ch 1-4 mine Flashcards
pharmacology
scientific study of the actions of drugs on a living organism
neuropharmacology
study of drug induced changes in NS cells
psychopharmacology
study of drug induced changes in mood, behaviour, and thinking
drug action
molecular changes produced by drug at target receptor site
drug effect
physiological/ psychological alterations caused by drug action
therapeutic effects
desired changes
specific drug effects
based on physical/ biochemical interxns of drug at target site
non-specific drug effects
based on unique individual characteristics
placebo
belief in fake drug causing real improvement
nocebo
belief in fake drug causing real pain (expectation-induced anxiety)
pharmacokinetic
factors contributing to bioavailability (admin, absorption, distribution, binding, inactivation, excretion)
bioavailability
concentration of drug in the blood that is free to bind to specific target sites
enteral
admin through GI tract (rectal or oral)
parenteral
admin elsewhere
oral admin
- drug must be resistant to stomach acid
- mostly absorbed after stomach (in small intestine)
absorption
mvmt from admin site to blood circulation
first-pass metabolism
liver metabolizes some of drug before it circulates (may reduce bioavailability)
rectal admin
- bioavailability is difficult to predict
- drug may avoid FPM
intravenous injection
- most rapid and accurate
- drug reaches brain almost instantly
intramuscular injection
- slower than IV
- more even absorption over time
intraperitoneal
- used in lab animals
- through abdominal wall into peritoneal cavity
- rapid effects
- variable bioavail.
subcutaneous
- just below skin
- slow and steady absorption
inhalation
- rapid absorption
- preferred when oral is too slow, and GI tract would destroy drug
topical
- admin through a mucous membrane such as oral cavity, nasal, or vagina
sublingual
- under the tongue
- rapid absorption
- avoids FPM
intranasal
- local effects
- avoids FPM
transdermal
- controlled and sustained delivery
- avoids FPM
- limited drugs can penetrate skin
epidural
spinal anaesthetic injected right into CSF
gene therapy
application of DNA through viral vectors
lipid-soluble drugs
mvmt across phospholipid bilayer of a cell (always from high to low concentration)
ionized drugs
extent of ionization depends on
1. relative acidity/alkalinity of solution
2. intrinsic property of molecule
ionization of weak acids
ionize easily in alkaline (basic) env’t
ionization of weak bases
ionize easily in acidic env’t
electrical charge and lipid solubility
less charge = more soluble
distribution
body parts where blood flow is the greatest will have highest concentration of drug
how are blood capillaries helpful in distribution
numerous pores allow for drugs to move from blood to body tissues regardless of lipid solubility (unless bound by protein)
blood brain barrier
- CSF remains stable (unlike blood plasma)
- many things entering organs do not diffuse into CSF/brain tissue
- selectively permeable
- many ionized drugs dont pass BBB
how are brain capillaries different from typical capillaries
brain capillaries have astrocytes surrounding the endothelial cell
astrocytes (astroglia)
star shaped glial cells w numerous extensions
- modulate env’t
- metabolically assist neurons
- phagocytosis for cellular debris
placental barrier
- easily lipid soluble
- less easily water soluble
acute toxicity
baby’s exposure to disproportionately high drug blood levels from mom
drug depot
aka silent receptors
- binding at inactive sites where no effect is inititated
- any drugs bound to depots cannot reach active sites nor can they be metabolized by liver
drug binding
is reversible (only bound until blood level drops causing gradual unbinding)
depot binding
has major effects on magnitude and duration of effects
- reduces concentration, delays effects
bioavailability
concentration of a drug present in the blood that is free to bind to target sites
bioactivation
metabolic process turning an inactive drug into an active drug
biotransformation
drug is eliminated through metabolism
first- order kinetics
exponential elimination of drugs from the bloodstream
steady state plasma level
desired blood concentration achieved when absorption/distribution = metabolism/excretion
how do half life and effects relate
quicker the half life, quicker the effects
zero-order kinetics
drug is cleared at constant rate regardless of concentration
role of liver in excretion
metabolizes drugs and chemically alters them before excretion
enzyme induction
- increase in liver enzymes
- speeds up biotransformation
- increased metabolic rate for all other dugs
(happens w repeated use)
enzyme inhibition
- inhibit action of enzymes
- decreases metabolism (intense, prolonged effects)
drug competition
- inhibition caused by competition for one enzyme
- bioavailability for one or both increases (can’t be metabolized)
therapeutic drug monitoring
blood samples taken after drug admin. to determine plasma levels of drug
receptors
large proteins located on cell surface or within cells that are responsive to biologically active agents
ligand
molecule that binds to a receptor w some selectivity
receptor agonists
bind to particular receptor to initiate a cellular response
affinity
ability of a molecule to bind to a receptor which then determines potency
efficacy
ability of an agonist to active its receptor
receptor antagonists
- no cellular action
- prevent an active ligand from binding by blocking receptor
partial agonists
drugs that bind to receptor but have low efficacy, producing weaker biological effects
inverse agonists
substances that activate the receptor but produces the opposite effect of an agonist
up regulation
receptor amount increases
down regulation
receptor amount decreases
dose response curves
describes extent of drug effect
potency
absolute amount of drug necessary to produce a specific effect
therapeutic index
TD50/ED50 margin of safety
competitive antagonists
compete w agonists to bind to receptors but fail to initiate an effect (reduces effect of agonists)
non-competitive antagonists
reduce agonist effectiveness in other way than competing for receptor
physiological antagonism
2 drugs acting in diff. ways but interxn reduces each others effectiveness
potentiation
combination of 2+ drugs producing a greater effect than sum of individual effects
tolerance
response diminishes w same dose after use
sensitization
response increases w same dose of drug
cross tolerance
tolerance to one drug creating tolerance for similar drugs
acute tolerance
happens after one use
metabolic tolerance
drug increases their own rate of metabolism
pharmacodynamic tolerance
most dramatic, changes in nerve cell function to compensate for drug presence (withdrawal)
behavioral tolerance
occurs in same env’t as drug admin
- classical/ operant conditiong
sensory neurons
sensitive to env’tal stimuli, signals interneurons
interneurons
within brain and spinal cord
motor neurons
direct biobehavioral responses
soma
cell body containing nucleus
dendrites
tree-like projections that receive info from other cells
axon
conducts electrical signal from cell body to terminal buttons
cytoplasm
intracellular fluid
convergence
dendrites receive and integrate info from numerous cells
divergence
dendrites transmit their info to others
axon collaterals
branches of axons
myelin sheath
fatty, insulating coating made of glial cells
nodes of ranvier
breaks in myelin sheath to increase conducting of AP
terminal buttons
enlargements at the end of axon, contain synaptic vesicles of NTs
transcription
mRNA makes a copy of active gene in nucleus and transports it to ribosomes to decode it and make a protein
DNA methylation
env’tally induced epigenetic covalent attachment or methyl groups to a gene to decrease its expression
chromatin remodelling
env’tally induced epigenetic attachment of methyl, acetyl, phosphorus that either + or - gene expression
axoplasmic transport
transportation of proteins along the microtubules of the cytoskeleton to designations throughout the neuron
axoplasmic transport — retrograde
moves waste from terminals to soma for recycling
axoplasmic transport — anterograde
moves new proteins from soma to terminals
ligand- gated channels
smth binds to receptor that will recognize it and channel changes shape
voltage- gated channels
opened by electrical charge to membrane surrounding the channel
schwann cells
- type of glial cell
- makes myelin for PNS neurons
- dedicated to a single neuron
- can regenerate a damaged neuron
oligodendroglia
- type of glial cell
- make myeline for CNS neurons
- wrap “arms” around many neurons
- cannot repair damage
microglia
small scavengers that remove dying cells by phagocytosis
name all 4 glial cells
schwann, oligodendroglia, microglia, astrocytes
potassium mvmt in the cell
can move freely due to non-gated channels
forces acting on potassium in the cell
inward elctrostatic pull, outward concentration gradient
Na/K pump
3 Na in, 2 K out
action potential
rapid change in membrane potential propagated down the axon (all or none)
local potentials
small stimuli causing channels to open momentarily
depolarization
make cell more positive (excitatory)
hyperpolarization
make cell more negative (inhibitory)
EPSPs and IPSPs
larger stimulus has larger effect, summation happens
absolute refractory period
no chance for another AP
relative refractory period
hyperpolarization, but AP is still possible, just needs extra
somatic NS
- controls voluntary muscle mvmt, spinal and cranial nerves
- sensory and motor neurons
sensory afferent neurons
signals going to spinal cord
sensory efferent neurons
signals going to muscle
autonomic NS
- regulate internal env’t (BP, temp…)
- sympathetic and parasympathetic
sympathetic NS
- part of autonomic
- dominates when energy expenditure is necessary (stress, excitement, exertion)
sympathetic NS origin in CNS
lumbar and thoracic segments
- axons project short distance to reach sympathetic ganglia
parasympathetic NS
- part of autonomic
- conserves energy
parasympathetic NS origin in CNS
cranial and saccral segments
- axons travel a little longer to reach ganglia
meninges
- lie just within skull
- dura mater (toughest, furthest)
- arachnoid (web filled w CSF)
- pia mater (closest to brain tissue)
cerebral ventricles
cavities of CSF in the brain
central canal
channel of CSF running length of spinal cord
CSF
protects brain and exchanges nutrients/waste
who makes CSF
choroid plexus
embryonic dev’t of CNS
starts as fluid filled tube and dev’ps 3 enlargerments (forebrain, midbrain, hindbrain)
axon terminology CNS vs PNS
CNS: axons = tracts, clusters of cell body = nuclei
PNS: axons = nerves, clusters of cell body = ganglia
myelencephalon
- part of hindbrain
- medulla
- regulate vital functions (respiration, heart rate, BP)
- area postrema
- corticospinal tract
area postrema
vomiting center
metencephalon
- part of hindbrain
- pons
- cerebellum
pons
- arousal, sleep, attention
- locus coerulus (distribute axons to forebrain and release norepinephrine)
- dorsal and median raphe nuclei (send serotonin to forebrain)
cerebellum
- connects to pons
- cerebellar peduncles (large bundle of axons connecting cerebellum to pons
- sensorimotor control
mesencephalon
- part of midbrain
- tectum
- tegmentum
tectum
- superior colliculi (visual system)
- inferior colliculi (auditory system)
tegmentum
- periaqueductal gray (PAG)
- substantia nigra
- ventral tegmental area (VTA)
periaqueductal gray (PGA)
surrounds cerebral aqueduct that connects 3rd and 4th ventricles
substantia nigra
cluster of cell bodies whos axons innervate striatum
ventral tegmental area (VTA)
region containing dopaminergic cells forming mesolimbic and mesocortical tracts
diencephalon
- thalamus
- hypthalamus
thalamus
process and distribute sensory and motor info to cerebral cortex
hypothalamus
maintains homeostasis, limbic system, emotions, reproduction
telencephalon
- basal ganglia
- limbic system
basal ganglia
caudate, putamen, globus pallidus
- help regulate motor control
limbic system
- hypothalamus
- hippocampus (LT memories)
- amygdala (emotions)
- nucleus accumbens (salience effects of activities)
fissures
deep grooves in the brain
sulci
smaller grooves in the brain
gyri
bulges of tissue b/w sulci and fissures
corpus callosum
connects 2 hemispheres
frontal lobe
mvmt, executive planning
occipital lobe
primary visual cortex
temporal lobe
primary auditory cortex
parietal lobe
primary somatosensory cortex
primary cortices
conscious awareness of sensory experience
secondary cortices
analyzes info from primary, to provide recognition/ perception of stimulus
tertiary association
(memories)
comee from interface of parietal-temporal-occipital association
anterior/ rostral
near front or head of animal
brainstem
includes medulla, pons, midbrain
caudal
towards tail
coronal plane/ frontal
cut parallel to face
dorsal
towards top of brain
inferior
towards bottom of brain
sagittal plane
cut b/w the eyes
posterior
near back/rear
promoter region
next to coding region of a gene that controls rate of transcription (directed by binding of transcription factors)
reticular formation
network of nuclei within pons extending to midbrain and medulla
presynaptic cell
sending info
postsynaptic cell
receiving info
axodendritic synapse
- most common synapses in brain
- axon from presyn. communicates w postsyn. dendrites
pyramidal neuron
principal output neuron of cerebral cortex
synaptic cleft
gap between presyn. and postsyn.
synaptic vesicles
small sacs of NTs
axosomatic synapses
axon communicates w cell body
axoaxonic synapses
axon and axon
presynaptic inhibition
signaling presynaptic cell to decrease NT release by the axon terminal of postsyn. cell
presynaptic facilitation
signaling presynaptic cell to increase NT release by the axon terminal of postsyn. cell
neuromuscular junction
connection (synapse) b/w muscle and neuron
criteria for being a neurotransmitter (not at must be present)
- presyn. cell should contain proposed substance and a manufacturing mechanism
- mechanism for inactivation
- substance should be released from axon upon stimulation
- receptors for substance should be present on postsyn. cell
- application of substance has same effect on postsyn cell as well as stimulating presyn. cell
- antagonist drug should inhibit both action of applied substance and stimulation of presyn.
amino acids
building blocks of protein
monoamines
single amine group derived from amino acids
4 classic NT categories
amino acids, monoamines, acetylcholines, purines (ATP, adenosine)
3 non classical NT categories
neuropeptides, lipids, gases
neuropeptides
peptides found in NS
orexin
neuropeptide that stimulates eating and regulates sleep wake cycle
orexin injection in brain
- induce periods of wake
- cannot pass BBB
narcolepsy and orexin
narcolepsy patients have a loss of orexin neurons in the hypothalamus
insomnia and orexin
- use of orexin antagonist block OX1 and OX2 receptors to treat insomnia
how are neuropeptides made
protein molecules are synthesized in the cell, and packaged up with enzymes in vesicles to break them up and free neuropeptide
neuromodulator
substances that regulate NT activity (don’t act like NTs), and act at distant location
volume transmission
diffusion of chemical signal through extracellular fluid to reach distant target cell
wiring transmission
tight cell-to-cell synaptic transmission
which ion is directly responsible for NT release (upon stimulation)
Calcium (Ca2+)
exocytosis
the journey through cell membrane into synaptic cleft; fusion of vesicle membrane with axon terminal membrane (exposing inside of vesicle)
active zones
release sites of exocytosis
vesicle recycling
removal of synaptic vesicle membrane components from terminal membrane after exocytosis
clathrin mediated endocytosis
clathrin protein forms a coating on the membrane to perform endocytosis
- slow process occuring in an area away from release site
ultrafast endocytosis
rapid vesicle retrieval in an area close to the release site through endosomes, and bud-off using clathrin dependent
kiss and run endocytosis
clathrin and endosomes not needed
bulk endocytosis
- used to retrieve large amount of vesicle membrane
- mix of clathrin and endosome properties
- away from release site
lipid and gaseous transmitters (vesicles)
cannot be held in a vesicle, they diffuse in and out of the cell as needed
lipid and gaseous transmitters release
released by postsyn. cell not presyn. cell (retrograde messengers)
regulation of NT release
- rate of neuron firing (more firing= more NTs)
- probability of transmitter release
- presence of autoreceptors (receptor for. same transmitter released from that neuron)
terminal autoreceptor
- located on axon terminals
- upon activation, the inhibit further transmitter release
somatodendritic autoreceptor
slow rate of cell firing (less transmitter release)
heteroreceptor
either enhance or reduce amount of transmitter being released
NT inactivation
enzymatic breakdown, reuptake
ionotropic receptors (ligand-gated)
- rapid
- made up of 4/5 subunits
- does not involve second messenger
- intrinsic ion channel
metabolic receptors (G protein coupled receptor)
- slow
- involves second messengers
- single subunit
explain steps of metabolic receptors
- activate G protein
2a. either inhibit or open channel
2b. either stimulate or inhibit enzymes in cell membrane (effector enzymes) - increased synthesis or breakdown of 2nd messenger
- changes in postsyn. cell
allosteric sites
binding site on receptor that modulates (allosteric modulators) receptor response to an agonist
how do second messengers work
- activate protein kinases (enzymes) that phosphorylate another molecule altering its function
second messenger systems and protein kinase pairs
- cyclic adenosine monophosphate (cAMP) + protein kinase A
- cyclic guanosine monophosphate (cGMP) + protein kinase G
- phosphoinositide + protein kinase C
- calcium (Ca2+) + calcium/calmodulin kinase II (CaMKII)
cAMP and cGMP inactivation
inactivated by phosphodiesterases (PDEs)
tyrosine kinase receptors
mediate the action of neurotrophic factors (proteins that stimulate survival and growth of neurons during dev’t)
- long term gene expression and neuronal function, not rapid synaptic events
synaptic plasticity
synaptic changes
how are hormones excreted
endocrine glands
adrenal glands
- lie over the kidneys
- 2 parts; adrenal medulla and adrenal cortex
adrenal medulla
- derived from NS tissue
- receives input from preganglionic fibers of symp. NS
- made of chromaffin cells which secrete epinephrine and norepinephrine
adrenal cortex
- ## secretes glucocorticoids (steroids)
ovaries
secrete estrogen and progesterone
testes
secrete androgens (testosterone)
pancreas
- islets of langerhans
- secrete insulin and glucagon
thyroid gland
- secretes thyroxine and triiodothyronine
pineal gland
secretes melatonin
pituitary gland
anterior pituitary:
- thyroid stimulating hormone (TSH)
- adrenocorticotropic hormone (ACTH)
- follicle stimulating hormone (FSH)
- luteinizing hormone (LH)
- growth hormone (GH)
- prolactin (PRL)
pituitary stalk:
- hypothalamic releasing hormone (HRH)
- thyrotropin releasing hormone (TRH)
- corticotropin releasing hormone (CRH)
- gonadotropin releasing hormone (GnRH)
correlation
does not involve cause
face validity
relationship b/w animal testing and correlation to humans
predictive validity
test closely or have parallel results
construct validity
measurement tool actually measures the characteristic being investigated
reliability
consistent scores
stereotaxic surgery
stabilizes head so surgeons can get ultimate precision
lesioning
inserting an electrode and passing a current through, killing all tissue at the end of the probe (or can insert a neurotoxin)
microdialysis
measures NTs released in specific brain region
intracellular recording
stereotaxically implanting a fine-tipped electrode into a single cell
extracellular recording
stereotaxically implanting a fine-tipped electrode into the fluid around a single cell
radioligand binding
measure affinity and relative density in a particular brain area
autoradiography
detects amount and location of bound radioligand by using specialize film