Chapter 4: psychopharmacology

Pharmacology

how drugs move through the body

concerned with the absorption, distribution, metabolism and excretion of drugs within the body

Dose response curve

can help us understand the relationship between a safe and unsafe dose

x axis includes the dose of drugs

y axis quantifies some behavior that the drug is presumably altering or may depict the percentage of drug depict to its endogenous receptor

ED 50

median effective dose- the dose at which 50% of the tested individuals display a desired effect/ behavior

LD 50

Median lethal dose- the dose at which 50% of the tested individuals die as a result of drug administration

Therapeutic index (TI)

the ratio between the LD 50 and ED 50

TI= LD 50/ ED 50

the further apart the ED and LD curves, the “better” the drug

a wide therapeutic index is good because it makes the drug more safer to consume

Potency

the drug effects are coming out at a lower dose

the left and right movement in the graph

effectiveness

differences in the maximum effect between two drugs

the up and down movement in the graph

subcutaneous (s.c.)

inject just under the skin- very slow absorption

ex: birth control

Intramuscular (i.m)

inject into a preferably large muscle moderate rate of absorption

ex: most vaccines

Intraperitoneal (i.p.)

injection into the peritoneum, but outside of the visceral organs- similar time course for intramuscular injections. Fast absoprtion

Intravenous (i.v.)

also known as mainlining, injection directly into a vein near the surface of the skin- very fast absorption

if air bubbles reach the bloostream, they can block blood flow in critical areas like the brain, heart or lungs, causing a stroke

intrathecal

injection into the CSF near the brain steam

intracerebrobentricular: inject directly into the brain via cannula

i.v. rate of absorption

the fastest as the drug to quickly it gets into the blood

i.p. rate of absorption

rich vasculature

i.m. rate of absorption

moderate rich vasculature allows for slightly less rapidly absorption

s.c. rate of absorption

slowest of these ROAs

Rate of absorption through lungs

• lungs are excellent for drug absorption

  • huge surface area

  • rich vasculature

• once something gets in your lungs, it reaches into the brain is very quickly because of the blood transport, in lungs and brain

oral administration

drugs can either be solid (tablets) or dissolved in liquid

for a drug to be effectively absorbed through the stomach, they must be able to withstand stomach acids

Titration

slowly increasing the dose of a medicine by very small amounts

First pass metabolism

liver produces enzymes tar breaks down most drugs

for rugs that the body has never seen before are also broken down because the enzymes breaks down drugs by known chemical groups

you can develop tolerance on drugs because your body produces more enzymes that break down that drug

Transdermal administration

only very lipid soluble drugs can pass through the skin

most acids will pass readily through the skin

slow rate of absorption makes this route adequate for sustained delivery (ex: nicotine patches)

Half life

the amount of time it takes for 50% of a drug to be systematically removed from the blood

Tolerance

Diminished effect of a drug due to repeated administration.

when people self administer a drug, they are more likely to develop a addiction because someone else is monitoring their drug

cross tolerence

when you take one drug , and metabolize it. When you take another drug that is unknown to the body, can also be metabolized because they belong to the same class

environment specific tolerance

body breaks down a drug recognized by specific environment clues (ex: urge to pee when going to the bathroom)

sensitization

“reverse tolerance” related to synaptic plasticity changes that makes neurons more sensitive to chemical signals

withdrawal

removal of the drug from the body produces unpleasant symptoms

competitive antagonistic

another drug binds to the receptor and just occupies the receptor and prevents the other drug from binding to the receptor, preventing overdose

agonists

drugs that bind to a receptor and facilitate postsynaptic effects

mimic the effect of the drug

antagonists

drug that bind to a receptor and inhibit postsynaptic effects

oppose the effects of the drug

Noncompetitive binding

drug binds to a secondary binding site on the receptor and may act as an agonist/ antagonist

Glutamate

Majority of excitatory activity is done by glutamate

receptor: NMDA (calcium channel), AMPA (sodium channels), Kainate

• NMDA is important for forming new memories and learning

• NMDA is very important for plasticity (allows increased levels of learning when given more to an animal)

glutamate signaling is critical for the development of synaptic plasticity (LTP/LTD)

PCP and ketamine are effective NMDA antagonist

Gluatamate

Majority of excitatory activity if done by glutamate

Receptor: NMDA (calcium channel), AMPA ( sodium channels), Kainate, mGluRs

• NMDA is important for forming new memories and learning

• NMDA is very important for plasticity

Glutamate signaling is critical for the development of synaptic plasticity (LTP/ LTD)

PCP and ketamine are effective NMDA antagonist

• ketamine can cause blackouts

GABA

Receptors: GABAa and GABAb

Has inhibiting experiences

Alcohol is a GABA agonist

is the break of the nervous system

when GABA is messed with can cause anxiety attacks to seizures

acts opposite of glutamate

prevents formation of new memories

Acetylcholine

Major areas: basal forebrain and pons- reticular formation complex projects to other forebrain structures

causes muscles to contract

• when messed with, causes muscles weakness and paralysis

Receptor types: muscarinic (autoreceptor), muscarine, Nicotinic

Nicotinic receptor

High affinity subtypes (beta subunit containing sub types)

• A2B2 most well known

Low affinity subtypes (alpha subunit containing sub types only)

• A7 subtype involved in synaptic plasticity

Cateholamines

dopamine

norepinephrine

epinephrine

they are all chemically similar

norepinephrine produces adernaline

• increases in heart rate

• dilated pupils

• involved in fight or flight

Norepinephrine

receptors: a1-2, b1-2

drugs: beta blockers, amphetamine acts like a NE agonist

• beta blockers slow downs the heart rate

• can be used in acute anxiety

mediate flight or fight

works well with epinephrine

Dopamine

four major pathways

1. Tuberofundibular (hormonal role)

2. Nigrostriatal

   • movement pathway '

   • basal ganglia pathway

   • parkinsons

3. Mesocortical (ventral cortical area, midbrain

   • attention pathway

   • ADHD because it concerns with thalamus

   • also concerned with schrizophrenia, which is the opposite of ADHD

   • ADHD concerns with less dopamine

4. Mesolimbic

   • addiction pathway

dopamine receptors

D1 family

• D1 and D5: metabotropic

D2 family

• D2- D4 metabotropic

serotonin

receptors: 5-HT1 and 5-HT7

all receptors are metabotropic

governs the throwing up response

MDMA works directly with serotonin

• very powerful effects in a short time and experience heavy withdrawal effects

• increases heart rate

• also affects appetite

• manages type 2 diabetes

• involved in sleep

• affects the mood

takes place in hypothalamus

adenosine

involved in sleep

receptors: A1, A2, A2B and A3

caffeine binds to A2B receptor and prevents adenosine to bind

adenosine helps you go to sleep easier

Endocannabinoids

receptorsL CB1 and CB2

role in LTD:

• anti cognitive effects

THC acts a CB 1 agonist

• active ingredient n cannabis

• cannabis has effects to calm down

endocannabinoids might be able to control seizures

can also be used as pain tolerance

Endogenous opioids

endorphins (morphine like molecules)

• natural pain relievers

receptors: mu, delta and kappa

pleasure related neurotransmitter system