Chapter 1: Principles of Pharmacology Flashcards
Neuropharmacology:
drug-induced changes in functioning of cells in the nervous system
Psychopharmacology:
drug-induced changes that alter mood, thinking, and behavior
Pharmacology:
study of actions of drug and their effects on a living organism
Drug action:
molecular changes produced by a drug when it binds to a target site or receptor
Molecular changes alter physiological or psychological functions, called …
drug effects
Therapeutic side effects:
drug-receptor interaction produces desired physical/behavioral changes
Side effects vs therapeutic effects?
side effects are everything else that doesn’t include the molecular binding interaction
T/F: Therapeutic side effects and side effects can change.
yes depending on the desired outcome
What shows the possibility of medications changing their therapeutic and side effects because of the desired outcome?
amphetamine-like drugs
can be used to prevent narcolepsy (produce primary side effect of anorexia)
OR
can be used as a weight loss supplement (produce insomnia and hyperactivity as side effects)
T/F: There are “good” and “bad” drugs.
false; it’s character is determined by the way it’s procured
Specific drug effects: […] and […] of a drug with a target site in a living […].
physical; biochemical interactions; tissue
Nonspecific drug effects:
effects not based on the chemical activity of a drug-receptor interaction but on certain unique characteristics
What are those unique characteristics involved in nonspecific drug effects?
neurochemical states existing within an individual:
mood, expectations, perceptions, attitudes
What is an example of nonspecific drug effects?
ethyl alcohol; self administered on the same person– they can experience lightheartedness one day and depressed on another
What factors influence the outcome of a drug (5)?
- individual’s background (drug taking experience)
- present mood
- expectations of a drug effect
- perceptions of the drug-taking situation
- attitude toward the person administering the drug
etc
Placebo:
a pharmacologically inert compound
T/F: Placebos are fake pills.
no; in some cases these placebos can hold the same therapeutic effects
Belief in a drug may have […] despite the […].
real physiological effect; lack of chemical activity
Physiological effects that can occur with belief in a drug:
- altered gastric secretion
- blood vessel dilation
- hormonal changes
and so forth
What are the 3 possible explanations for the placebo effect?
- Pavlovian conditioning (cues in the environment)
- conscious, explicit explanation of outcomes
- social learning
What’s more important than the dosage of the drug?
bioavailability
Bioavailability:
amount of drug in the blood that is free to bind at specific target sites to elicit drug action
Pharmacokinetic components are at work […].
simultaneously
List the PK components/factors:
- routes of administration
- absorption and distribution
- binding
- inactivation
- excretion
Absorption/distribution sites = […].
Target site = […].
Inactivation storage depot sites = […].
membranes of organs
neuron receptor
bone and fat
Depot binding:
drug binding to plasma proteins
How are drugs eliminated? What exactly is released?
biotransformation (metabolism)
metabolites are excreted
Inactivation can influence both the […] and the […] of drug effects.
intensity; duration
What are the two major methods of administration? What is involved?
- enteral– uses the GI tract
2. parenteral– include those that do not use the alimentary canal
The enteral method could administer through the […] or […].
oral cavity; rectal
Parenteral administration includes…
injection, pulmonary, and topical
Safest and easiest route of administration:
oral (PO)
What is the criteria for PO:
- dissolve in stomach fluids
- pass through stomach walls to blood capillaries
- resistant to destruction by stomach acid and enzymes
What medication is (at the moment) unable to be taken PO? Why?
insulin
it is destroyed by stomach acid and enzymes
Absorption:
movement of the drug from the site of drug administration to the blood circulation
When are drugs fully absorbed from the stomach?
when they reach the small intestine
What are some factors that influence the rate of absorption (3)?
- fatty food slows down the stomach
- amount of food consumed
- level of physical activity
etc…
First-pass metabolism (definition):
an evolutionary beneficial function to prevent the passage of harmful chemicals and toxins before passed on to other tissues/organs
What is the biggest ownfall to taking PO?
extensive metabolism may occur (more than 90%) reducing their bioavailability
Rectal administration is dependent on the […].
placement
If a suppository is placed on the lower end of the rectum…
it may avoid some first-pass metabolism
Deep placement of a suppository…
means drug is absorbed by veins that drain into the portal vein
For rectal administration, the bioavailability is […].
hard to predict
Intravenous is the […] and […] method.
most rapid; accurate
What are the dangers of IV?
quick onset leaves little time for corrective measure incase of overdose and allergies
Compared to IV, IM injection provides the advantage of…
slower and more even absorption over a period of time
Time of IM absorption:
10- 30 minutes
What can slow down the rate of IM?
- second drug that constricts blood vessels
2. suspension
Intraperitoneal injection (IP):
rarely used in humans but most common route for laboratory animals
Subcutaneous (SC) administration: the drug is […].
injected just under the skin
Use of a pellet or delivery device for SC […] the rate of absorption. Rubbing the area, and dilating the blood vessels on the other hand, […].
slows down; increases the rate
Why is inhalation fast-absorbing?
the area of pulmonary absorbing surfaces are large and filled with capillaries
Inhalation: The effect of the brain is […] because blood from […] travels only a short distance back to the […] before quickly heading to the brain via […]. which carries O2 generated blood to the […].
very rapid (seconds); the capillaries of the lungs; heart; carotid artery; head and neck
Inherent dangers of the inhalant drugs:
irritation of the nasal passages and damage to the lungs caused by small particles
Topical application of drugs to […] provide […].
mucous membranes; local effects
Some topically administered drugs can be readily absorbed into circulation. This is known as…
sublingual administration
Sublingual administration advantages:
- skips first metabolism
- quickly absorbs to capillaries and circulates
- not broken down by stomach acid/enzymes
Intranasal has what type of spread/effect?
local and sometimes widespread (more effective than oral)
What are the two advantages of intranasal administration?
- avoids first-pass liver metabolism (fast than oral)
2. bypasses the BBB and access the CSF and in between neurons
Transdermal through skin patches provides […] and […] at a preprogrammed rate.
controlled; sustained
Drugs with high lipid solubility move through cell membranes by […].
passive diffusion
The larger the difference in concentration of each side of a plasma membrane ([…]), the more […] is diffusion.
concentration gradient; rapid
Lipid solubility increases […] (2).
- ABSORPTION of drug into the blood
2. PASSAGE determines how readily a drug will pass the lipid barriers to enter the brain
Bioactivation is a […]; a substance that is dependent on […] to convert a(n) […] drug to a(n) […] one.
prodrug; metabolic reactions; inactive; active
What are the two factors that influence the extent of ionization?
- relative acidity/alkalinity (pH)
2. intrinsic property of the molecule (pKa)
The pKa of a drug represents the […] of the aqueous solution in which that drug would be […] ionized and […] nonionized.
pH; 50%; 50%
Drugs that are weak acids ionize more readily in…
an alkaline environment
Drugs that are weak acids become less ionized in…
an acidic environment
Ionization: A weak acid in the stomach compared to the intestine.
stomach– nonionized form; lack of electric charge means lipid soluble and readily absorbed to blood
intestine– pH is more basic in comparison; ionization increases and absorption is reduced
Intestine absorption advantages (2)
- greater surface area
2. slower movement of material
Drug redistribution: distribution of the drug from […] to […] in the body.
it’s target site; other areas/tissues
BBB purpose:
blood plasma that supplies brain cells with essentials and carries away waste products
CSF:
fluid that fills the subarachnoid space around the brain and spinal cord, ventricles, and canals
CSF is manufactured by cells of the […], which line the cerebral […].
choroid plexus; ventricles
BBB:
separation between brain capillaries and the brain/CSF
What is the principal component of the BBB?
distinct morphology of brain capillaries
Because the job of blood vessels is to […] to cells while […], the walls of typical capillaries are made up of […].
deliver nutrients; eliminating waste; endothelial cells
Intercellular clefts:
small gaps in endothelial cells that allow small molecular passage
Fenestrations:
larger openings in endothelial cells that allow large molecular passage
Pinocytotic vesicles:
envelop and transport larger molecules through the capillary wall
How are intercellular clefts opened and closed?
by adjoining the endothelial cells and forming tight junctions
Surrounding brain capillaries are numerous glial feet– extensions of glial cells called…
astrocytes or astroglia
What is the significant purpose of astrocytes?
contribute to both postnatal formation and maintenance of the BBB
T/F: The BBB is impermeable.
false the BBB is selectively permeable (lipid-soluble passes)
Area postrema, or […], is a […] in the brainstem that respond to […] in the blood and induces […].
chemical trigger zone; cluster of cells; toxins; vomiting
Teratogens:
agents that induce developmental abnormalities in the fetus
When is a child most susceptible to damaging effects during pregnancy? Why?
first trimester
around this time the fetus is developing organs
Drug depots are also known as…
silent receptors
What are drug depots?
inactive sites where drug binding occurs and no measurable biological effect is initiated
Most notable silent receptor:
albumin (plasma protein)
Any drug bound to depots cannot reach […], nor can they be […] by the […].
active sites; metabolized; liver
T/F: Drug binding to drug depots is reversible?
true; when the blood level drops these unbind and circulate through the plasma
Rapid binding to depots before reaching target tissue causes:
slower onset and reduced effects
Depot binding: Explain the individual differences in amount of binding and how it might alter the dosages prescribed.
high– less free drug so some people seem to need higher doses
low– more free drug, so these individuals are more sensitive
Competition among drugs for depot-binding sites:
higher than expected blood levels of the displaced drug, causing greater side effects and possibly toxicity
**Unmetabolized bound drug:
drug remaining in the body for prolonged action
Redistribution of drug to less vascularized tissues and inactive sites:
termination of drug action
A steady-state plasma level is when the desired blood concentration of drug is achieved. How is this done?
absorption and distribution phase is equal to the metabolism and excretion phase
First-order kinetics:
drugs are cleared though an exponential (half life) decline
Zero-order kinetics:
drug molecules are cleared at a constant rate (no matter dosage)
What is the prime example of zero-order clearance?
ethanol
although this can switch to first-order when biotransformation occurs at high levels of alcohol (toxication)
Drug metabolism is the greatest in which organ?
liver
List the 2 types of biotransformations:
- phase one
2. phase two
What occurs during phase one of biotransformation?
NONSYNTHETIC MODIFICATION of the drug molecule by oxidation, reduction, or hydrolysis
For phase one, what is the common modification of the drug?
oxidation
What occurs during phase two of biotransformation?
SYNTHETIC MODIFICATION reactions that require the combination (conjugation) of the drug with small molecules
List some of the small molecules that conjugate with phase 2 synthetic biotransformation (3):
Side Note: these small molecules are essential for converting/excreting these foreign substances (xenobiotics) out of the body.
glucuronide**
sulfate
methyl groups
**most common
The two phases of drug biotransformation ultimately produce one or two […] which are […]. so they can be excreted more readily than their […].
inactive metabolite; water-soluble; parent drug
After biotransformation of metabolites, what are the two paths for excretion?
- filtered out by kidneys
2. excreted into bile and eliminated with feces
Microsomal enzymes:
liver enzymes primarily responsible for metabolizing psychoactive drugs
Factors that influence an individual’s ability of drug metabolism (4):
- enzyme induction (increase of enzyme availability after stimulus)
- enzyme inhibition (decrease of enzyme availability after stimulus)
- drug competition
- individual differences in age, gender, genetics
Repeatedly used psychoactive drugs cause an increase in what effect.
TOLERANCE: enzyme induction within the liver; the repeated stimulus will allow more enzymes to be available
Increased number of enzyme molecules not only cause drugs to […] their own rate of […] by two-to threefold, but also can […] the rate of […] of all other drugs.
speed up; biotransformation; increase; metabolism
Increased rate of biotransformation and increased number of enzymes leads to…
tolerance
Enzyme inhibition can lead to…
Why?
toxicity
reduces metabolism of other drugs metabolized by the same enzyme
MAOIs (antidepressants) can turn […] potentially life-threatening because of […].
normal foods; enzyme inhibition
What food significantly inhibits biotransformation?
grapefruit juice
Drug competition occurs for drugs that share […]. This can cause an […] of either drug […] of the second, causing potentially toxic levels.
a metabolic system; elevated concentration; reduces the metabolic rate
Genetic polymorphisms:
genetic variations amoung individuals that produces multiple forms of a given protein
What is an example of genetic polymorphisms (2)?
- acetylation: treat TB and subsequently found to relieve depression
- Asian groups and enzyme to break down alcohol
What is the most important route of elimination?
urine through the kidneys
Ionization of drugs reduces […] because it makes drugs less […].
absorption; lipid-soluble
PD is the study of the […] and […] interaction of drug molecules with target tissue that is responsible for the ultimate effects of a drug.
physiological; biochemical
Receptors can be known as…
protein molecules located on the cell surface or within cells
Receptors are the […] of action of biologically active agents such as […], hormones, […] (all referred to as […]).
initial sites; neurotransmitters, hormones, and drugs; ligands
A ligand is defined as any molecule that…
binds to a receptor with some selectivity
List CNS stimulates:
amphetamine, cocaine, nicotine
List CNS depressants:
barbiturates and alcohol
List hallucinogens:
mescaline, LSD, psilocybin (shrooms)
List psychotherapeutics:
prozac and throazine
A receptor can be coupled either with…
an ion channel or with a G protein
List the two types of receptors:
- EXTRACELLULAR those on the surface of the cell
2. INTRACELLULAR those within the target cell (cytoplasm or nucleus)
Hormonal binding usually occurs […].
intracellularly (receptor is located within the target cell)
Receptor agonists:
has best chemical “fit” (highest affinity); attaches readily to the receptor, and produces a significant biological effect
Receptor antagonists:
also fit receptors but produces no cellular effect (low efficacy)
Partial agonists:
ligands that bind to the agonist recognition site but trigger a response that is lower than that of a full agonist at the receptor
Inverse agonists:
initiate a biological action that is opposite to that produced by an agonist, and also antagonize the effects of other agonists
Long-term regulation is called […] when receptor numbers […] and […] when receptors are reduced.
up-regulation; increase; down-regulation
Dose-response curve:
describe the extent of effect (response) produced by a given drug concentration (dose)
Potency:
absolute amount of drug necessary to produce a specific effect
On the dose-response curve, the position of the curves on the x-axis indicates […] and reflects the […].
potency; affinity
Non-competitive antagonists are drugs that […] the effects of agonists.
reduce
Physiological antagonism involves…
two drugs interact and reduce the effectiveness of both
Potentiation refers to the situation in which the…
combination of two drugs produces effects that are greater than the sum of their individual effects (additive effects)
Cross-tolerance:
development of tolerance to one drug can diminishing the effect
List the following:
drug that induces tolerance rapidly
drug that requires weeks of tolerance
drug that doesn’t cause significant tolerance
LSD
barbiturates
antipsychotics
T/F: Tolerance is reversible
yes when drug use stops
Acute tolerance:
tolerance develops during just a single administration
Example of acute tolerance:
alcohol
Drug disposition tolerance or […] occurs when repeated use of a drug […] the amount of that drug that is available at the […].
metabolic tolerance; reduces; target tissue
T/F: Drugs are capable of liver microsomal enzyme induction.
true
When does pharmacodynamic tolerance occur?
changes in nerve cell function compensate for continued presence of the drug
Why does the withdraw syndrome occur?
chronic drug user stops abruptly and and the mechanism remains functioning and causes a rebound
The occurrence of the withdrawal or abstinence syndrome is the hallmark of …
physical dependence
Behavioral tolerance (also known as […]) is seen when tolerance occurs in the same […] in which the drug was […].
environment; administered
What can behavioral tolerance explain with overdoses?
chronic users may not be as tolerant to the drug in a different location, environmental cues can contribute to overdoses occurrences
State-dependent learning: concept that is closely related to […]. Tasks learned under the influence of a psychoactive drug may subsequently be performed […] in the drugged state.
behavioral tolerance; better
Sensitization is sometimes called […].
reverse tolerance
Sensitization:
is the enhancement of particular drug effects after repeated administration of the same dose of the drug
Pharmacogenetics:
study of the genetic basis for variability in drug response among individuals
What is the goal of pharmacogenetics?
identify genetic factors that confer susceptibility to specific side effects, or predict therapeutic response
personalized medicine
Should there be any alteration to the following dosage:
intermediary metabolizer; with one normal allele and one inactive polymorphism
slightly reduced dosage for plasma concentration
Should there be any alteration to the following dosage:
patient with two highly functional genes (extensive metabolizers)
administered a somewhat high than normal dosage to ensure therapeutic effectiveness
Should there be any alteration to the following dosage:
ultrarapid metabolizer (have additional high-functioning polymorphisms)
higher dosage to reach adequate plasma concentration for effective treatment
Knowing genetic variation in metabolizing enzymes is beneficial to…
help individuals predict the bioavailability of a given drug so modifications produce optimum therapeutic concentrations
Hormonal binding alters cell function by…
triggering changes in gene expression
Efficacy:
capacity to initiate a biological action
Competitive antagonists:
drugs that compete with agonists to bind receptors but do not initiate intracellular effects, reducing effect of the agonist
Competitive antagonists can be replaced by…
an excess of agonist
What are the three ways that noncompetitive antagonists reduce the effect of agonists:
- binding to the receptor at a site other than the agonist binding
- disturbing the cell membrane supporting the receptor
- interfering with cell processes that were initiated by the agonist
Ways drugs act as agonists in the brain (2):
- enhancing synaptic function by increasing neurotransmitter synthesis or release
- prolonging action of the neurotransmitter within the synapse
Ligand-receptor binding is […].
temporary
Ligand binding causes change in receptor […] that […] a series of events in the cell.
shape; initiates
Receptor proteins have a […]; the number and […] or receptors can also change.
lifespan; sensitivity
Upregulation:
number of receptors increases
Downregulation:
number of receptors is reduced in response to absence of ligands or chronic activation
Comparing […] of different drugs shows differences in potency.
ED50
TD50 (50% toxic dose):
dose at which 50% of the population experiences a toxic effect
Therapeutic index (TI) =
TD50/ED50
What are examples of pharmacodynamic tolerance:
- receptor down regulation
2. receptor up-regulation
Operant conditioning may also play a part in […] tolerance
behavioral
The cytochrome […] have many polymorphisms that affect drug levels.
P450 enzyme family
