M2s2 Amphetamines And Cocaine Flashcards
Amphetamines and cocaine are two classes of blank drugs that have a history if being misused
Stimulant drugs
Overview of amphetamines
- look at good notes for image
-amphetamines are drugs of widespread misuse and are controlled substances (restricted to certain medical conditions like narcolepsy) in Canada
Chemistry
-synthetic organic compounds
-structurally similar to endogenous neurotransmitters norepinephrine and dopamine
-can be synthesized readily, resulting in illicit manufacturing of these substances, especially methamphetamine
-purity of these ilicit substances is variable
-may contain side-products of the chemical rxn, uncreated chemicals and “cutting” or filter agents (ex starch, baking sofa) which may be dangerous
Amphetamines and related compounds
-drug class includes amphetamine, dextroamphetamine, methamphetamine
Amphetamine-related compounds include:
Methylphenidate (Ritalin): used to treat attention deficit hyperactivity disorder (ADHD)
MDMA (Ecstasy): derivative of methamphetamine that is often misused, fosters the feeling of intimacy and empathy while improving intellectual capacities. It is neurotoxic, causing neuronal damage and death. Effects long lasting if not permanent
Pharmacology of amphetamines
-mechanism of action of ecstasy is similar to amphetamines, but it has a preferential effect on serotonin containing neurons and causes release of serotonin
-overall effect of amphetamines is standard - increase excitation by increasing the amount of dopamine or norepinephrine in the synaptic cleft
Do this by:
-amphetamines are substrates for the dopamine transporter which is the transporter that clears dopamine out of the synaptic cleft after neurotransmission.
-so, amphetamines compete with dopamine for the dopamine transporter
-results in amphetamines ending up in the presynaptic nerve
-once in this nerve, amphetamines block vesicular monoamine transporter, which brings dopamine into vesicles to be packaged for release when the next nerve impulse arrives
-since dopamine blocked from being packaged into vesicles, large increase ion the concentration of free dopamine in the neuron
-large concentration of dopamine in neuron forces the dopamine to travel through the dopamine transporter in the reverse direction, meaning back out into the synaptic cleft
-result is an increase in dopamine in the synaptic cleft and hence, an increase in CNS excitation
-same mechanism of action applies for norepinephrine, just with norepinephrine specific transporters
Amphetamines: CNS effect
4 major effects within CNS
- Decrease threshold for transmitting sensory input to the cerebral cortex, leading to CNS excitation
- A feeling of euphoria and reward
- Temperature-regulation and feeding centre modifications leading to appetite suppression
- An increase in aggressive behaviour and mood swings
The common amphetamines differ in the magnitude of their CNS effects
CNS excitation
Causes:
-increased alertness
-reduced fatigue
-increased heart rate and blood pressure
-overstimulation
-restlessness
-dizziness
-mild confusion
-tremor
In rare instances:
Panic and psychosis, especially with higher dose
Other effects of amphetamines
-additional to CNS effects, amphetamine use has different effects depending on duration of use and whether it is used concurrently with other drugs
Short term use
-short term effects of amphetamine use in non-CNS tissues may include:
-chest pain (I.e. angina) or heart attack
-cardiovascular collapse
-increased respiratory rate
Overdose may result in seizure, high fever, or stroke
Insomnia physiological effect
Effects of long-term use
-chronic sleeping problems
-poor appetite
-anxiety, repetitive behaviour, psychoses, aggressive behaviour
-elevated blood pressure and abnormal cardiac rhythm
Concurrent drugs use
-other drugs may be concurrently with amphetamines in attempt to antagonize various toxic effects of amphetamines
Ex. Individual who is experiencing sleeping problems due to chronic amphetamine, use may seek out an CNS depressant (e.g. benzodiazepines) to try to help them sleep
Alternatively, individual experiencing drowsiness due to options may speak out CNS stimulant (e.g. amphetamines) to be more alert and responsive during the day or while preforming tasks
*** could lead to additional issues such as drug-drug interactions, missing of additional drugs and potentially SUDs
Cardiovascular collapse
Severely low blood pressure resulting from a failure of the heart to pump blood around the body
Therapeutic use of amphetamines
Narcolepsy - chronic sleep disorder
ADHD - consists of hyperactivity, impulsivity, and/or difficulty controlling or refocusing attention. Drug therapy can calm hyperactivity and improve attention and control, enhancing task completion and scholarstic/occupational performance
Methylphenidate (Ritalin) can be used to treat both of these disorders due to decreased incidence of both cardiovascular and appetitive suppressing effects, compared to amphetamine
Amphetamines potential for misuse and SUD
-amphetamines produce euphoria and are effective CNS stimulants; so often misused
-mostly taken orally, injected or smoked
-occasionally sniffed or snorted
Potential for misuse
-extremely high as amphetamine and methamphetamine produce powerful euphoria
-water soluble salts form of the drug allow for large dose that readily injectable, resulting in rapid and intense response
-inherent harmfulness of amphetamine due to long-term toxicities, including cardiovascular effect and drug-induces psychoses
-not appear to be a deterrent to misuse and those involves with chronic use of amphetamines and long-term intravenous drug administration are at risk of substantial health problems
Potential for SUD
Tolerance - develops to the euphoria and mood elevating effects, the anorectic (substance produce loss of appetite) effects, cardiovascular and respiratory stimulatory effects and lethal effects of drug use. However tolerance does not develop to therapeutic effects or drug-induced psychosis
Withdrawal - cessation of use results in mood depression that may be profound, prolonged sleep, huge appetite, lack of energy, fatigue
Addiction - usually self-administered to produce euphoria and an abrupt awakening sensation (“rush”). These effects act as rewards and those who take drug will crave drug’s effects so intensely that if it is not available Experince panic
Pharmacology of cocaine
-cocaine classified pharmacologically as local anesthetic and as CNS stimulant
-in terms of law, cocaine classified as narcotic
-one of most popular recreational drugs, next to alcohol, caffeine, marijuana
Duration of action:
Short action, usually less than an hour compared to 12 hours with amphetamines
Routes of administration
Commonly sniffed or smoked, while amphetamines are commonly administered intravenously
Mechanism of action of cocaine
*refer to goodnotes for photo
-causes generalized CNS stimulation in a dose-dependent manner ( more cocaine = more CNS stimulation)
Reputable inhibition
Cocaine inhibits the active re-uptake of primarily dopamine and serotonin into the presynaptic neuron
Postsynaptic neuron activation
This increases concentration of these neurotransmitters in the synaptic cleft and in turn increases the activation of the postsynaptic neuron’s receptors
Therapeutic use of cocaine
-only legitimate use is local anesthetic for mouth and throat
-rarely used therapeutically, as better local anesthetics have been developed that have chemical structures similar to cocaine, but do not have same associate potential for misuse and SUD
Effects of long-term use of cocaine
-toxic psychosis, including paranoia
-hallucinations or sensations of insects crawling under the skin
-impaired sexual function
-permanent brain damage and impairment of neuronal function may occur
-high blood pressure and an irregular heart rhythm
-changes to the nasal mucosa, as the drug is sniffed
Consuming alcohol and cocaine at same time is very dangerous. Alcohol reacts with cocaine to form an active metabolite called cocaethylene. The cocaethylene temporarily increases the euphoria experienced, but also dangerously increases blood pressure, aggressive and violent thoughts, and poor judgement
Cocaine potential misuse and SUD
-widely misused as often used concurrently with other types of psychoactive drugs
-usually sniffed or smoked, but can be injected
Potential for misuse
-one of highest misuse liabilities amongst all drugs
-due to powerful euphoria, which can be reached rapidly by injecting the drug or smoking the freebase (a purified form of cocaine that has a low melting point and make easier to smoke)
-inherent harmfulness of cocaine involves the fact that those who take the drug will Experince physical and psychological deficits. These events do not appear to deter misuse
Potential for SUD
Tolerance: develops towards the mood-elevating effect of cocaine, but not the drug-induced psychotic effect. Tolerance does not develop as readily to the hallucinatory and behavioural effects of cocaine as compared to the amphetamines
Withdrawal: the withdrawal symptoms are similar to those with aphetamines (mood depression that may be profound, prolonged sleep, huge appetite, lack of energy and fatigue)
Addiction: can occur. The behavioural effects of cocaine usually perceived as pleasurable and rewarding, and therefore reinforce repeated drug use
Summary of amphetamines and cocaine
PLEASE GO TO GOODNOTES TO SEE THE CHART
