Pharmacokinetics

Question 1

Pharmacokinetics

Answer 1

how drugs enter & leave the body; plasma drug concentrations vs time; what the body does to a drug, and how to avoid complications. Aka ADME

Question 2

ADME

Answer 2

Absorption from site of administration, Distribution within the body, Metabolism, Excretion

Question 3

Systemic drug administration

Answer 3

Given into blood. Needs to act at inaccessible site.

Question 4

Local drug administration

Answer 4

Given direct to site of action. E.g. local anaesthetic

Question 5

Oral administration

Answer 5

<100%. Depends on solubility; drug pKa, pH of GI tract; stability (acid may destroy); gastric emptying and GI motility (mostly absorbed in upper GI; emptying slowed by food; motility depends on drugs and disease); GI blood flow; First pass effect (can get lost in hepatic portal vein before reaching systemic circulation)

Question 6

First pass effect

Answer 6

Most of GI tract goes through hepatic portal vein to liver, so drug can be metabolized before reaching systemic circulation.

Question 7

Bioavailability

Answer 7

% of dose reaching systemic circulation. Loss loss due to metabolism or excretion; direct effect on therapeutic outcome; different for different formulations; may vary with liver function

Question 8

Advantage of oral route

Answer 8

No need for drug to be pure or sterile; easy for patient, no pain - most common; cheap formulations, multi-dose bottles

Question 9

Disadvantage of oral route

Answer 9

Requires conscious, cooperative patient; slow, so no good for emergencies; variable absorption and bioavailability; loss of drug if patient vomits; potential for upper GI tract irritation (less damage if accompanied with food)

Question 10

Rectal administration

Answer 10

Obvious! fairly rapid absorption possible; less first-pass effect.

Question 11

Pros and cons of rectal

Answer 11

Good for patients who cannot swallow (unconscious); won’t swallow (children, psychotics); may be vomiting. Mildly inconvenient.

Question 12

Parenteral route

Answer 12

Means not via enteral route (ie not between glottis and anus), but not only injection

Question 13

Sulbligual

Answer 13

direct entry to systemic circ. (no first pass); rapid absorption possible despite low area; pH about 7 so acid-labile drugs are stable; fast, easy, comfortable

Question 14

IV

Answer 14

Can be rapid (IV push) or slow (IV drip or infusion) - concentration can increase quickly or gradually; acts quickly. Need skill to find veins; drug cannot cause pain or damage; need sterile solutions; greater risk and cost

Question 15

Other routes of administration

Answer 15

subcutaneous, vaginal, intramuscular, intracardiac, urethral, transdermal, inhalation, topical, intranasal, intrathecal, spinal, buccal, intra-articular, occular

Question 16

Drug distribution

Answer 16

Depends on solubility of drug in fat or tissue; pH of compartment and pKa of drug (effect of charge); plasma protein binding. this can affect the duration of action or how long the drug stays in body. Needs to be unbound and free for diffusion across membranes; binding to receptors and enzymes; hepatic metabolism and renal filtration

Question 17

Termination of drug effects

Answer 17

Biotransformation aka metabolism. Body wants to make it more polar Phase I: drug made more polar by cytochrome P450 enzyme families (CYPs) - change to drug; Phase II: drug conjugation to endogenous compounds from liver, so the addition makes it more polar

Question 18

Where does drug metabolism occur?

Answer 18

most occurs in the liver; may also occur in kidneys, gut, lungs, plasma and placenta; polar products undergo renal elimination

Question 19

Drug metabolites

Answer 19

may be many for a single drug; usually most are inactive; rarely have biological activity; more rarely, an inactive drug (called a “pro-drug”) may be activated by metabolism

Question 20

What can affect metabolic rate?

Answer 20

Can be increased or decreased by age, disease, genetics, diet, tobacco, alcohol, other meds

Question 21

How are drugs excreted?

Answer 21

Kidney: can be affected by kidney disease, renal blood flow, MW urinary pH, protein binding. Gall bladder: may get secreted from liver into bile; some drug reabsorption from bile in gut; termed enterohepatic circulation

Question 22

First order elimination

Answer 22

constant proportion lost per unit time. Proportional to the concentration. Straight line on a log graph. Easy calculations for initial conc. and t1/2. Drug is accepted as “gone” after 4 or 5 t1/2

Question 23

Zero order elimination

Answer 23

Less common. Constant amount lost per unit time. Straight line on a normal linear graph, nosedive on log scale. Often after enzymes are saturated. Classic example is ethanol.

Question 24

What effect does doubling the dose have for a first order drug?

Answer 24

It does NOT double the duration. It increases duration by one half the time, or by 50%. (think of it, half-life)

Question 25

Volume of distribution, Vd

Answer 25

Volume in which drug “seems” to be dissolved. If 10 mg is given via IV, and [plasma] .25mg/L, the Vd is 40L. Larger Vd indicates lots of drug binding so very little free in plasma. Vd affected by gender, age, disease. [plasma] = drug dose/Vd

Question 26

Drug clearance, CL

Answer 26

volume/unit time. volume refers to volume of plasma cleared of drug. CL is additive, so renal + hepatic + other

Question 27

Compartment models

Answer 27

Single: consider body as one box that it goes in and out of. 2 compartment: 2 boxes. Into one then into a second one or cleared directly from first; two phases of elimination: a is quick initially, then ß is slower

Question 28

Multiple drug dosing

Answer 28

Need to maintain therapeutic conc. Either increase dose (toxic?) or reduce dosing interval so you reach an equilibrium usually in 4-5 t1/2

Question 29

Loading dose

Answer 29

Decreases time to plateau. Best is loading dose plus continuous infusion. Reaches plateau fast and stays there