parasympathomimetic 

(cholingeric)

not quite as detailed chemical name, reflect effect of the drug

(methamphetamine) 

tolerance that develops from taking a drug in the same setting; 

a new setting can create overdose 

the response to the substance is decreased by cellular mechanisms

brain receptors adapt to continued presence of drug

(down-regulation) 

drug needed to avoid withdrawal symptoms

chronic need for a drug

not tolerance and not addiction 

taking a drug by mouth 

enter instestine, then stomach, then into the bloodstream

drug must be stable in stomach acid 

drugs carried into pulmonary veins to the left side of the heart first, then to pulmonary lung capillaries, to aeorta, to arteries, to brain

rapid absorption because of large surface area of lungs 

sublingual

under tongue, sniffing 

gum chewing

lollipops, pastilles 

drug is administered through transdermal patches that provides continuous and controlled release of a drug from a semipermeable membrane

slowly absorbed

3 types: 

IV

IM

Subcutaneous 

provides more accurate dose; bypasses processs of absorption through stomach and instestine

drug goes directly into bloodstream

precise dosage

allows for more of a drug with higher concentrations that would otherwise cause irritation (diluting) 

DANGEROUS (allergies, blood clots)

Two types:

rapid onsent and short duration

slow onset and prolonged action

specialized structural barrier required for the brain to function normally

a drug must be small and fat soluble in order to penerate the BBB readily 

drugs effects are restricted to outside the CNS if cannot penetrate BBB

median (50%) ionization pH

part of ANS (involuntary) effect 

(fight/flight)

more than one

drug sold in the stores 

propietary (drug manufacturers own patent)

the name when a drug is used recreationally 

cocaine (coke)

some effects are subject to tolerance, but others are not 

example phenobarpital 

treatment of seizures but causes sleeping

sleeping effect is able to be tolerated, but seizure treatment not

Therefore: can eventually take drug without sleeping

tolerance that develops very rapidly following either a single dose or a few doses given over a short period of time.

BAC curve (alcohol) more effects on up-swing than on the down-curve 

there is a decrease in response to one drug due to exposure to another drug due to similar pharmacological action 

(Carbamazepine and fluoxetine) 

more of an enzyme is available 

reduced sensitivity to a drug that results from the increased ability of the body to metabolize the drug 

predrug cues 

CS and CR

psychological and physical changes after stopping the use of the drug

reason for continuation of addiction (unpleasant symptoms)

water soluble 

base in an acid environment 

fat soluble drugs

matching pH (acid in acid environment; base in base environment)

ligand can both bind and disassociate from the receptor

temporary

hug/let go

"something that ties to" (receptors)

types:

drugs

neurotransmitters

hormones

mimicry 

creating a drug that fits better/same as the natural neurotransmitter

the minimum amount of the distributed drug necessary for the main effect

there are different effects for each dose 

you do not get more of one effect with more dosage

describes the time course of a particular drugs effects (onset and duration)

ADME

Administration/Absorption

Distribution

Metabolism

Excretion 

study of a drug's interactions with a drug, explore mechanisms of drug action that occur at the molecular level 

determined by taking desired dose and multiplying by the persons mass 

also measured in mg/dl of blood plasma after administration and absorption

There is no such thing as a placental barrier

baby and mama drugs are passed to each other through passive diffusion (fat-soluble substances diffuse rapidly and readily)

The first and more rapid decline; mainly a result of distribution of the drug from the plasma to other compartments

spreading a drug equally through major tissues of the body

how much of a drug administered of a drug actually reaches its target 

determined by the ADME in pharmacokinetics

socially unacceptable to use the drug 

(alcohol at Houghton)

using a drug in a way it is not intended 

taking the wrong dose

or using drugs that cause problems

using drugs that cause problems 

wrong dosage

responds to neurotransmitters from outside or G proteins from inside the cell

5 subunits with 4 helical coils that cross the membrane 

has a pore that spans membrane of the neuron

 molecules that relay signals from receptors on the cell surface to target molecules inside the cell, in the cytoplasm or nucleus

G-protein is an example (produce cyclic AMP: amplified signal; weak external signal to a strong internal signal) 

transports small organic molecules like neurotransmitters across cell membranes against concentraton gradients 

genetically encoded chains of amino acids; 12 helical arryas of amino acids 

activation of this receptor induces release of an attached intracellular G-protein that controls enzymatic function within the postsynaptic neuron 

change extracellular stimuli into intracellular signals 

break down neurotransmitters 

increase transmitter availability with inhibition by drugs 

examples: acetylcholine esterase 

monoanime oxidase

measures amount of dose with efficacy 

shows potency

steep slope-small amount of dose in between no effect and maximal effect

individual responses to a drug that differ 

steep: small diff b/t dose that produces barely any effect and dose that causes maximal effect

gradual: more diff b/t dose (etc)

The ratio of lethal dose to effective dose (animals)

OR

the ratio of toxic dose to effective dose (humans)

TI=1 (same dose that will help will hurt)

TI=2/1 (twice as much of dose that helps will hurt)

sham or simulated medical intervention that can produce a perceived or actual effect

(sugar pill)

neural pathways in the brainwhich transmit the neurotransmitter dopamine from one region of the brain to another

mesocortical pathway

mesoilmbic pathway 

nigrostriatal tract

transmits dopamine from the VTA to the frontal cortex.

meso (midbrain) cortical (cortex)

nonessential amino acid used as a precursor for GABA

controls cognitive, motor, and sensory function ,as well as "synaptic plasticity" 

does not readily penetrate BBB

synthesized through the breakdown of glucose, converted to glutamine, through presynaptic nerve terminals to active glutamate 

neuropeptide made of 11 amino acids 

a sensory transmitter associated with pain impulses from peripheral sites

dopamine-rich reward center (pleasure and addiction) 

collection of neurons that forms the main part of the ventral striatum (part of the basal ganglia) 

problems in secretion of this neurotransmitter is related to alzheimers disease (therefore, memory)

More ACh=greater memory (and vice versa)

synthesized by one-step reaction of choline and acetyl CoA then stored in synaptic vesicles for release

located in forebrain regions as well as midbrain 

other functions: REM sleep, sensory, energy, mood, attention

dopamine and norepinephrine neurotransmitters in the CNS and epinephrine in the PNS

one-step synthesis reactions except NE synthesis has extra step (oxidation of proximal carbon)

release controlled by autoreceptors with negative feedback mechanism (reduce synthesis and control excess)

inactivated by reuptake and enzymes  

the principal site for brain synthesis of norepinephrine 

branches project to cerebral cortex, limbic system, hypothalamus, cerebllum, and spinal cord 

neurotransmitter located in the upper brain (pons and medulla) 

cerebral cortex, hippocampus, hypothalamus, lymbic system

SSRI (serotonin reuptake inhibitors) for antidepressants and antianxiety

gammaaminobutryric acid

amino acid neurotransmitter 

the major inhibitory neurotransmitter in the central nervous system

binds to transmembrane receptors in the plasma membrane of pre/post synaptic membrane

two types of receptors: GABAa (fast, hyperpolarization, reduce excitability) GABAb (slow, treatment of bi-polar disorder)

an opioid-type peptide associated with pain perception, reward, emotional stability and energy high's

composed of 16-30 amino acids 

opioid-type peptide compsed of 5-amino acids in length

glutamate ionotropic receptor activated by glutamate 

at resting potential its ion channel is blocked by magnesium ions and is relieved when depolarized by activation of AMPA of kainate

binding site for PCP inhibits NMDA functioning 

it regulates synaptic plasticity 

excess: toxicity, rapid cell death, hypoglycemia, traumatic head injury

PROTECT NEURONS BY BLOCKING NMDA ACTIVITY

metabolite of acetylcholine (terminates action of acetylcholine) 

metabolize 50,000 molecules of acetylcholine in one second

change contractile function of the heart

Carbon Monoxide (CO)

Nitric oxide (NO) 

cell manufacturs on the spot, make it dump then bind (not stored in any structure; diffuse into adjacent neurons)

neurotransmitters and neuromodulatorsthat contain one amino group that is connected to an aromatic ring by a two-carbon chain 

Catecholamines (dopamine, norepinephrine, epinephrine)

Serotonin/Enzymes (MAO & COMT)

monoamine oxidase 

enzyme that catalyze the oxidation of monoamines (inactivation of neurotransmitters)

catechol-o-methyl transferase

degrade catecholamines such as dopamine, epinephrine, and norepinephrine

part of the brain situated in the medial aspect of the cortex. 

part of the limbic lobe

precursor to the neurotransmitters dopamine, norepinephrine, and epinephrine

as a drug, used in clinical treatment of Parkinson's disease

crosses the BBB, increase concentrations of dopamine

 a brain structure located in the midbrain that plays an important role in reward, addiction, andmovement.

parkinson's disease is related to death of dopaminergic neurons in this structure

part of basal ganglia 

monoamine neurotransmitter; catecholamine

produced in the VTA and substantia nigra

Parkinson's disease caused by less dopamine

schizophrenia caused by more dopamine

cannot cross the BBB

fight/flight response

neurotransmitter/catecholamine

1. The drug or other substance has a high potential for abuse.
2. The drug or other substance has no currently accepted medical use in treatment in the United States.
3. There is a lack of accepted safety for use of the drug or other substance under medical supervision

1. The drug or other substances have a high potential for abuse
2. The drug or other substances have currently accepted medical use in treatment in the United States, or currently accepted medical use with severe restrictions
3. Abuse of the drug or other substances may lead to severe psychological or physical dependence

1. The drug or other substance has a potential for abuse less than the drugs or other substances in schedules I and II.
2. The drug or other substance has a currently accepted medical use in treatment in the United States.
3. Abuse of the drug or other substance may lead to moderate or low physical dependence or high psychological dependence

1. The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule III
2. The drug or other substance has a currently accepted medical use in treatment in the United States
3. Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule III

1. The drug or other substance has a low potential for abuse relative to the drugs or other substances in schedule IV
2. The drug or other substance has a currently accepted medical use in treatment in the United States
3. Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in schedule IV.

a neurodevelopmental disorder with both positive and negative sysmptoms manifested in ages 16-40

added symptoms are positive symptoms 

negative symptoms are when an individual cannot do what the rest of us can do 

cells are produced taken to where they live and then make connections; less brain tissue and ventricles are bigger in patients of schizophrenia 

In combination hypothesis with dopamine, this is responsible for the negative symptoms of schizophrenia 

perception of objects with no reality usually arising from disorder of the nervous system or in response to drugs

mistaken impression 

50% of hallucinations in schizophrenia are auditory

a persistent false psychotic belief regarding the self or persons or objects outside the self that is maintained despite indisputable evidence to the contrary

(others are out to get me, I am the President, etc.)

the person expresses a very limited range of emotions, even in situations that would normally seem very exciting or very sad.

negative symptom of schizophrenia

negative symptom of schizophrenia 

when a patient is not expressive with words (logos)

negative symptom of schizophrenia

loss in will to do something/motivation

Anhedonia

negative symptom of schizophrenia

the patient deems "nothing to be fun" or pleasurable regardless of circumstances

negative symptom of schizophrenia

patient does not engage with others 

FGA: Butyrophenone

longer half-life

drug holiday of 3 days (allowed to forget to take the drug for one-three days and no harm is done)

more specific D2 blocker

fewer side effects and little sedation

negative side effects: parkinsonism and high prolactin levels

first drug in 23 years introduced to treat schizophenia

worked just as well as haloperidol except those who did not respond to previous drugs responded to clozapine

relieved positive and negative symptoms of schizophrenia

AGRANULOCYTOSIS AND NMS

changed from first-line treatment to last-line treatment

more expensive due to regular blood testing

Acts on DA, 5-HT, ACh, and histamine

best for suicide prevention

Chlorpromazine (Thorazine)

2nd phenothiazine 

1st neuroleptic drug

cut down dopamine activity by blocking D2 receptors

Also blocks: ACh, 5-HT, NE, and histamine 

sedating, sympathomimetic, and antiemetic effects

EPS symptoms: parkinsonism, tardive dyskinesia 

decreased interest in external stimuli

prolactin increases with D2 blockade

Risperidone (Risperdal)

SGA (antipsychotic) drug

Inhibits D2 and serotonin-2 receptors

low side-effects and therefore is used as first-line treatment 

well absorbed orally

similar to clozapine, but without the agranulocytosis

27-38 hr. elimination half-life

minimal EPS 

weight gain

low dose blocks 5-HT2 receptors

higher dose increases D2 blockade

Quetiapine (Seroquel)

5-HT2/D2 receptor-blocking action

comparable to haloperdol in that it reduces positive symptoms with little EPS

approved for treatment of schizophrenia and acute bipolar depression 

efficacy for treating schizophrenia with low liability for causing EPS

6 hour half life

major clinical advantage in weight gain 

blocks 5-HT2 and D2 receptors

partial agonist at 5-HT1A receptors 

moderate inhibitor of serotonin and norepinephrine uptake 

(antidepressant and anxiolytic) 

partial agonist at 5-HT1A and 5-HT2A 

D2 antagonist?

first of a new "third generation" because it has a different mechanism of action

stabilizes the dopaminergic system (high levels replaces dopamine with a lesser effect; low levels the drug can produce a net increase in dopaminergic action) 

METABOLIC

weight gain

glucose intolerance

elevation in blood lipids

cardiac electrographic abnormalities