Drugs of abuse

Question 1

Describe the reward pathway

Answer 1

The mesolimbic dopamine system: Dopaminergic neruones originating from the ventral tegmental area release dopamine in the Nucleus accumbens (ventral straital area) in response to rewarding stimuli.

Question 2

Why does smoking a drug cause a faster absorption than IV?

Answer 2

When smoking the drug passes straight the (thin alveoli) and enters the pulmonary circulation–> pulmonary vein to heart, then aorta to rest of body (brain). IV administration means the drug first drains via vena cava, then pulmonary artery before also entering the pulmonary circulation therefore slower.

Question 3

Describe 4 classes of drugs of abuse and give an example of each

Answer 3

Narcotics- heroin, depressants- alchohol, stimulants-cocaine, miscellanous-cannabis

Question 4

What is the name of the plant that cannais comes from:

Answer 4

Cannabis sativa

Question 5

What is the positive and the negative cannaboid?

Answer 5

Positive: cannabiDIol and negative: delta-9-tetrahydrocannabiNOL

Question 6

What’s the difference between Reefer and Skunkweed? (2)

Answer 6

Great concnetration of cannaboid in more developed Skunkweed (so more potent) and a greater Delta-9THC: Cannabidiol ratio (so stronger association with negative effects)

Question 7

Describe absorption of cannabis a) orally and b) via inhalation?

Answer 7

Orally: 5-15% Inhalation: 25-35%

Question 8

What happens to cannabis in the body?

Answer 8

It forms fatty-acid conjuagtes that are very lipid-soluble and hence accumulate in fatty tissue which is also usually poorly perfused. Can lead to a 10^4:1 ratio in fatty tissue:plasma. One cannabis cigarette can persist for 30 days in the body.

Question 9

Desrcibe the metabolism and excretion of cannabis?

Answer 9

Metabolised to the more potent 11 OH THC in the liver. 65% excretted via the GIT but sereve enterohepatic recycling (lipid soluble). 25% excreted via kidneys.

Question 10

Describe the basic pharmacodynamics of cannabis.

Answer 10

Has two receptors in the body CB1 (neural) and CB2 (peripheral, immune cells). Both are Gi. They are also receptors to the endogenous hormone anandamide.

Question 11

How does cannabis cause euphoria?

Answer 11

Disinhibition of the mesolimbic dopamine pathway by inhibitory CB1 receptors on GABA neurones.

Question 12

Describe 5 other CNS effects of cannabis?

Answer 12

Hypoactivity of anteroir cingulate cortex (monitors performance and makes behavioral adjustments to avoid losses). Also increases food intake by 1) preseynaptic inhibition of GABA neurones, which leads to increased MCH neuronal activity and 2) increased orexin production in LATERAL hypothalamus (not acruate nulcues or ventral medial). Pyschosis/ schizophrenia. Memory problems (decreased BDNF in limbic), Pyschomotor problems.

Question 13

How does cannabis cause tachycardia and vasodilation?

Answer 13

Stimulates vaniloid recepotrs which increase calcium influx. Bloodshot eyes.

Question 14

What is the main component of dronabinol and what is it used to treat?

Answer 14

Delat-9-Tetrahydrocannabinol. Anti-emetic, specifically for chemotherapy patients and AIDS patients.

Question 15

What are the components of saltivex and what is used to treat?

Answer 15

CannabiDIOL and delta-9-tertahydrocannabinol. Used to redcue symptoms (pain reg) in MS patients.

Question 16

What is rimonabant and what was it used to treat? Problem?

Answer 16

CB receptor antagonist. Used to be an anti-obesity drug but led to increased depression and risk of suicide.

Question 17

What plant is cocaine derived from? Concentration?

Answer 17

Erythroxylum coca. 0.6-1.8%

Question 18

Describe the four forms of commercial cocaine. Which two forms are for inhalation?

Answer 18

1) PASTE- 80% cocaine, oragnic solvent. 2) Cocaine HCl 3) CRACK- precipitate with alkaline. 4) FREEBASE- dissolved in ammonia and ether. Crack and freebase are for inhalation.

Question 19

Why is cocaine NOT absorbed well from the GIT?

Answer 19

pKa 8.7 so is ionized in the gut. (The higher the pKa, the less acidic it is, weak acids around 5)

Question 20

Describe the metabolism of cocaine.

Answer 20

Very rapidly metabolized by plasma and liver cholinesterases, so half life only 20-90 minutes. This contibutes to its addictive potential. 75-90% is metabolized to either ecgonine methylesther or benzoylecgnonine, which are inactive metabolites.

Question 21

How does cocaine induce euphoria?

Answer 21

Upatke 1 blocker at dopimanergic synapses (as wellas NA and 5HT)

Question 22

How does cocaine act as a local anaesthetic?

Answer 22

Sodium channel blocker

Question 23

Describe 5 ways in which cocaine contributes to CVD?

Answer 23

Enhanced sympathetic output increase HR, BP and contractility. Cocaine also activates platelets, inducing thrombosis, increases ET-1 and decrease NO from endothelial cells which adds to the vasoconstrictor effect. At high doses, the local anaesthetic sodium-blocking effect kicks in, which can contribute to arrythmia.

Question 24

Describe cigarrette smoke

Answer 24

95% volatile (CO, nitrogen, benzene, hydrogen cyanide) and 5% particulate. (tar and alkalodis like nicotine)

Question 25

Describe possible dosings of nicotine. Which is most effeicient and why?

Answer 25

Gum 2-4mg, spray 1mg, inhalation 9-17mg, patch 15-22mg. Patch is most effieicnt (70% absorption) because pKa of niotine is 7.9- acidic- no buccal absoprtion.

Question 26

Describe the metabolism of nicotine

Answer 26

Hepatic CYP2A6 metabolises 70-80% of it to cotinine. Half life 1-4 hours.

Question 27

How does nicotine induce euphoria?

Answer 27

Stimulates the nAchR on the cells bodies of dopaminergic neurones in the ventral tegmental area. Increases firing rate of the neurone.

Question 28

Describe 5 ways nicotine induces CVD

Answer 28

Sympatehtic stimulation- means increased HR, SV. Increased lipolyis–> FFA and LDL. Increased TXA2, decreased NO.

Question 29

Why does smoking make you lose weight?

Answer 29

Incraesed metabolic rate and decreased hunger

Question 30

What plant does nicotine originate from?

Answer 30

Nictona tabacum

Question 31

Describe how smoking could be neuroprotective

Answer 31

It increases brain CYPs, which metabolise neurotoxins and protects against Parkinsons. It also decreases B-amyloid toxicity and amyloid precursor proetin, which proetcts agains Alzheimer’s disease. .