What is drug? Why is it used? How is it administered? How much is used? Metabolism? Affects on the cell? Addiction? Benefits? Harms? Individual experience may vary

 Nicotine  Caffeine  Cocaine  Amphetamines  MDMA (Ecstasy)  Antidepressants What do these drugs have in common- about how they make you feel/side effects?

Nicotine Caffeine (it IS a drug!) Cocaine Amphetamines Ecstasy Anti depressants

1. Yes 2. Infrequently 3. I tried once 4. I used to 5. No We don’t have clickers, so we won’t do this part, but you should know how it would work in the college setting.

1. Yes 2. Maybe 3. No 4. Doesn’t matter How would this feel to you?

Stimulant Mild euphoriant Calming effect

8-20 mg/cigarette Approx. 10% withstands the burning Smoking contest – 100 cigarettes = lethal From The New Straits Times (August 11, 1997), quoted in What is this graph showing?

 Explain why it would be dangerous (and not just unpleasant) for a toddler to EAT a cigarette (and it happens regularly) Use the numbers provided to justify response.  What is the therapeutic index for nicotine? Use 20.0 mg/cigarette. Why is this only an estimate? Explain.

CYP2A6 How is Nicotine Metabolized? Activity 4 Source: ½ Life 1-2 hours

 Why do you think these studies have been performed?  What might be the difference between an individual with a ½ life of 1 hour and one with a ½ life of 2 hours?  If you were developing a test to see if someone smoked in the last month, what would you test for and why?

1. Hawaiians are likely to have longer intervals between cigarettes 2. Hawaiians are likely to make cotinine from nicotine more quickly 3. Hawaiians will show more tolerance 4. Hawaiians will experience more euphoria with nicotine

Source:

Graphic – Conn McQuinn

Indirect – endorphin release (which calms user) Also, non-nicotine effect of less MAO, prolonging ½ life of serotonin and norepi

1. Na+, when nicotine binds, it stimulates an action potential. 2. K+, when acetylcholine binds, it stimulates repolarization 3. Cl-, when nicotine binds, it hyperpolarizes a neuron. 4. Cl-, when nicotine binds it stimulates an action potential.

Three parts to most addictive drugs 1)Stimulate the reward pathway (get you to reuse ) 2)Develop tolerance (need more to get the same effect) 3) Develop dependence (miss it when it’s gone – withdrawal) a) Increase CYP2A6 b) Desensitization of AchR        a) Miss euphoria b) Miss stabilization of monoamines (not nicotine) c) Endorphin production turned down

1) Unable to quit: tolerance can develop within hours – tobacco 77%, alcohol 40%, marijuana 34%, cocaine 38% 2) Feel sick upon withdrawal – tobacco 35%, alcohol 9%, marijuana 10%, cocaine 19% (revised this to include not just nausea – because alcohol withdrawal can be lethal! 3) smoke more than ONE  15% chance of remaining a non- smoker!

Damage to insula  trivially easy to quit smoking! Insula

 Treat sepsis – infection  Treat hypoglycemia  Treat Alzheimer’s Treat symptoms of Parkinsons Reduce risk as well, although not due to nicotine, but other chemical in tobacco

Diabetes Impotence Mouth ulcers Yellowed teeth, bad breath Premature aged skin

 PMID PMID Non smokers Light smokers Former smokers Heavy smokers 1% 29% 23%61% Damages insulin producing cells in pancreas

nicotine Acetylcholine receptor

CYP2A6 T i m e s i n c e s m o k i n g Nicotine remaining Bad CYP2A6 Good CYP2A6 What genes influence nicotine habits??

1. Nicotine is the alkaloid, tobacco is the plant. 2. Nicotine binds to receptors in the VTA. 3. Nicotine can be lethal at high doses. 4. Nicotine binds antagonistically to acetylcholine receptors. 5. Nicotine is broken down by CYP 2A6.