Basic Pharmacology and Tolerance

Question 1

Drugs

Answer 1

any substance that alters the physiology of the body except food and nutrients

intention of user must be taken into account

Question 2

Psychoactive Drugs

Answer 2

substances that impact the NS to alter mood, perceptions, and level of consciousness

Question 3

Chemical Name

Answer 3

describes a drug’s chemical structure

e.g. 5-ethyl-5-phenyl-1,3-diazinane-2,4,6-trione

Question 4

Generic Name

Answer 4

describes a drug’s chemical structure and similarity to other drugs in its class

stem-; -stem-; -stem

e.g. pheno-barb-ital is a part of the sedative/hypnotic barbituates

Question 5

Excipients

Answer 5

fillers, colouring agents, binding agents, flavours, preservatives, coating, etc.

affect absorption and distribution of drugs
-different formulations with the same active
ingredient may not be equally effective

Question 6

Trade Name

Answer 6

for marketing a drug

refers to the drugs active ingredients and excipients

always capitalized

belongs to a company

e.g. Luminal (Bayer)

Question 7

Street Name

Answer 7

selling names for recreational drugs

e.g. purple hearts, goof balls

Question 8

How are dosages described?

Answer 8

ratio of the amount of drug per body weight

e.g. mg/kg

a certain concentration is needed for an effect to be present; taking more doesn’t increase the therapeutic benefit but can increase/add side effects

Question 9

Dose-Response Curves

Answer 9

describe the level of drug effect by dose

horizontal axis represents dosage
vertical axis represents either the percent effect or the percent of subjects showing response

measures one effect at a time

Question 10

Efficacy

Answer 10

maximum response a drug is able to produce

e.g. Aspirin and Morphine both have analgesic effects, but Morphine is much more effective

Question 11

Potency

Answer 11

the dosage of a drug required to produce a particular response

Question 12

ED50

Answer 12

dose at which 50% of an effect is observed or dose at which the effect is present in 50% of subjects

a lower ED50 means a higher potency

Question 13

LD50

Answer 13

dose at which 50% of subjects die

represented on lethality dose-response curves

Question 14

Therapeutic Index

Answer 14

ratio of a drug’s lethal dose-effect to its therapeutic dose-effect value

Standard: LD50/ED50
Ideal: LD1/ED99

Generally speaking, the higher the TI, the safer the drug

Question 15

Drug Interactions

Answer 15

when you add a second drug in the mix, you could increase or decrease the effects of the first drug

Question 16

Potentiation

Answer 16

lowering the ED50 of a drug

raising a drug’s potency

Question 17

Antagonism

Answer 17

raises the ED50 of a drug (lowers potency)
and/or
reduces the efficacy of a drug (lowers max. effect)

Question 18

Primary Effect

Answer 18

the intended effect(s) of a drug

the reason a drug was taken

Question 19

Side Effect

Answer 19

any effect produced unintentionally by the administration of a drug

not necessarily negative

Question 20

Pharmacokinetics

Answer 20

the study of how drugs move into, get around in, and are eliminated from the body

Question 21

Absorption

Answer 21

the entry of a drug into the circulatory system

Route of Administration (RoA) has major effect on absorption

    - it impacts the # of membranes the drug has to pass through
    - since most drugs are hydrophilic, they cannot utilize simple diffusion to pass through membranes

Question 22

Parenteral Administration

Answer 22

injection through the skin into various parts of the body

farther subdivided depending on specific point in body where bolus is left by needle
e.g. intravenous, subcutaneous, intraperitoneal, intramuscular, intracerebral, etc.

Question 23

Vehicle

Answer 23

the liquid into which a drug is dissolved/suspended

necessary because most drugs are naturally powders

injected to form a bolus

Question 24

Rate of Absorption (Parenteral Administration)

Answer 24

determined by…
volume of blood flow (can be increased with heat and exercise)
richness of capillary supply (drug must pass through capillary walls by diffusing through intercellular gaps/fenestrations to enter circulation)

Question 25

Depot Injections

Answer 25

drug is dissolved in a high concentration of viscous oil and then injected into muscle drug slowly diffuses from the oil into the body fluids over a long period of time used for drugs that need to be taken continuously or chronically to prevent symptoms from reappearing (e.g. antipsychotics)

Question 26

Inhalation

Answer 26

RoA lungs are high surface area gas exchange system with a direct connection to the heart and brain inhalation is regulated by diffusion and can thus be controlled with precision when ash, vapour, or smoke make contact with surface of lungs, the drug dissolves and diffuses into the blood

Question 27

Difference between smoke and gasses

Answer 27

drugs in smoke particles will not revapourize when dissolved in blood they cannot be exhaled and must be eliminated by alternative means

Question 28

Challenges with Oral Administration

Answer 28

low stomach pH can destroy some drug molecules liver enzymes can break down drug molecules these two combined are an example of First Pass Metabolism

Question 29

First Pass Metabolism

Answer 29

a phenomenon in which the concentration of a drug in the body will be greatly reduced before it reaches general circulation

Question 30

Oral Absorption and pH

Answer 30

an acidic molecule carries a charge, if it is protonated it becomes neutral a basic molecule on its own is neutral, if it is protonated it carries a positive charge the pH of the GI tract is acidic, and as such basic drugs do not absorb well from it acidic drugs absorb well from an acidic environment and vice versa

Question 31

PKa

Answer 31

the pH of the solution at which 50% of drug molecules will be ionized

Question 32

Distribution

Answer 32

passage of a drug through the body | impacts a drug's bioavailability

Question 33

Bioavailability

Answer 33

the ability of a drug to reach its intended site of action for psychoactive drugs; the drug's ability to reach the brain drugs cannot produce desired effects if they can't get to where they need to be

Question 34

Factors that affect drug distribution

Answer 34

``` Lipid solubility Ion trapping Distribution to CNS (central nervous system) Active/passive transport Protein binding The placental barrier ```

Question 35

Lipid Solubility

Answer 35

hydrophilic substances cannot use simple diffusion to get through membranes; lipid soluble drugs can if a drug is extremely lipophilic it will stay in a lipid, meaning it doesn't reach the site of action at least not quickly (this is the principle behind depot injections)

Question 36

Ion Trapping

Answer 36

weak acids ionize in basic solutions, weak bases ionize in acidic solutions once a drug is ionized on one side of a membrane, it cannot diffuse back across happens where different pHs are separated by a membrane e.g. GI Tract/Blood or Blood/Urine

Question 37

Blood-Brain Barrier

Answer 37

protects the brain from harmful substances in the circulatory system there are no pores in the capillary endothelial cells (tight junctions instead) - makes simple diffusion impossible for non-lipid-soluble drugs astrocytes extend processes that wrap around capillaries creating an extra layer of membrane through which to pass - makes it harder for lipid-soluble drugs to diffuse

Question 38

Active and Passive Transport

Answer 38

transport mechanisms needed depend on solubility, concentration gradient, and electrostatic pressure

Question 39

Simple Diffusion

Answer 39

passive transport moves down concentration gradients possible for lipid-soluble or small, uncharged molecules

Question 40

Channel Proteins

Answer 40

passive transport mechanism filled with water allow water-soluble molecules in

Question 41

Carrier Proteins

Answer 41

passive transport mechanism molecule that cannot diffuse binds to a transmembrane protein protein flips conformation to allow molecules to cross membranes

Question 42

Active Transport

Answer 42

utilizes carrier proteins | requires energy input to move substances against their electrochemical gradients

Question 43

Protein Binding

Answer 43

some drug molecules have an affinity for plasma proteins in blood while bound to a protein, the drug is unavailable reduces the concentration of usable drug in the body at any given time can be impermanent

Question 44

Placental Barrier

Answer 44

similar to blood-brain barrier usually ineffective against psychoactive drugs concentration in fetus can be equal to mother's bloodstream

Question 45

Drug Metabolism

Answer 45

process of converting drugs into metabolites most often takes place in the liver with the helpy of Cytochrome P450 Enzymes purpose is to make drugs more water-soluble and/or more likely to ionize to make it easier to extrete from kidneys

Question 46

Factors that alter Drug Metabolism

Answer 46

depression of enzyme systems stimulation of enzyme systems age (systems slow with age) species (smaller species tend to have faster metabolisms)

Question 47

Elimination

Answer 47

prepping/removing the drug from the body | mostly done using the kidneys

Question 48

Pharmacokinetics

Answer 48

the study of how drugs move into, get around in, and are eliminated from the body

Question 49

Function of the Kidneys

Answer 49

filter everything out of the blood and selectively reabsorb what is required via diffusion and active/passive transport unless reabsorbed by special transport systems, ionized or non-lipid-soluble drug molecules will be excreted

Question 50

Nephron

Answer 50

the basic functional unit of the kidney

Question 51

Peritubular Capillaries

Answer 51

capillaries responsible for reabsorption and secretion

Question 52

Afferent Arterioles

Answer 52

provide blood supply to nephrons

Question 53

Efferent Arterioles

Answer 53

how blood leaves nephrons after filtration

Question 54

Bowman's Capsule

Answer 54

where filtered blood goes

Question 55

Renal Tubule

Answer 55

leads to collecting duct, from which filtered substances will be excreted in urine

Question 56

pH of Urine

Answer 56

Acidic (approx. 6.0) while blood is basic basic metabolites become ionized and remain in urine (unable to diffuse) while acidic metabolies concentrate in the blood if sodium bicarbonate is taken to alkalinize urine, more basic drugs such as barbiturates may be reabsorbed

Question 57

Half-Life

Answer 57

the amount of time it takes to reduce the concentration of a substance in the blood by half

Question 58

First Order Kinetics

Answer 58

100%-50%-25%-12.5% etc. over consecutive and consistent time intervals usually takes 5-6 half lives of drugs that reduce via first-order kinetics to eliminate the drug from the body creates a curve

Question 59

Zero Order Kinetics

Answer 59

some drugs (e.g. alcohol) are eliminated at a constant rate (e.g. 15 mg/ 100mL blood/ hr.) creates a linear graph

Question 60

Elimination Rate

Answer 60

amount of drug eliminated from the body over time typically occurs in half-lives as demonstrated by first order kinetics determines how long a drug's effects will last (i.e. how frequently meds should be taken to produce a steady state... want to maintain a high enough concentration to be effective but not high enough to have adverse effects)

Question 61

Combining absorption and elimination rates

Answer 61

rapid absorption=rapid elimination slower absorption=longer-lasting effects

Question 62

Therapeutic Window

Answer 62

the range of blood concentrations of a drug between the level that it is minimally effective and the level that has adverse side effects (between therapeutic and toxic levels)

Question 63

Mechanisms of Tolerance

Answer 63

3 mechanisms by which tolerance develops Pharmacokinetic tolerance Pharmacodynamic tolerance Behavioural tolerance

Question 64

Tolerance

Answer 64

decreased effectiveness or potency of a drug that results from repeated administrations or the necessity of increasingly large doses of a drug to maintain its effectiveness after repeated administrations

Question 65

How tolerance works

Answer 65

some effects of a drug develop tolerance more quickly than others, some do not develop tolerance at all the tolerance develops to drug effects not the drug

Question 66

Other relevant factors that affect tolerance

Answer 66

functional disturbances cross tolerance acute tolerance

Question 67

Pharmacokinetic tolerance

Answer 67

increase in the rate or ability of the body to metabolize a drug, resulting in fewer drug molecules reaching their intended site of action results from enzyme induction

Question 68

Enzyme Induction

Answer 68

increasing number or activity of enzymes | reduces all drug effects because less of the drug reaches its site of action

Question 69

Homeostasis

Answer 69

the ability of a living organism to keep conditions inside it the same despite any changes in the conditions around it maintained via feedback loops

Question 70

Pharmacodynamic tolerance

Answer 70

arises from adjustments made by the body to compensate for an effect of the continued presence of a drug - result of homeostasis if a drug is repeatedly administered, the body gets better and better at restoring normal function and diminishing the disruptive effects of the drug

Question 71

Up/downregulation of receptors (Pharmacodynamic Tolerance)

Answer 71

Neurotransmitters (NTs) work on NT receptor proteins - the neuronal response depends on the presence of receptors If there is more communication desired, more receptors may become available (upregulation) and the opposite can also occur (downregulation) Many psychoactive drugs mimic NTs and therefore can influence receptor population

Question 72

Behavioural Tolerance

Answer 72

through exposure with a drug, an organism can learn to decrease the effect that the drug is having through operant and classical conditioning aka learned tolerance

Question 73

Classical Conditioning

Answer 73

the association of an unconditioned response with a stimulus to create a conditioned response NS+US=UR CS=CR

Question 74

Operant Conditioning

Answer 74

association of a voluntary behaviour with a consequence (reward or punishment)

Question 75

Acute Tolerance

Answer 75

with some drug effects, the effect can be greater at a given blood level during absorption than it is at the same blood level during elimination this does not require repeated administrations e.g. alcohol: you are more intoxicated during the absorption

Question 76

Brain Mechanisms responsible for Sensitization

Answer 76

there is no single neuronal effect responsible mesocorticolimbic dopamine (DA) system - general motivation system - responsible for reinforcement

Question 77

Functional Disturbances

Answer 77

physiological disruptions alone are not sufficient to cause tolerance, the change must be MEANINGFUL e.g. amphetamine supresses appetite in rats, but if a rat is starving and food is available it will develop a tolerance to this effect. if no food is available this tolerance will not develop

Question 78

Sterotypies

Answer 78

repetitive or ritualistic movements, postures, or utterances e.g. body rocking, self-caressing, etc. can be induced by amphetamine consumption repeat administrations of dosages causing only behavioural activation will cause stereotyped behaviour

Question 79

Sensitization

Answer 79

in some circumstances an effect of a drug can increase with repeat administrations seen primarily with drugs that at high doses cause stereotypies

Question 80

Withdrawal

Answer 80

physiological symptoms/changes that occur when the use of a drug is stopped or the dosage is decreased symptoms may vary in intensity drugs of the same family tend to produce ssimilar symptoms can be stopped by giving the drug or one of the same family

Question 81

Dependence

Answer 81

a state in which withdrawal symptoms occur when drug use stops physiological state does not equal addiction

Question 82

Cross Tolerance

Answer 82

tolerance to one drug diminishes the effects of another e. g. by acting on the same receptors or processed by the same enzymes e. g. alcohol and sedatives

Question 83

Opponent Process Theory

Answer 83

views withdrawal symptoms as a compensatory adjustment made by homeostatic mechanisms to a drug effect after repeat exposure with the repeat administration of a drug, the body changes its functioning when a drug is discontinued and its effects disappear it takes the body some time to readjust to the drug's absence (withdrawal occurs) A-process (euphoric drug effect) B-process (dysphoric homeostatic mechanism) Over time, the user requires more of a drug to feel normal because the B-process acts more quickly and increases in magnitude

Question 84

Placebo Effect

Answer 84

inert substances can improve a patient's condition because the patient expects them to help

Question 85

Nocebo Effect

Answer 85

inert substances/suggestions of them can have a negative effect on a patient if they expect it to psychogenic in nature but can cause real and measurable physiological changes

Question 86

Top-down processing

Answer 86

voluntarily engaged, higher abstract modalities of thought and expectations coloured by perceptions

Question 87

Bottom-up processing

Answer 87

stimuli reaching receptors