psyc exam ch 1-4 review

pharmokinetics

how the body handles drugs

processes to pharmokinetics

ADME - absorption, distribution, metabolism, elimination

absorption of drugs

through gastrointestinal tract - enteral 

without using gi tract - parenteral

enteral absorption

GI tract - oral, rectal 

parenteral absorption

without using GI tract - injection, inhalation, absorption through skin, absorption through mucous membrane

intraveneous (IV)

fast - seconds to minutes

immediate effect, precise control of dose, 100% bioavailability

requires sterile techniqu, risk of infection, vein irritation, difficult for self administration, requires trained person

Intramuscular (IM)

fast - minutes to 30 min

pain at injection site, variable absorption depending on blood flow, requires trained person

subcutaneous (SC)

moderate - 15/60 min, easy for self administration, steady absorption

slower than IM/IV

oral (PO)

slow - 30/90 min, variable, easiest, convenient, non invasive, good for chronic use

first pass metabolism in liver, slower onset, not for unconscious/vomiting patients

sublingual/buccal

rapid - minutes,  bypasses first pass metabolism, easy, good for lipophilic drugs

rectal

moderate - 15/60 minutes, variable, useful if oral not possible, partial avoidance of first pass metabolism

discomfort

inhalation

moderate - 15/60 min, large surface area of lungs, rapid absorption, avoids first pass

requires special device or tech, can irritate lungs, dosing less precise

topical (skin)

slow to variable, minutes to hours, local effect, minimal systemic side effects, easy application

poor systemic absorption

transdermal (patch)

slow - hours, sustained release, continuous delivery, bypasses GI tract, convenient for chronic use,

slow onset, possible skin irritation

intranasal

fast, minutes, avoids first pass metabolism, rapid absorption, easy

can irritate nasal mucosa

intrathecal/epidural

very fast - local to CNS, direct delivery to CNS, does not require blood brain barrier passage

invasive, requires skilled admin, infection/nerve injury risk

blood stream distribution

faster than via GI tract, circulates entire body within 1 min

first pass metabolism distribution

drugs adiminstered enterol must go through liver where they are first metabolized

CSF distribution

cerobrospinal fluid - very fast, does not require crossing blood brain barrier

normal metabolizer

the persons genes produce a typical amount of enzyme

antidepressant helps persons depression, causes few side effects

follow recommended dosage

slow metabolizer

persons genes produce too little enzyme

antidepressant builds up in body causing intolerable side effects

switch antidepressants or reduce dosage

fast metabolizer

produce too much enzyme

antidepresssant eliminated too quickly, providing little to no relief for the persons depression

switch antidepressants or increase dosage

exretion of drugs

renal, urinary - exretion of drug metabolites produced by biodegradation of drug in liver

drug half life

time for plasma level of drug to fall by 50% - how long drug remains in body

although diff absolute amount of drug is metabolized within each half life, the time interval remains constant

steady state concentration

drug administration approximates rate of excretion

time to reach steady state concentration

about six times drug elimination half life; independent of actual drug dosage 

steady regular interval dosing

leads to predictable accumulation with steady state concentration reached after about 6 half lives s

sinusodial drug half life curve

shows maximal and minimal drug concentration s at beginning and end of each dosage interval

dashed line - avg concentration achieved at steady state

plasma drug concentrations during repeated oral admin of drug at intervals equal to its elimation half life

therapeutic window

well defined range of blood levels associated with optimal clinical response

if too much drug - effect may not be any betterm more undesirable side effects

if too little - no beneficial effect

drugs concentration must be in therapeutic window

drug tolerance

state of progressively decreasing responsiveness to the same dose of a drug

metabolic tolerance

body becomes more efficient at metabolizing drug; happens over days, weeks

pharmacodynamic tolerance

cells or recceptors adapt to presence of drug

acute - tachyphlaxix - changes happen in minutes to hours, sometimes after first few doses

chronic - over days to weeksb

behavioral conditioning

environmental cues trigger body to compensate for drug before it is even taken

receptor desensitization - cause tachyphlaxis

receptors become less responsive after being repeatedly activated

receptor internalization/downregulation - cause tachyphlaxis

receptors pulled into cell and removed from surface

depletion of mediators - cause tachyphlyaxis

the body runs out of neurotransmitters or signaling molecules drug acts on

physiological adaptation - cause tachyplaxis 

opposing systems in body counteract drugs effect 

sensitization - reverse tolerance

amplified or potentiated response to drug after repeated exposure

often occurs with cocaine, mdma

physcial dependence

drug is taken to avoid withdrawal symptoms

abstinence sydnrome

withdrawal symptoms when drug is no longer taken

discontinuation syndrome

symptoms when someone suddenly or rapidly stops taking a medication - often psychiatric meds

division of human nervous system

CNS, PNS

CNS

central nervous system - includes brain and spinal cord

composed of neurons and glia

PNS

peripheral nervous system - includes nerves that originate in spinal cord and connect to organs in the body

spinal cord

made up of neurons and fiber:

afferent fibers (arrive) - carry sensory info to brain and modulate sensory input

efferent fibers (exit) - organize and modulate motor outflow to muscles and provide autonomic (involuntary) control of vital body organs

limbic system

second major subdivision of telencephalon

amygdala and hippocampus 

contributes to regulation of mood, affect, emotion, emotional experience responses 

reward circuit

4 main structures in neuron

cell body (soma), dendrites, axon, terminal buttons

oval shaped head (soma), fibrous branched ends (dendrites) arise from it

from soma long thin tube (axon) covered by myelin sheath goes out that branches into two ends, fibrous ends called terminal buttons

direction of messages is from axon to branching terminal buttons

glia

glue - provide physical support, control nutrient flow and are involved in phagocytosis

astrocytes

provide physical support remove debris, transport nutrients to neurons

microglia

involved in phagocytosis and brain immune function

oligodendrocytes

provide physcial support and form myelin sheath around CNS axons

synthesis

formation of transmitters, precursors are main ingredient - brough to neuron by bloodstream, taken up cell body or terminal

enzymes put ingredients together

transmitters stored in vesicles

release = exocytosis - vesicles fuse with presynaptic membrane and release transmitters into synapse

binding - attachment of transmitter to receptor

ionotropic receptors 

direct - fast, short lasting, ligand gated

metabotropic receptors 

indirect - located close to G protein, activates enzyme that stimulates production of chemical called second messenger 

changes take longer to begin and last longer 

inactivation

termination of synaptic transmission - re uptake, metabolism (enzymatic degradation), reuptake by glia cell

acetylcholine (ACh)

made from choline and acetyl CoA in axon terminal - binds to receptors and immediately broken down at receptors

choline recycled and acetate diffuses away

acetylcholinesterase (AChE)

in snaptic cleft, ACh rapidly broken down by enzym AChE

Choline

tranported back into axon terminal and used to make more ACh

receptor specificity

each neurotransmitter binds to several receptor subtypes

only drugs/neurotransmitters/hormones with particular shape and strcutre can bind - receptor is the loc, drug/neurotransmitter/hormone is the key

ionotropic receptor types 

glutamate, GABA, acetylcholine, serotonin, glycine

metabotropic

glutamate, GABA, acetlycholine, serotonin, dopamine, norepinephrine, neuropeptides

nicotinic - cholinergic receptors

ionotropic - ligand gated ion channels, found in neuromuscular junctions, roles in attention, arousal, reward, addiction pathways

fast signaling, short acting, excitatory

muscarinic - cholinergic receptors 

metabotropic 

g protein coupled receptor, works through second messenger system, parasympathetic nervous system, roles in learning memory arousal

slower signaling, longer acting, excitatory/inhibitory

catechol and catecholamine structure - monoaminergenic neurotransmitters

all catecholamines share catechol nucleus, benzene ring with two adjacent hydroxyl OH groups

structures and synthesis of catecholamines

tyrosine - amino acid found in foods, converted into dopa, then dopamine, next to norepinephrine, finally in PNS as epinephrine depending on which enzymes are present in cell

norepinephrine - monoaminergic neurotransmitters

projects from brainstem to cortex, limbic system,hypothalamus, cerebellum

produces alerting, focusing, orienting response, positive feelings of reward, analgesia

dopamine families - metabotropic

D1 like (D1 and D5) - excitatory, facilitate movement, involved in reward, learning, cognition, distributed in cortex, striatum, limbic system

D2 like (D2, D3, and D4) - inhibitory, suppresses unwanted movements, important in reward, motivation, psychiatric regulation, distributed in striatum, limbic regions, pituitary 

serotonin

synthesis - tryptophan

multiple receptors - most metabotropic, ionotropic (5-HT3)

pathways - largely parralel DA

amino acids - glutamate

major excitatory, comes from metabolic pathway (krebs cycle) or glutamine via glutaminase

binds to several receptor types: NMDA (mediated by glutamate/glycine/serine, requires membrane depolarization by kainate or AMPA), involved in memory formation,kainate, AMPA

amino acids - gaba

inhibitory transmitter, high concentrations found in brain and spinal cord, receptors GABA A and GABA B 

termination by reuptake with transporters on. neuron or glia cell

gaba a

fast, ionotropic, found i npostsynaptic membrane

gaba b

metabotropic found in pre and postsynaptic membranes

peptides 

small proteins, chains of amino acids molecules attached in specific order

act on g protein couple receptors - substance p is peptide neurotransmitter involved in pain 

include endogenous opiod peptides: endorphine, enkephalins 

bind to opiod receptors: mu, kappa, delta 

activate pathways that reduce neurotransmitter release and excitability, dampen pain and modulate mood/reward 

substance P - gut brain peptide

11 amino acids in length - plays role as sensory transmitter, pain impulses that enter spinal cord and brain from peripheral site of tissue injury

opiods, serotonin agonists, norepinephrine agonists exert analgesic effect by acting on substance p terminals to limit release of pain inducing peptide

neurotransmitter activation of ionotropic receptor

ion channels have subunits

diff molecules bind to diff subunits

ionotropic receptors 

activation opens channel, allowing flow of ions to trigger or inhibit neural firing 

metabotropic receptors

induce release of intracellular protein, trigger second messengers that directly/indirectly open/close ion channels

carrier proteins

bind to neurotransmitters to transport them back to presynaptic neuron

many drugs block carrier proteins for a specific neurotransmitter (SSRIs)

enzymes

break down nuerotransmitters in synaptic cleft 

inhibition by drugs increases transmitter availability, irreversible acetylcholine esterase inhibitors used as pesticides and nerve gases, monamine oxidase inhibitors inhibit breakdown of NE and DA 

isomer

drug has same chemical compounds, arranged differently

may have different actions

racemix mixture: contains both isomers

enantiomers

same molecular formula and sequence but differ in 3D spatial arrangement

acute receptor effects

when psychoactive drug binds to a receptor it can produce immediate (acute) response

chronic receptor effects

when drug is given over longer peiod of time produces long term changes in properites of receptors: down regulation, upregulation

dose response relationships

relationship between dose and response is DRC (curve) - intensity of response plotted as percentage of maximum obtainable response 

potency -DRC

how well drug molecules attach to their sites of action (receptors) - more potent drugs. usually attach better than less potent ones, bindmore tightly

variability - DRC

individual differences in drug responses

differences in genetic make up of metabolic enzymes

slope - DRC

mostly linear central part of curve - how sharply effect changes with each change i ndose 

small change in dose produces large change in effect - steep slope 

large change in dose produces small change in effect - shallow slope 

efficacy - DRC

maximum effect obtainable with additional doses producing no effect

more efficacious produce greater peak, max

bindings refers to affinity

more potent drug has greater affinity for its receptor, less potent drug has less affinity for its receptor, does not bind so tightly and can be more easily knocked off the receptor

diff drugs may bind to same receptor, w different affinities

binding results in 1/3 actions

binding to site of normal endogenous neurotransmitter - initiates similar cellular response (agnostic action) 

binding to nearby site to facilitate transmitter binding (allosteric action)

binding to receptor site, blocking access of transmitter to binding site (antagonistic action) 

agonist

by itself produces no response - can produce maximum possible effect

gind to receptors to produce a functional response

full, partial, inverse

partial agonist

not able to elicit maximum effect at any dose

antagonist

does not produce overt effect, block or reduces effect of agonist 

can be competitive or noncompetitive/irreversible

inverse agonist

produces an effect opposite to that of an agonist

therapeutic index

measure of drugs safety margin: ratio of LD50:ED50

the greater the TI the safer the drug

lethal dose LD50

drugs have many effects, drug will be lethal in 50 % of subjects at level of dose 

polypharmacy 

use of multiple medications taken at same time 

rational for treating complex conditions 

irrational when prescribed unnecessarily 

pharmocodynamic interactions

two drugs have same or overlapping mechanism of action

pharmokinetic interactions

one drug affects the others AdME