Second Week: Pharmacokinetics & Pharmacodynamics Flashcards
Pharmacokinetics
What the body does to the drug
- what happens to the drug in the body?
- think MOTION
- refers to absorption, distribution, metabolism, and excretion of drugs
Pharmacodynamics
What the drug does to the body
- think EFFECTS
- primary and secondary effects of the drug
Pharmacokinetics: 4 Steps
- Absorption
- Distribution
- Metabolism
- Excretion
Absorption
Movement of the drug from the site of administration into the blood stream
- the medication has to be broken down into a solution that can be absorbed into the bloodstream:
- passive diffusion
- facilitated diffusion
- active diffusion
- endocytosis/pinocytosis
- the rate of absorption determines when a drug becomes available to exert its action; absorption influences metabolism and excretion
Passively Absorbed
the drug moves from an area of high concentration to an area of lower concentration by osmosis
-the drug does not need any energy to move across the membrane and it usually results in a higher percentage of the medication being abosrbed
Active Absorption
the drug must pass from an area of lower concentration to an area of higher concentration
- since this is going against the gradient, the drug must have a carrier, which will be included in the medication itself
- a smaller percentage of drugs requiring active absorption are absorbed
Pinocytosis
process by which the cells carry a drug across their membrane by engulfing the drug particles
Factors Affecting Absorption
- Route of Administration
- Blood flow to the site
- Absorbing surface area
- Drug solubility
- pH/ ionization
Factors Affecting Absorption: Drug Solubility
refers to the ability of a medication to be transformed into a liquid form that can be absorbed into the bloodstream
- drugs are best absorbed through tissue that has a similar solubility
- lipid soluble drugs are well absorbed in GI environment
Enteric-Coated Drug
cannot be decomposed by gastric secretions; the coating thus prevents the medication from being diluted before it reaches the intestines
- the coating delays the action of the medication
- decreases irritating effects of the medication on the stomach
Timed-release (sustained-release) Medications
medications are formulated to dissolve slowly, releasing small amounts for absorption over several hours
Factors affecting absorption: pH/ Ionization
The pH (relative acidity or alkalinity) of the local environment also effects absorption of a drug
- the acid content of the stomach aids in transporting the medication across the mucous membranes, so acidic medications such as aspirin are more readily absorbed in the stomach than basic (alkaline) medications such a sodium bicarbonate, which are readily absorbed in the more alkaline small intestine
- the ionized molecules are lipid insoluble and cannot pass easily through the phospholipid layer of cell membranes
Identifying pH- The lower the number____
the lower the number, the more acidic the environment is
Factors Affecting Absorption: Blood Flow
medications are absorbed rapidly in areas where blood flow to the tissues is greatest (e.g. oral mucous membranes)
-areas with poor vascular supply (e.g. skin, scarred areas) experience delayed absorption
Distribution
Drug is transported to tissues and organs by body fluids (usually bloodstream)
- because blood goes to all parts of the body, theoretically a drug can produce effects (intended and unintended) anywhere
- rate of absorption depends on adequacy of local blood flow in the target area (site where the drug effect occurs)
- influenced by permeability of capillaries to the drugs molecules as well as protein-binding capacity of drug
Factors Affecting Distribution
- Volume of drug distribution (Vd)
- local blood flow
- membrane permeability; barriers
- protein-binding affinity
- tissue-binding affinity
Factors Affecting Distribution: Membrane Permeability
drug molecules must leave the blood and cross capillary membranes to reach their sites of action
- some capillary membranes act as barriers
- the capillary networks in some organs consist of tightly packed endothelial cells that prevent some drugs from crossing them
Factors Affecting Distribution: Protein-binding Affinity
a drugs tendency to bind to plasma proteins in the blood also affect distribution
-for a given amount of a drug some molecules bind to plasma proteins, and the remainder will be “free”
(what your body can use)
ex: if given 100%, 80% binds to protein, only 20% can be used
Low Protein-binding Affinity
more available free drug
High Protein-binding Affinity
less available free drug
The Patient has low serum albumin and protein levels and elevated renal function blood levels. How would the nurse expect these lab values to affect the patients ability to tolerate their medications?
more drug will be actively available in the system and there would be decreased excretion of the medication
Metabolism
Biotransformation- chemical conversion of drug metabolism
- chemical inactivation of a drug through its conversion into a more water-soluble compound or into metabolites that can be excreted from the body
- once a medication reaches its site of action, it is metabolized (changed into the inactive form) in preparation for excretion
- takes place mainly in the liver (first pass effect), but can be detoxified in kidneys, blood plasma, intestinal mucosa and lungs
Factors Affecting Metabolism
- Liver function: if liver function is impaired (e.g. due to liver disease or aging) the drug will be eliminated more slowly, and toxic levels may accumulate
- Health Disease Status: disease status also affect drug metabolism
- First-pass effect: Bio-availability of oral drugs is determined after first pass (may be as little as 20 to 40%)
Factors Affecting Metabolism: First-pass Effect
oral medications are absorbed from the GI tract and circulate through the liver before they reach the systemic circulation; many oral medications can be almost completely inactivated this way
-oral medications are formulated with a higher concentration of the drug than are parenteral medications
Excretion
Elimination of the drug
- for excretion to occur, drug molecules must be removed from their sites of action and eliminated from the body
- drugs may be metabolized completely, partially, or not at all when they are excreted
- common organs of excretion:
- lungs
- exocrine glands (sweating)
- liver
- GI tract
- Kidneys
Factors Affecting Excretion
How well they work:
- kidneys
- liver
- lungs
- exocrine glands
Therapeutic Range
range of plasma concentration of a drug that produces a therapeutic response without causing toxicity in the patient
-minimal effect dose vs maximum non-toxic dose
Within the Therapeutic Range
- plasma concentration
- peak level
- trough level
- Therapeutic level; measure of Margin Safety, prediction of drug potency
Therapeutic Index
measurement of the Margin of Safety of the medication that is identified during the testing phases pf the drug development
Onset of Action
time needed for a drug concentration to reach a high enough blood level for its effects to appear
-this is the minimum effective concentration
Peak Action
concentration of medication is highest in the blood and not harm
Therapeutic Level
concentration of a drug in the blood serum that produces the desired effect without toxicity
Peak Level
occurs when the drug is at its highest concentration (when the rate of absorption is equal to he rate of elimination)
-after that, metabolic and excretory processes begin to remove the drug from the tissues and blood
Trough Level
drug is a its lowest concentration, right before the next dose is due (lowest effective dose)
Concentration of Active Drug
the effectiveness of a medication depends ultimately on its concentration at the intended site
Biological Half-life
The time it takes for metabolism and excretion to eliminate 50% (half) of the drug from the body
- the time it takes for half of the drug to be eliminated
- the longer the half-life the more dangerous the medication is for the patient; if the patients drug level becomes too high, it will take a longer time for the body to clear itself of the drug
Steady State
-amount of drug in equals amount of drug out
-loading dose vs several doses
-Goal: maintain an appropriate drug level
(it may take up to 5 half-lives to reach a steady state)
The Patient is taking a drug that has a half-life of 24 to 30 hours. In preparing discharge teaching, what is the dosing schedule the nurse anticipates will be prescribed for this medication? A. Three times a day B. Twice a day C. Daily E. Every other day
C. Daily
-Half-life: time it takes for half of the dose to be excreted; want to keep drug at therapeutic levels in the blood
Factors Affecting Pharmacokinetics
- age
- body mass (weight)
- sex
- genetic factors
- pregnancy
- route of administration
- timing of administration
- pathological states
- fluids
Primary Effects
(therapeutic effects) Effects that are: -predicted -intended -desired -reason the drug was prescribed
Types of Primary Effects
- Palliative
- Supportive
- Substitutive
- Restorative
- Chemotherapeutic
Primary Effects: Palliative
relieve the signs and symptoms of a disease but have no effect on the disease itself
Primary Effect: Supportive
support the integrity of body functions until other medications or treatments can become effective
Primary Effect: Substitutive
replace either body fluids or a chemical required by the body for improved functioning
ex: insulin or thyroid
Primary Effect: Restorative
return the body to or maintain the body at optimal levels of health
Primary Effects: Chemotherapeutic
destroy disease producing microorganisms or body cells such as antibiotics or antineoplastic drugs
(destroys everything but goal to destroy cells)
Secondary Effect
- unintended
- non-therapeutic
- can be:
- predictable
- harmless
- harmful
Types of Secondary Effects
- side effects
- adverse reactions
- toxic reactions
- allergic reactions
- Idiosyncratic reactions
- Cumulative effect
Secondary Effects: Adverse Reactions
harmful, unintended, usually unpredictable reactions to a drug administered at the normal dosage
-they are more severe than side effects and often require discontinuation of the drug
Secondary Effects: Idiosyncratic Reactions
unexpected, abnormal, or peculiar responses to medications
- take form of extreme sensitivity to a medication, lack of response, or a paradoxical (opposite of expected) response, such as agitation in response to a sedative
- unusual (never heard of)
- changes from person to person (individual)
Secondary Effects: Cumulative
increased response to a repeated dose
-too much
Drug Receptor Interactions
- Affinity
- Efficacy
- Agonist
- Antagonist
Drug Receptor Interactions: Affinity
how tightly the drug binds to the receptor
Drug Receptor Interactions: Efficacy
degree to which the drug activates receptors
think of efficiency
Drug Receptor Interactions: Agonist
molecule that activates a receptor
Drug Receptor Interactions: Antagonist
molecule that blocks the receptor
Iatrogenic Response
drug induced disease
-adverse condition induced by a prescribed treatment, drug or diagnostic procedure
Drug Tolerance
decreased physiological response after prolonged or repeated use of a drug
-may need to increase dose over time to reach a therapeutic response
Drug Dependence
physical or psychological dependence on a drug
-physical and/ or psychological disturbance occurs when a drug is withdrawn
Drug Interaction
One drug modifies or effects the other, increasing or decreasing the pharmacological action of each
Synergy
type of drug interaction where the combined effect of two drugs is greater than each one alone
-drugs maybe be order in combination for their synergistic effect
Antagonistic Response
the combination effect of two drugs is less than the sum of the drugs acting sepaately
Which of the following is the best determinant of the biologic activity of the drug?
A. The fit of the drug at the receptor site
B. The misfit of the drug at the receptor site
C. Inability of the drug to bind to a specific receptor
D. Ability of a drug to be rapidly excreted
A. The fit of the drug at the receptor site
Which type of drug can be eliminated through the kidneys?
water-soluble
Route of Administration: Sublingual
medications dissolve quickly and are absorbed into bed of blood vessels under the tongue
-most rapidly absorbed from the GI tract
Serum Drug Levels
blood tests
- blood tests to determine amount of drug present in the patients bloodstream
- helps ensure that we maintain a therapeutic drug level to support the response we are looking for
Modify a bodily function: stimulation or suppressing or irritating a cell
- Stimulation: type 2 diabetic medication that stimulates the pancreas to secrete more insulin
- Suppressing: a narcotic pain medication that blocks the pain receptors decreasing pain response
- Irritates: laxative
Active Metabolite
the drug that is left in its lipid soluble state
Inactive Metabolite
the drug that is converted to a water soluble state
