Cocaine administration route

Hitri A., Little K., Ellinwood D. Effect of cocaine on dopamine transporter receptors depends on routes of chronic cocaine administration. Neuropsychopharmacology. 14 205, 1996. 

In neurochemical terms, amphetamine and cocaine boost monoamine activity. Amphetamine has a threefold mode of action first, it causes dopamine and noradrenaline to leak into the synaptic cleft second, it boosts the amount of transmitter released during an action potential and third, it inhibits the reuptake of neurotransmitter back into presynaptic vesicles. These three modes all result in more neurotransmitter being available at the synapse, thus generating an increase in postsynaptic stimulation. Cocaine exerts a similar overall effect, but mainly by reuptake inhibition. The main neurotransmitters affected are dopamine and noradrenaline, although serotonin is boosted to a lesser extent. These modes of action are outlined in Chapter 3, and the neurochemical rationale for drug tolerance is covered more fully in Chapter 10. The main differences between amphetamine and cocaine are their administration routes (summarised above) and the more rapid onset and shorter duration of action for cocaine. 

A two-compartment open linear model has been described for the pharmacokinetic profile of cocaine after intravenous administration.14 The distribution phase after cocaine administration is rapid and the elimination half-life estimated as 31 to 82 min.14 Cone9 fitted data to a two-compartment model with bolus input and first-order elimination for the intravenous and smoked routes. For the intranasal route, data were fitted to a two-compartment model with first-order absorption and first-order elimination. The average elimination half-life (tx 2 3) was 244 min after intravenous administration, 272 min after smoked administration, and 299 min after intranasal administration. 

Adverse effects of cocaine include constricted peripheral blood vessels, dilated pupils, and increased body temperature, heart rate, and blood pressure. Cocaine induces several immediate euphoric effects, such as hyperstimulation, reduced fatigue, and mental clarity, all of which depend on the administration route. The faster the absorption of cocaine, the more severe the effects. In contrast, faster absorption limits the duration of action. For example, the effect from snorting cocaine may last 15 to 30 minutes, whereas effects from smoking may last 5 to 10 minutes. Increased use can reduce the period of stimulation, as addicted humans may develop tolerance. In rare instances, sudden death may occur on the first use of cocaine or unexpectedly thereafter. 

The high-dose transition is defined as a transition phase in which the individual suddenly increases the doses of stimulants or switches to smoking (e.g., cocaine crack ) or IV route of administration (Gawin and Ellinwood 1988). This change leads to a rapid escalation of plasma levels and intense euphoria (i.e.. rush) often with subsequent increase in dosing frequency. In its most severe form, the high-dose pattern is characterized by binges of... 

Abuse of phencyclidine hydrochloride (PCP) is a national problem that has reached epidemic proportions in urban areas of the United States. The drug is inexpensive, readily obtainable, and is usually used in combination with other drugs such as marijuana, heroin, cocaine, and alcohol (Golden et al. 1982). The routes of PCP use include inhalation, ingestion and parenteral administration. 

Evans SM, Cone EJ, Henningfleld JE (1996) Arterial and venous cocaine plasma concentrations in humans relationship to route of administration, cardiovascular effects and subjective effects. J Pharmacol Exp Ther 279 1345-1356... 

There is perhaps no better illustration of the impact of the route of administration than the sad story of cocaine. For centuries, coca leaves were chewed by the indigenous peoples of South America for a boost of energy while working in... 

Perez-Reyes et al.8 estimated that only 32% of a dose of cocaine base placed in a pipe is actually inhaled by the smoker. Cone9 compared the pharmacokinetics and pharmacodynamics of cocaine by the intravenous, intranasal, and smoked routes of administration in the same subjects. Venous plasma cocaine concentrations peaked within 5 min by the intravenous and smoked routes. Estimated peak cocaine concentrations ranged from 98 to 349 ng/ml and 154 to 345 ng/ml after intravenous administration of 25-mg cocaine hydrochloride and 42-mg cocaine base by the smoked route, respectively. After dosing by the intranasal route (32 mg cocaine hydrochloride) estimated peak plasma cocaine concentrations ranged from 40 to 88 ng/ml after 0.39 to 0.85 h.9 In this study, the average bioavailability of cocaine was 70.1% by the smoked route and 93.7% by the intranasal route. Jenkins et al.10 described the correlation between pharmacological effects and plasma cocaine concentrations in seven volunteers after they had smoked 10 to 40 mg cocaine. The mean plasma... 

Cone, E.J. et al., Cocaine metabolism and urinary excretion after different routes of administration, Ther. Drug Monit., 20, 556-560, 1998. 

Cocaine acts as a potent local anesthetic and is a strong CNS stimulant it extends and intensifies the effects of dopamine, norepinephrine, serotonin neurotransmitters [3], The effects of cocaine can vary in relation to the individual characteristics, the administered dose, frequency of use, and route of administration. The intranasal administration causes plasma peak concentrations after 5-20 min, the euphoric effect in 15-20 min with a half-life of 40 min. The oral route involves a slow and low absorption with plasma peak concentrations after approximately 90 min and euphoric effect in 15-20 min. Intravenous plasma peak is immediate, euphoric effect occurs after 4-8 min with a half-life of about 40 min. Finally it may be administered through inhalation of combustion products or crack vapors, with great absorption speed. 

Volkow ND, Wang GJ, Fischman M, Foltin R, Fowler JS, Franceschi D, Franceschi M, Logan J, Gatley SJ, Wong C, Ding Y-S, Hitzemann R, Pappas N (2000) Effects of route of administration on cocaine induced dopamine transporter blockade in the human brain. Life Sciences 67 1507-1515. 

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