ratio of LD₅₀ to the ED₅₀ is used as an index of relative safety of the drug

LD₅₀ / ED₅₀

LD₁ / ED₉₉ 

Ratio of lethal dose for 1% to effective dost for 99%

1. Pharmacodynamics

2. pharmacokinetics

3. pharmacogenetics 

drugs' actions and the receptors responsible for making drug effects

what is does in biological systems

Movement of drugs in the body

absorption, distribiution, metabolism, excretion of drug

how does it reach brain? how quickly does it leave the body?

how genetics play a role in drugs' properties, individual differences

ex: metabolism

publicly observable

"your heart rate is 120"

Describe drugs' effects

cannot directly be observed

feelings, thoughts, emotions

either the participant (if you're most concerned about subject bias) or the person running participants (if you're most concerned about experimenter bias) is unaware of who's receiving what level of the treatment.

Everyone knows what drug everyone is getting

more practical and easier to get participants for study

how is machinery/model similar to what we have in humans?

Will this experiment measure what it is supposed to?

How well does your study predicy that it'll help others?

If it works in an animal model, will it actually work in humans?

Can it be generalized?

Thalidomide

reduced morning sickness in pregnant women. Teratogenic effects

Rats do not contain certain specific enzymes that change the drug; CANNOT BE GENERALIZED TO HUMANS!

Institutional Animal Care and Use Committees

Replacement

Reduction

Refinement

1. Develop strategy

2. Make drugs

3. initial screening

4. further screening w/ animal models

5. safety pharmacology

6. Clinical Trials (4 Phases)

1. small number of participants, low dose

2. higher dose, more participants (most drugs are eliminated here) may have comparison drug

3. More participants, higher dose, people with more diverse background. wider sample

4. look at adverse side effects in certain populations (smoking, comorbid disorders, etc)

maintain homeostasis

form myelin

provide support and protection for the brain's neurons

1. Soma

2. dendrites

3. Receptors

4. Axon

5. Synapse 

6. Synaptic cleft

7. first messenger

8. Myelin Sheath

9. Nodes of ranvier

contains neurotransmitters

all parts found within structure

ex: nucleus accumbens

axon going into struture

ex: dopamine goes from VTA to nucleus accumbens

1. facillitate blood-brain-barrier formation

2. Respond to injury

3. terminate neurotransmission

glial (astrocytes) cells swell up and create scar tissue, prevents brain recovery after damage

GLIOSIS

astroctyes

ogliodendrocites

1. substantia nigra

2. Reticular formation

1. cerebral cortex

2. basal ganglia

3. limbic system

4. hypothalamus

5. thalamus

depresses brain stem action

inhibits medulla + autonomic functioning

motivating factors (like hunger)

integrates autonomic nervous system

helps control eat, sleep, emotion, regulation of body temperature, etc

emotion

fight/flight

amygdala

hippocampus

nucleus accumbens

Gyri

Sulci

Lobes

Prefrontal Cortex

Parietal lobe

occipital lobe

temporal lobe

integrates emotion, cognition

somatosensory cortex

auditory

speech

Parietal

occipitial

temporal

Frontal 

helps process information from the senses and transmit it to other parts of the brain.

relay sensory impulses to the cerebral cortex

lateral corticospinal tract (hands, feet, limbs)

medial corticospinal tract (posture, balance, etc)

movement of extremities

hands, feet, limbs

posture

balance

stored memories

can recollect

-active cerebral cortex

-reticular activating system

-glucose and oxygen levels

keeps cerebral cortex active/aroused

faster neuronal firing

glucose

oxygen

low blood flow

(plaque, clots, vascular depression)

too much blood flow

(overdosing)

1. cushions brain

2. supplies cells with nutrients and chemicals

material that covers the brain

cushions the brain using cerebrospinal fluid

around cells

ventricles

cerebral aqueduct

central canal

meninges

1. Small

2. Lipid solluble

3. uncharged

4. active transport

channel for substance to move across Blood-Brain-Barrier

ex: glucose

found on DNA

encode for proteins/traits

decrease or increase gene transcription

-RNA sends copy of gene outside of nucleus for protein synthesis

fails to express traits encoded by a gene

stop codes in DNA; transcription factor does not activate gnee

-compensatory changes

RESTING POTENTIAL (inside is more negative, Sodium channels are closed)

EXCITATORY POSTSYNAPTIC POTENTIAL (Sodium ions enter cell and becomes DEPOLARIZED)

THRESHOLD (Sodium channels open and charge becomes more positive for a brief period. sodium closes and potassium escapes from neuron and returns to negative state

REFRACTORY PERIOD (stimulus cannot evoke response)

RESTING POTENTIAL (Steady, negative state. no ion flow)

baseline state

more NEGATIVE charge inside cell, sodium channels closed

difference of electrical charges

Sodium channels open

neurotransmitter is released from the axon

ions can travel through receptors. require neurotransmitter to bind before they can open. It is the fastest.

ligand-gated: opens when chemical binds 

activated by neurotransmitter, no channel involved. 

neurotransmitter attaches to the receptor, receptor bends + releases G protein.

G-protein then can attach to an ion channel, react on 2nd messengers, alter metabolic activities, or effect gene transcription factors.

THIS IS THE SLOWEST.

1. GLUTAMATE

2. GABA

ionotropic: AMPA, NMDA

metabotropic: mGlu    

Group I (excitatory)  Group II (inhibitory)

inotropic receptors: GABA_A 

Metabotropic receptors: GABA_B

Phenylalamine

tyrosine (from diet)

DOPA

Dopamine

Norepinephrine

Epinephrine

DA cell bodies found in VTA and substantia nigra

Axons terminate in: basal ganglia, limbic system, cortex

D₁ and D₅ EXCITATORY

D₂ through D₄  INHIBITORY

1. catecholamines

2. indoleamine

on receptor

chemical substance site on protein that doesn't activate protein but may influence protein's ability to be activated

Alpha

Beta

Tryptophan

5-HTP

5-HT

Catecholomethyltransferase

COMT

MAO-A  (found in brain and body)

MAO-B (found in body)

What are the synthesis steps for acetylcholine?

Acetyl CoA

Choline

Acetylcholine

Nicotinic: ionotropic, alpha and beta subunits

muscarinic: metabotropic; M₁ - M₅

Astercholinesterase

AChE

1. Gas, neurotransmitter

2. no synaptic vessicle storage

3. diffuses through membrane

4. bonds with intracellular proteins

5. No membrane receptors

6. increases blood flow/activity in brain

Neuronal Growth Factor (NGF)

Brain-Derived Neurotrophic Factor (BDNF)

1. Track A

2. Track B

3. Track C