Nicola Eriksen

Question 1

history of drugs

Answer 1

identified over 2000 years ago and 250 years we have developed useful drugs

Question 2

what are the three historical influences on drugs

Answer 2

civilization
poison
religion

Question 3

Civilization

Answer 3

Ancient Places:
Greece; opium is obtained by opium poppy to relieve pain.
morphine (10% from the plant) and codeine (0.5% from the plant and is similar to Tylenol.
China; Ephedrine is used to treat people with high blood pressure and asthma
Egypt; papyrus used as a textbook drug but caused bowel movements

Question 4

Poison (2 drugs)

Answer 4

Curare:
poison was used to dip their arrows into curare and this would cause paralysis and death in the animal’s
drug was used to relax muscle tension for procedures
Ergot:
found on rye wheat, poison effects were hallucinations, constriction of blood vessels (limbs could fall off), violent contractions of the uterus. used this during pregnancy to help deliver the baby out faster
drug effect was used as two types Ergotamine (used to treat migraines, one believed it was due to palpitations that caused migraines; this drug constricts blood vessels) and Ergonovine (to help blood bleeding after childbirth)

Question 5

Religion

Answer 5

medicine men acting as a med school student and priest thought certain drugs were so powerful that communication could occur with god
in Mexico a certain cactus was used for a mystical state, it caused hallucinations, feeling of well-being, and similar effects of distortion to LSD

Question 6

Article Question

What compounds were found in the ancient tablets?

Answer 6

zinc oxide was found there and is now in creams, including diaper rash creams, and calamine lotion

Question 7

Reserpine and chlorpromazine (acting on the brain)

Answer 7

chlorpromazine is used over reserpine as it is difficult to prescribe it, they are used to treat patients with anxiety, tense, hostile, into someone who is placid and tranquil

Question 8

LSD (acting on the brain)

Answer 8

• similar structure to ergotamine and ergonovine
• psychedelic effects of LSD suggested mental illness people who experience these effects might be due to potent substances in the brain that could produce psychic disturbance

Question 9

Anesthetics (two drugs)

Answer 9

Nitrous Oxide - known as the laughing gas, however, caused a volunteer to become aggressive and hurt himself but never felt the pain, later was used by a dentist by extraction of the teeth
Ether - soon ether become an anesthetic drug in hospitals in Massachusetts

Question 10

drugs acting against infectious diseases

Answer 10

Organoarsenicals - bounded to parasites and cured syphilis
Sulfa - is a synthetic drug (a drug similar to narcotics) where it was the first to treat bacterial disease
Penicillin - first antibiotic
Streptomycin - treatment in tuberculosis and gram-negative bacterial diseases

Question 11

what are the steps of drug development process

Answer 11

1) Drug Discovery
2) Pre-Clinical (is the drug safe and effective? - first, need to look at toxicology studies (effecting other organs) and pharmacology studies (ex how it will lower blood pressure)
3) Clinical Trials: Initial Steps, phase 1 (conducted to a limited amount of healthy volunteers), phase 2 (a bit larger and is to treat individuals who are unhealthy), phase 3 (controlled randomized clinical trials, massive group of individuals who are affected by the disease)
4) Health Canada Review (if toxicity is acceptable and the drug is effective it will move onto manufacturing)
5) Manufacturing (bioequivalent, two drugs that are generic and brand name, have the same active ingredient(s) and give similar blood levels)
6) Phase 4, post-approval (post-marketing surveillance)

Question 12

Drugs target two places where

Answer 12

• receptors; drugs that bind to and stimulate a receptor are called agonists and drugs that bind/block response at the receptor are called antagonists.
• others without receptors; chemical reactions and physical-chemical forces

Question 13

Drug Response

Answer 13

• dose-response relationship where dose is defined to the amount of drug taken
• dose-response curve - once enough receptors are stimulated it will reach a threshold and have a linear response. However, an increase in this drug will cause no therapeutic effects but only adverse effects

Question 14

Efficacy and Potency

Answer 14

Efficacy - (effectiveness of that drug like morphine and aspirin, morphine is more effective than aspirin) max pharmacological response
Potency - (how much dose of the drug to treat the individual) dose of that drug to cause a response usually around 50% of maximal response of that drug

Question 15

Therapeutic range

Answer 15

the aim is to give a dose above the minimum therapeutic concentration in order for the dose to have a response and to stay below the toxic concentration. (in between)

Question 16

pharmacokinetics

Answer 16

movement of a drug into, through, and out of the body

Question 17

Administration of a drug

Answer 17

Topical - on the skin (treat acne,etc), through the skin (gets absorbed in like a patch), Inhalation ( through the lungs)

Enteral - mouth (when a drug is first absorbed through the blood by the GT it then goes to the liver where enzymes can decrease the amount of active drug left, this is called first-pass effect), Rectum (can be used to bypass the stomach and small intestine), sublingual(under the tongues) and buccal(the cheek) (enzymes of stomach, liver and small intestine is bypassed)

Parenteral - intravenous( directly into the blood), intramuscular(directly deep into a muscle), subcutaneous (drug is injected into the deepest layer of skin)

Question 18

Bioavailability (administration)

Answer 18

as the fraction of administrated dose that reaches the systemic circulation (blood) in an active form

Question 19

absorption

Answer 19

• the movement of the drug from the site of administration into the blood
• must be able to cross the biological membrane

Question 20

Distribution

Answer 20

• is defined by the drug being moved by the blood to the site of action and other tissues
• can also lead to termination

Question 21

Metabolism

Answer 21

• Biotransformation is another term for metabolism
• conversion of a drug into another chemical compound
• products of metabolism are metabolites that usually get terminated out of the body
• majority of biotransformation occurs in the liver
• to be excreted out as a metabolite in the kidneys it must be a water-soluble product
• see phone for image

Question 22

Excretions

Answer 22

Kidney, GT(feces) after biotransformation from liver, Lungs, Breast Milk, Saliva and Sweat

Question 23

what does it mean by the half-life of a drug?

Answer 23

means it takes the kidneys and liver to remove half the drug out of the body

Question 24

variation in drug response - why do people respond to drugs differently?

Answer 24

Genetic - some individuals can be slow at biotransformations
Environmental - exposure to a certain drug can increase the chance of more enzymes to get rid of that drug more often
Other Disease States - the presence of a disease can alter the manner of that drug - example; someone with liver disease will have a slower metabolism
Altered Physiological States - age when we get older things slow down and get altered slowly to excrete drugs and could cause a greater effect on this individual - pregnancy, women who are pregnant are already going through many symptoms
Other Drugs Present - when multiple drugs are taken at the same time, it is possible that one drug can alter the second drug leading to variability in drug response

Question 25

Drug Toxicity

Answer 25

Adverse Effect and Drug-Drug and Food-Drug interactions

Question 26

Adverse Effect

Answer 26

extension of therapeutic index - overdose unrelated to the main drug action - nausea allergic reaction drug dependence and addiction teratogenesis - drug develops defects in the developing fetus adverse biotransformation effects - a drug can turn into a chemically reactive metabolite that binds to tissues and affects the organ

Question 27

Drug-Drug interactions

Answer 27

Absorption - a drug can increase the speed of intestinal movement therefore when a second drug passes by it passes by faster and will not get absorbed Metabolism - a drug can block another drug in the liver causing an increase in blood level and pharmacological effect on the second drug Excretion - a drug can facilitate the excretion of a second drug by the kidney causing decrease blood level and pharmacological effect on the second drug

Question 28

Drug-Food interactions

Answer 28

Tyramine - found in cheese, it is able to raise blood pressure and is broken down by the liver with an enzyme called MAO. If a patient is receiving an antidepressant to inhibit MAO and they eat food with tyramine, it will not be broken down, causing a greater intensity of blood pressure. Grapefruits - will inhibit an enzyme that biotransforms certain drugs that are located in the GT. Grapefruits will cause more of the drug to absorbed because it has not been broken down causing an increase in blood levels - leading to overdose.

Question 29

The CNS

Answer 29

Brain and Spinal Cord

Question 30

The Brain three regions of the brain

Answer 30

Forebrain Midbrain Hindbrain

Question 31

Forebrain

Answer 31

cerebral cortex - largest part of the brain, sensory and motor coordination, mental processes, intelligence, memory, vision, judgement, thought, speech, emotions, and consciousness. can be stimulated (excited) or depressed (inhibited) Thalamus - relay motor and sensory signals to the cerebral cortex Limbic System - integrates memory, emotion, and reward. its controls emotion and behaviour with the hypothalamus Hypothalamus - releases hormones pituitary gland - secretes hormones

Question 32

Midbrain

Answer 32

- links the forebrain with the hindbrain | - relays information for visual (eye) and auditory (hear)

Question 33

Hindbrain

Answer 33

pons - connect the midbrain to the medulla and cerebellum, involved in conducting information to these places first receiving it from the cerebral cortex medulla - site of many cranial nerves, controls our digestive, respiratory, and circulatory systems cerebellum - responsible for coordination and balance, such as alcohol disturbs this region of the human body

Question 34

neurogenesis

Answer 34

neurons are generated continuously

Question 35

neuroplasticity

Answer 35

constantly being reshaped

Question 36

chemical in nature

Answer 36

a substance that is released by a neuron to activate the next neuron

Question 37

Neurotransmitters

Answer 37

glutamate - primary excitatory NT in the CNS, it acts on receptors called glutamatergic, these are important for learning GABA - a primary inhibitor of the CNS, GABAergic neurons and receptors found high in the cerebral cortex, hippocampus, and cerebellum. A number of depressants (benzodiazepines) enhance GABA receptor function Acetylcholine - produces an excitatory response in CNS, Nicotinic receptors; stimulated by acetylcholine and nicotine, muscarinic receptors; involved in learning, memory, and cognitive function, stimulated by acetylcholine and muscarine. Drugs that block acetylcholine at receptors are thought to have amnesia and Alzheimer's disease Catecholamines - Dopamine and Norepinephrine; dopamine controls hormonal systems, motor coordination, and motivation and reward..... can lead to Parkinson's disease and schizophrenia if pathway damaged. And norepinephrine, bing to two large receptor types a and b. and leads to excitation. Serotonin - the happy chemical, hyperactivity of the serotonergic system involved in anxiety and hypoactivity implicated in depression. Opioid Peptides - there are three; enkephalins, endorphins, dynorphins. they all go to three receptors mu, delta, kappa

Question 38

substance use disorder

Answer 38

when a person uses a drug or the substance leads to health issues, problems at work, home, school, etc.

Question 39

factors influences sbstance use disorder

Answer 39

Genetics - ex sons that have alcoholic parents with become alcoholics compared to sons without alcoholic parents Coexisting Disorders - ex, people who already experience anxiety, depression, schizophrenia..... are at higher risk Environmental Factors - family, work, friends, like social group, pressure, however, well stable support will decrease this chance Developmental Factors - adolescence and young adults are more at risk

Question 40

Dopamine reward

Answer 40

the more dopamine the greater the reward (limbic system) the more use of that drug. As-well, food and sex plus video gaming and gambling are not drugs but can add to dopamine effects. However, drugs cause a great amount of dopamine to be released into the synaptic cleft

Question 41

Addictive drugs classed into three categories

Answer 41

1) Increase dopamine - CNS stimulants; cocaine, nicotine, caffeine, amphetamines. Opioids; Morphine, Heroin, oxycontin, and others; alcohol, and weed 2) Produce Novelty - LSD and Ecstacy (MDMA) 3) Reduce Anxiety - CNS depressants can become addictive because they reduce anxiety such as; benzodiazepines and barbiturates

Question 42

Abuse Potential of a Drug (three factors)

Answer 42

1) Dependence Liability - the tendency of the drug to cause dependence and addiction. it is determined by three factors. 1) Nature of the drug - drugs act as reinforcers, the ones giving pleasurable effects will cause that individual to take more than is needed. 2) Route of administration - drugs that have the ability to be absorbed faster will tend to be more abused. 3) Amount/Frequency - greater the dose and greater the use will lead to abuse like alcoholics 2) Availability - the more widespread a drug the more potential to be abused 3) Inherent Harmfulness - potential of a drug to cause harm, such as methanol alcohol can cause blindness and death from a little amount, it's widely available but not used as much

Question 43

Drug Dependence

Answer 43

leads to withdrawals - causes fear in people which is the continuous habit to take drugs

Question 44

Drug Addiction

Answer 44

when an individual tries to stop the drug but the cravings take over

Question 45

Drug Tolerance

Answer 45

become tolerant to a drug where it no longers has a pharmacological effect

Question 46

stimulate drugs

Answer 46

amphetamines cocaine nicotine caffeine

Question 47

Amphetamines

Answer 47

-are controlled substances (that the use of this drug is only used to treat certain medical conditions) -drugs included are: Amphetamine, Dextroamphetamine, and Methamphetamine others related: Methylphenidate (Ritalin treats both narcolepsy ADHD) used to treat ADHD -this drug is similar to ecstasy (MDMA) -narcolepsy (a chronic sleep disorder)

Question 48

What does Amphetamines do?

Answer 48

- decreased threshold for transmitting sensory input to the cerebral cortex, increase excitation - feeling of euphoria and reward - temperature-regulation and appetite suppression - increase in aggressive behaviour and mood swings

Question 49

abuse potential and dependence of amphetamines

Answer 49

-this drug gives you the feeling of euphoria and a effective stimulus for the CNS, for this reason, this drug is widely abused Abuse Potential - abuse liability - nature of the drug, due to the euphoria effect, route of administration can rapidly get into your system as it is water-soluble and Inherit harmfulness is cardiovascular effect but this doesn't see to be a big enough problem Dependence: Tolerance - occurs to the mood-elevating effects and euphoria but not the therapeutic effects Dependence - mood depression, lack of energy, prolonged sleep, huge appetite Addiction - cravings of euphoria are massive and can cause panic attacks

Question 50

cocaine

Answer 50

- as a local anesthetic and stimulant of CNS, it is a narcotic and popular recreational drug - blocks the re-uptake of dopamine and serotonin in pre-synaptic which then stays in the synaptic cleft and will activate the post-synaptic neuron receptors - cocaine only lasts less than an hour compared to amphetamines that last 12 hours - it is a local anesthetic for mouth and throat but there are better anesthetics out there that does not cause dependence liability

Question 51

abuse potential and dependence with cocaine

Answer 51

-abuse liability is very high, are a massive euphoria -inherent harmfulness is low physical and psychological effects but it is not massive enough to stop the user -dependence: Tolerance - only affects the mood-elevating Dependence - mood depression, lack of energy, prolonged sleep, huge appetite addiction - pleasure and rewarding which causes the reinforcement

Question 52

Nicotine

Answer 52

found in tobacco 1) Absorption - very small particles that get rapidly absorbed from the GT, oral mucosa, and across the skin 2) Distribution - fast and gains access to the brain 3) Metabolism - rapidly metabolized in the liver 4) Excretion - metabolites are secreted in the urine and half-life of nicotine is about 2 hours - nicotinic receptor-mediated release of the CNS neurotransmitters, dopamine and serotonin - passive-smoker

Question 53

abuse potential and dependence of nicotine

Answer 53

abuse potential - high degree of abuse liability dependence: Tolerance - does not appear to be great, only need to keep the same levels of nicotine in the body Dependence - irritability, restlessness, anxiety, insomnia, fatigue, inability to concentrate Addiction - occurs, and manifest to have an extreme urge to smoke

Question 54

Caffeine

Answer 54

nicotine increases the metabolism of caffeine therefore, caffeine does not work

Question 55

abuse potential and dependence of caffeine

Answer 55

abuse liability and inherit harmfulness is low dependence: Tolerance - some do in certain individuals Dependence - headaches, fatigue, and drowsiness Addiction - mild addiction can occur

Question 56

amphetamines in sports

Answer 56

- it increases indurance and speed | - withdrawals are huge crashes

Question 57

anabolic steroids in sports

Answer 57

- to increase muscle mass and strength - androgenic effects is reduced in men - second characteristics of men - anabolic effects building of muscle mass

Question 58

anabolic steroid mechanisms

Answer 58

anti-catabolic - athletes can train so hard they use their protein as a source of energy from their muscles to fuel their training anabolic - protein production motivation - this steroid can produce roid range which can be helpful in competition

Question 59

anabolic steroids affect male and women differently

Answer 59

Men - increase in lean body mass, body weight, and strength plus aggressive behaviour Women - increase in facial and body hair, lowered voice, enlarged clit and libido, increased aggression, tough skin - acne, amenorrhea

Question 60

Withdrawals from anabolic steroids

Answer 60

mood swings, increase acne, cardiovascular disease, altered liver function, reduction in testosterone decrease in libido

Question 61

Growth Hormone

Answer 61

increase muscle mass - strength repairs tissue difficult to detect - if they stop using after 2 days before the competition it is hard to find

Question 62

Benzodiazepines

Answer 62

valium a drug that comes anxiety before their competition such as skydivers

Question 63

Blood Doping and Erythropoietin

Answer 63

Blood Doping - is where the athlete removes red blood cells and stores for later. Therefore the body will produce more red blood cells, now when the athlete injects the stored red blood cells back into their blood they will have this sudden increase in red blood cells. Which will offer the athlete mote oxygen where is needed in the body during the competition. -detected by the age of red blood cells Erythropoietin - is a natural hormone the body produces in the bone marrow that produces red blood cells. An athlete would inject themselves more erythropoietin into their bone marrow to make more red blood cells. - thrombotic events can occur - stroke and heart attack - hematocrit levels can be detected - volume percent of the amount of red blood cells in the blood

Question 64

Diuretics

Answer 64

causes kidneys to excrete water and salts from the body in order to lose weight and the athlete can compete at a lower weight level -will cause an increase in electrolytes and water depletion which leads to blood pressure drop and kidney failure

Question 65

sedative-hypnotics

Answer 65

treat anxiety, used as a sedation, hypnosis, used for anesthesia

Question 66

Sedative-hypnotics treat

Answer 66

tries to treat anxiety and sleep - glutamate is the primary excitatory neurotransmitter in the brain. That causes individuals to feel anxious and have a difficult time sleeping. Sedative-Hypnotics inhibits glutamate by GABA neurons which will cause a decrease in glutamate nerve firing

Question 67

Sedtive-hypnotics binds too

Answer 67

chloride ion channel - cause an increase in synaptic and thus damping neural response

Question 68

Benzodiazepines

Answer 68

- high therapeutic index - treat anxiety, sedation, and amnesia - suppress a small amount of REM-sleep - decrease in aggression - can treat seizures - produce skeletal muscle relaxation (diazepam) - antidote = flumazenil

Question 69

Benzodiazepines - abuse potential, tolerence, dependence, addiction

Answer 69

abuse potential: abuse liability - is low have weaker reinforcers inherent harmfulness - is low tolerance - less common dependence - occurs with therapeutic use addiction - may in some users but not all

Question 70

Zolpidem

Answer 70

- bind to GABA receptors to cause sedation, they have an effect on REM-sleep - more sedative then treating anxiety

Question 71

Barbiturates

Answer 71

- used to cause anesthesia and treat seizures - ultra-short (20min) - thiopental - short (3-8hours) - secobarbital - long-acting (1-2 days) - phenobarbital - low therapeutic index - full spectrum of dose-dependent CNS depression - suppress REM-sleep - depress respiratory system - slowing the heart and decrease in blood pressure

Question 72

Barbiturates - potential abuse, tolerance, dependence, addiction

Answer 72

potential abuse: abuse liability - greater than alcohol inherent harmfulness - is very high tolerance - can develop dependence - can occur after chronic use, a form is called postural hypotension (low blood pressure level - can cause an individual to fall over when standing up or stretching) addiction - cravings are high can cause a panic attack if out of reach of the drug

Question 73

GHB

Answer 73

- considered the day rape drug - puts in an area of loss of memory the next day - acts with GABA receptors

Question 74

Buspirone

Answer 74

- treat general anxiety and does not have additive effects with other sedative-hypnotics - acts with serotonin receptors

Question 75

alcohol (ethanol)

Answer 75

1) absorption - by the stomach and small intestine 2) Distribution - distributes across the entire body of water - including placenta 3) Metabolism - 1) ethanol is converted to acetaldehyde by an enzyme called ADH - this is the rate-controlling step 2) some individuals metabolize alcohol fast into acetaldehyde which is great for abuser because excess of this cause an unpleasant feeling 3) another pathway is MEOS - part of the P450 system - it is useful when the other enzyme is running rapidly 4) acetaldehyde is converted into acetate by the enzyme ALDH 5) acetate is further metabolized into carbon dioxide and water by other tissues FACT^ is that alcohol is metabolized at a constant rate - each hour dues to the rate-limiting step 4) Excretion - 95% is eliminated by biotransformation in the liver

Question 76

Alcohol binds to?

Answer 76

alcohol binds to chloride ion channel to inhibit GABA and Glutamate

Question 77

alcohol - abuse potential, tolerance, cross-tolerance, dependene, addiction

Answer 77

abuse potential - high reinforcements and dependence liability is moderate tolerance - occurs cross-tolerance - occurs between sedative-hypnotics and general anesthesia people have a tolerance to alcohol will need a higher dose of these drugs dependence - high addiction - high

Question 78

ways to treat alcohol

Answer 78

disulfiram - inhibits ALDH to keep alcohol in the form of acetaldehyde causing cardiovascular and respiratory changes which are unpleasant feeling naltrexone - stops cravings of ethanol, its blocks the dopaminergic reward to the brain acamprosate - is an ethanol substitute - acts as a GABA activator and a weak glutamate receptor antagonist

Question 79

Cannabis

Answer 79

- forms from a hemp plant - CNS depressant - THC or anandamide (released by the postsynaptic neuron and attaches to receptors on the presynaptic neuron - this process is reversed) and they bind on CB1 receptors located on the brain or spinal cord - CB1 many are in the brain, THC is not very effective here as an agonist - CB1 found in the cerebral cortex and cause distortions of colour, taste, time, sound, cognitive function, and concentrating - CB1 in the hippocampus can cause memory and learning changes - no CB1 are present in the brain stem, thus doesn't depress the respiratory system - CB2 found outside the CNS, they are not involved in the psychotomimetic effects but only in inflammation, binding THC to CB2 on lymphocytes is thought to be responsible for immunosuppressive properties of THC

Question 80

THC Facts

Answer 80

- slowly metabolized and has a half-life of 30 hours | - long term effects is amotivational syndrome mental slowing, loss of memory, loss of ambition, and emotional flatness

Question 81

Abuse - THC

Answer 81

abuse potential: dependence liability and inherent harmfulness are both low tolerance - can occur to psychoactive properties dependence - occurs with high doses addiction - more evident in users who use it for psychoactive properties - search for that craving to feel less stressed

Question 82

narcotic analgesics

Answer 82

release pain opiate - any drug that came from opium opioid - opiates, related to morphine (structurally), or different from morphine, endogenous peptides that exert analgesic actions (ex - endorphins) -endogenous substances called endorphins bind to these specific receptors -three families of endorphins; enkephalins, dynorphins, and b-endorphins -endorphins (associated with reward pathways in the brain) can act as neuromodulators that activate and deactivate neurotransmitters

Question 83

opioid receptors

Answer 83

MU - in the brain and spinal cord, cause analgesia and responsible for morphine-mediated depression of respiration in the brain stem KAPPA - analgesia, dysphoria (unease), and miosis (pinpoint pupils) DELTA - analgesia levels at the brain and spinal cord, emotional response too what these receptors do is when opioids bind to these receptors they will stop the pathways of pain

Question 84

Therapeutic use of opioids

Answer 84

analgesia - to help pain in surgeries diphenoxylate (Lomotil) - control diarrhea cough suppressants

Question 85

abuse potential of opioids

Answer 85

abuse potential: -opioids have very high euphoric and analgesic effects -oxycodone and hydrocodone are prescribed meds but users can get addicted as these pills have long-lasting (12hours) analgesia effects inherent harmfulness: -high does life-threatening -opioid antagonist naloxone is used when people overdose from opioids -naltrexone opioid antagonist that treats alcohol dependence

Question 86

opioid tolerance, dependence, and addiction

Answer 86

tolerance - effects the pharmacological effects dependence - very high addiction - can develop -treatment is methadone less abused