CH1 Flashcards
The study of the actions of drugs and their effects on living organisms
Pharmacology
Prescribes medicinal drugs, knows therapeutic effects, side effects, contraindications
pharmacist
Creates molecules that bind to targets in body/brain
medicinal chemist
Identifies chemical substances that act on the nervous system to alter behaviour
Neuropsychopharmacology
Neuropsychopharmacology uses ______ agents as _____ to gain an understanding of the neurobiology of behaviour. It ranges from ______ (studies in cells/animals) to _____ (working with human patient populations)
chemical, probes, pre-clinical, clinical
Primary goals of neuropsychopharmacology
- understand the neural/neurochemical basis of normal behaviour, 2. identify the causes / treatments of behaviour abnormalities in psychiatric illnesses
Study of drug induced changes in the nervous system cell functioning
neuropharmacology
emphasizes drug-induced changes in mood, thinking and behaviour
psychopharmacology
molecular changes produced when a drug binds to a receptor/target
drug action
alterations in physiological/psychological functions induced by drug action
drug effect
the drug-receptor interaction produces desired physical or behavioural changes
therapeutic effects
Physiological/biochemical interactions of drug with target site in living tissue; what the drug does to the body that nothing else can do (e.g. alcohol depressing neural activity)
specific effects
based on unique characteristics of individual background, mood, expectation of effect, perceptions (e.g. alcohol can augment pleasant moods or amplify unpleasant ones, placebo effect)
nonspecific effects
Factors that contribute to bioavailability
pharmacokinetics
the amount of drug free to bind at target sites
bioavailability
five main factors contributing to bioavailability
- route of administration, 2. absorption / distribution, 3. binding, 4. inactivation, 5. excretion
drug effect also depends on how ____ the drug reaches its target, and ____/______ of prior drug use
rapidly, frequency, history
Oral administration is the most popular method, because it is ____, ______ and economical. The disadvantages are that it is _____, has variable _____, and _____ levels. Drugs taken orally are absorbed from the ____ into circulation. Some are absorbed from the ____ but most are taken up through the ____ ____. These drugs must be resistant to destruction by ____ ____ and _____.
safe, self-administered, slow, absorption, plasma, gut, stomach, small intestine, stomach acid, enzymes
through oral administration, the factors that influence absorption include
- amount/type of food in the stomach, 2. rate that stomach empties, 3. physical activity
potentially harmful chemicals (taken orally) pass through the liver (via portal vein) where they are chemically altered
first pass metabolism
the liver may render some drugs _______, with the need to administer by _____ or in higher doses. Other drugs are metabolized into _______ forms by the liver and need to be taken orally to have an effect
inactive, injection, active
Injection routes deliver drugs into the _____, which bypass the _____. The advantages are that it is ______, and has the most accurate blood _______. The disadvantages is that there is the greatest risk of _______.
bloodstream, first pass metabolism, fast, concentration, overdose
______ or _____ methods of intake allow absorption through capillaries around skin/muscles which allow for _____ and _____ absorption
subcutaneous, intramuscular, slow, even
_______ is when the drug is absorbed rapidly from the lungs, which can provide ______ and _____ to nasal passages and ______
inhalation, irritation, damage, lungs
The route of administration alters the rate of ____ and ___ ____ of a drug. The ______ that a drug is dissolved in can impact how long it stays in the system after _______. Other factors affecting absorption are the _____ and ____ of an individual
absorption, blood levels, vehicle, injection, size, sex
An intramuscular injection delivered through oil takes _______ to take effect, and drug concentration in the blood declines at a ______ rate. The same method but using ______, results in faster _______ and ______
longer, slower, saline, drug concentration, decline
A larger person has more ______ to dilute a drug, thus needing a higher dose. Likewise, women tend to have less, and a different physiology, resulting in a ______ dose required
body fluid, lower
A key factor determining plasma brain drug levels is the rate of passage by molecules through _____ ______. These prevent most molecules from passing through unless they are ______ soluble. ______ are completely soluble.
cell membranes, lipid, steroids
_______ (heroin), is more lipid soluble than _____, has a more rapid ____ and more potent reinforcing properties
diacetylmorphine, morphine, onset
Once the drug is in the bloodstream, it is carried throughout the body within _______ minutes. Capillaries in the body are very _____, allowing drugs to enter tissues regardless of _____ ______. However, in the brain, many substances would have ____ effects on brain function if permitted to cross freely. The ______ reduces the diffusion ______ particles, as brain capillaries have no _____/_________ sites.
1-2, porous, lipid solubility, disruptive, blood brain barrier, ionized, clefts, pinocytotic
fills the subarachnoid space around the brain, spinal cord, ventricles, and canals
cerebrospinal fluid
separates the brain capillaries and the CSF
blood brain barrier
extensions of glial cells that surround brain capillaries restricting movement of non lipid soluble molecules
astrocytes
Molecules that the brain needs, such as _____, are carried in via _______ ______ transport
glucose, carrier mediated
For a drug to be centrally active, it typically needs to be ________ _____, in both _____ and _____ environments
lipid soluble, acidic, basic
Some regions have a weaker blood brain barrier, such as the ____ ______ “vomit center” which senses noxious molecules in the blood, the _____ ___, which release neurohormones in the blood, and parts of the ______
area postrema, median eminence, hypothalamus
the elimination of drugs via bio-transformation and metabolites and excretion
drug clearance
Drug clearance is usually _______ (first order kinetics), meaning only a small fraction of _____ ____ are occupied, so the rate is __________
exponential, clearance sites, concentration dependent
time required to remove 50% of the drug in the system
half life
some drugs are eliminated via ______ kinetics, meaning that they are eliminated at a constant rate regardless of concentration. This occurs when drug levels are ____, and routes of metabolism elimination are _______ (aka more ____ than there are clearance sites)
zero order, high, supersaturated, molecules
_____ and ____ have relatively long half lives, while _____ ____ and ____ have shorter half lives, requiring frequent administration
caffeine, ibuprophen, nicotine, morphine, cocaine
Most biotransformation occurs in the ______. The _______ enzyme family are responsible for oxidizing most psychoactive drugs, making them easier to _____
liver, cytochrome P450, clear
modification of a drug by oxidation, reduction, or hydrolysis (non-synthetic); involving adding or removing an ion from the molecule to convert it into a less lipid soluble or less active form
phase I
sometimes, phase I metabolism can convert the drug molecule to another _____ form, resulting in a _____ ____ effect
active, long lasting
involves conjugation (synthetic) attachment of the drug to other small molecules (glucuronide, sulfate, or methyl groups), which ionizes them and makes them inactive; synthesizes a new molecule
phase II
Some drugs are metabolized directly by ___ /____, while others need ____ phase I or III processes
I, II, multiple
Inactive metabolites are excreted via the ____ or ______.
kidneys, bile
factors that modify biotransformation capacity (3)
- induction or inhibition of enzymes involves in metabolism, by other drugs, foods, etc., 2. drug competition (when two drugs require the same enzyme to be metabolized), 3. genetic polymorphisms for drug metabolizing enzymes create individual differences
molecule that binds to a receptor with some selectivity
ligand
amount of attraction between ligand and receptor (concentration needed to achieve a certain amount of firing)
affinity
how well the ligand initiates a biological action upon binding to the receptor
drug efficacy
absolute amount of ligand necessary to produce a specific effect, typically measured by ED50
drug potency
the dose needed to produce 50% of the maximal response
ED50
one individual ____ of a drug may have a different ______ than another effect of the same drug
effect, potency
_____ curves describe the extent of the effect produced by a given drug. Most curves are _____ shaped. However, some drugs have _____ effects, with a lower dose having one effect, and a higher dose having ___ effect, or even the _____ effect. This is because the drug starts to lose _____, and other parts of the brain are activated that _____ the main effect
dose-response, sigmoidal, biphasic, no, opposite, selective, counteract
smallest dose that produces a measurable effect
threshold dose
when all the receptors for the drug are occupied
maximum response
the dose causing 50% of the population to experience a toxic effect
TD50
TD50/ED50; want this to be high to prevent toxic effect at low doses
therapeutic index
the range from ED50 –> the TD for a specific toxic effect
margin of safety
Most drugs do not ___ into neurons, but instead act on ___ receptors, such as metabotropic or ionotropic receptors
pass, surface
receptors that activate second messengers inside the cell, causing multiple effects; is generally slow
metabotropic receptor
second messenger effects
- modulates ion channels to affect neural activity, 2. alters protein synthesis, 3. alters metabolism of the cell
Receptors that open or close ion channels, allowing ions to flow through and excite or inhibit neurons; generally fast
ionotropic receptors
ligand receptor interactions are ______, meaning after the ligand separates, the receptor is free to ____ again. It is also ______, meaning the likelihood of the ligand binding to a receptor is influenced by the number of molecules of the ______, the ______ of the ligand, and the presence of _______
temporary, bind, probabilistic, ligand, affinity, competitors
increase in the number/sensitivity of receptors in response to the absence of ligands
up-regulation
reduced number of receptors or their sensitivity after chronic activation
down-regulation
the degree to which a drug binds to a particular receptor compared to other receptors; is relative, and highly dependent on dose
drug sensitivity
have the best chemical fit and high efficacy, readily attaches to the receptor and produces a biological effect; may even activate or stick to the receptor better than the endogenous ligand
receptor agonists
binds to the receptor and activates it but is less potent and have intermediate efficacy
partial agonists
initiates an action opposite to that produced by the agonist; ultimate effect is similar to an antagonist, but pharmacological action is different
inverse agonists
drugs that can also act like agonists, even though they may not directly interact with a particular receptors e.g. by increase NT synthesis or release, or increasing binding of NT to a receptor
indirect agonist
fit receptors but produce no cellular effect (low efficacy); reduces the effect of the endogenous ligand; ability to block the effect of the agonist depends on the relative concentrations and affinities of the two drugs
competitive antagonists
reduces the agonist effect by 1. binding to the receptor at a site other than the agonist binding site (e.g. blocking an ion channel) 2. interfering with second messengers initiated by the agonist, 3. disturbing the cell membrane supporting the receptor (protein shape changed)
noncompetitive antagonists
competitive agonists essentially reduce the _____ of an agonist, and shift the dose response curve so that a ____ dose of agonist is needed to achieve the maximal effect. Adding enough agonist can ____ the effects of the antagonist. However, noncompetitive agonists change the _____ of the dose response curve, often preventing the agonist from achieving _____ effect, irrespective of how much more agonist is added
potency, higher, block, shape, maximal
two drugs interacting to reduce the effectiveness of both drugs
physiological antagonism
When two drugs combine to produce effects that are equal to both drug effectiveness combined
additive effects
when the combination of 2 drugs produces effects greater than the sum of their individual effects; important for things like sedation
potentiation / synergistic interactions
diminished response to a drug after repeated exposure; dose of drug must be increased to achieve the same magnitude of effect
drug tolerance
when tolerance to one drug diminishes effectiveness of another drug, usually ones that work on similar mechanisms
cross tolerance
4 characteristics of drug tolerance
- reversible when drug use stops, 2. dependent on dose/frequency of drug use and drug taking environment, 3. may occur rapidly, after long periods of use, or never, 4. multiple forms explained by different mechanisms
repeated drug use reduces the amount of the drug available at the target tissue; by more efficient metabolism (more enzymes), so less drug gets to site of action
metabolic (drug dispositional) tolerance
when changes in cell function compensates for repeated drug exposure; typically occurs at the site in the brain or body where the drug exerts its effects (ex. downregulation)
functional (pharmacodynamic) tolerance
When the brain makes associations between the drug effects and the context where they occurred; and tolerance is maximal when the drug is given in environments similar to those previously experienced; results in body increasing or decreasing response in advance to prepare for the drug effects
behavioural tolerance / conditioned tolerance
The placebo effect can result in both ______ evaluation of relief and measurable ____ changes
subjective, physiological
Increase in anxiety and influence in treatment outcome when having negative expectations
nocebo effect
movement of drug from the site of administration to the blood circulation
absorption
____ administration may avoid some first pass metabolism, but has irregular _____.
rectal, absorption
injection used for lab animals that involves injection into the abdominal wall; has rapid effects but variable absorption
intraperitoneal (IP)
______ ____ of drugs have local drug effects
topical application
______ (under the tongue), _______, or _______ administration all by pass the first pass metabolism
sublingual, intranasal, transdermal
_______ (into CSF), ______, _____ or ______ (into ventricles) are central routes of administration
intrathecal, epidural infusion, intracranial, infusion pump
Plasma levels of drug gradually fall as it is absorbed into the ____, _____, _____ ___, etc. Drug _______ reduces the drug concentrations in organs again to restore equilibrium and ____ the action of the drug
heart, brain, kidneys, liver, redistribution, terminate
inactive sites where no measurable biological effect is initiated (e.g. fat and bone)
drug depots/silent receptors
____ binding reduces the concentration of drug at the sites of ______. It results in prolonged drug time in the body
depot, action
Drug clearance depends on (3)
- biotransformation rate, 2. depot binding, 3. storage in fat reservoirs
the range of plasma drug levels that are high enough to be effective, but not so high that they cause toxic or intolerable side effects
therapeutic window
the desired blood concentration of drug achieved when the absorption / distribution phase is equal to the metabolism / excretion phase
steady state plasma level
enzymes on the smooth ER that lack specificity, like cytochrome P450
microsomal enzymes
baseline receptor function in the absence of ligand
constitutive activity
receptor proteins for a given drug or NT have different characteristics in different target tissues
receptor subtypes
The dose of drug that is lethal to 1% of the population compared with the dose that is lethal therapeutically effective in 99% of the population (LD1/ED99)
safety factor index
when tolerance develops after a single administration
acute tolerance
a physiological state in which the body adapts to the chronic presence of a drug and elicits a drug-specific withdrawal syndrome if the drug is abruptly stopped
physical dependence
tasks learned under the influence of a psychoactive drug may subsequently be performed better in the drugged state than in the nondrugged state and vis versa
state dependent learning
enhancement of particular drug effects after repeated administration of the same dose of drug
sensitization
sensitization is ___ dependent, can have ______ effects, and be conditioned; more sensitization in a ____ environment, and persist for long periods of ______
dose, cross-sensitization, novel, abstinence
