Uptake and Distribution of IV Agents Flashcards
Pharmacokinetics
- absorption
- distribution
- metabolism
- excretion
“what the body does to a drug”
Pharmacodynamics:
- mechanism of effect
- sensitivity
- responsiveness
“what a drug does to the body”
Commonly measured pharmacokinetic parameters of injected drugs are:
a. elimination half-time
b. bioavailability: How much of drug is available for effect.
c. clearance: out of blood not body
d. volume of distribution (Vd)
Compartmental Models:
Divides the body into compartments that represent theoretical spaces with calculated volumes.
The body is divided into 2 compartments: Central and Peripheral
Central
Central:- highly perfused tissues
- rapid uptake of drug
- drug first introduced into the central compartment distributes to the 2nd compartment and returns to central compartment for clearance
- kidney, liver, lungs, heart, brain
- receives 75% of the CO
- represents only 10% of the body mass
Peripheral:
- large calculated volume
- extensive uptake of drug
**rate of transfer between compartments decreases with aging, leading to greater plasma [ ] in certain drugs (thiopental).
DISTRIBUTION:
- Following systemic absorption of a drug, the highly perfused tissues (heart, brain, kidneys, liver) receive a large amount of the total dose of drug.
- As the plasma [ ] of drug decreases below that in these tissues, drug leaves and is redistributed to less well-perfused sites, i.e. muscle and fat.
- With continuing elimination of drug, the plasma [ ] declines below that in tissues, drug leaves tissues to re-enter the circulation.
Tissues that accumulate drug preferentially act as a?
-Tissues that accumulate drug preferentially act as a reservoir to maintain the plasma [ ] and prolong effect.
Peripheral compartment act as reservoir.
Fat is the biggest reservoir.
Large or repeated doses saturate inactive tissue which affects?
Large or repeated doses saturate inactive tissue negating redistribution, again prolonging duration of action; now reduction of effect depends on metabolism rather than redistribution.
Body Tissue compartments make what percent? Vessel rich group Muscle group Fat group Vessel poor
Vessel rich is 10% of body mass and at 75% of blood flow (CO)
Muscle group 50% of mass and 19% of blood flow.
Fat group is 20% of Body mass and 6% of Blood flow (CO)
Vessel Poor group 20% of body mass and less than 1% of blood flow (CO)
Lung Uptake:
- Lung uptakes basic lipophilic drugs (lidocaine, fentanyl, demerol) and acts as a reservoir to release drug back into the systemic circulation.
Opium are basic in nature.
CNS Distribution and Blood Brain Barrier (BBB) prevents?
- Blood-brain barrier prevents ionized, water soluble drugs from crossing the barrier into the brain circulation.
How can the CNS BBB be over come?
- Blood-brain barriers can be overcome with large doses of drug, in head injury and hypoxemia.
Elderly, trauma
What kind of drugs don’t cross the BBB
Ionized drugs do not cross the BBB
Effect site:
- Drugs exert their biological effect at the “biophase,” also called the “effect site”.
- It is the immediate milieu where the drug acts upon the body, including membranes, receptors, and enzymes.
Ke0 is
ke0 is the rate constant of drug elimination from the effect site.
Volume of distribution Vd
Sum of all the volumes of the compartments
Vd (volume distribution) is influenced by?
The physiochemical characteristics of the drug:
- Lipid solubility
- Binding to plasma proteins
- Molecular size
Mathematically: Vd =
Dose of IV drug/ Plasma [ ] before elimination
Elimination Half-time:
Time necessary for the plasma [ ] of drug to decline 50% during the elimination phase.
E1/2t of a drug is directly proportional to its Vd
Elimination half-time is independent of the dose of drug administered
Lipophilic drugs and distribution
Lipophilic drugs have a large volume of distribution.
Gets to effect site quickly.
Time necessary to eliminate 50% of the drug from the body
Elimination Half-life
Drug accumulation occurs if dosing intervals are less than the elimination half times.
Explain Context Sensitive Half time
-The context-sensitive half-time is the time required for blood or plasma concentrations of a drug to decrease by 50% after discontinuation of drug administration.
Refers to discontinuing an infusion.
Depends on distribution and excretion.
Depends on physiochemical properties of the drug, and length of infusion.
Explain ABSORPTION
Systemic absorption, regardless of the route of drug administration, depends on the drug’s solubility.
Oral route.. Pros and Cons
- Oral:
most convenient
most economic
Disadvantages:
- Emesis
- Destruction by enzymes or acidic gastric Fluid
- Irregular absorption with food or other drugs
What is the First-Pass Effect:
First-Pass Effect: - Drugs absorbed from GI system enter the portal venous blood and pass through the liver before entering the systemic circulation for delivery to tissue receptors. Here they are extensively extracted and metabolized.
Sublingual, transmucosal has what kind of onset? Why?
Rapid onset: bypasses the liver and prevents first pass effect.
Where does Transdermal route of a drug takes place
Transdermal:
- Provides sustained therapeutic plasma [ ] of drug.
Absorption occurs along sweat ducts and hair follicles that function as diffusion shunts.
- Rate-limiting step is diffusion across the stratum corneum of the epidermis.
Thickness and blood flow are factors reflected in the skin’s permeability for drugs.
- Contact dermatitis can occur at the site.
Explain the unpredictable responses that follow rectal administration of drugs.
- Proximal rectum- transport to the portal system via superior hemorrhoidal veins, thereby, first- pass effect.
- Distal rectum – bypasses portal system.
When does IV administration take effect
Achieve therapeutic plasma levels precisely and rapidly
