Module 2 - Pharmacokinetics

Question 1

Pharmacokinetics (determines…)

Answer 1

Determines the onset, duration, and intensity of a drug’s effect.

Question 2

Drug Plasma Concentration Curve

Answer 2

Helps visualize how much and how long a drug is in the body.

Drug-concentration (y-axis) vs time (x-axis)

Question 3

C-max

Answer 3

Cmax = The highest drug concentration achieved in the body (Max Concentration). Cmax is important because it helps predict the therapeutic benefit and the likelihood of side-effects.

Question 4

T-max

Answer 4

The time at which C-max occurs.

Question 5

Half Life

Answer 5

Time it takes for the concentration of the drug in the plasma or the total amount in the body to be reduced by 50%.

• 1/2 C-max - Half of the Max Concentration.
• 1/2 T-max - Half life! Time from the T-max to 1/2 T-max, noted as t-1/2.

Question 6

Area Under Curve

Answer 6

The AUC represents the total exposure to a drug that the body receives. This is a function of how high the concentration of the drug gets as well as how quickly it’s excreted.

Question 7

Absorption

Answer 7

Describes the way the drug moves from its site of administration across one or more membranes, often into the bloodstream, if it was not administered there directly. Generally, the drug will need to enter the bloodstream so it can travel through the body to reach the desired site of action. The absorption process is highly dependent on the route of administration.

Question 8

Bioavailability

Answer 8

The proportion of a drug or other substance which enters the circulation when introduced into the body and so it can have an active effect. (aka what fraction of the drug made it into circulation).

Question 9

First-pass Effect

Answer 9

Phenomenon of drug metabolism where the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemic circulation.

(See “Oral Metabolism and Absorption”)

Question 10

Oral Metabolism and Absorption (process) :

Answer 10

1. The drug taken orally enters the stomach, where some of the drug is absorbed (the stomach is acidic). So, basic drugs will react and lose some properties.
2. The drug enters the intestines, where the enzymes break down the drug (gut wall metabolism).
3. The rest is absorbed and goes through the portal vein to the liver, where the blood is filtered and drugs are metabolized. (Hepatic)
4. Finally, the drugs goes through the hepatic vein and into systemic circulation!

Question 11

Plasma

Answer 11

A component of blood that carries water, enzymes and salts. The role of plasma is to take nutrients, hormones and proteins through the body.

Question 12

Hydrophilic vs. Lipophilic Drugs:

Answer 12

• Hydrophilic refers to the ability to dissolve in water. - Lipophilic is the ability to dissolve in oils, lipids, and fats.

Note - Drugs need to get into cells to produce their effects  Cell membranes are composed of lipids  lipophilic drugs can enter the cell much easier than hydrophilic drugs

Question 13

Factors which Affect Distribution:

Answer 13

• Lipophilicity
• Anatomical Barriers
• Protein Binding (Drugs attaching to proteins in blood cannot reach their target).
• Vd (See “Volume of Distribution”)

Question 14

Volume of Distribution

Answer 14

The volume in an organism throughout which a drug appears to have been distributed. Vd is specific to each drug and patient (Based on height and weight of a patient)!

• Vd = Drug in body / Drug in plasma
• If Vd is small: Then a lot of drug is in the blood.
• If Vd is large, then a lot of drug is in the tissue

Question 15

Drug Metabolism

Answer 15

Biotransformation (breakdown) of drugs in the body so that they can be eliminated more easily. Usually occurs through enzymes (aka special proteins that break down molecules). The products of this reaction are called: METABOLITES.

Ex. Salicylic acid and acetic acid are metabolites of aspirin (See Aspirin and Metabolism) !

Question 16

Metabolism Purpose:

Answer 16

• To make drugs more hydrophilic so they can be eliminated!

In the liver, there is metabolism…

• Oxidation
• Hydrolysis
• Reduction

*Note - Note that some drugs need to be metabolized to function, but other drugs do not. When they’re metabolized, they’re actually destroyed because the drug was already in the active ingredient form

Question 17

Active Ingredient

Answer 17

Thecompound in a pharmaceutical drug that is biologicallyactive (aka has the desired effect).

Sometimes, the initial metabolism is desired in order to turn a drug into its pharmacologically active form.

Question 18

Aspirin (and Metabolism):

Answer 18

• A drug which chemically blocks your body’s pain signals and also reduces the risk of heart attacks and certain strokes.
• The product salicylic acid is the active ingredient. Meaning, aspirin has to be metabolized in order to have an effect! You can’t give salicylic acid directly, it causes ulcers in the stomach.

Question 19

Drug Excretion

Answer 19

The drug (or it’s metabolites) are irreversibly removed from the body.

This can occur though:

• Sweat
• Feces
• Urine

Urine is the most common form of excretion (remember, in metabolism we’re making drugs more hydrophilic so we can eliminate them through the kidneys.)

Question 20

Drug Concentration Curve for different methods:

Answer 20

• If oral, the c-max will be low and the curve will continue for a longer period of time.
• If injected, the c-max will be higher, and excreted faster (since the dosage gets in fast).
• If inhaled, the c-max will be very high, and the dose will also be excreted much faster (Very steep curve).

Question 21

Like Dissolves Like Principle

Answer 21

To cross a cell membrane, a drug must be sufficiently lipophilic. This means that the drug should be uncharged and nonpolar to dissolve in oil (since lipids are not charged or polar).

Hydrophilic drugs are charged and polar since water is polar, and only like-substances can dissolve in each other.

Question 22

Hydrophilic Pharmacokinetic Properties (ADME):

Answer 22

• Poorly absorbed by the surrounding tissue due to inability to cross the cell membrane.
• Excreted rapidly from the body due to slow reabsorption.

Question 23

Lipophilic Pharmacokinetic Properties (ADME):

Answer 23

• Can pass easily through surrounding tissue (The stronger the blood supply to the tissue, the more drug taken into the organ)
• Metabolized in the liver.
• Excreted somewhat poorly from the body since they can be reabsorbed from the kidney.

Question 24

Metabolism Rate:

Answer 24

If metabolism is slow, much of the drug can remain in systemic circulation (reabsorbed), but if it is rapid, the drug is excreted rapidly. This is important to determining DOSAGE.

• Differs individually
• Age- dependent (Older = Less dosage)
• Affected by pathological effects and medication.

Question 25

Blood-brain barrier:

Answer 25

A three-layered protective barrier which can only be crossed by highly lipophilic substances (uncharged, nonpolar).

Question 26

Clearance

Answer 26

CL is how fast the drug gets eliminated in the body, and this depends on a lot of things like enzymes in your liver and such. This is one of the factors to determining the drug plasma concentrations and is extremely complicated to change.

Question 27

Passive Diffusion

Answer 27

Depends on concentration gradients (drugs will move from an area of high concentration to an area of low concentration).

Question 28

Facilitated Diffusion

Answer 28

Movement of molecules across a membrane through a membrane carrier.* (Still dependent on the concentration gradient, from high to low)

*Carrier protein in the membrane