Unit 1 Flashcards
Drug
Substance that changes the chemical makeup of your body (Not including food)
-Can be legal
-Can be illegal
Acute VS Chronic Drug Taking
Acute - Drug is taken, even the first time
Chronic - Multiple use, even over years
Drug Diversion
Stealing or buying someone else’s drugs, or acquiring them from doctors, pharmacies, or even veterinarians without a valid prescription
Poly-Drug Users
Using more than one drug
Drug Scale in US
1) Tobacco
2) Alcohol
3) All illegal drugs
4) Marijuana
5) Rx drug misuse
Monitoring the Future (MTF)
Association survey 8th, 10th, and 12th graders for their drug use
National Survey on Drug Use & Health (NSDUH)
Those 12 and up. Similar questions while asking about treatment.
-Those who used drugs within the last 30 days are considered regular users
Instrumental VS Recreational Drug Use
Instrumental - Medical use
Recreational - Like how it feels
During early US (first ~100 years), most common drugs
Tobacco, alcohol, and opium
-Mostly taken orally
-OTC (no prescriptions)
-Expired, adulterated, or poorly made
Medical use of early drugs in the US
-Alcohol and opium were anesthetics and painkillers
-Alcohol was (and is) commonly used as a disinfectant.
-Opium and its derivatives (like morphine, codeine, and heroin) are effective against coughing and diarrhea
-Cocaine is a pretty good local anesthetic; it was replaced by Novocain
United States Pharmacopeia (USP)
Database of all medicinal drugs, with a set of standards in how they are made, and recommendations for approved uses
-1820
The First and Second Opium Wars
British East India Company, US via Turkey, began to sell opium to China. Emperor felt that too much money was used to get opium and started a war (mostly w/ UK). Resulting in no control of opium sales, influencing US drug laws.
Opium Discovery
Friedrich Setürner isolate chemical from a plant, discovered morphine in opium in 1804.
-Named after Morpheus due to drowsy, dreamlike effects of opium
Cocaine Discovery
In 1859 Albert Niemann would discover cocaine in coca.
-Drug and chemical experimentation, Bayer markets heroin after altering morphine molecule in 1895
-Vin Mariani, had 36 mg of cocaine
-Powder popular in the 1900s
Route of Administration (ROA)
How a drug is taken
Oral ROA
-Slow route
-Stomach > small intestine > liver (breaks down drug) > bloodstream > brain
-Stomach is v acidic w/ enzymes, breaking down drugs majorly
Insufflation (snorting) / intranasal / transmucosal administration ROA
-Fast
-Nasal mucosa > bloodstream
-Can cross can mucus membrane including sex organs and the rectum
-Sublingual route (under the tongue), also using mucosa
Intravenous ROA
Veins > bloodstream (bypassing digestive system and liver)
-After 1844
-only delivery system w/ no barriers to cross
-Drip - Pump regulates flow in fluid bag
-Push - Quantity of drug pushed into the vein all at once
Chinese Opium Dens
-Commonly smoked by Chinese
-Drank in US as well as morphine
-During gold rush, dens were opened and used by all races
-First US drug law: San Francisco banned opium dens in 1875
Patent Medicines
Businesses making their own “medicines.”
-Claims of miraculous effects, pain relief, ect
-Snake oil salesman
COCA Cola
John Pemberton made a tonic of coca wine and kola nut extract (natural caffeine source) to help morphine addiction from Civil War
-Coca Cola was invented, sold OTC 1886
-Cocaine removed as ingredient in 1903
Freud and Cocaine
1884 wrote a medical article praising cocaine use (praising Pemberton)
-Believed it had mental and medical benefits (curing opium and alcohol addiction)
-Stopped personal cocaine use in 1894 from aversive effects
Pure Food and Drug Act in 1906
Passed by congress doing:
-Require all food and drug needed to be honestly labeled
-Gave authority to what would be the FDA
-Leading to fall out of patent medicine
Elixir Sulfanilamide
1937 used to treat strep infections, led to the death of hundreds because it dissolved easily in diethylene glycol, which was poisonous.
-FDA could only fine them
-1938 a law was passed that companies have to prove their product is safe
Thalidomide
Used as an anesthetic with almost no risk of OD (Common w/ barbiturates)
-Cause the 1962 Kefauver-Harris Amendment
-Used to prevent morning sickness in UK and Germany, later leading to baby death or birth defects
-Is a teratogen
+ & - of the Modern Drug Approval Process
Advantages:
-Drugs legally sold should be reasonably safe
-Better medical decision making
-Prevents companies from misleading the public
Disadvantages:
-Can take 10-15 years
-Is expensive to government and company
-Increases their cost, even in generic medicines
Dirty Drugs
Drugs with more than one action
Investigational New Drug (IND) Application Leads to Clinical Trials
Once FDA is involved, drug goes through three trials. Less than 10% are approved. Prove:
-Drug does what intended
-Dosage and time interval
-Side effects & how to manage them
-Metabolism and how long active
-Other substances safe & unsafe to take w/ drug
Phase I Clinical Trial
-Usually the first time it is given to people
-20-80, 10-100 HEALTHY people
-Show how drug works
-Drug is safe and side effects are well-tolerated
-How long a drug is active, body takes to break down & excrete the drug (metabolism)
-Find maximum tolerated dosage
-Route of administration
-Regimen
Phase II Clinical Trials
-Randomized, controlled experiment
-Usually done many times, costing 10s of millions of dollars
-100-300 participants
-Average of 31% make it
-Testing people with the disease/sickness
-Double-blind placebo-controlled experiment
Phase III Clinical Trials
-Large, multicenter (meaning studies are being carried out at multiple sites), randomized, controlled studies
-Enrolling thousands
-Last about one or two years
-Conducted in as close to normal, real-world medical settings as possible
-Larger sample allows to better see effectiveness
-At least 2 trials
-No minors or pregnant women
Label use
Specific uses for which a drug has been shown to be effective
-DR can prescribe drug for off label use
MedWatch
System for DRs or patients to report side effects as part of post marketing surveillance
Vioxx
approved in 1999 but withdrawn in 2004 after causing heart attacks when company wasn’t required to do clinical trials.
-Peer reviewed journals were required to pre-announcements/pre-registration
-Clinical trial plans must be pre-written
Phase IV Clinical Trials
Not usually required by FDA
-Studies of the drug undertaken after approval
-Can be large scale monitoring of patients prescribed, randomized trials, ect.
-FDA can demand a trial be done and more research be done
-Easier to study once approved
-Sometimes serious side effects only happen in a small number of people
-Can be initiated by the company themselves
-Can approve drugs for more than one use
Black Box Warning
FDA decides benefit outweighs risk of drug, warns of severe side effect
Generic Drugs
Manufactured after original drug’s patent ends
-Selling same product for cheaper
-FDA’s office of generic drugs make sure that the drug is almost identical
-Company must submit an Abbreviated New Drug Application (ANDA)
-Prove does not contain anything harmful, is made safely and consistently, and has the same label as name brand
Evergreening
Companies modify product to extend patent before patent runs out
-Creating an extended-release formulation of a drug
-Creating a new combination of old drugs
OTC Drugs
Drugs deemed safe enough for people to self diagnose, buy drug, and then take it without supervision.
-Drug companies want to sell more OTC because anyone can easily buy an OTC drug, sales go up.
GRASE
Generally Regarded As Safe and Effective.
-Food additives
-Not considered new drugs, do not have to go through clinical trials, but usually cannot be patented
Dietary Supplements
Not considered drugs
-Herbal supplements are like gingko biloba or Echinacea, vitamin and mineral supplements, fish oil, and also blends of natural ingredients that are touted to help you lose weight, focus better, or have more energy.
-Do not have to go through clinical trials, show safety, or effectiveness
-Little regulation
-FDA can removed those mis-labeled and those deemed unsafe
Spanish-American War (1898)
US got territories overseas, Philippines in 1898, which had a growing opium problem, due in part to its proximity to China.
-Potential contribution from Cholera breakout in 1902, Philippines thought that opium cured/prevented cholera.
1914 - Harrison Narcotics Tax Act
At this time everything was considered to be a narcotic
-Required that “every person who produces, imports, manufactures, compounds, deals in, dispenses, sells, distributes, or gives away opium or coca leaves or any compound, manufacture, salt, derivative [thus including heroin, morphine, and cocaine powder], or preparation thereof,” register with the IRS and pay a tax. Done so in hopes to limit trade and possession of drugs.
-In short, GOVT can tax drug trade, sale, and purchase
Marijuana Tax Act
Harry Anslinger, a native of Altoona, PA, huge advocate for stricter laws regarding all drugs of abuse.
Prohibition
1920-1933
Comprehensive Drug Abuse Prevention and Control Act (1970)
-Controlled Substances Act
-DEA created
-Department of Justice
-Meth, LSD
-Schedule 1-5
Schedule I
Heroine, marijuana
-High abuse potential
-Addiction
-No medical use
Schedule II
Cocaine, morphine
-Medical use, 1 prescription no refills, prescription has to be renewed
-Same risk as Schedule I
Schedule III
Steroids
-Less abuse/addictive potential
Schedule IV & V
IV: Xanax
V: Cough syrup with codeine
Drug Action
What a drug does on a microscopic chemical level in the body
Drug Effect
Visible signs of what a drug does on a psychological or medical level
-Observable changes
Dose
How much of a drug taken
-Mg
-Higher the dose, stronger response
Potency
How much of a drug needed to be taken to get an effect
-Fentanyl & LSD are very potent
-Dose given to a person weighing 120 would get the same dose as a person weighing 220
-ED50 - Effective dose to get half of its effect (or effects 50% of those who take it)
Efficacy
Maximum effect a drug can have
-Morphine can provide the same relief as fentanyl, but it takes a higher dose to get there.
-Fentanyl is more potent than morphine, but their efficacy is the same.
Toxicity
Real, measurable damage that a drug can do, including permanent impairment and even death. –Can be short or long term OR acute or chronic
Acute Toxicity
Damage a drug can do from a single dose, or from a small number of doses over a short period of time
-No confirmed cases of death from acute poisoning
LD50
Lethal dose killing the average person
-Should you get to LD50, doesn’t mean you’ll die
Therapeutic Index (TI)
Ratio of LD50 / ED50. How many times greater is lethal to effective?
-High TI is good
Chronic Toxicity
A drug bioaccumulates in the body
-Tobacco, nicotine
Set
Mental set someone is in when taking a drug
Setting
Where someone is when taking a drug
Bioavailability
How much of a drug reaches the blood
Site of Action
Where in the body a drug works
Pharmacodynamics
The study of drug action - What it does at the site of action
Pharmacokinetics
The study of how a drug moves around the body and changes - How it gets there, how it moves around, and how it metabolizes
Lipophilic
Dissolves in and attracted to oil and fat
-Psychoactive drugs must be able to do this
-More easily move around the body
Hydrophilic
Dissolves in and is attracted to water
Lipophobic
Does not dissolve in and is repelled by fat or oil
Hydrophobic
Does not dissolve in and is repelled by water
Cell Membranes: Lipo, hydro, phobic, and philic explained
Cell membrane made of phospholipids which have a hydrophilic part and two tails that attract oil while repelling water (prevents molecules from passing thru membrane).
-Small lipophilic can pass
Blood Brain Barrier (BBB)
Blood vessels in the brain link together and form tight junctions, there’re almost no pores for large and/or lipophobic molecules to pass
-pore channels are made of selective proteins
Area Postrema / “vomit center”
Triggers vomiting when it detects poisons that enter it from the blood
Enzymes
Break down proteins
Inhalation ROA
Inhaling a drug similar to breathing in oxygen
-Smoke or vapor is easily able to quickly pass through lung walls that are rich in blood vessels
-Almost as fast as IV
Subcutaneous (s.c.) and intramuscular (i.m.) injection
Bolus of drug put into bodily tissue where it will stay for a while, and slowly be absorbed into the blood supply
-Along with i.v., most common kinds of injection.
-Subcutaneous (usually pronounced “sub-cue”) injections are just underneath the skin (TB Test)
-Intramuscular injections place the drug into a muscle, often either the deltoid (shoulder) or gluteus (butt) muscle, avoiding the stomach (how must shots are done)
-“Skin popping”
Chippers
People who use drugs occasionally
Transdermal ROA
Patches or creams applied to the skin and contain a drug that slowly crosses into the blood supply
Hepatic First-Pass Metabolism
When a drug is taken orally, it must pass through the liver and are partially broken down first before getting to the heart.
-Stomach > small intestine > liver > heart
Metabolism of Common Drugs
Drugs are metabolized/broken down by enzymes. t ½:
-THC - 1.3 days
-Depakote - 9-16 horus
-Crack cocaine - 48 minutes
-Dopamine - 120 seconds
More of a drug taken, faster it is broken down
Cytochrome P450
Most common type of enzyme
Exogenous
Something made outside the body.
-Most drugs are exogenous
-Some drugs can change how your body expresses enzymes and how other drugs work
-Antidepressants and nicotine
Endogenous
Something made within our body.
-Neurotransmitters and enzymes are endogenous.
Elimination Half Life
The period of time in which the body clears half of the drug from the blood supply. Is influenced by:
-Genetics
-Age
-Experience
-Endo VS exogenous
-Other substances being taken
Precursors
Building blocks for active drugs inside the body
Drug Alteration Process
Precursor (nutrient/pro-drug) >Enzyme> Active drug/neurotransmitter >Different Enzyme> Metabolite
Excitation VS Inhibition
Excitation - Ions that make the cell more positive and more likely to fire an action potential
Inhibition - Ion that makes the cell more negative and less likely to fire an action potential
Once Upon A Firing Neuron
1) In Pre-syn, n/t is synthesized by enzyme
2) Put into a pre-syn vesicle.
3) Cell becomes + as n/t are synthesized, Ca+ channel opens, Ca+ floods in
4) Vesicle merges w/ cell membrane
5)Vesicle released and diffused across the membrane and into the syn.
6) Some n/ts bind w/ the post- syn protein receptors. Cell either becomes + (excite) (closer to firing an AP) or - (inhibit) (less likely to fire an action potential)
7) The n/t is either metabolized/destroyed
8) Reuptaken back into the pre-syn
Cell fires an AP once it reaches a certain threshold
Agonist
Mimic n/t behavior
Antagonist
Blocks n/t activity via blocking the site
Acetylcholine (ACH)
Moves muscles, activates autonomic nervous system
-Released from a small number of cholinergic cells
-Involved in cognitive functions
-Sustaining attention, learning, memory
-Nicotinic receptor - An excitatory, ionotropic receptor
-Nicotine acts as an agonist here
-The muscarinic receptor is an inhibitory, metabotropic receptor
-Nicotine does not bind to this receptor
-Muscarine found in the mushroom amanita muscaria is an agonist at this subtype of cholinergic receptor
-Decreases w/ age
-Alzheimers is extreme ACH loss
-Nucleus basalis in basal forebrain
-Nicotine, AD medications
Dopamine (DA)
Increases urine production, dilates blood vessels, can be turned into norepinephrine
-Important for movement & motivation
-Role in addiction
-Role in attention, memory, and appetite
-D1-D5 receptors
-In the midbrain
-Mesolimbocortical pathway: Ventral tegmental area > Nucleus accumbens > Cortex > Hippocampus
-Mesostriatal Pathway: Substantia nigra > Striatum
Cocaine, meth (amphetamine), Ritalin, antipsychotics
Epinephrine / Norepinephrine
Activates sympathetic nervous system
-Noradrenaline
-Important for arousal, mood, alertness, and wakefulness
-Controls fight or flight
-Role in memory formation and retrieval, and attention
-Drugs reducing norepinephrine are usually for sedation
-Receptors, same as adrenaline
-ɑ (Alpha)
-β (Beta)
-Strattera, Effexor, and Ecstasy
-Locus coeruleus > Hippocampus >
Serotonin
Aids digestion, blood vessel constriction, blood clotting
-Effects mood
+Inhibiting either reuptake or the enzymatic breakdown of serotonin alleviates depression
+Increasing ST levels either causes or relieves anxiety
-Regulate sleep and appetite
-Over a DOZEN types of receptors, each with its own purpose
-Mesencephalic serotonergic cells > thalamus, hypothalamus, basal ganglia, and cortex
-Zoloft, LSD
Glutamate
Excitatory n/t
-Changes synapses to help form new memories
-Ionotropic receptors
GABA
Inhibitory n/t
-Receptor has several binding sites and is ionotropic
-When bound to receptor, keeps gate open and cell becomes hyperpolarized
-Alcohol and anti-anxiety drugs modulate GABA
Central Nervous System (CNS)
-Brain & spinal cord
-All n/t
Peripheral Nervous System (PNS)
-Somatic NS - Body
+ACH (nicotinic)
-Outside of BBB
-Autonomic NS
+Sympathetic NS - ACH (nicotinic), norepinephrine, epinephrine
+Parasympathetic NS - ACH (muscarinic)
Drug Use as A Behavior
People take drugs repeatedly in a way that hurts them, often at higher
doses than would be prescribed for the drug’s instrumental uses (if they have them)
Substance Use Disorder
Psychiatric diagnosis for addiction
-Most sought drug is alcohol
-Men have higher rates of abuse than women
-Native Americans and those of more than one race abuse drugs more
-Asians and Latinx have the lowest rates
-The unemployed are at high risk.
-Some drugs are more addictive than others
Dependence
A person has taken a drug so often that they have a hard time functioning without it.
-Psychological
-Physical
-Is a symptom for SUD
-Everyone who is addicted is dependent, but not all who are dependent are addicted
Withdrawal (Abstinence Syndrome)
A set of symptoms that happen when the drug is not there
-Drives them to continue to use, even when the drug may no longer be helping
-Usually the opposite of the effects of the drug
addicted person may do more dysfunctional and destructive things to continue to acquire it
-Dysphoria
Tolerance
Needing higher doses than they used to, just to get the same effect
Psychological Dependence
Cravings for the drug, and experience states like dysphoria (unhappiness), irritability, and feeling out of sorts when the drug is not present
Physical Dependence
The person has bodily withdrawal symptoms if they go too long w/out it
-Withdrawal
SUD Criteria
2 to be diagnosed mild, 4 or more for moderate, and 6 or more for severe, all over a 12 month period.
-Taking the drug in larger amounts and for longer than intended
-Wanting to cut down or quit but not being able to do it
-Spending a lot of time obtaining the drug
-Craving or a strong desire to use
-Repeatedly unable to carry out major obligations at work, school, or home due to drug use
-Continued use despite persistent or recurring social or interpersonal problems caused or made worse by drug use
-Stopping or reducing important social, occupational, or recreational activities due to drug use
-Recurrent use in physically hazardous situations
-Consistent use despite acknowledgment of persistent or recurrent physical or psychological difficulties from using
-Tolerance (Does not apply for diminished effect when used appropriately under medical supervision)
-Withdrawal, or substance is used to avoid withdrawal (Does not apply when used appropriately under medical supervision, also, the DSM does not recognize withdrawal for hallucinogens or inhalants)
The Four Cs of Addiction
-Cravings
-Loss of CONTROL of amount or frequency of use
-Compulsion to use
-Continued use despite bad consequences
Risk Factors
Factors that correlate w/ heavy drug use, which can tell ahead of time which people who try drugs are more likely to develop problems
-Not set in stone
BIO Addiction Risk Factors
-Genes related to addiction
+Polygenetic inheritance
+Genetic vulnerability
+Receptors, enzymes, and transport pumps for important n/ts
+Inherited and childhood temperament
+Predisposed to criminal activity
+Trauma
+Early use especially for M
-Brain changes from drug use making someone more likely to use again
+Gateway drugs (nicotine)
PSYCH Addiction Risk Factors
-Sensation-seeking and impulsive, with a tendency to act without thinking, and seek out exciting situations and people
-Social M
-Aggressive hostile people are more likely to abuse alcohol
SOCIAL Addiction Risk Factors
-Availability of drugs
-Peer use and opinions on drugs
-Family use and mental illness
-Child abuse and neglect
-Taxation
-Culture norms
-Location/neighborhood characteristics
Pharmacodynamic Tolerance
At the site of action, receptors and proteins have been altered from previous use, making the drug weaker.
-Down regulation, fewer receptors
Pharmacokinetic (metabolic) tolerance
The body can also become more effective at breaking down and eliminating a drug
-From repeated presence of a drug, body will up regulate the enzymes to break it down
-Damage in the area the drug is administered
Behavior Tolerance
Learning to function normally while taking a drug
Cross-Tolerance
Drug causes one or more of the mechanisms of tolerance which makes us tolerant to other substances
Cross-Dependence
A drug that a person is dependent on can be substituted with a similar drug that has the same drug action
What is Addiction?
-A moral failing
-A brain disease
-A result of stress and loneliness
-Not easily definable
Conditioned Place Preference (CPP)
Association of a space with a reinforcing stimuli
-Rat will spend more time in the side of the cage it receives food
Self-Administrative Behavior
Already known behavior (ex, dog salivating at sight of food), usually fulfilling a survival need
Acquisition of Behavior
Original association between stimuli and reinforcer
Extinction of Behavior
The link between the behavior and the reinforcement are severed permanently
Spontaneous Recovery of Behavior
Learned behavior previously extinct immediately comes back
Nucleus Accumbens
Receives an important dopaminergic input from the midbrain
-Part of VTA
-Receives input from the cortex, limbic system, and midbrain, and then sends its output back to the prefrontal cortex
-Can also be triggered from unpleasurable events
Ventral Tegmental Area (VTA) (mesolimbic pathway)
The nucleus of dopaminergic cell bodies
-Starts in the midbrain (a.k.a. the mesencephalon) and ends in the limbic system
-Reward Pathway
-Theory that the pathway exists to motivate survival behavior
-Drugs activate the VTA
+DA block in cocaine and meth
+Indirect, marijuana stops other cells that prevent DA release
Criticism of Addiction Being a Disease
-Just because the brain changes with addiction doesn’t define addiction because everything changes the brain
-People may see it as “Me VS my brain” but you are your brain
-Almost every bad behavior has been proposed to be an addiction, as long as a person does it more than once despite a bad outcome, or doesn’t want to stop
-The current scientific climate overemphasizes medical treatment for addiction.
Cue-Elicited Craving
Craving for drug that comes from experiencing a cue, which can be a place, person, object, or smell
Which is why only 10% of soldiers would relapse after returning home
Drug Interactions
When a drug interacts with something else, having unwanted and dangerous effects
-Drug-drug, drug-food, and drug-condition (medications) are different ways drugs can interact with other substances.
-Drug effect can be amplified, decreased, longer endured, wear it off, ect.
Pharmacological violence
Violence caused by the drug itself
-Some drugs increase violence or aggression as one of their effects.
-Stimulant drugs (alcohol, barbiturates)
-Cocaine (including crack), methamphetamine, and -PCP
-Withdrawal from marijuana and opioids
Economically Compulsive Crime
Drug users engage in crime as a means to get money for their drug.
Systemic Violence
Crime committed due to the trafficking and sales of drugs
-Territory disputes
-Robbery
-Retaliation
-Violence against drug dealers
-Violence against police and bystanders
