psb exam

what is a drug (biologist def)

an exogenous chemical not necessary for normal cellular functioning that significantly alters cells functions (taken in relatively low doses)

define pharmacology

the study of the interactions between a living organism and drugs that affect normal or abnormal biochemical function

drug effect

biochemical and physiological changes that occur as a consequence of drug action

therapeutic effects

desired physiological or behavioral changes produced by the drug

drugs effects can be studied on what two levels

molecular and systemic

define molecular/cellular level drug effects

molecular changes produced by a drug when it binds to a target site

define systemic level drug effects

changes physiological or psychological functions

where can systemic level drugs effect be coming from? ie why is it difficult to study

local or remote drug interactions

example of local vs. remote drug interactions

eye dilation drops and opioids

define specific drug effects

are based on physical and biochemical interactions of a drug with a target site

example of specific drug effects

therapeutic effects, side effects

define nonspecific drug effects

based on certain unique characteristics of the individual (mood, perception, attitudes etc)

examples of nonspecific drug effects

placebo, hawthorne effect, disease progression

describe possible mechanism for placebo effect

belief in a drug may produce real physiological effects despite the lack of chemical activity

why is placebo significant in controlled clinical studies

allows researchers to distinguish between specific and nonspecific drug effects

define pharmacodynamics

interactions of drug with target receptors, cells, tissues (what drug does to body)

define pharmacokinetics

the amount of drug in the blood that is free to bind at target sites or bioavailability (what body does to drug)

how does pharmacokinetics contribute to drug and therapeutic effects

the amount of drug in the body influences the level or intensity of specific drug effects and therefore therapeutic effects

how does pharmacodynamics contribute to drug and therapeutic effects

it is directly causing the drug and therefore therapeutic effects

advantages of oral administration

easily self-administered, low discomfort, safe, economic

disadvantages of oral admin

have to get past first pass metabolism so slower, less bioavailability, and must be resistant to stomach acid

advantages of IV admin

most rapid and accurate method

disadvantages of IV admin

drug can’t be removed from body, requires sterilization, overdose danger

advantages of IM admin

slow and even absorption

disadvantages of IM admin

needs sterilization, localized irritation at injection site

advantages of SC admin

slow and prolonged absorption

disadvantages of SC admin

variable absorption depending on blood flow

advantages of inhalation

large absorption surface, rapid onset, no sterilization needed

disadvantages of inhalation

irritation of nasal passages, lung damage

advantages of transdermal admin

controlled and prolonged absorption

disadvantages of transdermal admin

local irritation, needs to be lipid soluble drug

what is the most important factor of drug bioavailability

rate of drug passage through cell membranes

why are more lipid soluble drugs absorbed into blood and brain easier

they can pass through cell membrane with passive diffusion

what happens to weak acids in alkaline environment ?

they ionize more readily

what happens to weak acids in acidic environment

become less ionized

weak bases in alkaline environment

become less ionized

weak bases in acidic environment

ionize more readily

an ionized drug is..

harder to pass through cell membrane passively

how to design a drug with good BBB permeability ?

non-ionized in plasma, similar structure to endogenous ligand with receptor found in BBB

what happens at drug depots (plasma albumin, muscle, fat)

circulating drug can bind to inactive sites so no drug effect is initiated

therapeutic outcome of rapid binding to depots before reaching target tissue

slower onset and reduced effects

therapeutic effects of competition btwn drugs for depot binding sites

higher-than-expected dose of drug, possible toxicity and risk

therapeutic effect of high drug depot binding in an individual

need higher doses

therapeutic effect of bound drug not being metabolized

stays in system for longer (think THC)

therapeutic effect of drug depot binding after rapid action at targets

rapid termination of drug action

drug elimination is usually first order kinetics which is

exponential and the metabolic rate is conc-dependent

what is half-life

amount of time required for removal of 50% of the drug

a few drugs are eliminated according to zero order kinetics

drugs are cleared at a constant rate (conc-independent) until a certain point

how does zero order kinetics happen?

drugs levels are so high that routes of elimination are saturated (ex more alc than liver enzymes)

where does most biotransformation take place

liver

which enzyme family are responsible for oxidizing most psychoactive drugs?

cytochrome P450 (CYP450)

define phase 1 metabolism

nonsynthetic modification by oxidation, reduction or hydrolysis

define phase 2 metabolism

synthetic reactions requiring combination of drug with a small molecule (sulfate or methyl group)

what is the point of phase 2 metabolism

the products are ionized, less lipid soluble and usually biologically inactive so they are easier to get rid of

define enzyme induction

repeated use of a drug increases number of enzyme molecules therefore faster biotransformation, aka tolerance

cross-tolerance

also speeds biotransformation of other drugs the enzyme acts on

define enzyme inhibition (grapefruit juice)

some drugs inhibit liver enzymes leading to slower biotransformation (prolonged effects or toxicity)

how can drug competition affect inactivation

number of enzyme molecules is limited increasing bioavailability of one drugs and possible toxicity

what is the most important route for drug elimination

kidneys and urine

what is a receptor

something that accepts a ligand

what is a ligand

anything that binds to a receptor

example of surface receptors

dopamine

define intracellular receptor and one example

found in the cytoplasm or nucleus , estrogen

ligand-receptor binding causes — and is —-

change in receptor shape, temporary

agonist

best chemical fit and produce significant biological effect

antagonist

fit receptors and produce no cellular effect

partial agonist

have intermediate efficacy

inverse agonist

initiate a biological effect that is opposite to that produced by an agonist

inverse agonist effects are readily observed in receptors which have

baseline activity

define EDmax

maximum response

define ED50

the dose that produce ½ of a maximal effect

define threshold dose

smallest dose to produce measurable effect

when is ED vs EC used?

EC is only used for in vitro studies, so ED is more applicable for us rn

define TD50

dose at which 50% of population experiences a toxic effect of the drug

define therapeutic index (TI)

TD50/ED50 - margin of safety btwn toxic and desired effects

the more leftward a curves ED50 is on a dose response curve..

the more potent

the higher the ED100 on a dose response curve…

the more efficacy it has

higher affinity

lower dissociation

lower affinity

higher dissociation

define competitive antagonist

drugs that compete with agonists for the same binding site on a receptor (narcan)

define noncompetitive antagonists

bind to the receptor at a different place than agonists and block function

competitive antagonists decrease — why

potency, can reach the max if you outcompete it

noncompetitive antagonists decrease — why

efficacy, can never outcompete because its different sites

physiological antagonism (looks like competitive antagonism)

two drugs reduce the effectiveness of each other but they just cancel out physiologically (histamine and epi)

how do PAMs work

change receptor shape to appeal to the natural substance it responds to

why can PAMs be dangerous?

its allosterically bound so you can’t outcompete it, have to wait out the effects

define drug tolerance

diminished response to a drug after repeated exposure

define drug sensitization

enhancement of a drug after repeated exposure of the same dose

behavioral effects of tolerance

reversible, dependent on dose, frequency and environment, not all drug effects have same tolerance, lots of mechanisms

explain metabolic tolerance (enzyme induction)

more enzymes means less drug available therefore diminished drug effects

explain pharmacodynamic tolerance

changes in a receptor that compensate for repeated use of drug (down or upregulation or desensitization)

explain behavioral tolerance

decrease in impaired behavior by learning process (classical or operant)

explain behavioral sensitization

enhancement of drug effects after repeated same doses

why does the body make compensatory physiological adaptations in response to drugs?

it wants to maintain homeostasis

do all drugs produce all types of tolerance?

no

in pharmacodynamic tolerance will the body up or down regulate against an agonist drug

downregulate

in pharmacodynamic tolerance will the body up or down regulate against an antagonist drug

upregulate

example of classical conditioning in behavioral tolerance

environmental overdose

example of operant conditioning in behavioral tolerance

alcoholics and the peg board

describe the steps of synaptic transmission inside the presynaptic cell

NTs synthesized, AP invades presynaptic terminal, depolarization of presynaptic terminal opens voltage gated Ca2+ channels, Ca2+ goes into cell through channels, Ca2+ causes vesicles to fuse with presynaptic membrane