PharmacoKinetics And Dynamics Flashcards
Pharmacokinetics
Study of the drug actions on the body. How drugs are transported into and out of the body
To have its desired effect, what must a drug do?
Reach its target, be of sufficient concentration
What are the 4 factors that influence drug concentration?
Absorption, distribution, bio transformation, elimination
Absorption
The movement of a drug from the site of application to the specific target
Distribution
The process whereby a drug is transported from the site of absorption to the site of action
Biotransformation
How a drug is metabolized or broken down into different chemicals
Elimination
Movement of a drug out of the body
Factors that affect the rate of drug absorption
Drug solubility, drug concentration, drug pH, site of absorption, absorbing surface area, circulatory status, bioavailability
Drug solubility
Tendency of a drug to dissolve, “like dissolves like”, drugs given in water based solutions are more quickly dissolved than those in oil-based solutions. It may sometimes be beneficial to have slower or faster absorption
Drug concentration
Drugs given in high concentration are more quickly absorbed than those in low concentration, drugs administered by more than one route may have various concentrations
Drug pH
Acidic vs alkaline (basic), acidic drugs more readily absorbed in acidic environments (stomach), basic drugs more rapidly absorbed in alkaline environments (kidneys)
Site of absorption
Affects rate of absorption (subcutaneous, intravenous), drugs have to pass through various membranes prior to entering the general circulation
Absorbing surface area
Drugs are absorbed more quickly if the surface area is larger. Drugs given by inhalation or down the endotracheal tube absorbed rapidly due to large pulmonary surface area
Blood supply to the site of absorption
Different body tissues and organs have varied degrees of blood supply. Pulmonary, epithelium, sublingual tissues have rapid absorption.
What will affect systemic blood flow?
Hypothermia, shock, dehydration
Bioavailability
The amount of drug that is still active after it reaches its target tissue, there must be sufficient amount of the drug still available to produce the desired effect
What are the 4 factors of distribution?
Cardiovascular function, regional blood flow, drug storage reservoirs, physiological barriers
Normal Cardiovascular function
Drugs are distributed first to highly perfused areas (brain, heart, liver, lungs). Drugs are delivered secondly to less perfused areas (GI system, muscles, skin then fat)
What does impaired cardiovascular function result in?
Slower unpredictable drug distribution, with decreased perfusion, there is decreased drug delivery
What would cause impair distribution in cardiovascular function?
Heart disease (CHF)
How does regional and systemic blood flow impact drug distribution?
Cardio genie shock states could impede circulation of diuretics to kidneys, drugs intended to reduce cerebral edge a may not reach all parts of the brain if cerebral circulation is already significantly compromised
What circulating proteins do drugs bind to, to travel through the body?
Hemoglobin, albumin, globulin
Distribution
Onset of action
Bound drug
If the drug binds with the receptor protein or becomes stored in the body’s fatty tissues
Free drug
The unbound; available to target tissues
What is the most common circulation protein?
Albumin
Physiological barriers
Considered a protective mechanism
What are the two main physiological barriers?
Blood-brain barrier, placenta barrier
Blood-brain barriers
Tightly packed cell membranes restrict damaging drugs and toxins; only non protein bound, highly lipid soluble drugs can cross these barriers
What does the blood-brain barrier consist of?
Network of capillary endothelial cells (no pores), surrounded by glial connective tissues, impermeable to water-solvable drugs
What’s is the blood-brain barrier ineffective against?
Fats, fatty acids, oxygen, CO2, fat soluble molecule, anaesthetics, nicotine, entonox, alcohol
Placental barrier
Placenta acts as a barrier to some substances passing from mother into fetal circulation; to cross the barrier drug must be: lipid soluble, non-protein bound
What is biotransformation dependent on?
Chemical composition, protein capacity, metabolizing system function
Where does biotransformation occur?
Usually occurs in the liver (hepatic biotransformation), can occur in the kidneys, liver, GI Tract
Hepatic “first pass” metabolism
Affects orally administered drugs
GI tract blood supply passes through the liver
May reduce avaliablility of drug
IV meds bypass this system
Decreased biotransformation
Cumulative drug effects may occur
Increased biotransformation
This effect results in the need for some drug addicts and alcoholics to gradually increase their “dose” as the body becomes more efficient at metabolizing the drug
Biotransformation inhibition
Alternately some drug can inhibit the metabolism of other drugs (acetaminophen and alcohol)
Elimination
Movement not a drug out of the body
What can elimination be affected by?
Accumulation of drug in the body, a drugs half life
Drug half-life
Time required for the total amount of a drug in the body to diminish by half
Pharmacodynamics
What the drug will do to the body, drug and receptors bind to initiate a response
Predictable responses
Anticipate responses beyond the desired effect
Factors affecting drug response
Age, weight, gender, environment, time of administration, condition of the patient, genetic factors
Drug activity; therapeutic index
Minimum drug amount, excess drug, dosage
Iatrogenic responses
An adverse condition inadvertently induced in a patient by the treatment given; most common - allergy to drug, infection from procedure
Unpredictable responses
Tolerance, minimum concentration, drug dependency
Tolerance
Decreased response to the same amount of medication
Minimum concentration
Concentration needed to become effective
Drug dependency
Prolonged administration may lead to this. Significant symptoms if stop using the medication
What are the 4 effects of multiple medications?
Cumulative effect, summation effect, synergism, potentiation
Cumulative effect
Increase effort of a drug given in several successive doses
Summation effect
2 drugs, doubles the response
Synergism
2 drugs, response greater than the sum of their individual responses
Potentiation
2 drugs that causes the effects of one drug to be enhanced
