Phar 442 - Drugs Of Abuse (Part 1/2)

Front 1

What is the definition of Dependence?

Back 1

A progressive pharmacological/physiological adaptation to a drug resulting in tolerance

Front 2

What is the definition of Tolerance?

Back 2

The same dose of drug producing a smaller effect each subsequent time it is taken

Front 3

How do you know if someone is dependent?

Back 3

Manifests by the appearance of withdrawal symptoms

Front 4

What is the definition of Addiction?

Back 4

A behavioural pattern characterized by compulsive use and obsession with obtaining the drug and its use, as well as a high relapse rate after withdrawal, despite the physical, emotional and societal damage the drug causes to the individual

Front 5

Does it mean that a patient taking opioids for pain is addicted if they show tolerance or dependence?

Back 5

No!

Front 6

What influences the risk for Addiction?

Back 6

Biology, Social Environment, Age and Stage of Development

Front 7

What are the neural pathways that mediate positive reinforcement of drugs of abuse?

Back 7

The mesolimbic dopamine system is the prime CNS target of addictive drugs.

DA neurons in the VTA discharge and release DA onto the nucleus accumbens and the prefrontal cortex

Front 8

What are the three distinct classes of molecular targets that addictive drugs engage in the Ventral Tegmental Area?

Back 8

1) G-protein Coupled Receptors (GPCRs)

2) Ionotropic receptors and Ion channels

3) DA Transporter

Front 9

How do drugs activate the GPCRs of the Ventral Tegmental Area?

Back 9

Addictive drugs cause postsynaptic hyperpolarization (inhibition) and presynaptic regulation (suppression) of transmitter release

Front 10

How do drugs activate the Ionotropic and Ion channels of the Vegmental Trigemntal Area?

Back 10

Addictive drugs enhance the release of DA from DA neurons

Front 11

How do drugs activate the Transporter of the Ventral Tegmental Area and Nucleus Accumbens?

Back 11

Addictive drugs block the reuptake or stimulate non-vesicular release of DA causing an accumulation of extracellular dopamine in target structures

Front 12

Which drugs activate the GPCRs of the Ventral Tegmental Area?

Back 12

Opioids, THCs, GHB

Front 13

Which drugs activate the Ionic Channels of the Ventral Tegmental Area?

Back 13

Benzodiazepines, Nicotine, Ehtanol

Front 14

Which drugs activate the Transporters of Ventral Tegmental Area and Nucleus Accumbens?

Back 14

Cocaine, Amphetamines, Ecstasy

Front 15

Which of the commonly abused Opioids is more common in health care professionals?

Back 15

Meperidine

Front 16

What is the MOA of Opioids for Abuse?

Back 16

Mu receptors in the VTA are selectively expressed on GABA neurons

(which they inhibit leading to disinhibiton and increased release of DA)

Front 17

Why do K-opiods agonists cause Euphoria while K agonists cause dysphoria?

Back 17

Mu opioid receptors inhibit GABA neurons and so increase release of DA.

K opioid receptors inhibit DA neurons.

Front 18

What is the definition of Detoxification?

Back 18

Refers to the treatment of acute withdrawal symptoms

Front 19

What are the options of Detoxification?

Back 19

1) Switch to long acting opioid (methadone) and wean off slowly

2) Clonidne to relieve physical symptoms (DOES NOT RELIEVE CRAVINGS)

Front 20

What is the recommended Opioid addiction Treatment?

Back 20

i) Switch to Methadone or other long acting opioid and wean off

ii) Clonidine, relieves some physical symptoms but not helpful for cravings

iii) If patient is not treated after detoxification there is high chance of relapse

Front 21

How long can withdrawal symptoms of opiod addiction last?

Back 21

Can persist for up to 6 months

Front 22

What are the withdrawal symptoms of opioid addiction?

Back 22

Anxiety, Insomnia, Cravings, Cyclic Changes in weight, pupil size, respiratory center sensitivity

Front 23

What are the benefits of Buprenorphine for Opioid Addiction Treatment?

Back 23

A partial agonist at mu receptors;

1) Low abuse potential

2) Low risk with overdose

3) Minimal withdrawal upon discontinuation

4) Can block heroin effects

Front 24

What is the relative risk of addiction with Opioids?

Back 24

4 out of 5

Front 25

What are the signs of Acute Opioid Toxicity?

Back 25

Coma, Miosis, Depressed Respiration

Front 26

What are the treatment options for Opioid Toxicity?

Back 26

1) Naloxone is an opioid antagonist which reverses morphine/heroin effects within minutes

2) Long acting opioids (Methadone, Buprenorphine) usually administered in supervised setting

Front 27

How is Marijuana prepared?

Back 27

Prepared from the dried flowering tops and leaves.

Hashish (2-20%) from the dried cannabis and compressed flowers extracted for its resin Hashish oil (15-80%)

Front 28

Which of the cannabinoids in Marijuana is a powerful psychoactive substance?

Back 28

Δ9-Tetra Hydrocannabinol (THC)

Front 29

How much THC is in local BC Marijuana?

Back 29

10-20%

Front 30

What is the CNS MOA of Marijuana?

Back 30

1)Endogenous cannabinoids bind to CB1 receptors in CNS

2) THC binds to CB receptors in the brain which causes disinhibtion of DA neurons

3) Mainly presynaptic inhibition of GABA neurons in the VTA which releases DA in reward/pleasure centers

Front 31

How is Marijuana usually administered?

Back 31

Usually smoked and ~3 times more potent by this route compared to the oral route

Front 32

How do the onsets of actions of Marijuana compare ?

Back 32

1) Onset with smoking in seconds/minutes CNS effect duration lasts 2-3 hours

2) Onset with oral administration is within 30min-2hrs , CNS effects last 5-12hrs

Front 33

What are the dose related CNS effects of Marijuana?

Back 33

i) 2mg smoked/5mg Oral: Euphoria well being, relaxation, disinhibtion, fragmented thinking, exaggerated laughter altered time passage perception

ii) >7mg smoked: Marked alteration of time sense akin to LSD sensory changes: lights visual, auditory clarity

iii) >15mg smoked: Psychotic like symptoms, fragmented thinking, impaired memory paranoia, depersonalization, hallucinations, marked sedation

Front 34

What are the other pharmacological effects of Marijuana?

Back 34

1) Tachycardia (dose related)

2) Conjunctival Inflammation (red eyes)

3) Minimal drop in body temperature

4) Minimal decrease in blood pressure

5) Dy mouth and Throat; Irritation in chronic users

6) Increased appetite, anti-emetic actions, decreased IOP and relief of Chronic Pain

Front 35

What are the symptoms of Marijuana withdrawal syndrome?

Back 35

Restlessness, Irritability, Mild Agitation, Insomnia, Nausea and cramping

Front 36

What is the relative risk of addiction with Marijuana?

Back 36

2 out of 5

Front 37

What are long term consequences of Marijuana use?

Back 37

1) Brionchiole/Lung tissues

2) Tolerance/Dependence

3) Mild Withdrawal

4) Apathy, loss of desire to work, decreased productivity, energy, tiredness

5) Impaired memory cognition, relationships

6) Immune system may be compromised, hormone changes

Front 38

What preparations of Marijuana are available?

Back 38

i) Dronabinol; Cannabinoid Agonist, Antiemetic, Appetite Stimulant

ii) Nabilone: Older Δ9-THC analog-Antiemetic

Front 39

What are the adverse effects of Marijuana?

Back 39

Drowsiness, Orthostatic Hypotension, Dry Mouth, Dizziness, Disorientation

Front 40

What are the uses of Marijuana?

Back 40

i) Analgesic

ii) Glaucoma (Decreased IOP)

iii) Ant-convulsant

iv) Hypertension

v) Sedative

Front 41

What are the Hallucinogens?

Back 41

Lysergic Acid Diethylamide (LSD), Mescaline, Peyote alters one's state of consciousness

Front 42

What are the central effects of Hallucinogens?

Back 42

1) Altered Perception

2) After images are prolonged

3) Visual illusions perhaps progressing to Hallucinations

4) Subjective Responses: Increased color perception

5) Non logical thought Sequences

6) Synesthesia 7) Loss of Boundaries

8) Disorientation 9) Feeling of being outside oneself

10) Effect comes in and out

11) Initial feelings of Anxiety and Apprehension

Front 43

What are the factors of a good trip with Hallucinogens?

Back 43

Good set, Setting, Good Quality Drug, Guide or Guardian nearby

Front 44

What are the factors of a bad trip with Hallucinogens?

Back 44

Bad set, Fear, Anxiety, Impure drugs, Anxiety --> Psychosis (most are acute panic reactions)

Front 45

What is the relative risk of addiction with Hallucinogens?

Back 45

Hallucinogens do NOT lead to addiction/physical dependence

Front 46

What are the effects of Hallucinogens outside the CNS?

Back 46

1) Pupillary dilation 2) Tachycardia 3) Facilitation of monosynaptic reflexes 4) Increased body temperature, pulse rate, respiratory rate and systolic BP

Front 47

What is the MOA of Hallucinogens?

Back 47

Interacts with 5HT2 receptors as an agonist currently though to activate Thalamic 5HT2 receptors causing disruption of Thalamic gating with sensory overloads of the cortex.

LSD mimics 5HT at 5HT1A autoreceptors on raphe cell bodies, producing a marked slowing of the firing rate of serotonergic neurons

Front 48

What are the characteristics of Tolerance for Hallucinogens?

Back 48

i) Develops rapidly

ii) Dissipates rapidly iii) Cross tolerance with Mescaline and Psylocybin iv) No cross tolerance with Cannabis or Amphetamine

Front 49

What are the Toxicity signs of Hallucinogens?

Back 49

1) Most are psychological problems and dose related.

2) Flashbacks (Hallucinogen, Persisting, Perception Disorder)

3) Chromosomal Breakage 4) Teratogenic/Miscarriages

5) Epileptic Foci Activation

6) Problems while under the influence

Front 50

What are the prescription uses of LSD in Canada?

Back 50

There are currently no approved uses of LSD for any of these scenarios

Front 51

What are the preparations of LSD-like drugs?

Back 51

i) Mescaline (Peyote) 200-500mg; Nausea,

Vomitting more prominent i

i) Psilocybin or Psilocin 10-50mg: From Magic Mushroom

Front 52

"Alcohol is likely to contribute to more morbidity, mortality and public health costs than all of the illicit drugs combined" True or False?

Back 52

TRUE

Front 53

What is the definition of Alcoholism?

Back 53

The compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinkers health, personal relationships and social standing

Front 54

What are the Environmental factors that may increase risk of Alcoholism?

Back 54

i) Economic, Social Factors

ii) Employment, Educational Factors

iii) Legal drinking age

iv) Cost of Alcohol

v) Alternative activities for Pleasure

Front 55

What are the Genetic factors that may increase risk of Alcoholism?

Back 55

i) Tolerance

ii) Personality

iii) Predisposition does NOT mean predestination

Front 56

What are the Premorbid condition factors that may increase risk of Alcoholism?

Back 56

i) Maleness

ii) Societal

iii) Related to an Alcoholic

iv) Anti-social people; lack control of environment

v) Unhappy Childhood

Front 57

What are the treatment options for Alcoholics?

Back 57

We cannot treat alcoholics, Alcoholics recover because they want to treat themselves

Front 58

What is the CNS MOA of Alcohol?

Back 58

1) A principal CNS depressant agent

2) Enhances pre & postsynaptic GABA-A inhibition

3) Depresses excitatory transmission (blocks NMDA receptor mediated excitation)

4) Increases the release of DA in the reward center of the brain

5) Releases β endorphins, activation of μ receptors 6) Increases 5HT synaptic levels

7) Increased CB1 activity--> Changes in DA, GABA, Glutamate activity

8) Alcohol increases ACh in VTA with a subsequent increase in the DA in the nucleus accumbens

Front 59

What are the CNS behavioural effects of Alcohol?

Back 59

1) Affects discrimination, memory, concentration, insight, coordination proportionally to blood concentration

2) Increases confidence, decreases ability , increases risk taking behaviour

3) Emotional Swings (happy but also belligerent aggressive)

4) Heavy Drinkers (blackouts, memory deficits) >14 drinks/week

Front 60

Does the behavioural effects of alcohol correlate with Blood Alcohol Concentrations?

Back 60

Yes

Front 61

What level of BAC is the BC driving impairment level?

Back 61

0.05 g/dL

Front 62

What are the characteristics of a BAC of 0.05 g/dL?

Back 62

i) Approximate threshold for impairment of motor coordination ii) Relaxation iii) Lowering of Inhibitions

Front 63

What are the characteristics of a BAC of 0.05-0.15 g/dL?

Back 63

i) A progressive increase in the impairment of motor function (staggering) ii) Slowing of visual accommodation iii) Slurring of Speech iv) Deficits in performance, particularly in focusing attention v) Confusion

Front 64

What are the characteristics of a BAC of 0.15-0.30 g/dL?

Back 64

i) Marked Staggering ii) Irrational Behaviour iii) Blackouts iv) Amnesia

Front 65

What are the characteristics of a BAC of 0.3-0.5 g/dL?

Back 65

i) Anesthesia ii) Respiratory Depression iii) Cardiovascular Depression

Front 66

What are the characteristics of a BAC of 0.5-0.7 g/dL?

Back 66

Death

Front 67

What are the steps of Alcohol metabolism?

Back 67

Alcohol --(Alcohol Dehydrogenase)--> Acetaldehyde --(Aldehyde Dehydrogenase)--> CO2 +H20

Front 68

How is Alcohol dehydrogenase elimination essentially linear(zero order)?

Back 68

Alcohol Dehydrogenase is saturated at low concentrations and therefore the elimination of alcohol is essentially linear

Front 69

What are the effects of Alcohol on the Cardiovascular System?

Back 69

1) Vasodilation of skin, redness, heat loss

2) Hypertension possible when drinking, Hypotension afterwards

3) Chronic Capillary Enlargement "Whiskey Nose"

4) 1-2 drinks/day decreases occurrence of myocardial infarction

Front 70

"1-2 drinks/day decrease the occurrence of MI" True or False?

Back 70

TRUE

Front 71

What are the effects of Alcohol on the GIT?

Back 71

1) Irritating, Increases Acid, Pepsin can lead to Aspiration, Vomitting

2) Diarrhea/Constipation

3) Interacts with NSAIDs

Front 72

What are the effects of Alcohol on the Liver?

Back 72

1) Interacts with Acetaminophen

2) Increases mobilization of Fat, Accumulates in Liver (fatty liver)

3) Can go on Hepatitis Cirrhosis

Front 73

What are the effects of Alcohol on the Kidney?

Back 73

1) Diuretic Action

2) Blocks ADH release 3) Lose more fluid than one takes in leading to

Dehydration

Front 74

What are the effects of Alcohol on the Brain?

Back 74

1) Directly toxic to Brain (worsened by Thiamine deficiency

2) Wernicke's Disease 3) Korsakoff's Psychosis

Front 75

What is Wernicke's Disease?

Back 75

Damage to the Thalamus, Mammary Bodies resulting in Psychosis

Front 76

What is Korsakoff's Psyhosis?

Back 76

Impaired memory, loss of contact with reality

Front 77

What is the effect of Alcohol on Sex/Hormones?

Back 77

1) Decreased Inhibitions, Promotes Desires, Decreases performance 2) Causes Testicular Damage, Decreases Testosterone 3) Gynecomastia (Decreased Testosterone, Decreased LH, ICSH, Increased Prolactin)

Front 78

What is the life expectancy of Alcoholics?

Back 78

Decreased Life Expectancy of 15 years

Front 79

Why is the life expectancy of Alcoholics shorter than the general population?

Back 79

1) Heart Disease 2) Cancers (esophagus, mouth, lungs , stomach) 3) Suicide 4) Anemia (Folic Acid Deficiency)

Front 80

What are the issues with Chronic Alcoholisms?

Back 80

1) Thiamine Deficiency

2) Seizures

3) Decreased Life Expectancy

Front 81

What are the signs of Alcohol withdrawal syndrome?

Back 81

i) 12-16hours: Tremors, Anxiety, Restlessness, Weakness, Cramps, Nausea, Vomitting, Hypotension, Fainting ii) 24+ Hours: Delirium, Convulsions

Front 82

What are the Agents for managing Alcoholism?

Back 82

a) Disulfram

b) Naltrexone

c) Ondansetron

Front 83

What is use of Disulfram?

Back 83

Reinforces one's motivation to abstain Alcohol by accumulating Acetaldehyde

Front 84

What is the MOA of Disulfram for managing Alcoholism?

Back 84

Interferes with the conversion of Acetaldehyde to Acetyl CoA. Acetaldehyde accumulates and produces distressing effects.

Front 85

What are the signs of Acetaldehyde accumulation?

Back 85

1) Flushing 2) Palpitations 3) Dyspnea 4) Nausea and Vomitting 5) Severe Headaches 6) Marked Hypotension

Front 86

What is the MOA of Naltrexone for managing Alcoholism?

Back 86

Decreases the high and desire to drink

Front 87

What is the MOA of Ondansetron for managing Alcoholism?

Back 87

Decreases the desire to drink

Front 88

What are the prescription uses of Alcohol?

Back 88

1) As a solvent 2) Externally as a cooling agent 3) Skin Disinfectant 4) Neurolytic agent used locally to destroy nerves (Trigeminal Neuralgia) 5) Manage Methanol Poisoning