Chapters 2 & 6 (Textbook Notes)

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18 Feb 2011
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PSYC62: Drugs and the Human Brain
Midterm Notes (Chapters 2 & 6)
Professor Suzanne Erb
Chapter #2: Basic Principles of Pharmacology
- WÇZ}o}P]o((}(ÇZ}}]µPv}vW]v[l]vPUZ}ÁµPZvP]À]]]vE^U
route of administering drug, amount of drug administered, how frequently drug is taken, etc.
- Drug = no specific/medical definition
o Any substance used in chemistry/medical practices
o Any agent used in medicine or ingredients in medicine
o Narcotic agent or illicit substance
o General def = chemical that affects 1+ biological processes t but not all substances that affect biological
processes are considered drugs (e.g. carbs, vitamins, nutrients, etc.)
- ^X:}Zv[t}A]Çµouv}(vµZov]vt not classified as a drug tho
~o}Z}olZv}ovv]}]vv[}v]ZµP[]Z
- Chemicals originating/produced w/in organism used to carry out normal biological functions in body not usually
o](]ZµP[
o Known as endogenous substances (drugs = exogenous substances)
- Drug = nonfood chemical that alters 1+ normal biological processes in living organism
- Drug dose = quantity of drug administered at 1 time t unit of drug/body weight of org (e.g. mg/kg)
- Drug dosage = administrations of drug/unit of time (e.g. 10 mg/kg 4xday for 3 days)
Drug Effects
- Pharmacodynamics = biochemical and physiological effects of drugs and mechanisms of action
- Drugs act at specific site in body = receptors
o Large (protein) molecules where ligands (active chemicals) induce their effects
o Chemicals bind to receptors t can then become activated
Binding is usually temporary/reversible t when it leaves the receptor, it disassociates
- Affinity = relative capacity of compound to maintain contact w/ or be bough to a receptor
- Efficacy = degree of biological activity/relative capability of a compound to activate receptor after it is bound
- Affinity and efficacy are independent but usually without affinity, not much efficacy
- Each neuroactive ligand in NS has several diff types of receptors on which in acts t each w/ own separate
function t drugs can mimic ligands
- Agonists = compounds w/ both affinity for and capability of activating a receptor
- Sometimes drugs enhance the amount of endogenous ligands available for receptor = indirect agonist
- Antagonists = drug exerts effect by blocking the action of an agonist
- Partial agonist = drugs that display intermediate efficacy in receptor activation between efficacy of full agonist
and antagonist
o Can sometimes have greater affinity than a full agonist but will not achieve maximal response of full
agonist t therefore reduces effects of full agonist seeing as full agonist cannot bind to receptor
- Inverse agonist AµPZµu}P}v]µ}µ((}}]}P}v][t still viewed
as an agonist
- Mixed agonist-antagonist = drug acts as agonist by itself but blocks the activity of another agonist in the same
system
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- Mixed agonist-antagonist and partial agonists have similar properties in function t by themselves, they exert
agonist effects but are capable of reducing effects of full agonists in same system
o Difference between the 2 is that partial agonist works on same receptors as full agonist but because of
]o}ÁuÆ]uo((v]o]Ç}µooP}v][}Z}UZuÆ]uo((}(
full agonist reduced if both are give together
o Mixed agonist-antagonist can be full agonist at 1 receptor but an antagonist at another receptor t when
w/ full agonist that activated both receptors, mixed agonist-vP}v]o}l}uZ(µooP}v][
effects than if the full agonist were alone
Receptors t different views
- Receptors have Z]v]vP][vZ((}][ = ionotropic receptors t for fast changes in neuroactivity
o Agonist = drug compatible with both sites
o Antagonist = drug only compatible w/ binding site t blocks agonist from binding and prevents its effect
- Receptors have active and inactive configurations t µP[((v}v]}vv]}v (also ionotropic)
o At low concentrations, drug with a high affinity for active configuration = agonist because it is more
likely to bind and have an effect
o At high concentrations, an agonist can act as an antagonist also because some may bind to the inactive
configuration blocking access to active binding site = antagonist
- Allosteric modulators Ao]PvZ}v[]oÇo]}v(o}Áµu}µo~]vl]v(ve of
agonists binding to other sites on receptor t like indirect agonist
- Physiological antagonism = drugs that induce opposing actions on neuron
o E.g. alcohol which enhances GABA and nicotine which enhances acetylcholine = opposing affects
- Metabotropic receptor = slow-developing, long-lasting effects on neurons
o Long string of amino acids that loop back and forth thru neuronal membrane t couple w/ G protein
linked to effector unit
G protein either linked to ion channel = breaks off and links to ion channel to open it
G protein binds to enzyme that triggers formation of other molecules in neuron = secondary
messengers
- Pharmacogenetics = try to discover differential effects of drug in different patients, depending on presence of
inherited variations in genes
- Pharmacogenomics = try to discover differential effects of compounds on gene expression
Dose-Response Relationships
- Dose-response function = relationship between dose administered and response observed
- Placebo = substance w/out any physiological effects t Z}v}o[
o In animals, placebo usually a saline solution = water w/ same amount of sodium chloride found in body
- Active placebo = substance that mimics noticeable physiological characteristic of drug being evaluated but
w/out effects on brain that researcher is interested in
- Double-blind procedure = neither subjects or researcher administering drug knows whether it is a drug or
placebo
- Therapeutic window = optimal therapeutic effect in patients obtained when concentration levels in plasma are
in certain range t levels below/above window have poorer outcomes
- Plasma half-lives = time taken to eliminate half of drug from bloodstream t can help predict desirable drug
doses and intervals between administrations
- Regarding dose-response relationships:
o v[ ÇÁZ((µPÁ]ooZÀµvo][](]ÁZ}}(ZµP]t and in what species
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