Fundamentals of Pharmacology (Pharmocodynamics/kinetics) (LO1) Flashcards
Pharmacokinetics
what the body does to the drug
ADME
determine how and how much of a drug arrives at its target body tissues and how long it exerts its therapeutic effect
(A) Absorption
(D) Distribution
(M) Metabolism
(E) Excretion
Absorption
refers to the transfer of medication from its site of administration into the body to specific target organs and tissues
The rate of absorption determines the onset of action
The extent of absorption determines the intensity of action
factors affecting the absorption of a medication including
Solubility of the drug
Concentration of the drug
pH of the body
Site of absorption
Absorbing surface area
Blood supply to absorption site
Medication’s bioavailability (the amount of medication that is still active once it reaches it’s target tissue)
Distribution
As a drug passes through the body, its form and its concentration in the tissues influences the effect it will have
Plasma protein binding is an important mechanism of distribution
bound drug
free drug
bound drug: Plasma protein binding is an important mechanism of distribution.
Drugs are bound in variable degrees to proteins or become stored in fatty tissues
free drug: Only those drug particles that are not bound can be active in the cells
metabolism (biotransformation)
changes a drug into forms that can be used by the body or which can be readily excreted (or both)
Metabolism occurs immediately and most often in the liver.
first pass effect: the liver inactivates some medications and some can only be given parenterally
Excretion
A drug and its metabolites must be excreted
If a drug is excreted more slowly than it is administered, accumulation occurs causing adverse effects and toxicity.
Drug Half-Life
represents the time required for the amount of the drug in the blood serum to diminish by one-half
the concentration (M) of a drug in the blood during a period of time after administration of a single dose
The minimum effective concentration (MEC) or therapeutic index
is a term indicating the lowest concentration of drug in the blood able to produce a therapeutic effect
useful in determining adequate dosages
The therapeutic range describes
the range between MEC and the toxic concentration where the drug can seriously harm the client
Onset of Action
is the time after administration when the drug reaches the MEC and begins to produce its effects
Principles Related to Onset of Action
Route of administration
sometimes a loading or priming dose is given to achieve the MEC quickly
Some drugs have a latency period
peak effect occurs when blood level is highest
The duration of action
The termination of action
–The duration of action–
is usually defined as how long the medication can be expected to remain above the minimum level to provide the effects
it is the time the blood level is above the MEC
-The termination of action-
the amount of time after the concentration level falls below the minimum level to the time it is eliminated from the body
Duration of action of :
- fentanyl (Sublimaze®),
- meperidine (Demerol®),
- morphine,
- acetaminophen (Tylenol®),
fentanyl (Sublimaze®), 1–2 hours
meperidine (Demerol®), 2–4 hours
morphine, 3-7 hours
acetaminophen (Tylenol®), 4–6 hours
Principles Related to Duration of Action
Short acting drugs must be given frequently.
Duration of action can be maintained by giving drugs at regular intervals (maintaining the blood level).
Duration can be used to help predict the time of next dose.
Occasionally a drug’s effects may persist even after it has been excreted.
Duration is influenced by pharmacokinetics and can vary with different routes of administration.
Sites of Elimination
Kidneys (main site of elimination)
GI tract
Perspiration
Respiration
Pharmacodynamics
what the drug does to the body
Drugs either alter the ——- —- or change the —— — — — —-
Drugs either alter the cell environment or change the rate of cell functions
the receptor theory of drug action
Drugs “attach” to cells because their molecular structure matches
All cell receptors will be exposed to the drug circulating in the blood stream but only those that fit (visualize a lock and key) will bind to each other
If many receptors are available, we can increase the drug dosage and thus drug effect.
If few receptors are available, increasing the drug dosage will have no effect.
the cell is said to be receptive to the drug if…
If at least three sites on the surfaces of both drug and cell match
what are receptors usually made of
cellular proteins or nucleic acids but can be enzymes, carbohydrate residues, and lipids
Agonist
a drug that directly alters the rate of a cellular process
Affinity for the target tissue
An agonist has a natural tendency to bind with the receptor
Efficacy
ability to initiate drug action
Partial agonists
are agonists that produce only moderate effect.
They occupy a receptor site and produce moderate effect
prevent any other drug from binding to those receptor sites.
Antagonists
do not alter cellular rates or environments.
they compete with agonists to occupy the same receptor site
If successful in binding more tightly, the antagonist will prevent the agonist from acting
Antagonists are often given to act as antidotes
excreted more rapidly than the agonist they oppose, therefore have short-lived actions and must be administered repeatedly to prevent toxicity from recurring
Numerous factors affect an individual’s response to drugs, including:
Age Weight Gender Environment Time of administration Condition of the patient Genetic factors Psychologic factors
Types of Responses
predictable
unpredictable
iatrogenic
Predictable response
extensive research to determine the therapeutic action (desired effect) of a drug
in order for a response to be classed as predictable it must have occurred in 50% of the population
going to be some potential negative results that may occur (side effects)
Through research and testing, most side effects can be anticipated
Unpredictable response
If the response seen is unique to that patient and not seen in other patients in a similar setting, the response is classed as an idiosyncrasy
When medications are given in successive doses or in conjunction with other medications, we can see unpredictable responses as well
idiosyncrasy
an abnormal or unusual response to a drug
Tolerance
decreased effects of a drug due to long term use
These patients will build a tolerance to that medication resulting in the need for a higher than normal dose to achieve the same result
Cross-tolerance
drug tolerance in which patients who takes a medication for an extended period of time can build up a tolerance to other medications in the same class
Tachyphlaxis
condition where patient rapidly becomes tolerant to a medication
Drug dependence
a physical or emotional need for drug
Cumulative effect
occurs when several does of a medication are administered or when absorption occurs more quickly than elimination
If repeat doses are given too quickly, a cumulative effect may result, causing possible nontherapeutic effects
Summative effect
the process where multiple medications can produce a response that the individual medications alone do not produce
If two medications of similar effect are given to a patient
Synergism
combined action of two drugs that is greater than the sum of their individual responses
Potentiation
enhanced action of the drug by another administered concurrently
Iatrogenic response
is an adverse condition that is inadvertently induced in a patient by the treatment given
An example of this would be a patient developing an urinary tract infection after the insertion of urinary catheter.
in the metabolic phase The liver can act on a drug in 2 phases
Phase1: the enzymes may oxidize the drug or bind it with oxygen molecules and can also hydrolyze the medication; both causes medication to be more soluble with water
Phase 2: the medication molecules combine with a chemical found in the body (known as conjugation reaction)
excretion occurs primarily through the kidneys 3 mechanisms
Glomelur filtration
Tubular secretion
Partial reabsorption
Glomelur filtration
a passive process in which blood flows through the glomeruli of the kidneys
a differential in pressure forces waste away from the blood into the capsule where it is transported for excretion
Tubular secretion
an active transport process in which medications are bound to specific transporters aiding in their elimination
Partial reabsorption
this occurs when some amount of the drug is reabsorbed after being filtered
Medications cause their action on the body by four mechanisms:
They may bind to a receptor site
They may change physical properties of cells
They may chemically combine with other chemicals
They may alter a normal metabolic pathway
A medication molecule witll have 1 of 2 effects when it binds to a receptor site
It may stimulate the receptor site to cause the response it normally does (agonist)
It may block the receptor site from being stimulated by other chemical mediators and inhibit the normal response (antagonist)
The autonomic nervous system
is composed of nerve fibers that send impulses from the CNS to smooth muscles, cardiac muscles, and glands
The autonomic nervous system (ANS) consists of two further subdivisions:
Parasympathetic nervous system
Sympathetic nervous system
Nerve fibers associated with the parasympathetic system originate
from the spinal cord at the level of the cervical and sacral regions
Parasympathetic nervous system is responsible for actions such as:
Decreased heart rate
Decreased cardiac contractile force
Decreased blood pressure
Increased circulation to digestive organs
Increased peristalsis
Constriction of the pupils
Bronchoconstriction
The principle neurotransmitter of the parasympathetic nervous system is
acetylcholine
uh · seh · tuhl · kow · leen
acetylcholine
Acetylcholine is very short lived.
within seconds of release it is deactivated by another chemical called acetylcholinesterase
Within the parasympathetic nervous system there are two main types of acetylcholine receptors
nicotinic and muscarinic
Muscarinic receptors
are primarily responsible for parasympathetic overactivity responses
Muscarinic responses and what reverses them
including bradycardia, miosis (pinpoint pupils), sweating, blurred vision, tearing, wheezing, SOB, coughing, vomiting, abdominal cramps, diarrhea
atropine reverses them
nicotinic receptors
are primarily responsible for sympathetic overactivity response and neuromuscular disfunction
causes muscular contractions
opened by nicotine
nicotinic responses
responses include tachycardia, hypertension, dilated pupils, muscle fasciculation (involuntary twitching etc) and muscle weakness
cholinergic receptors
these receptors respond to acetylcholine
nicotinic and muscarinic
parasympathomimetic or cholinergic agonists
producing effects that resemble (mimic) the stimulation of the parasympathetic nervous system
If a medication binds to and stimulates those receptors
parasympatholytic or anticholinergic
blocking effects or producing effects that resemble interruption of the parasympathetic nervous system
If a medication blocks the actions of the parasympathetic nervous system
ex: atropine
Nerve fibers associated with the sympathetic system originate
from the spinal cord at the level of the thoracic and lumbar regions
Sympathetic nervous system is responsible for actions such as:
Increase heart rate
Increase blood pressure
Peripheral vasoconstriction
Increase circulation to vital organs
Sweat gland stimulation
The principle neurotransmitters of the sympathetic nervous system are
catecholamines
norepinephrine
epinephrine
Within the sympathetic nervous system there are two main types of receptors
adrenergic and dopaminergic.
Dopaminergic receptors
are believed to cause renal, coronary, and cerebral artery dilation
Adrenergic receptors
are the receptors that are most common within the sympathetic nervous system
the receptors stimulated by prehospital medications
Adrenergic receptors 4 classes
Alpha1
Alpha2
Beta1
Beta2
where are the following receptors primarily located
Alpha 1
Alpha 2
Beta 1
Beta 2
Alpha 1: on peripheral blood vessels
Alpha 2: on nerve endings
Beta 1: within the cardiovascular system
Beta 2: on bronchial smooth muscle
Alpha 1 stimulation results in:
Peripheral vasoconstriction
Mild bronchoconstriction
Increased metabolism
Stimulation of sweat glands
Alpha 2 stimulation results in:
Control release of neurotransmitters
Beta 1 stimulation results in:
Increased heart rate (positive chronotropic)
Increased strength of cardiac contraction (positive inotropic)
Increased cardiac conduction (positive dromotropic)
Beta 2 stimulation results in:
Bronchodilation
Peripheral vasodilation
sympathomimetic or adrenergic agonists
If a medication binds to and stimulates any of the adrenergic receptors
what do sympathomimetic or adrenergic agonists do
producing effects that resemble the stimulation of the sympathetic nervous system
sympatholytic or adrenergic antagonist
blocking effects or producing effects that resemble interruption of the sympathetic nervous system
Selective beta blockers
bind and block only beta 1 or beta 2 receptors
non-selective beta blockers
would block both beta 1 and beta 2 receptors
