Lecture 4 - CNS stimulants Flashcards
What are 2 examples of stimulants?
Amphetamine and cocaine.
What is amphetamine?
Based on the compound ephedrine.
First used for treatment of epilepsy and depression.
Examples are MDMA and methamphetamine.
What is the ROA for amphetamine?
- Tablets are oral
- Powder inhaled, snorted, rubbed on gum or injected.
- Crystals smoked or injected.
All absorption is rapid.
Where are amphetamines distributed?
- Lungs
- Kidney
- Brain
- Cerebrospinal fluid
How are amphetamines absorbed?
- Metabolised in the liver via
aromatic hydroxylation (which if accumulates
may induce amphetamine psychosis), oxidative
deamination (by cytochrome P450), β
hydroxylation and N-oxidation.
How are amphetamines eliminated?
Parent drug is unchanged in urine, around 45% excreted without being metabolised.
Depends on pH of urine - acidic around 80%, alkaline around 2%.
What is the mechanism of action for amphetamines?
- CNS stimulation by increasing
release of, and inhibiting reuptake, of serotonin,
dopamine and norepinephrine in the brain at nerve
terminal storage vesicles. - The release of dopamine causes hyperstimulation of
dopaminergic receptor neurons in the synaptic cleft.
In addition, upon entry to the cytoplasm
amphetamines further reduce accumulation of
norepinephrine and dopamine. - This continuous release of neurotransmitter at low
doses of amphetamine reinforces the affect of the
drug on the user.
What are 3 side effects of amphetamines?
Increased energy
Increased blood pressure
Euphoria
What are the withdrawal effects of amphetamines?
- Tired, restless.
- Larger doses - depression, anxiety. Suicidal thoughts common in methamphetamine.
What are the medicinal uses of amphetamines?
- Narcolepsy and depression.
- In form of Ritalin in ADHD.
- Also obesity.
What is cocaine?
- Naturally occurring alkaloid found in plants with the genus erythroxylum.
- Commercially synthesised found in ecgonine - fully synthesised very expensive.
What are the ROA for cocaine?
- Powder snorted, swallowed or injected.
- Crack cocaine smoked.
How is cocaine distributed?
Within all body tissues.
Crosses blood-brain barrier.
Accumulates in CNS and in adipose tissue due to high lipid solubility.
What are the bioavailability of each route?
-Ingestion - low BA (20%), as first pass metabolism.
-Intranasal - depends on dose, 25-94%.
-Injection ‘mainlining’ 100% BA, rapid.
-Inhaled ‘freebasing’ 60-80% BA, instant effects.
How is cocaine metabolised?
Hydrolysis using plasma and hepatic esterases
* Oxidation using mixed function oxidases
* Hydrolysis accounts for most of the
metabolism, producing benzoylecgonine,
ecgonine methyl ester and ecgonine
* Oxidation produces norcocaine which is an
active metabolite
How is cocaine eliminated?
Metabolites excreted.
Usually depend on ROA.
5-20% appears unchanged in urine.
Met and elim are rapid but can be detected up to 144 hours in urine after administration.
What is the MOA of cocaine?
Cocaine primarily works by blocking
transporter proteins responsible for the re
uptake of certain neurotransmitters
* Cocaine inhibits Na+/K+ ATPase, this blocks
pain signals crossing synapses, therefore it is
used as a topical anaesthetic
What are 3 side effects of cocaine?
High energy
Increased heart rate
Paranoia
Tolerance
What are the withdrawal effects of cocaine?
- Unpleasant
- 3 phases
-Crash phase (depression-insomnia, cravings, agitated)
-Withdrawal phase - cravings better, sleep better, lack of energy.
-Extinction - no cravings, no moodiness.
What are the medicinal uses of cocaine?
- High potential for abuse, only very limited medicinal uses.
- Topical
administration as an anaesthetic in ear, nose
and throat operations.
