Stimulants Flashcards
What plant is cocaine from? What is it medically used for?
Found in leaves of Erythorxylon coca (Andes)
licensed use limited to ophthalmic procedures (local anaesthetic/dilatant)
What is the mechanism of action of cocaine?
CNS: Blocks: Dopamine active transporter (DAT) Norepinephrine transporter (NET) Serotonin transporter (SERT) Block increases synaptic levels of these three transmitters.
DAT: Nucleus accumbens – reward and reinforecment effects
SERT: cortex reward and reinforcement effects
NET: Activation of sympathetic system
Increased arterial pressure
Tachycardia
Ventricular arrhythmias
How is cocaine produced?
Cocaine is extracted by
Mashing coca leaves in a gasoline and alkali mixture
Gasoline containing the dissolved alkaloid is drained into a barrel and a dilute acid added (sulphuric) to create aqueously soluble cocaine suphate
Gasoline layer is removed and NaHCO3 is added to neutralise the acid and cocaine hydrochloride precipitates out of solution
Cocaine base is filtered though a cloth and dried
This produces powder cocaine
CocaineHCl can be mixed with baking soda and warmed to obtain “crack cocaine” (freebase)
What are the routes of cocaine administration?
Cocaine hydrochloride is absorbed through mucosal membranes
intranasally via insufflation
inhaled when free base is heated
Injected
Typically i.v.
Often mixed with other drugs (e.g. heroin = ‘speedball’)
The route of administration can be indicative of the level of dependence
Routes produce similar levels of DAT blockade but…
Users report stronger “highs” through inhaled cocaine (speed of delivery)
i.v. wastes less material
What are the short term side effects of cocaine and how long do they last for?
Increased sense of energy and alertness
Extremely elevated mood
Feeling of supremacy
Irritability Paranoia Restlessness Anxiety Dilated pupils Excited, exuberant speech
Numerous peripheral effects (see right)
Duration of action: 0.5 to 2 hr
Describe the long term use side effects of cocaine?
Cardiac:
Increases heart rate and blood pressure
Lethal arrhythmia
CNS: Central vasoconstriction Increased risk of stroke Seizures Bizarre or violent behaviour
Lungs:
Caustic and can damage the nose and sinuses.
Gastrointestinal tract:
Vasoconstriction in gut leading to ulcers or perforation
Sexual function:
Impaired sexual function in men and women
What are the withdrawal symptoms of cocaine?
Depression and anxiety
Fatigue
Difficulty concentrating
Inability to feel pleasure
Increased craving for cocaine
Physical symptoms including aches, pains, tremors, and chills
Formication (feeling of insects under the skin)
Withdrawal is rarely medically serious but very difficult to resist
Can cause suicidal thoughts.
Withdrawal symptoms resolve within 1-2 weeks but intense craving can return even years after the last use.
What are the treatments for cocaine addiction?
There are no approved medications to treat cocaine addiction
Treatment must be comprehensive:
neurobiological
social
medical aspects
Although no approved medication for cocaine addiction, what medications can be used?
Antidepressant and tranquilizers (e.g. desipramine or diazepam) to reduce anxiety and depression.
Amantadine: dopamine reuptake inhibitor used in Parkinson’s Disease may reduce cocaine craving.
Bromocriptine: D2 receptor agonist to decrease the craving for cocaine during detoxification and to reduce mood disturbance
Propanolol: a beta-blocker drug used to treat high blood pressure, may be useful for severe cocaine withdrawal symptoms, as it reduces peripheral effects of adrenaline, inhibiting the “fight or flight” response to stressful situations
What is MPH (Ritalin) usually used for? What schedule is it?
generally recommended as the first choice medication for ADHD in Europe
Schedule II drug, it has high potential for abuse and is available only through a prescription that cannot be refilled
What is the mechanism of action of MPH (Ritalin)?
Mechanism of action similar to cocaine
“amphetamine-like”drug, with regards to the pharmacological, dopamine-releasing properties
Major effect in the basal ganglia
What were amphetamines used for? Which form is abused
Early amphetamine use was primarily via nasal insufflation. In 1932, Smith, Kline, and French began marketing the amphetamine inhaler Benzedrine for use in asthma and congestion.
Methamphetamines - abused as stimulant
What is Methamphetamines abused for?
to increase alertness, relieve fatigue, control weight, treat mild depression, and for its intense euphoric effects
What are the routes of administration of Methamphetamine
often begin with intranasal or oral use
progress to intravenous use, and occasionally smoking.
How long are the duration of effects of Methamphetamine ?
Onset of effects is rapid following intravenous use and smoking, while effects onset more slowly following oral use. Overall effects typically last 4-8 hours; residual effects can last up to 12 hours.
