Lecture 3: Basic Principles of Pharmacology III

Question 1

What’s the equation for volume of distribution?

Answer 1

Vd = Dose (D) / Concentration in plasma (Cp)

Question 2

What are the factors affecting distribution?

Answer 2

1. Blood flow (drugs will distribute first to the more vascular organs with higher blood flow)
2. Ability of drug to enter a fluid space (pH, binding, transport, lipid solubility)
3. Time after administration (Equilibrium with various compartments may take a long time to achieve)
4. Redistribution - drug may have to distribute from initial compartments to the target tissue
5. Size of the patient - Vd can vary with the size of the pt.
   (Many drugs are dosed on the basis of weight or body surface area, especially in Pediatrics or chemotherapy)

Question 3

What are the two special considerations for distribution?

Answer 3

1. Placenta

2. Blood brain barrier

Question 4

What kind of drugs can cross the placenta?

Answer 4

drugs that are < 1,000 weight or lipid soluble b/c fetal liver and kidney are immature

Question 5

Blood brain barrier

Answer 5

an anatomical protective barrier, created by the existence of tight junction between the capillary endothelial cells and also between the choroid plexus cells in the ventricles

Question 6

To enter the CNS, a drug must be

Answer 6

1. lipid soluble

2. transported by a carrier mediated

Question 7

apparent Vd can be larger

Answer 7

if tissue binding occurs

Question 8

apparent Vd can be smaller

Answer 8

if plasma protein binding occurs

Question 9

What are the consequences of protein binding of drugs?

Answer 9

1. It binds to albumin, other plasma proteins or tissue sites
2. can change the apparent Vd
3. can result in unexpected drug toxicities - act as reservoirs of active drugs
4. drug storage: may need to fill the storage sites before enough free drug is available to interact with receptor (eg- loading dose)

Question 10

Drug displacement is equal to

Answer 10

more free drug at receptor = greater pharmacologic response

Question 11

To predict plasma conc what equation do you use?

Answer 11

Cp = Dose / Vd

Question 12

If significant limitations in bioavailability then:

Answer 12

Cp = (F X Dose) / Vd (F=bioavailability)

Question 13

the quickest absorption will occur with

Answer 13

solution > suspension > capsule > tablet > timed release

Question 14

factors affecting absroption

Answer 14

1. enteral - form of drugs, good in stomach

2. parenteral - blood flow

Question 15

in clinical what is the equation for Vd?

Answer 15

Vd = liters / kg (weight)

Question 16

what is special about thiopental?

Answer 16

high potency, high lipid solubility, B. B. King on O PIATES PROPOses FOOLishly.
rapid entry into brain. Used for induction
of anesthesia and short surgical procedures.
Effect terminated by rapid redistribution into
tissue (i.e., skeletal muscle) and fat. -1- cerebral
blood flow.

Question 17

To enter the CNS a drug must be

Answer 17

1. lipid soluble

2. transported by carrier mediated mechanism

Question 18

L-dopa is neutral thus can cross

Answer 18

BBB and becomes dopamine (which is charged and can’t cross the BBB)

Question 19

What are the 2 weak acid drugs?

Answer 19

aspirin, barbiturate

Question 20

adding bicarbonate to weak acid drugs will prevent the drugs crossing the BBB will facilitate

Answer 20

the excretion

Question 21

in case of weak base,

Answer 21

add acids to prevent the drug crossing the BBB

Question 22

Cp

Answer 22

Dose / Vd

- Vd = 0.61 L / Kg

Question 23

agonist leads to

Answer 23

desensitization of the receptors

Question 24

antagonist leads to

Answer 24

hypersensitivity or up-regulation of receptors

Question 25

loading dose equation?

Answer 25

LD = Cp X Vd

Question 26

maintenance dose equation?

Answer 26

MD = Cp X CL

Question 27

warfarin (coumadine) can be easily

Answer 27

displaced by other drugs