1. Pharmacokinetics & pharmacodynamcs
Jessica Tagerman, PharmD, RPh

2. Pharmacokinetics & pharmacodynamics
Pharmacodynamics: What the drug does to the body
Pharmacokinetics: What the body does to the drug

3. “What the drug does to the body”
pharmacodynamics
“What the drug does to the body”

4. To best understand how drugs work, we are going to compare their mechanism of action to a “lock and key” model.

5. Unless you have the correct key, the lock won’t open!

6. Physiological Response
Receptor
agonist
An endogenous agonist is a natural substance produced by the body. The agonist binds to a specific receptor, and causes some sort of physiological response in the body. Similar to the “lock and key” model, the agonist must fit perfectly into the receptor to cause activation.
Agonist moves towards and then binds to the receptor
Endogenous agonist- substance products naturally by the body
Physiological response:
Medications may work by altering any of the following at the site of action:
Physical properties
Chemical properties
Osmolarity
Normal cell function
Metabolism
Ion transport
Movement of glucose into cells
Creation/release of hormones
Physiological Response

7. No Physiological Response
Receptor
Agonist
Agonist
Molecule
If the Molecule doesn’t fit perfectly into the receptor, the cell won’t activate and a physiological response will not occur. (therefore, the molecule isn’t considered to be an agonist)
Not a perfect fit, so this molecule will NOT activate the receptor
Receptor
Agonist
No Physiological Response

8. This molecule is only an agonist for…
If the Molecule doesn’t fit perfectly into the receptor, the cell won’t activate and a physiological response will not occur. (therefore, the molecule isn’t considered to be an agonist)
This molecule is only an agonist for…
Agonist
THIS RECEPTOR!

9. Now, let’s talk about how medications relate to this model.
Drugs can be exogenous agonists, in which they mimic the endogenous agonist, bind to the receptor, and produce the pathological response.
Or, drugs can be antagonists, which block the receptor, and therefore prevent the endogenous agonist from binding and causing a physiological response (See next slide)

10. No Physiological Response
Agonist
Receptor
Agonist
Agonist
Antagonist
Antagonists: Bind to the receptor in order to block the endogenous agonist from binding. therefore, no physiological response will occur.
Agonist moves towards the receptor, but can’t bind, because the antagonist is blocking the receptor
Agonist
No Physiological Response

11. Summary
Agonists BIND to the receptor, and ACTIVATE a cellular response
Antagonists BIND to the receptor, but DO NOT activate a cellular response
When you are studying the medications, understanding the physiological processes behind the diseases will help you understand treatment options!

12. Switching gears

13. What the body does to the drug
Pharmacokinetics
What the body does to the drug

14. Absorption
Distribution
Metabolism
Excretion
Pharmacokinetics

15. absorption
Absorption = Describes the process whereby a drug enters the circulatory system
Unless the drug is given via IV route, it needs to move from the site of administration into the bloodstream, so 100% of the drug may not be available as active medication (AKA, a drug’s BIOAVAILABILITY)
Oral Medications:
esophagus  stomach  withstand stomach enzymes  small bowel  liver  systemic circulation
First pass effect= when liver inactivates most of the drug, so it is never actually able to make it to the bloodstream and create a pathological response

16. Distribution
Distribution = The movement of the drug throughout the bloodstream and delivery to the site of action
Common sites of distribution: blood, muscles, fat tissue, organs
You need to be sure the drug is being delivered to where your body needs it!
(Remember carbidopa/levodopa? We needed the dopamine to be delivered directly to the brain, otherwise the medication wouldn’t work!)
First pass effect= when liver inactivates most of the drug, so it is never actually able to make it to the bloodstream and create a pathological response

17. Metabolism
Metabolism = when the drug is broken down or changed by various enzyme systems
Purpose of metabolism: mainly to begin elimination!
Drugs that have been metabolized = metabolites, may be active or inactive
Metabolites are formed with the help of enzymes
Some drugs are inactive until they are metabolized to the active form that will cause the effect (These drugs AKA pro-drugs)
Some metabolites are responsible for the toxic side effects of medications.
First pass effect= when liver inactivates most of the drug, so it is never actually able to make it to the bloodstream and create a pathological response

18. Excretion
Excretion = how the drug and it’s metabolites are eliminated from the body
Routes of excretion depend on physiochemical properties of drug and function of excreting organ
Mainly excreted through urine and feces
Can also exit the body through exhalation and sweating, but to a lesser extent
Patient with kidney failure: adjust medication dose, otherwise concentration of drug may increase to a toxic range
How drug is eliminated depends on physiochemical properties and the function of the excreting organ

19. Half-life
Half-Life: Amount of time it takes for the blood concentration of a drug to decline to ½ of the initial value
Example: Medication with ½ life of 3 hours
Five times the half-life is used to estimate how long it takes to essentially remove the drug from the body.
This would be 5 times the half-life of 3 hours, or 15 hours in the example above.
Time
Concentration
At 3 hrs (max concentration)
60 mcg/mL
At 6 hrs
30 mcg/mL
At 9 hours
15 mcg/mL
First pass effect= when liver inactivates most of the drug, so it is never actually able to make it to the bloodstream and create a pathological response

20. Blood concentration-time profiles
Minimum Toxic Concentration: Largest drug concentration beyond which there are toxic/undesirable effects
First pass effect= when liver inactivates most of the drug, so it is never actually able to make it to the bloodstream and create a pathological response
Minimum Effective Concentration: Smallest drug concentration needed for effect

21. bioequivalence
Bioequivalence = drug products with same bioavailability
Pharmaceutical Equivalents
Same active ingredient (same salt form)
Same amount of active ingredient
Same dosage form
Inactive ingredients can be different
Pharmaceutical Alternatives
Same active ingredient (but different salt form)
Amount of active ingredient can be different
Dosage form can be different
Therapeutic Equivalents
Pharmaceutical equivalents that produce the same effects in patients
First pass effect= when liver inactivates most of the drug, so it is never actually able to make it to the bloodstream and create a pathological response

22. Questions?