L9: CNS Stimulants Flashcards
How do you classify whether a drug is a depressant or a stimulant?
According to their main effect. Even though there can be some overlap that depends on the dose (higher doses can act on other sites) and whether the exposure is chronic or acute.
What are the most common CNS stimulants?
Cocaine, amphetamine and its derivatives, and caffeine
What are the different forms of cocaine?
- Powder form: cocaine hydrochloride
2. Solid form (free base): crack
Why is cocaine so addictive?
It has a rapid onset when consumed.
Where does cocaine act?
- Reuptake pumps in the synapse for more than one transmitter in the brain and in the sympathetic nervous system. Therefore, it has affects in the periphery as well.
- Ion channels at axons
What kind of reuptake pumps does cocaine act on and what pathway does it affect?
- Dopamine (reward pathway)
- Serotonin (many brain pathways)
- Noradrenaline (ANS)
What does cocaine do to the reuptake pumps? What is the consequence?
Blocks reuptake of neurotransmitters. Blocks reuptake of dopamine, serotonin, and noradrenaline in the CNS and only noradrenaline in the periphery.
The consequence is an increased post-synaptic response due to higher levels of neurotransmitter in the synapse.
What is cocaine derived from?
Coca plant.
Why did the indigenous people in South America chew the coca leaves?
Because it is an appetite supressant.
What was cocaine’s first medical use?
A local anaesthetic.
Why was cocaine added to wine?
Because they thought that excitation caused by cocaine would balance out the addiction to CNS depressants caused by ethanol.
What are the different ways to administer cocaine hydrochloride (powder)?
Inject, held in mouth, snorted (absorbed from nasal mucosa).
What are the different ways to administer free base cocaine (crack)?
Smoked.
Why is cocaine an effective local anaesthetic?
Because it blocks voltage gated sodium channels on axons which prevents axonal conduction and blocks action potentials.
What is cocaines effect on glucose utilization?
Decreases glucose utilization.
Why can cocaine have an affect on many parts of the body?
Because sodium channels (which are blocked by cocaine) are present on all excitable tissue. Ex: brain, ANS, heart.
What is the affect of an acute high dose of cocaine?
Initially, there is an excitatory affect on the CNS due to decreased reuptake of dopamine, noradrenaline, and serotonin which results in convulsions. Next, there is inhibition at the sodium ion channels at the axons. If the dose is high enough, inhibition can lead to respiratory arrest (which can be lethal).
What can happen to someone who has never taken cocaine and takes an acute high dose?
The excitatory phase can pass quickly and the inhibition phase can be lethal.
Why are cardiac arrest, arrhythmias, and myocardial infarct a risk of taking cocaine?
Because cocaine can block the sodium channels of the SA node and the His perkinje system. This would cause no depolarization of the heart due to blockage of action potentials.
What gives cocaine users a “high”?
The blockage of neurotransmitter reuptake of dopamine on dopamine transporters on the presynaptic terminals. This increases dopamine available in the reward pathway and causes a “high”. Excess dopamine is neurotoxic.
What family does cocaine block?
The NSS family: Neurotransmitter/Sodium Symporter family
What is dopamine reuptake coupled to?
Sodium and chloride go into the presynaptic neuron (same direction as dopamine reuptake). Potassium goes out of the presynaptic neuron into the synaptic cleft.
How was the excitatory effect of cocaine studied?
Two rats were put in a cage, one tagged with a red light and given cocaine, the other tagged with a white light not given cocaine. With time lapse photography you can see that the red rat moved all over the cage whereas the white rat didn’t. This is because the cocaine rat was excited psychologically and physically.
Why was the red rat in the cocaine experiment so hyper-excited?
- Psychological excitation: The cocaine increases dopamine neurotransmitter in the synapse which activates the reward pathway.
- Physical excitation: Cocaine inhibits the reuptake of noradrenaline which has an important function on the sympathetic nervous system. Since the sympathetic nervous system controls the fight-or-flight response, increased noradrenaline causes fight-or-flight even when it is not necessary (increased HR, decreased blood flow to intestine, increased blood flow to skeletal muscle).
What happens when you destroy the dopaminergic neurons in the nucleus accumbens?
Since the nucleus accumbens is a region of the reward pathway, destroying the dopaminergic neurons causes lost interest in taking cocaine.
What type of receptor are dopamine receptors?
GPCRs.
What is the major receptor in the mesolimbic dopaminergic pathway? What is the effect of this receptor?
D2 receptor is the most predominant and gives the reward effect.
Are dopamine receptors only found in the reward pathway?
No, they are found all over the brain.
What is the fastest to slowest absorption rate of cocaine based on the method of administration?
- IV
- Smoking
- Snorting
- Oral
Why does oral consumption of cocaine have mild effects?
Because it is absorbed from the mouth slowly so there is a lower peak in the blood. Also, there is a high first pass (75%) and therefore little euphoria.
What is the consequence of snorting cocaine?
Snorting cocaine causes intense vasoconstriction which opposes absorption of cocaine. The vasoconstriciton can lead to tissue death in the nose due to decreased blood flow. The vessels can be constricted to the point of “ischemia”.
