21.02 Nicotine, Addiction and Pharmacokinetics

As discussed previously acetylcholine is widespread neurotransmitter in the autonomic nervous system and central nervous systems. The subtypes of receptors for acetylcholine were initially distinguished by using nicotine and muscarinic, which stimulated different acetylcholine receptors with those being stimulated by nicotine becoming nicotinic receptors. In the periphery, the predominant effect of nicotine is to mimic the sympathetic nervous system. Nicotine does this by stimulating nicotinic acetylcholine receptors on ganglionic cells, and hence the release of noradrenaline, and also by stimulating the adrenal medulla to secrete adrenaline. The noradrenaline and adrenaline then cause an increase in heart rate, vasoconstriction, and a resulting increase in blood pressure.

In the central nervous system, nicotine stimulates N_N-receptors to increase the release of dopamine, which is pleasurable. Nicotine also stimulates memory and alertness. Nicotine also enhances cognitive skills requiring speed, reaction time, vigilance and work performance. In high doses, nicotine causes tremors. Initially when people try smoking, they feel sick, but unfortunately tolerance develops to this effect. Nicotine causes reinforcement, which means the users find it pleasurable, making them wish to take again.

The nicotine in cigarette smoking leads to nicotine addiction. Probably, the best known characteristics of addiction are physical dependence and withdrawal, but they are not the main factor underlying addiction, which is psychological dependence.

Physical dependence is a state that develops as a result of adaptation produced by a resetting of homeostatic mechanisms in response to repeated drug use. With nicotine this will be the repeated stimulation of the sympathetic and central nicotinic receptors. Withdrawal is the appearance of withdrawal syndrome when the repeated use of a drug is stopped. The withdrawal syndrome with nicotine consists of irritability, impatience, hostility, anxiety, depression, difficulty in concentration, restlessness, decreased heart rate, increased appetite, and weight gain. We can treat the physical dependence and withdraw but it is much harder to treat the psychological dependence.

Psychological dependence is the main reason why people take drugs. People smoke cigarettes because they find it pleasurable. Being pleasurable makes the user wish to take the drug/nicotine again, and this is known as reinforcement. The greater the reinforcement, the greater the abuse is.

Nicotine is very addictive, the risk of addiction is measured as the number addicted to the number of ever use, and tobacco is the highest risk with one in three people who try it becoming addicted. The risk of addiction is higher with nicotine than with heroin, where one in four people who try it become addicted.

The term substance abuse or addiction is used to cover physical dependence and withdrawal, psychological dependence and reinforcement. Off these, it is the psychological dependence which is the most difficult to overcome, as we have drugs to lessen the withdrawal associated with the physical dependence.

The pharmacokinetics of nicotine when it is smoked, and when it is used as nicotine replacement therapy, are different. When it is smoked, nicotine is readily absorbed from respiratory tract and buccal membranes, and readily crosses the blood brain barrier. Thus, after inhaling nicotine, there can be a central effect in as little as 7 seconds. The half-life of inhaled nicotine is 2 hours. Nicotine is metabolized mainly in the liver, and nicotine and its metabolites are eliminated from kidney. Nicotine is excreted in the milk of lactating women smokers, making their newborns smokers too.