Cumulative Info (w/o Unit 4) Flashcards
what is pharmacology?
the study of drug
what is psychopharmacology?
drugs that effect thinking, mood, and Bx
what is neuropharmacology?
drugs that effect neurons and the NS
what is neuropharmacology?
drug interaction with neurons and their effect of mood, thinking, and bx
what are psychoactive drugs?
biologically active substances that chemically alters cell structure or function of neurons that effect mood, thinking, and bx
what are three functions of neurons?
transmit, intergrate, store
what is the neural model?
sensory cell -> sensory neuron -> interneuron -> motor neuron -> effector
what do sensory cells do?
transduction (turn environ. signal into a biochemical signal)
what to effectors do?
muscles and glands that produce bx and excite/inhibit motor neurons
what is specific drug effect?
drug-receptor interaction (alc binds to GABA-R and causes sleepiness)
what is nonspecific drug effect?
environmental effects, individual differences (sex, weather, diet)
what are the four different names for a drug?
chemical
generic
trade
street
what do each of the four names for drugs describe?
chemical: IUPAC ID, molecular structure
generic: official name after paten, not capitalized
trade: paten name, capitalized
street: societal name that changes generation to generation
what are the five different drug types?
CNS stimulants (cocaine)
CNS depressants (alcohol)
Analgesics (sleepy, morphine)
Hallucinogens (distort perception and mood)
Psychotherapeutics (help with depression, anxiety)
what are the three different drug equivalences?
chemical
biological
clinical
what is chemical equivalence?
same chemical compound
same drug effect
same systems
different drug names
what is biological equivalence?
different chemical compound
same drug effect
same systems
what is clinical equivalence?
different chemical compound
same drug effect
different systems
Drugs are ____ and have ____ effects
variable, multiple
how many drug schedules are there and what are they used to determine?
5 schedules
-determines abuse potential and medicinal value
Schedule 1
-high abuse
-no medicinal value
-not prescribed
-heroin
Schedule 2
-high abuse
-accepted medicinal value
-prescribed, but no refills
-cocaine
Schedule 3, Schedule 4, Schedule 5
3: moderate abuse
4: low abuse
5: lowest abuse
5 refills over 6 months
how long does it take for a drug to get approved? how long does the patent last?
-takes 10yrs for approval
-patent lasts 20 yrs
what two things does animal testing test?
-carcinogenicity (cancer risk)
-teratogenicity (embryo affects)
how many human phases does a drug go through to get approved?
4 phases
what is phase 1 of human clinical trials? (years it takes, size of group, what is being tested)
safety & dosage
-1.5 yrs
-sm. group (20-100) healthy people
-how drug effects body
what is phase 2 of human clinical trials? (years it takes, size of group, what is being tested)
efficacy and side effects
-2 yrs
-medium group (100-1,000) diagnosed people
what is phase 3 of human clinical trials? (size of group, what is being tested)
efficacy and adverse rxns
-lg. group (1,000-3,000) diagnosed people
-appropriate dosage
what is phase 4 of human clinical trials? (years it takes, size of group, what is being tested)
real world impact
-ongoing and never stops
-safety monitoring
after which phase does the drug get approval?
after phase 3
what is pharmacokinetics?
what body does to drug (absorption, administration)
what is pharmacodynamics?
what drug does to body (drug effects)
what does is the difference between enteral and parenteral administration methods?
enteral: GI tract
parenteral: all other routes
what is the per Os (PO) administration method? (include kinetics)
-1st pass metabolism
-absorbed through gut membranes
-slow onset, low magnitude, long duration
what is the sublingual administration method? (absorption)
absorb through mucous membranes and glands (LSD)
what is the transbuccal administration method? (absorption)
absorb through mouth lining (chewing tobacco)
what is IV injection administration method? (include kinetics)
-does not cross membranes
-fastest onset, high magnitude, short duration
what is IM injection administration method? (include kinetics)
-deltoid and glute muscle injections (deltoid is faster)
-has two solutions it is mixed with (aqueous is faster than oil)
-faster onset than PO, slower onset than IV
what is the SC injection administration method? (include kinetics)
-under skin (insulin)
-slow onset
what is the IP injection administration method? (include kinetics)
-abdomen
-similar kinetics to IM (fairly fast onset)
what is inhalation administration method? (include kinetics)
-passes through capillary membrane in lungs (smoking)
-slower onset than IV (fairly fast onset though)
what is intranasal administration method? (include kinetics)
-passes through mucous membranes
-no 1st pass metabolism (bypasses BBB)
-slower onset than inhalation
list the onset peaks from highest to lowest (inhalation, SC, PO, IV, (IM,IP,intranasal))
IV (highest peak, highest magnitude, shortest duration)
Inhalation
IM,IP,Intranasal
SC
PO (lowest peak, lowest magnitude, longest duration)
when is absorption complete?
when concentration at target area = concentration at administration site
what are capillaries and what do they do?
-one cell thick w/ pores and spaces b/w cells
-exchange materials b/w blood and cells
-typically leaky
what is the blood-brain-barrier and what does it do?
-barrier b/w blood and brain
-selectively permeable
-water soluble molecules need active transport to enter
-maintains stable CNS environment
-incomplete at birth until 2 yrs old
what happens when toxic neurons enter the BBB at the area postrema CTZ (chemical trigger zone)?
vomitting
what does ionization do to molecules?
decrease lipid solubility
-dependent on pH (acidic)
what does ion trapping do?
-traps drugs so it can’t cross membranes
-prolongs drug effects (creates ‘free’ drug)
what are the characteristics of molecules best at absorption? (size, polarity, pKa/pH, ionization)
-small molecules
-lipid soluble (non-polar)
-low in ion-trapping
-pKa matches fluid pH
what is depot binding?
similar to ion trapping EXCEPT
-no ionization
-still decreases bioavailability of drug and creates more ‘free’ drug
what is nonselective binding?
competition for sites
-increases bioavailability of drug
what is half-life? what are the two types (describe them)?
-time drug decreases by 1/2
-types (1st-order and 0-order)
1st-order: constant fraction eliminated, small % of clearance sites occupied, decreasing exponential line
0-order: constant amount eliminated, all clearance sites occupied, decreasing linear line
what are the two phases of biotransformation?
Phase 1: non-synthetic modification (reduction, oxidation, hydrolysis)
Phase 2: synthetic modification / adding something (conjugation, ion trapping, acetylation)
where does biotransformation take place?
liver
what are cytochrome P450’s?
detoxification enzymes that oxidizes psychoactive drugs during phase 1 of biotransformation
what is enzyme induction?
creates more enzymes to reestablish homeostasis
-tolerance, brussel sprouts
what is enzyme inhibition?
lessens the effect of enzymes
-creates more ‘free’ drug
what does the kidney do to molecules?
ionizes them to be released as urine
-pH 4.5-7.5
what is the antidiuretic hormone (AHD)? what inhibits ADH?
ADH inhibits water excretion
-alc and caffeine inhibit ADH (causing more urination)
what is the effective dose? threshold dose?
dose that produces a biological response
-threshold dose: minimum response
what are the two types of dose-response curves?
% of population responding
response magnitude (mean response)
what is potency?
drug A has same effect as drug B but at a lower dose
-drug A is more potent
what is maximum efficacy?
drug B has a higher maximum efficacy due to a higher y-axis point
what is the equation for the therapeutic index? do bigger or small numbers mean it is more safe
LD50/ED50
-bigger number means it is more safe
what are three different things that can affect dose-response curves?
sex, age, tolerance
what are cumulative effects?
single drug
-repeated administration before drug is completely eliminated
-the effect decreases before drug is completely eliminated
what are additive effects?
multiple drug
-drugs with same effects (add together)
what are physiological effects?
multiple drug
-drugs with opposing effects (the difference)
what are potentiation effects?
multiple drug
-the whole is greater than the sum of products
-bigger than additive effects
what is tolerance?
decrease in response to same dose of drug
what is metabolic tolerance?
production of more enzyme (enzyme induction)
what is pharmacodynamic tolerance?
decreased NT synthesis
what is behavioral tolerance?
conditioned response (pavlovian conditioning)
what is acute tolerance?
decrease of effect b/w doses (nic hits)
what is cross tolerance?
tolerance to drugs that work by same mechanism (alc and phenobarbital)
what is sensitization?
increase response to same dose of drug
-due to repeated exposure to a stimulus
what is rate dependency?
interaction of drug and the baseline rate of bx
-different effects produced due to initial activity of system
-low dose: increases affects
-high dose: decreases affects
-EX: ADHD
what are the 6 steps of the synaptic transmission model?
- precursor transport
- synthesis
- storage
- release
- activation
- termination
what occurs during precursor transport (1)
NT at axon terminal
sm. peptide at soma
what occurs during synthesis (2)
enzymes and cofactors are loaded into axon terminal
what occurs during storage (3)
NT, ATP, GTP, Ca2+ stored in synaptic vesicles
what occurs during release (4)
exocytosis
-anchored to axon terminal by synapsin-actin linkages
-vesicle is next to synapse and action potential reaches vesicle
-Ca2+ influx to release NT and open voltage gate
-Ca2+ bind calmodulin to activate CaMK2
-CaMK2 phosphorylated synapsin to release vesicle
membrane fusion
-vesicle diffuses toward synaptic membrane
-SNAPs and NSFs primes for fusion (alpha, gamma, beta)
-SNAREs open configuration and intertwine (synaptobrevin, syntaxin, SNAP-25)
-synaptotagmin binds Ca2+ and fuses everything together
what occurs during activation (5)
NT binds to receptor and changes conformation
what occurs during termination (6)
4 different ways
-diffusion
-enzymatic degradation
-reuptake
-autoreceptors
what is diffusion termination (6)
receptor becomes inactive
what is enzymatic degradation termination (6)
cuts up NT
what is reuptake termination (6)
active transport of NT out
-goes back to vesicle it came from
-OR degraded by an astrocyte / glial cell
what is autoreceptor termination (6)
binds NT on presynaptic cell
-decreases depolarization
-decreases NT release
what occurs at presynaptic facilitation? (K+, Ca2+ channels, NT release)
decreases K+ efflux so Ca2+ channels stay open, increase NT release
what occurs at presynaptic inhibition? (K+, Ca2+ channels, NT release)
increases K+ efflux so Ca2+ channels close, decreases NT release
what is affinity?
ability to bind to receptor
what is efficacy?
ability to activate receptor
what are some characteristics of ligand binding?
-lock and key model but has the ability to change structure of drug to fit
-still specific!
-L and D isomers (levo is more active)
-ligand binds and activated 2d messenger systems (EPSP, IPSP)
what does direct mean?
at NT postsynaptic R
what does indirect mean?
at sites other than NT’s binding site
what is an agonist?
mimics or increases NT effect
-affinity and efficacy
what is an antagonist?
blocks or decreases NT effect
-affinity, NO EFFICACY
what are competitive antagonists?
competes for same R site
-decreases potency (takes more of drug to produce same effect)
what are noncompetitive antagonists?
binds at different site but same R (allosteric binding)
-effects maximum response
what is an ionotropic receptor?
channel and binding site on same protein
-NT directly controls channel
-acute tolerance
what is a monotropic receptor?
channel and binding site in different proteins
-GTP required
-neuromodulation
explain the 2d messenger system of NE
beta adrenergic R
Gs
increases adenyly cyclase
increases cAMP
increases protein kinase A
explain the 2d messenger system of DA
D2 R
Gi
decreases adenylyl cyclase
decreases cAMP
decreases protein kinase A
where are monoamines found, released by, and the two types?
-found at axon terminals that bind at postsynaptic R
-released by action potentials
-types: catecholamines (1 ring) & indolamines (2 rings)
what are the catecholamine NT?
DA, NE, EPI
what are the indolamine NT?
5-HT, melatonin
how are all monoamines terminated?
monamine oxidase (MAO)
how are only catecholamines terminated?
catechol-O-methyltransferase (COMT)
what does reserpine do to monoamines?
blocks monoamine transporters
-decreases NT storage
-indirect ANT
where is DA found?
midbrain
what are the DA receptors?
D1: Gs proteins
D2: Gi proteins
what are the three ascending pathways in DA?
nigrostriatal (substantia nigra -> striatum) parkinson’s disease
mesolimbic (VTA -> limbic)
mesocortical (VTA -> cortex)
how is DA synthesized? what is the major metabolite?
tyrosine –(tyrosine hydroxylase)–> DOPA –(AADC)–>DA
-homovanillic acid
where is NE found?
adrenal glands, locus coeruleus
what are the NE receptors?
alpha: 1(Gq=increases Ca2+), 2(Gi)
beta: 1&2 (Gs)
how is NE synthesized? what are the major metabolites?
tyrosine –(tyrosine hydroxylase)–>DOPA –(AADC)–> DA –(dopamine beta hydroxylase)–> NE
-MHPG, VMA
where is 5-HT found?
raphe nucleus
are the 5-HT receptors ionotropic or metabotropic?
all metabotropic
-EXCEPT 5-HT3
how is 5-HT synthesized? what is the major metabolite?
tryptophan –(tryp. hydroxylase)–> 5-HTP –(AADC)–> 5-HT
-5-HIAA
what degrade ACh?
acetylcholinesterase
how is ACh synthesized?
choline + acetyl CoA –(choline acetyltransferase)–> ACh
what are the two types of receptors for ACh?
nicotinic
muscarinic
what are nicotinic receptors? (characteristics, location)
found in PNS (skeletal muscle, autonomic ganglia)
-excitatory: Na+ and Ca2+ channels
-desensitizes: makes channel inactive
-depolarization block: R reaches a maximum efficacy
what are muscarinic receptors? (characterisitics, location)
-excite and inhibit 2d messenger systems
-increases cAMP
-decreases phosphoionsitide activity
-G protein: K+ efflux
what are two excitatory AAs?
glutamate
aspartate
what are two inhibitory AAs?
GABA
glycine
where is glutamate found?
cerebral cortex, hippocampus, cerebellum
what can an increase of glutamate lead to?
excitotoxicity = cell death
what is GABA degraded by?
aminotransferase
-through presynaptic and glial reuptake
what are the two GABA receptors? what do they do, and are they ionotropic or metabotropic?
GABA(A): ionotropic, Cl- influx, allosteric binding
GABA(B): metabotropic, decreases cAMP, opens K+ channel
how is GABA synthesized?
glutamine –(glutaminase)–> glutamate –(glutamic acid decarboxylase)–> GABA
what are two types of neuropeptides?
substance P
endorphins
what is substance P?
pain transmission, slow & long enduring pain
what are endorphins?
bind at opioid receptors (mu, delta, kappa)
-enkephalins, naloxone insensitive
what do antihistamines do?
stop the inflammatory response
what NT is responsible for the sympathetic NS?
NE
what are the lengths of the pre- and post- ganglia for the sympathetic NS? where are the ganglia located (near spinal cord or effector)?
short preganglia, long postganglia
-near the spinal cord
what outflow does the sympathetic NS have? what is the strength and rapidity of the activation?
thoracolumbar outflow (lateral horns)
-strong and fast activation
what NT is responsible for the parasympathetic NS?
ACh
what are the lengths of the pre- and post- ganglia for the parasympathetic NS? where are the ganglia located (near spinal cord or effector)?
long preganglia, short postganglia
-near the effector
what outflow does the parasympathetic NS have? what is the strength and rapidity of the activation?
craniosacral outflow
-slow and discrete activation (not all activate at same time)
how many neurons do the adrenal glands have?
one neuron!
what does the reticular activating system do? where does it get its signal from?
activates alertness
-inputs come from classical sensory afferents (sensory info)
what are the cortical arousal streams of the reticular activating system? describe the process
Vental Stream (RF -> BF)
Dorsal Stream (RF -> thalamus -> BF)
what increases arousal in the reticular activating system?
ACh and NE
what decreases arousal in the reticular activating system?
5-HT
what does GABA do to arousal in the reticular activating system?
can increase or decrease
-high GABA = low arousal
what are nociceptors?
free nerve endings used in pain signaling
-three types (mechanical, thermal, chemical)
what is the anterolateral system? names the two branches
the pathways of pain
-Two Branches: Sensory-discriminative (locus, intensity, type), Affective-motivational (emotion, Bx)
what do 1st order sensory neurons do?
release glutamate and substance P
-dorsal root ganglia neurons
what do 2nd order sensory neurons do?
send signal to anterolateral branches (PAG & thalmus->cortex)
-gray matter of dorsal horn
what is behavioral analgesia?
decreases perceived pain, decrease in nociception
-in the supra-spinal!
what receptors mediate analgesia?
opioid and non-opioid receptors
what is a direct ANT of analgesia?
naloxone
what is the descending analgesia circuit?
anterolateral branches -> PAG -> RN or LC -> spinal cord
what neurons does PAG contain?
GABA, ACh, opioid
what neurons does the spinal cord contain?
5-HT, NE, enkephalin
what neurons directly inhibit neurons in pain circuits?
enkephalin
GABA
