Fundamentals of Clinical Pharmacology Flashcards
Pharmacokinetics
what the body does to the drug
Enteral
something that goes through the gi tract
First-pass metabolism
anytime a drug is metabolized before the drug reaches systemic circulation/target site
First-pass metabolism is very significant for which organ? Why?
Liver: very significant for enteral (oral, rectal) administration
Where does first-pass metabolism occur and what is metabolized at these locations?
- Liver: very significant for enteral (oral, rectal) administration
- Lung (some fentanyl uptake, propofol metabolism)
- Plasma esterases in the blood/pseudocholinesterase (succinylcholine goes thru first pass metabolism in the blood via plasma esterases)
Bioavailability
= the fraction of drug that reaches systemic circulation
What is the bioavailability for drugs given IV or IM?
= 1 (100%) for parenteral (IV, IM) drugs because there's is no hepatic first-pass effect
Sublingual route
– direct absorption into systemic venous system (vena cava) Ex: nitroglycerin and fentanyl)
- Avoids portal circulation, therefore there is no hepatic first-pass effect because it bypasses hepatic metabolism
Different routes of drug absorption:
- enteral (oral, rectal)
- parenteral (IV, IM)
- sublingual
- transcutaneous (through the skin)
- subcutaneous (unreliable, injected under the skin),
- intramuscular (reliable but slower)
- Intrathecal (CSF)
- epidural
- perineural (around a nerve)
- inhalational
Once the drug is absorbed around the body what happens?
- The drug is distributed to one of four groups of tissue per the body’s cardiac output.
- The four main categories of tissue include:
- Vessel rich group
- Muscle
- Fat
- Vessel poor group
Four Classic Tissue Groups
- VRG (vessel-rich group) = gets most cardiac output even though it makes up a small percentage of body weight
- Muscle
- Fat
- VP (vessel-poor group) gets almost no cardiac output even though it makes up about 20% of body weight
Lipophilic drugs rapidly equilibrate where? And why is this important?
Lipophilic drugs rapidly equilibrate into CNS
tissue. This is important bc our anesthetic drugs work in the CNS tissue
Can protein-bound drugs get taken up by an organ?
No. Therefore they also cant be taken up by the kidneys for excretion either.
Which protein binds most drugs in the body?
Albumin - binds most acidic / neutral drugs, some basic drugs (ex: benzodiazepines, SSRIs)
What does a pt’s protein levels have anything to do with how our drugs are distributed?
Low protein levels (due to malnutrition, chronic illness) = less protein-bound drugs in circulation that cant be absorbed into organs = higher free drug levels in circulation = pt will be affected by a drug to a greater degree or require less of a drug to obtain the same effect
What happens once a drug gets to its target site?
It needs to get transported into its target cell
Unlike in the rest of the body, what type of transport must hydrophilic drugs undergo in the CNS?
active transport
Passive transport
= passive movement of a drug down a concentration gradient across the cell membrane into the cell
- Generally limited by blood flow (not lipid solubility)
- This means the drug will diffuse across as quickly as it can be delivered to the tissue
Facilitated diffusion
= requires carrier proteins to transport a drug across the cell membrane and into the cell, but no energy (ATP) is required to do so
Active transport
= carrier proteins require energy (ATP) to move the drug across the cell membrane into the cell. It can be done even against a concentration gradient
- Both lipophilic and hydrophilic drugs need active transport to deal with concentration gradients
Acid
A substance that can lose a proton and become negatively charged
H+ + A– ↔ HA (substance)
Base
a substance that can gain a proton and become positively charged
H + + B (substance) ↔ HB+
Why do we care about the concept of acids and bases when it comes to the drugs we administer?
- Because CHARGED (ionized) species don’t cross membranes very well. Most drugs work best when they are non-ionized.
- We determine whether an environment is acidic or basic based on the drug molecule’s pka value.
- pka = the pH at which half of the drug species is ionized and half is non-ionized
Remember…
Acids: H+ + A– ↔ HA
Bases: H+ + B ↔ HB+
…Acidic (H+) environments drive these equations to the RIGHT
Ex: If pKa = 6 and the pH is 2 (much more acidic)
———Then the “excess protons” will drive the equation to the RIGHT
Ex: If pKa = 6 and the pH is 7.4, the equation will be driven to the LEFT
What happens to a drug after its inside its target cell?
Biotransformation = alteration of the drug via a metabolic process (usually in liver)
- Most drugs need to be hydrophilic (water-soluble) for excretion to occur
- Some drugs do NOT require biotransformation in order to be excreted in the urine