Pharmacokinetics -Absorption/Distribution Flashcards
Pharmacokinetics
What the body does to the drug
4 Pharmacokinetics that determine how the drug will interact
- Absorption
- Distribution
- Metabolism
- Elimination
Where does drug absorption take place when oral (enteral) medications are taken
In the SI. The villi increase the surface area and aid in uptake.
What other features of the SI make it a good site for drug absorption
- Fewer tight junctions (compared to the LI)
2. Permeability decreases from duodenum to colon
Which route of drug administration skips the absorption phase?
IV
3 types of parenteral drug administration
- IV
- IM
- SC
What is the oral drug absorption process
- Dose
- Disintegration (occurs in gastric fluids)
- dissolution
- Diffusion (into blood stream)
Sublingual absorption
Occurs under the tongue and goes directly into the capillary network and into circulation relatively quickly. (Bypasses the stomach acids - first pass metabolism)
What area is the buccal drug administration route similar to
sublingual
Intramuscular absorption (IM) - 2 variations
Drug dissolves slowly at sight of injection (muscle) if in a depot solution. Provides a sustained dose over longer time. Or if drug is in aqueous solution it will be absorbed rapidly!
IV (parenteral)
Immediate “absorption” goes directly into the blood stream and has a rapid effect.
Subcutaneous absorption
Occurs via simple diffusion at site of injection. Similar to IM. Cannot use drugs that cause tissue irritation
Inhalation absorption
Oral and nasal. provide rapid delivery of a drug across large area of mucous membranes in the respiratory tract and pulmonary epithelium.
How fast is inhalation absorption
Almost as fast as IV injection
What types of meds are typically inhalation drugs
Meds that are gases
Intrathecal absorption
Drugs that are introduced directly into the CSF in order to bypass the blood brain barrier
Transdermal absorption
Slow and sustained absorption at the sight of the patch. Rate of absorption also varies depending on characteristics of the skin and the lipid solubility of the drug (nitroglycerin)
Rectal absorption
The rate is slightly uncontrollable, but it partially bypasses being metabolized by the liver. Ideal if pt is vomiting and can’t keep drugs down
Extended-release preparations
Drugs that have a special coating that control how fast the drug is released from the pill into the body. Extends the duration of action
Depot preparations
Used with IM injections. Consist of a suspension of the drug in a non aqueous vehicle (polyethylene glycol). Provides a slow release because it takes the vehicle longer to break down
Implanted pumps
Pumps that are programmed to deliver drugs (usually under the skin)
Rate of absorption of transdermal patches
Varies depending on the characteristics of the skin and the lipid solubility of the drug. It is a slow and sustained release
Types of slow release forms
- Extended-release preps
- Depot preps
- Transdermal patches
Enteric-coated preparations
Drugs that have a coating on them that resist the acidic enzymes in the stomach, but can be easily dissolved in the SI.
What are the two scenarios that utilize enteric drugs
- Drugs that are unstable in acids
2. Drugs that are irritants to the stomach (i.e. aspirin)
Bioavailability
The fraction of the drug that actually reaches systemic circulation
4 ways that drugs are absorbed in the GI tract
- Passive diffusion
- Facilitated diffusion
- Active transport
- Endocytosis and Exocytosis
Does a weak acid or weak base get absorbed better in the stomach
Weak acid (because it is the non-ionic form)
Which pH level absorbs better in the SI
Weak base
How do you determine bioavailability
By comparing plasma levels of a drug after a route of administration with plasma drug levels that would be achieved when given IV (EV/IV)=F
Which route of drug administration confers 100% bioavailability
IV
Factors that influence bioavailability
- 1st pass metabolism
- Solubility of the drug
- Chemical instability
- Nature of drug formulation
What is 1st pass metabolism
When drug is administered orally it first enters the portal circulation before entering systemic circulation. Thus is will get metabolized in liver 1st (less drug available)
Which types of drugs are poorly absorbed
Hydrophilic drugs because they can’t cross lipid cell membrane
Drug distribution
The process by which the drug reversibly leaves the blood stream and enters the EC fluid and then tissue
The rapid fall in concentration represents what phase of the drug process
Distribution of drug (time when drug rapidly disappears from circulation and enters tissue)
Loading dose
A single does used to achieve the desired plasma level (SS) RAPIDLY, followed by infusion to maintain steady state
When would you use loading dose
When a delay in reaching a desired plasma drug level is unacceptable (IE emergency situations - nitro)
What is patient controlled administration (analgesic)
Any method of drug administration in which the pt gives themselves their own pain relief
Forms of PCA
Oral, IV, epidural, inhaled, nasal, transdermal
Which route requires more drug IV or Intrathecal
IV
Which route requires more drug IV or Oral
Oral
How does the blood brain barrier prevent drugs from entering
The capillary structure is continuous in the brain and their are no slit junctions for things to permeate through. Much more of a tight junction set up
How do drugs enter the brain
- Must be lipid soluble
or - Drugs must pass through the endothelial cells of capillaries in the CNS or be actively transported
(LARGE or HYDROPHILIC DO NOT CROSS)
What types of proteins do drugs bind to
- Plasma proteins (ie Albumin)
- Tissue proteins
- Glycoproteins (transmembrane protein)
How do plasma proteins affect drugs
Slows their transfer out of the vascular compartment (less free drug)
What is the main plasma protein
albumin
What does plasma protein due in terms of free drug concentration
It acts as a drug reservoir. As the FREE DRUG is metabolized or excreted, the drug that is still attached to protein is released into system for use as more FREE DRUG. Thus plasma proteins help maintain free drug concentrations
How do drugs get into tissue
- Result of binding to lipids, proteins or nucleic acids
OR - Actively transported into tissue
What is the function of having drug in the tissue
The tissue acts as a reservoir allowing for prolong drug action. But may also induce harm by causing local drug toxicity.
Which drugs cross the membrane rapidly
Lipid soluble or hydrophobic. They can easily dissolve in lipid membranes, permeate entire cell.
Volume of distribution
Fluid volume that is required to contain the entire drug in the body at the same concentration measured in the plasma. (Dose that ultimately gets into the system divided by plasma concentration at time 0 - iv injection)
What is Vd useful in comparing
Compares the distribution of a drug with the volumes of water compartments in the body
What fluid compartment would a large molecule or one that extensively binds to proteins end up in
The drug would most likely be trapped within the plasma (vascular) compartment because it cannot move through endothelial slits of capillaries in the tissue. (6%/4L of body weight)
Where would a drug with low molecular weight and HYDROPHILIC end up
It would move into the endothelial slit junctions of the capillaries and into interstitial fluid (EC). Will NOT enter cells because it is hydrophilic - Distributes to 20% (14L)
Where would a drug with low molecular weight and HYDROPHOBIC end up
It will move into BOTH interstitial fluid (EC) and into the cell membranes (IC) - Distributes to 60% of body weight (42L)
What factors contribute to drug distribution
- Blood flow (rate of)
- Capillary permeability
- Protein binding
- Volume distribution
Where in the body do drugs bind to lipids
Adipocytes (fat)
Where in the body do drugs bind to proteins
Plasma
Where in the body do drugs bind to nucleic acid
Nucleus of cell
Large Vd = ? in terms of half life and elimination
Large Vd means the drugs is mostly EC and is unavailable for excretion. Therefore the half life with be higher as will the length of time for excretion
If you have a small Vd, where will most of the drug be
Intravascular fluid (either a large molecule or bound to albumin)
If you have a large Vd, where will most of the drug be
Extraplasmic - in the tissues
How does hypoproteinemia influence therapeutic effect of drug (ADME)
There will be less circulating plasma proteins, which therefore decreases the amount of proteins a drug can bind to= more FREE DRUG. Which means increase in distribution, metabolisms, and elimination
How does hypovolemia influence therapeutic effects of a drug
- Low drug distribution
- Low blood volume leads to increase in drug concentration
- Albumin level will be decreased which means more free drug
What kind of drug would have a small volume of distribution
Something that is LARGE and binds extensively to plasma proteins
What kind of drug would have a large volume of distribution
Something that is SMALL and hydrophobic
What kind of drug has a medium volume of distribution
Something that is relatively small and hydrophilic
