cocaine and nicotine

Question 1

what are the different forms of cocaine? (write them in an order of inc. strength)

Answer 1

• oral, IV, intransal (paste = 80% cocaine, cocaine HCl = dissolved in acidic solution
• inhalational (crack = precipitated with alkaline solution, freebase = dissolved in a nonpolar solvent)

Question 2

describe the methods of admin of cocaine and how fast they are

Answer 2

• IV fast onset

- smoking, nasal, oral have slower onset

Question 3

what is the pKa of cocaine? what does that mean?

Answer 3

pKa = 8.7
so cocaine is ionised in GIT
slower absorption and prolonged action

Question 4

describe the metabolism of cocaine

Answer 4

• 75-90% metabolised very fast into ecogonine methyl ester and benzoylecgonine
• 20-90 mins half life
• plasma and liver cholinesterases

Question 5

how do the pharmacokinetics cause addictive capabilities?

Answer 5

• fast onset of action
• short half life
• lots of methods to take drug

Question 6

how does high dose cocaine cause local anaesthetia?

Answer 6

• cocaine (+ve charged)
• can block Na channels to cause effect
• inhibits conduction of AP

Question 7

what can low dose cocaine cause?

Answer 7

• reuptake inhibition
• MAO-A re-uptake inhibitor
• affect reuptake of NA, DA, 5-HT
• doesn’t change affinity or efficacy of dopamine
• just inc. DA in synaptic cleft

Question 8

how does cocaine cause euphoria?

Answer 8

• reduces re uptake of DA into pre-synaptic neurone

- more DA into NAcc from VTA

Question 9

what does acute use of cocaine cause?

Answer 9

• mild moderate effects

- initially positively reinforcing effects

Question 10

what are the positive/reinforcing effects?

Answer 10

• modd amplifciation
• heightened energy
• sleep disturbance
• inflated self esteem
• hyperactive
• talkativeness
• inc. libido

Question 11

what are the effects of chronic use cocaine?

Answer 11

• severe effects

- tend to start to exhibit severe effects e.g. total insomnia, dec. libido

Question 12

what are the negative/stereotypic side effects?

Answer 12

• irritability
• total insomnia
• total anorexia
• dec. sexual interest
• possible extreme violence

Question 13

what are the CV effects of cocaine?

Answer 13

• inc. catecholamines and inc. sympathetic drive on heart = inc. oxygen demand on heart
• vasocontriction dec. delivery of oxygen to heart
• results in ischaemia of heart muscle

Question 14

what are the CNS effects of cocaine?

Answer 14

• vasoconstriction

- hyper-pyrexia (fever) –> epilepsy

Question 15

what do cigarettes produce?

Answer 15

• 95% voltaile substances e.g. N2, Co, benzene, HCN
• 5% particulates e.g. alkaloids, nicotine, tar
  nicotine diffuses out of tar droplets in lings when deposited

Question 16

what is the dosing of nicotine in each method of admin?

Answer 16

• nicotine spray (1mg) = 20-50% effective
• nicotine gum (2-4mg) = 50-70% effective
• cigarettes (9-17mg) = 20% effective
• nicotine patch (15-22mg) = 70% effective

Question 17

what is the pKa of nicotine? what does that mean?

Answer 17

pKa = 7.9
cigarette smoke is acidic so no buccal/mouth absorption
absorption in alveoli is independent of pH

Question 18

what makes nictoine addictive?

Answer 18

• short lasting action

- fast reduction in plasma conc

Question 19

describe nicotine metabolism

Answer 19

half life = 1-4 hours
Hepatic CYP-2A6 metabolised 80% into cotinine
- cotinine is not active and rapidly cleared

Question 20

when nicotine binds to nicotininc receptors, what happens?

Answer 20

stimulates Na transport

Question 21

what are the CV effects of nicotine?

Answer 21

• stimulation of nAChRs leads to SNS activation (inc. HR/SV, vasoconstriction of skin arterioles, vasodilation of coronary arterioles, skeletal muscle arterioles)
• inc. lipolysis, FFAs, VLDLs, dec. HDL
• inc. TXA2, reduced NO

Question 22

how does nicotine cause euphoria?

Answer 22

• nAChRs are found on soma of dopamine nuclei in VTA

- stimulation of these receptors stimulates DA release in the NAcc

Question 23

what are the effects of nicotine on metabolism?

Answer 23

• nicotine leads to inc. in metabolic rate and dec. appetitie
• after stopping, can get weight gain

Question 24

how is nicotine protective against neurodegenerative disorders?

Answer 24

• Parkinson’s: inc. brain CYPs (neurotoxin) –> inc. breakdown of neurotoxins
  Alzheimer’s: dec. beta amyloid toxicity and dec. amyloid precursor protein