EXAM 1 Flashcards
What is Drug Addiction?
A complex disorder characterized by poor decision making and pathological use of psychoactive drugs that leads to poor social/personal health
What is drug addiction?
It is a complex disorder lead by poor decision making and pathological use of psychoactive drugs that leads to poor social/personal health
Why it is that Aspirin becomes “trapped” in the blood
after it moves from the stomach?
Aspirin moves from the gut to progressively higher pH body compartments and becomes highly ionized in neutral pH blood.
Why are drugs of abuse often inhaled or injected?
Results in the most rapid accumulation of high doses of drug in the brain to produce the greatest euphoric effects
Routes of Administration: Why does it matter?
Depending on objective; if it is for high and fast peak or steady state
What is is difference in applications of drugs for recreational usage vs. medical uses?
Medical use: maintain the minimum effective concentration, over a long time period
Rec use: Highest effect, quickly high quickly low
Imagine 2 agonist drugs used to treat pain. Compound A
is highly effective pain reliever used for post-operative analgesia,
although pain relief is observed only at doses > 5mg/kg. Compound B
is a drug of the same class and exhibits pain relief at 1mg/kg, but has
more modest effects on overall pain thresholds, even at very high
doses. Imagine the dose-response functions for these two
compounds. How would we describe these compounds’ efficacy and
potency in relation to one another?
Compound A has higher efficacy
Compound B has higher potentcy
What is potency?
How much drug is needed to produce an effect; on the x-axis; how potent a drug needs to me
What if efficacy?
maximum effect that can be produced by a drug; y-axis; highest peak on drug
What are partial agonists?
Drugs with intermediate levels of intrinsic activity at a receptor
(compared to “full agonist”)
Example of a partial agonist
Buprenorphine
What are the two properties of a drug that can modulate its efficacy?
- Mechanism of Action
- Intrinsic Activity
Why do some drugs have higher efficacy than others?
The may act on different receptors; less intrinsic activity at the same receptor
Explain the effect of tolerance on a dose-response curve.
What are 2 processes that lead to tolerance?
- Right shift in dose curve
- Learning, homeostatic /enzyme induction (pharmacokinetic ), changes in
receptor number/location (pharmacodynamic)
Changes in a dose curve with tolerance?
Curve shifts to the right
What is the difference between negative reinforcement and punishment?
Negative Reinforcement is taking something away from a system and punishment is adding something to the system to stop a behavior.
A rat was previously trained to self administer heroin. In a new
experiment, that same rat exhibits an exaggerated locomotor
response to an amphetamine injection. What is this effect on the
response to amphetamine an example of?
Cross-Sensitization: Previous exposure to one drug emphasizes the effect of a second, novel drug on a particular response
What is sensitization?
Can occur from many factors including metabolic
Example of sensitization
Heavy Alcohol use leads to reduced capacity to metabolize alc
When can cross-sensitization occur?
-between drugs (coke and amphetamine)
- between drugs and stress
What is a conditioned reinforcer?
a neutral stimulus that acquires reinforcing properties from its association w/ a primary reinforcers
Drugs can be classified in many ways, including what they do, where
they act, and what they are derived from. Give an example of a
natural, semi-synthetic, and synthetic analgesic.
Opium/morphine, heroin, fentanyl
We discussed 2 key enzymes in the metabolism of alcohol. Which
contributes to sex differences in alcohol tolerance, and which directly
controls how bad of a hangover someone gets?
enzyme to contribute to sex differences: alcohol dehydrogenase – women have less than men
enzyme to contribute to hangover: aldehyde dehydrogenase
What is the major difference between the synthesis of
classical and non-classical neurotransmitters?
Classical: Has dietary precursor; synapse at A.T
Non-Classical: New protein synthesis ;Synapse in Soma then travel down A.T
What is the difference between a competitive and non-competitive
antagonist? Relate to response curve
competitive must fight to bind to receptor and non -competitive binds elsewhere onto molecule
On a response curve:
Comp = shifts to the right
Non-Comp = lowers the curve
What is an autoreceptor?
Receptors on a terminal where the same NT binds
We talked about a lot of different self-administration procedures,
which best captures the behavioral and pharmaco-kinetic profile of
drug abuse?
Intermittent Access(IntA) self administration procedure
Which of the two major types of synapses do drugs of abuse typically act on?
Chemical synapses
What are the two major types of synapses in the
brain?
Electrical and Chemical
Starting with the binding of a neurotransmitter to a Gs-
coupled GPCR, describe the pathway leading to a
change in gene transcription.
The catalytic subunit of
PKA can cross the
nuclear membrane to phosphorylate CREB to increase/decrease transcription of certain genes
Where are neurotransmitters stored after synthesis, but before release?
Vesicles
Psychopharmacology
Influence of drugs on behavior and psychological function
Pharmacology
Brand of medicine that deals with the uses, effects, and modes of action of drugs
What is a Drug?
A substance that is used primarily to bring about a change in some existing process or state, be in psychological, physiological or biochemical
Chemical entity or mixture alters biological function outside the maintenance of normal health
Neuropsychopharmacology
Influence of drugs on brain, behavior and psychological function
Neuropharmacology
Influence of drugs on brain function
What are the ways to name and classify drugs?
1.By Source (e.g. manmade or natural)
2. Therapeutic Use (e.g. analgesic)
3.Mechanism of Action (e.g opioid receptor)
4.Chemical Structure
5.Legal / Social status
What are the naturally occuring drugs and where do they come from?
- Opium from unripe seed pods of opium poppy
- Cocaine, from the leaves of the coca plant
- Ephedrine, extracted from Ephedra plant
What are some semisynthetic drugs?
- Heroin from Morphine
- LSD from grain ergot fungus
What are some synthetic drugs?
Fentanyl (synthetic opioid)
Amphetamine (powerful stimulant)
MDMA (Ecstasy: stimulant+ hallucinogen)
Analgesics
Morphine
Codine
What are the Stimulants?
-Amphe
-Coke
-Nic
What are the three main questions of pharmacokinetics?
How much drug?
How Fast?
How long to activate?
Drug Schedule #1
substances that have no accepted medical use and high abuse potential
What are the CNS depressants?
Barbiturates and alcohol
Hallucinogens
LSD and Psilocybin
Drug Schedule #4
Even lower abuse potential than 3
Drug Schedule #2
Substances that have a high abuse potential w/ severe psych or physical dependence liability
Drug Schedule #3
Substances with lower abuse potential than 1 and 2
Drug Schedule #5
Contain limited amounts of narcotics and used for medical use.
Cons of Oral Admin
First pass metabolism – the amount of drug that gets lost in stomach acid before it goes into blood
(Poor control)
Pharmacokinetics
the life and movement of a drug from its site of action till excretion
What is the most common route of administration?
Oral (PO)
Pros of Oral Administration
Easy and more accessible
Slow and steady concentration (No spikes)
ALL Routes of Admin
Oral, IV, IM, SC, Inhale, Topical, Transdermal, Intranasal
Non-invasive routes of drug administration
Oral
Nasal – up nose
Sublingual – under tongue
Rectal – Up anus
Transdermal
Inhale – smoking
What if Half-Life in terms of drugs?
Time for plasma drug conc to fall to half of peak level
Subcutaneous Injection (SC)
Needle under skin, not into muscle
In the skin layer(epithelium)
Intramuscular Injections (IM)
Into Muscle (absorbed faster – more in blood)
Intravenous Injection (IV)
Into Vein – directly into circulatory system
where doesn’t the IV dyes spread e
CSF and Brain
How did the BBB arise?
Distinct properties of brain capillaries
What are the different routes of administration in order from highest peak to lowest (refer to graph)
Inhalation>Injection>Snorting/Sniffing>ingestion
Degree of Ionization
More ionized = less lipid soluble = less absorption = less effect
Brain Caplilaries
More selective (through lipid-soluble molecules)
What kind of drug can pass the lipid bilayer?
-Lipid soluble, neutral, small molecules
Other factors that affect rate of absorption
-Blood circulation at the site of administration
-Surface area available for absorption
-Amount of drug destroyed immediately (e.g. by stomach acids)
-Extent of binding to inactive sites (depot binding
Pharmacodynamics
Subfield of pharmacology dealing with “the study of the biochemical effects of drugs and their mechanism of action
What is a Drug receptor?
the molecule(s) a drug (or other ligand) interacts with, to initiate its biological effects
What is the Law of Mass Action?
Maximal effect when all receptors are occupied; larger drug doses have a larger effect up to a certain point
What are Agonists?
A drug that binds to a receptor and has a biological effect
Do Agonists have intrinsic activity?
Yes
What are Antagonists?
They bind to receptors; have no intrinsic activity
What are the two characteristics of agonists?
potency and efficacy(max effect)
Why do some drugs have a higher potency than others?
- access of drugs to brain – if it is lipophilic or not
- some drugs have a higher affinity than others
True or False: Higher intrinsic activity = higher efficacy
True
Agonist vs. Antagonist
Agonist – makes something happen
antagonist – blocks activity making no reaction
What are the forms of tolerance?
Acute, Protracted, Cross
What are inverse agonists?
If a drug reduces the ligand bonding activity
If drug effect gets bigger, it is…
Sensitization
If drug effect gets smaller it is….
Tolerance
What is Acute Tolerence?
Drug effect decreases rapidly - within a single session
What is Protracted Tolerance?
Drug effect decreases w/ repeated administration
What is cross tolerance?
Drug effect decreases with repeated administration of another drug
Mechanisms of Tolerance
Pharmacokinetic/Metabolic; Pharmacodynamic
What is dependence?
After tolerance, stopping the drug results in withdrawal
- used instead of addiction
Significant characteristics of tolerance
- reversible when drug use stops
- dependent on drug dose, frequency and environment
- can happen rapidly, over long periods or never
Withdrawal results in
opposite feelings from what the drug does
With Sensitization the curve shifts…
to the left
Behavioral Pharmacology
The study between the physiological actions of drugs and their effects on behavior and psychological function
What are Unconditioned effects of drugs?
how drugs affect a wide range of naturally- occurring behaviors (lab experiments)
Conditioned effects of drugs
Train animals to perform tasks; examine how motivated the animals are to work for drugs
What is Drug Discrimination?
A method to ask animals about the interoceptive cues associated with diff drugs(how it feels)
Fixed Ratio
Reinforcement after every n responses
ex. reward after every 5 responses
Fixed Interval
Reinforcement for the first press after a fixed delay
Advantages of a progressive ratio schedule?
Dose response is easier to interpret than FR1
Readily compare different drugs
Limitations to progressive ratio schedules
Just one data point
Long Access Models (LgA)
Administration for six hours a day
Result: Use becomes excessive and uncontrolled
Short Access(ShA)
2 hour sessions
Synapse
Site of action for most psychoactive drugs
Are electrical synapses bidirectional?
Yes
Steps in chemical synaptic transmission
- Synthesis
- Transport
- Storage
- Release
- Receptor binding
- Inactivation
Steps in Secretion
- Open Ca channels
- Influx of Ca
- Bind to Ca calmodulin
- phosphorylation of proteins
- proteins move into vesicles
- exocytosis
What is the most toxic substance on Earth?
Botox
How do NT move/travel?
Diffusion
Terminating synaptic transmission: two ways
Enzymatic degradation
Reuptake
Where do drugs act on the neuron
Outside on he receptors (Ligand binding)
Two Classes of NT receptors
Ionotropic (ligand gated ion channels)
Metabotropic (G-protein-coupled receptors)
What are allosteric modulators
They can bind to receptors, alone have no effect but can modify action of agonist
Ligand-Gated Channels effects
fast and rapidly reversible
how many genes code for GPCrs
one gene; 7 segments; slower than ionotropic receptors
G-protein process
- Receptor binds to ligand
- Activates effector enzyme adenylyl cyclase
- Converts to cAMP
- Activates PKA
- Phosphorylation
- Response
How does it differ from signaling from the membrane to nucleus? (in gpcrs)
Will phosphorylate CREB to increase transcription of certain genes
Second messengers can alter gene regulation
True
Drugs can also have epigenetic effects
True — can change gene expression for a lifetime
