Pharmacokinetics & pharmacodynamcs Jessica Tagerman, PharmD, RPh

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

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

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

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

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

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

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!

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)

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

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!

Switching gears

What the body does to the drug Pharmacokinetics What the body does to the drug

Absorption Distribution Metabolism Excretion Pharmacokinetics

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

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

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

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

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

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

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

Questions?