Topic 1: Pharmacology and Pharmacokinetics

Question 1

What is neuro-psychopharmacology?

Answer 1

the study of the actions of drugs on the central nervous system and their subsequent effects on human behavior

Question 2

What are drug actions?

Answer 2

specific molecular changes resulting from drug binding to a target site or receptor

Question 3

What are drug effects?

Answer 3

widespread alterations in physiology or psychology resulting from drug actions

what the drug does to behavior

Question 4

What is therapeutic effects?

Answer 4

drug-target interactions producing the desired physiological or behavioral changes

what the goal of the drug is

Question 5

What are side effects?

Answer 5

all other drug effects

any other effect that is not the goal

means you can use some drugs for different therapeutic effect

Question 6

What are adverse effects?

Answer 6

undesirable or harmful drug effects

Question 7

What are specific effects?

Answer 7

occur as a result of biochemical interactions between drug and target receptor

Question 8

What are nonspecific effects?

Answer 8

occur as a result of interactions beyond the receptor (e.g., lipid membranes, fluid compartments)

may occur as a result of unique characteristics of an individual or an individual’s state

not the drug binding directly caused by chain reaction secondary effects

Question 9

What is a placebo effect?

Answer 9

measurable therapeutic effect of a treatment without specific activity for the respective condition

affected by expectancy and conditioning

Question 10

In what way is the placebo effect a confound in neuropsychopharmacology?

Answer 10

antidepressants have efficacy of ~50-70% in major depression

placebo is effective in 20-30% of cases

during development fluoxetine (Prozac) had to endure 5 clinical trials to achieve 2 showing significantly better response than placebo

Question 11

What is the classic experiment on ulcer patients given placebo?

Answer 11

group A given placebo by physician who assured the medication would give relief (efficacy of 70%)

group B given placebo by nurse who described it as experimental in nature (efficacy of 25%)

Question 12

What is pharmacokinetics?

Answer 12

the dynamic factors contributing to the bioavailability and efficacy of drugs in the human body

provides performance guidelines for efficacy and efficiency of drug use in clinical settings

Question 13

What are the principal of pharmacokinetics?

Answer 13

absorption: administration and absorption of the drug into body fluids

distribution: dispersal of drug through body fluids to the target tissues of the body; depot binding in bodily fluids and non-target tissues

metabolism: biotransformation or inactivation of drugs in the body into metabolites

excretion: removal of substances or metabolites from the body

Question 14

What are the routes of administration?

Answer 14

oral administration
intravenous
intramuscular
subcutaneous
inhalation
topical
sublingual (below the tongue)
transdermal (e.g. nicotine patch)

Question 15

What routes of administration are only used in experimental studies?

Answer 15

intraperitoneal (IP)
intracranial
intracerebroventricular
intracisternal

Question 16

What is oral administration?

Answer 16

most convenient

safe self administration

first-pass effect

blood-brain barrier (BBB) affects usefulness for neuropharmacology

Question 17

What is the first-pass effect?

Answer 17

blood flow from stomach/intestines goes directly to the liver for detox

oral route has greatest breakdown of drug

Question 18

What is delivery to cerebral spinal fluid?

Answer 18

epidural, intracranial, intracerebroventricular or intracisternal most direct way to access the CNS

bypasses liver and BBB

highly invasive

effectively for experimental use only

slow steady release possible with implantable shunts or osmotic minipump

Question 19

What is drug absorption?

Answer 19

movement of drug from the site of administration to the circulatory system

largely dependent on passive diffusion through biological membranes

Question 20

What is drug absorption affected by?

Answer 20

drug concentration: affected by age, sex, body, size, body fat content

breakdown by metabolic or digestive processes

solubility and ionization of drug

Question 21

What are polar molecules?

Answer 21

water soluble

hydrophilic (loves water)

lipophobic (fears fat)

polar molecules are freely transported through aqueous compartments (e.g., blood, CSF, ECF)

Question 22

What are non-polar molecules?

Answer 22

lipid soluble

hydrophobic (fears water)

lipophilic (loves fat)

non-polar molecules freely diffuse across semi-permeable membranes (e.g., intestinal wall, BBB, cell membranes)

Question 23

How is absorption dependent on drug polarity?

Answer 23

non-polar, lipid soluble drugs can freely diffuse across cell membranes

passive diffusion down concentration gradients

non-polar molecules ted to be less soluble in water

polar or charged (ionized) drugs are prevented from diffusing through membranes

many orally administered drugs are weak acids or bases - gaining or losing charges based on the pH of the external environment

Question 24

What are the factors affecting drug absorption?

Answer 24

intrinsic properties of the drug: polarity, solubility, pKa

pH of body compartments

surface area of body compartments: stomach has a relatively small surface are (slow absorption), intestine have relatively large surface area (fast absorption) and are the site of most (oral) drug absorption

Question 25

What is drug distibution?

Answer 25

once in the bloodstream drugs circulate to the entire body within minutes drug concentration is highest in tissues with greatest blood flow (heart, brain, kidney, liver) peripheral capillaries are highly porous allowing ready distribution of drugs (lipophilic or hydrophilic) into tissues blood-brain barrier permits passive diffusion of only lipophilic drugs

Question 26

What is the blood brain barrier?

Answer 26

peripheral capillaries are porous, allowing hydrophilic drugs to freely enter tissues brain capillaries are coupled by tight junctions and lined by astrocyte endfeet creating a highly impermeable barrier

Question 27

How do drugs cross the blood brain barrier?

Answer 27

the blood brain barrier limits access to 98% of small molecule pharmaceuticals (and 100% of large molecule pharmaceuticals) passage of solutes through the BBB often occurs at specific transporters (e.g. glucose and amino acid transporters) some drugs are actively removed from the ECF by efflux transporters (i.e. p-glycoprotein, a.k.a.multidrug resistance protein-I)

Question 28

What are the permeable sites of the blood brain barrier?

Answer 28

chemoreceptor trigger zone hypothalamus

Question 29

What is the chemoreceptor trigger zone (CTZ)?

Answer 29

of the medulla (area postrema - vomit centre) allows direct detection of toxins in the blood

Question 30

What is the hypothalamus?

Answer 30

allows direct access to capillaries for secretion of neurohormones and hormone-releasing factors

Question 31

What is the placental barrier?

Answer 31

the placenta creates a similar selective barrier (unique to pregnant mammals) drugs (licit and illicit), alcohol, gaseous anesthetics, and gases (e.g. carbon monoxide) readily cross the placental barrier and can cause acute toxicity or teratogenic effects to the fetus

Question 32

What is depot binding?

Answer 32

drug depots are inactive drug binding sites with no measurable biological effect: adipose tissue (lipid-soluble drugs), muscle tissue, albumin (plasma protein) decreases circulating drug concentration prolongs drug action: can function s reservoirs for drug release, protects stored drug from metabolism can explain individual differences in drug efficacy

Question 33

What is drug metabolism?

Answer 33

biotransformation and elimination affects bioavailability metabolism occurs primarily in the liver under control of microsomal enzymes cytochrome P450 family (CYP - 57 in total) oxidize the majority of psychoactive drugs metabolism is a non-specific detoxification process that occurs in two distinct types or phases

Question 34

What is type I metabolism?

Answer 34

non-synthetic modifications oxidation, reduction, and hydrolysis

Question 35

What is type II metabolism?

Answer 35

synthetic modifications conjugation with glucuronide, sulfate, or methyl groups

Question 36

What is biotransformation?

Answer 36

type I metabolism during first pass can produce active metabolites of the pharmaceutical preparation of drugs metabolic products (active and inactive) are returned to circulation from the liver and can reach target sites of action or sites for excretion (kidneys, biliary, or facial excretion)

Question 37

What is simvastatin (Zocor)?

Answer 37

pharmaceutical preparation is the lactone form - hydrophobic simvastatin is hydrolyzed in the liver to the bioactive acid form

Question 38

What are the factors influencing metabolism?

Answer 38

enzyme induction enzyme inhibition drug competition individual differences

Question 39

How does enzyme induction influence metabolism?

Answer 39

repeated use results in increase in liver enzymes accelerates rate of biotransformation of all drugs metabolized by a given enzyme (contributes to tolerance and cross tolerance)

Question 40

How does enzyme inhibition influence metabolism?

Answer 40

drugs targeting enzymes (e.g. monoamine oxidase inhibitors - MAOI) decrease their own clearance and other drugs

Question 41

How does drug competition influence metabolism?

Answer 41

competition for enzymes may prevent some drugs being metabolized in a safe fashion

Question 42

How do individual differences influence metabolism?

Answer 42

genetic polymorphisms have been identified in metabolic enzymes different individuals have different rates of clearance for drugs

Question 43

What is drug excretion?

Answer 43

routes of excretion include breath, sweat, saliva, feces, breast milk and urine primary means is filtration by kidney and excretion through urine most drugs are excreted by first-order kinetics: exponential elimination - constant fraction removed in a given time very few drugs removed by zero-order kinetics (constant rate)