Ch1 Pharmaco Basics

Question 1

neuropharmaco, psychopharmaco, and neuropsychopharmaco

Answer 1

neuropharm = drugs on nervous system
psychopharm = drugs on beh’r/mood
neuropsychopharm = drugs on nervous to alter beh’r/mood

Question 2

psychoactive drugs 5 kinds

Answer 2

act on brain
CNS stimulants (cocaine/nicotine)
CNS depressants (alcohol/barbiturates)
Analgesics (pain relief morphine)
Hallucinogens (LSD/psilocybin)
Psychotherapeutics (prozac/thorazine)

Question 3

What is a drug’s action vs drug’s effect

Answer 3

action = molecular changes produced when binding to target site
ex: L-dopa is converted to DA
effect = the effects the molecular change (action) has on physical/psych processes
ex: L-dopa increases DA in striatum = improved motor function

Question 4

Therapeutic vs side effects

Answer 4

therapeutic = desired changes from drug-receptor interaction (phys. and beh’r)
ALL OTHER EFFECTS ARE SIDE

Question 5

Specific vs non-specific effects

Answer 5

Specific = based on the phys/biochem interactions of drug and target site (therapeutic and side effects)
Non-specific = not based on drug/receptor interaction (PLACEBO EFFECT, no chem activity but still effects)
emphasizes the need for double-blind experiments to test drug effects vs placebo

Question 6

pharmacokinetics vs pharmacodynamics

Answer 6

kinetics = what body does to drug (RABIE)
dynamics = what drug does to body

Question 7

bioavailability and 5 factors of it

Answer 7

bioavail = conc. of drug that is free to bind to target RABIE
Route of Admin
Absorption/Distribution (speed due to how much bloon in area eg. faster to brain)
Binding
Inactivation
Excretion

Question 8

2 main types of admin route and biggest hurdle

Answer 8

Enteral (GI tract= oral/rectal)
Parenteral
influences how much/quickly drug reaches target

Drug must move from site of admin to blood (absorption), unless IV it must cross semi-impermeable membrane to blood

Question 9

ORAL (PO) route and 1st-pass metabolism

Answer 9

drug pass through stomach/intestine wall
undergoes first-pass metabolism = passed to liver and is chemically altered from CYP450 enzymes that REDUCE BIOAVAIL of drug
rate of gastric emptying = food slows movement of drugs into intestine (stay longer in stomach). most absorption in small intestine (more SA/slower/more permeable), empty stomach thus speeds absorption

Question 10

inhalation route

Answer 10

direct from lungs to brain through heart
rapid absorption (many capillaries)
rapid effect on brain seconds

Question 11

Intravenous IV

Answer 11

passes to heart, lungs, heart again to brain
most rapid and accurate

Question 12

Intranasal

Answer 12

local effects: nasal passage
systemic effects: moves across single epithelial layer into blood to brain! immediate
BYPASS blood-brain barrier - ‘olfactory transfer’, direct access to CSF via olfactory nerve pathways
“insufflation” = snorting

Question 13

gene therapy route admin

Answer 13

application of DNA encodes protein (CAR-T cell therapy, mRNA vaccines)

Question 14

most important factor in plasma drug levels

Answer 14

rate of passage through cell membranes
route admin alters absorption into bloodstream

Question 15

lipid solubility and ionization rules of thumb

Answer 15

lipid soluble = pass through membranes passive diffusion down conc. gradient (want high lipid solubility to get to brain)
MOST DRUGS NOT LIPID SOLUBLE
ionization depends on pH and pKa
most drugs are weak acids/bases
weak acids ionize in basic
weak bases ionize in acidic
IONIZED ARE POORLY ABSORBED IN GI (CANT BE GIVEN PO).
IONIZED CANT CROSS MEMBRANES (stuck)

Question 16

aspirin story and ionization

Answer 16

aspirin is a weak acid
in stomach (high acid) it is non-ionized and thus lipid-soluble, absorbed into blood.
reaches blood (weak basic), becomes ionized and stuck in circulation to body (no back-absorb)
when aspirin reaches intestine (weak acid), ionized, slower passage to blood than when in stomach
if take antacid (basic), aspirin becomes ionized and isn’t absorbed to blood when in stomach

Question 17

blood brain barrier differences

Answer 17

normal capillaries have pores
BBB has no openings (so molecules must be lipid-solube)
separates brain capillaries and brain/csf
functions are protect/shield/maintain
some areas not isolated (circumventricular organs CVOs = area postrema of medulla (chem trigger zone to vomit), median eminence of hypothal)
need lipid-soluble to cross ex: L-dopa instead of dopa, or imodium with helper drug to move it across

Question 18

placental barrier and teratogens

Answer 18

separates mother and fetus blood
newborns don’t have all necessary enzymes to metabolize drugs
neonatal absitence syndrome = withdrawl in infants due to mother’s drugs
teratogens = drugs that induce devo abnormalities, accutane and thalidomide

Question 19

drug depots what is and effects of it

Answer 19

binding at inacitve sites, no effect (plasma proteins, muslce, fat)
affects magnitude and duration of drug
REDUCE conc./effect (can terminate action)
DELAYS effect (drug testing, remains in body)
individual variabilty in drug response

Question 20

depot binding selectivity and termination

Answer 20

depot binding is nonselective - drug remains in body for long time. drugs compete for same binding sites can lead to OVERDOSE
responsible for TERMINATION of drug action - rapid redistribution from brain to fatty tissue (inacitve site) to bind, anesthetics sequester in fat = rapid acting/short duration

Question 21

biotransformation and two types of elimination rates

Answer 21

metabolism
process by which drugs elimination/excreted
first-order kinetics = exponential
zero-order kinetics = linear

Question 22

first order kinetics

Answer 22

most drugs
CONSTANT FRACTION ELIMINATED per time unit (ex 50% per hour)
proportional to drug conc.
RATE IS CONC.-DEPENDENT (slows as time goes on)
plasma half life = amt time for 50% drug removal from blood. about 5 half lives

Question 23

steady state and therapeutic goal

Answer 23

steady state -> absorption/distribution = metabolism/excretion
therapeutic goal -> maintain conc. of drug at a constant level

Question 24

zero-order kinetics

Answer 24

rare
molecules cleared at constant rate, linear
because metabolism routes are saturated
becomes first order at very end when levels go under saturation level
RATE IS CONC.-INDEPENDENT
ex: alchohol

Question 25

where most biotrans and goal/two major types

Answer 25

liver. goal = produce inactive, water soluble (ionized) metabolites., return to circulation for kindey excretion TYPE 1 = Phase 1 (CYP450 enzymes). Non synthetic using Oxidation (most), reduction, hydrolysis. could produce a metabolite that is MORE ACTIVE than drug itself (psylocibin metab. into active) TYPE 2 = Phase 2 (non-cyp enzymes). synthetic requires conjugation. ex: glucuronide conjugation can undergo both phases/mulitple

Question 26

microsomal enzymes

Answer 26

liver enzymes that metab. drugs LACK specificity cytochrome p450 family only 6 ARE RESPONSIBLE FOR 90% OXIDATION OF DRUGS, phase 1

Question 27

4 influences on biotrans

Answer 27

1. enzyme induction 2. enzyme inhibition 3. drug competiton 4. individual diffs (age gender genes of metab. enzymes)

Question 28

enzyme induction

Answer 28

influence on biotrans repeat drug = MORE enzymes = MORE BIOTRANS leads to drug cross/tolerance, LOSE DRUG EFFECTS

Question 29

enzyme inhibition

Answer 29

biotrans influence drug INHIBITS ENZYME = REDUCE METAB. of other drugs too ex: monoamine oxidase inhibitors prevents breakdown of tyramine = hypertension from too much tyramine in cheeses

Question 30

drug competiton

Answer 30

biotrans influence lots of one drug = LOWER METAB. OF SECOND DUE TO ENZYME COMPETITION alcohol plus sedative = BAD, compete for same enzyme, OD on one

Question 31

excretion

Answer 31

urine is most important route kidneys flter water soluble ionized molecules water is reabsorbed in kidneys, makes drug conc. HIGH in tubules, could be reabsorbed into blood due to gradients, BUT ionization reduces reabsorb, pH dependent (can change pH of urine)

Question 32

ligand-receptor binding interaction

Answer 32

most binding is temporary reversible (nerve gas is permanent) NTs bind and release many times for effects receptors have specificity for ligands due to shape receptors can have many subtypes throughout body (5-HT in diff locations)

Question 33

Receptor agonist vs antagonist

Answer 33

agonist = best fit (best affinity) antagonist = also has affinity/fit, but prevents active ligands from binding. no effect

Question 34

partial agonist, inverse agonist, indirect agonist

Answer 34

partial - meh efficacy at max binding inverse = opposite effect to agonist indirect = enhances release/effect of drug but doesnt bind to receptor itself

Question 35

up/down regulation

Answer 35

receptor proteins have dynamic life cycle and #/sensitivity can change up regulation = inc. # receptors due to absence of ligands or chronic antagonism down regulation = dec. # receptors bc chronic activation

Question 36

threshold dose

Answer 36

smallest dose for a measurable effect

Question 37

Emax

Answer 37

efficacy, max response achieved by a drug. assumes all receptors are saturated

Question 38

ED50

Answer 38

50% effective dose dose that produces half Emax for indivdual or dose at which 50% population responds

Question 39

TD50

Answer 39

50% toxic dose dose at which 50% population experiences a toxic effect

Question 40

therapeutic index

Answer 40

TI = TD50/ED50 higher number is better, means larger quantity needed for toxicity

Question 41

Potency

Answer 41

absolute amount of drug required to produce a specific effect. Comparing ED50s of drugs show differences in potency (further right = less potent) If linear portion of dose response curve is parallel, drugs work in same mechanism

Question 42

Affinity and Kds

Answer 42

tenacity with which drug binds to receptor rates of dis/association are compared to get estimate of affinity. Disassociation constant Kd High affinity = low Kd, readily bind, slowly release Low affinity = high Kd, slowly bind, quickly release

Question 43

competitive antagonists and dose response curves

Answer 43

bind reversibly to the same receptor as antagonist (competes) and does NOT produce effects Shifts the curve right of OG drug bc need more of it now to outcompete

Question 44

Partial agonist and dose response curve

Answer 44

drugs produce a lower response at saturation than normal agonist. Not due to decreased affinity, just bc weaker activity at receptor Partial agonist dose curve will be shorter (not reach same Emax as og drug) Agonist curve in presence of partial agonist is shifted right bc must outcompete it

Question 45

Non-competitive antagonist

Answer 45

binds at allosteric site (non-competitive) inside receptor reduces magnitude of max response (Emax) of any amount of agonist effects CANNOT be negated no matter how much agonist Shifts dose curve right and shorter (will never reach same Emax and still needs more to do an effect) For both allosteric binding (noncomp) and irreverisble comp. antagonist at orthosteric site (actual receptor site, bc now can't do as many receptors if irreversible so lower Emax, and shifted right)

Question 46

3 biobeh'r interactions of multiple drugs

Answer 46

Physiological antagonism = like wave destruction. Positive A plus negative B = smaller positive effect Additive effects = like wave constructive. Positive A + Positive B = big positive equal to parts Potentiaion = whole is bigger than sum. Positive A + Positive B = HUGE positive effect bigger than individual additive

Question 47

tolerance

Answer 47

diminshed response to a drug after repeat exposure

Question 48

cross tolerance

Answer 48

tolerance to drug A diminishes effect of Drug B that's in the same class

Question 49

Metabolic Tolerance

Answer 49

repeat drug reduces amt of drug available at target tissue this is due to enzyme induction (more enzymes = more metabolism/biotrans = less drug)

Question 50

Acute tolerance

Answer 50

decrease in response after single exposure of drug in alcohol occurs independently of BAC after single administration. during increase of BAC, effects more severe than during elimination even if BAC constant

Question 51

Pharmacodynamic tolerance

Answer 51

changes in nerve cell function to compensate for continued pre/absence of drug for homeostasis (up/down regulation)

Question 52

Behavioral tolerance

Answer 52

tolerance in same environment reduced tolerance in novel environment

Question 53

Pavlovian conditioning

Answer 53

food = ucs saliva = ucr bell = neutral stimulus train bell = cs saliva = cr "needle freak" sight of a needle (cs) induces euphoria (cr) for addicts

Question 54

operant skinner conditioning

Answer 54

plays part in beh'r tolerance too repeated reinforcement/exposure, compensate drug changes in beh'r ex: functional alcoholic rewarded for acting normal

Question 55

state-dependent learning

Answer 55

tasks learned while doing drug are better if do drug again than doing in non-drug state (take exams in same lecture hall)

Question 56

Sensitization

Answer 56

reverse tolerance enhancement of effects after repeat drug (shifts dose curve LEFT!) some drugs induce tolerance for some effects and sensitize others (opioids tolerance analgesia, sensitize constipation)

Question 57

pharmacogenetics

Answer 57

study of genetic basis of drug response variability of individuals. goal to identify genetic factors of the side effect susceptivility or predict therapeutic response

Question 58

genetic variation for drugs

Answer 58

variation in drug-metab. enzymes = need to adjust dosage. low metab. need less drug (more sticks around) high metab. need more drug (less sticks around) genetic polymorphisms also influence drug sites like receptors/transported/intracellular signaling