effect on Km? NO CHANGE

effect on pharmacodynamics? DECR EFFICACY

Question 11

A non-competitive inhibitor…?

resemble substrate?

Overcome by incr [S]?

Bind the active site?

Effect on Vmax?

Effect on Km?

effect on pharmacodynamics?

Answer 11

A non-competitive inhibitor…?

resemble substrate? NO

Overcome by incr [S]? NO

Bind the active site? NO

Effect on Vmax? DECR

Effect on Km? NO CHANGE

effect on pharmacodynamics? DECR EFFICACY

Question 12

define pharmokinetics v pharmacodynamics?

Answer 12

pharmacokinetics = effect of the body on the drug

pharmacoDynamics = effect of the Drug on the body

Question 13

The sympathetic nervous system generally uses what types of receptors?

2 exceptions?

Answer 13

SNS generally uses Adrenergic receptors (and neurotransmitters are thus catecholamines)

Exceptions:

• sweat glands (Cholinergic receptor, Muscarinic type)
• Adrenal Medulla (Cholinergic receptor, Nicotonic type)

Question 14

Cholinergic receptors use what neurotransmitter? what are the 2 subtypes?

Answer 14

Acetyocholine

Nicotinic and Muscarinic

Question 15

Nicotinic Cholinergic receptors:

2 types?

how does the receptor work?

Answer 15

2 types: N_N (nicotinic neuronal) and N_M (nicotinic muscular)

Ach binds to outside; ligand-gated Na/K receptor –> Na+ enters the cell.

Question 16

Muscarinic Cholinergic receptors:

subtypes?

how does the receptor work?

Answer 16

5 subtypes (M1, M2, M3, M4, M5)

GPCR rather than a channel: Ach binds to outside and G protein coupled second messengers transmit signal in cell.

Question 17

How will the Vd (volume of distribution) change for a patient who has liver or kidney disease?

Answer 17

Probably will increase Vd due to decreased proteins, therefore decr protein binding of these drugs. Since the drugs are trapped in the plasma when they are protein bound, having fewer proteins frees the drugs to leave plasma and enter another compartment.

Question 18

Chemical/structural qualities of drugs that have a small Vd?

Answer 18

Large/charged molecules, drugs that are bound to plasma proteins

Compartment will be blood (4-8 L)

Question 19

Chemical/structural qualities of drugs that have a medium Vd?

Answer 19

Small hydrophilic molecules - won’t be able to get into cells, so will stay in ECF.

Question 20

Chemical/structural qualities of drugs that have a high Vd?

Answer 20

Small lipophilic molecules, especiall if they are bound to tissue protein. Compartment will be all tissues including fat.

Question 21

equation for half life (T_1/2)?

Answer 21

T_1/2 = (0.7 x V_d) / CL

Question 22

If a drug takes 4-5 half lives to reach steady state, what do we know about the rate of infusion?

Answer 22

Constant rate of infusion. This is a general rule of thumb for how long any drug will take to reach steady state.

Question 23

How many half lives does it take for a drug to reach 90% of its steady state level?

Answer 23

3.3

(Jen assumes this is with constant infusion)

Question 24

Define clearance (CL)

What can impair clearance?

Answer 24

volume of PLASMA that is cleared of drug per unit time.

Impaired by defects in cardiac, hepatic, or renal function.

Question 25

Equation for clearance (CL)?

what are the units?

Answer 25

CL = (rate of elimination of drug) / (plasma drug concentration)

= V_d x K_e (K_e = elimination constant)

Units are volume/time (ie L/min)

Question 26

Which is impacted by renal/liver disease: Loading dose or Maintenance dose?

Answer 26

Maintenance dose. Loading dose does not depend on clearance rate (which is affected by hepatic/renal fxn).

Question 27

Loading dose = ?

Answer 27

Loading dose = (C_p x V_d) / F

= (target plasma concentration x vol of distribution) / Bioavailability

Question 28

Maintenance dose = ?

Answer 28

Maintenance dose = (C_p x CL x t) / F

= (target plasma concentration x clearance x dosage interval) / Bioavailability

Question 29

what is the dosage interval (t) if drug is a continuous infusion?

what is the dosage interval if drug is given every 15 min?

Answer 29

just drop it from the Maintenance Dose equation

15? 4 (since 4times/hour?)? fuck if I know.

Question 30

CL (clearance) is pretty straightforward: but what do we not want to get it confused with?

Answer 30

Renal Clearance

Eqn = (U_x x V) / P_x

U_x = urine conc of Drug X

V = urine flow rate

P_x = Plasma conc of Drug X

Question 31

What is zero-order elimination?

What are the 3 most impt drugs that Zero–Order elmination?

Answer 31

Drug is cleared from body at a constant/linear rate regardless of quantity in body. Ie, alcohol is cleared at a rate of 1 ‘drink’ per hour even if you did 50 shots at once. Tempting.

3 most impt = Phenytoin, Ethanol, Aspirin (PEA). Think that a pea is round like a ZERO.

Question 32

Define first-order elimination.

If you had OD’d on something, would it be better if it had first-order elimination or zero-order elimination?

Answer 32

Rate of drug elimination is dependent on quantity in body. (ie constant % of drug is eliminated per unit time). Not linear.

(Jen is making this up for memory so this might not be accurate: better for a drug that you ODd on to use first order elimination: it would initially be processed by your system more quickly even though it might take more time overall to clear completely)