Pharmacokinetics (determines…)
Determines the onset, duration, and intensity of a drug’s effect.
Drug Plasma Concentration Curve
Helps visualize how much and how long a drug is in the body.
Drug-concentration (y-axis) vs time (x-axis)
C-max
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.
T-max
The time at which C-max occurs.
Half Life
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.
Area Under Curve
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.
Absorption
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.
Bioavailability
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).
First-pass Effect
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”)
Oral Metabolism and Absorption (process) :
- 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.
- The drug enters the intestines, where the enzymes break down the drug (gut wall metabolism).
- The rest is absorbed and goes through the portal vein to the liver, where the blood is filtered and drugs are metabolized. (Hepatic)
- Finally, the drugs goes through the hepatic vein and into systemic circulation!
Plasma
A component of blood that carries water, enzymes and salts. The role of plasma is to take nutrients, hormones and proteins through the body.
Hydrophilic vs. Lipophilic Drugs:
- 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
Factors which Affect Distribution:
- Lipophilicity
- Anatomical Barriers
- Protein Binding (Drugs attaching to proteins in blood cannot reach their target).
- Vd (See “Volume of Distribution”)
Volume of Distribution
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
Drug Metabolism
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) !
Metabolism Purpose:
- 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
Active Ingredient
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.
Aspirin (and Metabolism):
- 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.
Drug Excretion
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.)
Drug Concentration Curve for different methods:
- 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).
Like Dissolves Like Principle
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.
Hydrophilic Pharmacokinetic Properties (ADME):
- Poorly absorbed by the surrounding tissue due to inability to cross the cell membrane.
- Excreted rapidly from the body due to slow reabsorption.
Lipophilic Pharmacokinetic Properties (ADME):
- 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.
Metabolism Rate:
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.
