CNS Stimulants and Depressants

NPHARM; Unit 3

What is a stimulant?

is a type of drug that stimulates the CNS

What is a depressant?

It is the opposite of a stimulant, meaning that they depress or slow down the central nervous system

Caffeine is ______ to adenosine receptors and has ______ effect

antagonist, inhibitory

What effects does caffeine have on the CNS?

increases neuronal firing, releasing glutamate and dopamine. Moreso, this firing causes adrenal gland to release epinephrine because the pituitary gland thinks we are in emergency situation

What does caffeine do to your body? 

It inhibits adenosine from going into our sleep wake cycle, causing the body to remain alert and active. Epinephrine is released as well which boosts the system. DA is also released for the “feel good” factor. Overall, it has a short-term effect if you are fatigued.

How does caffeine affect the sleep ?

Because caffeine has a 6-hour half-life, good sleep is affected as REM cycles decrease. Essentially, making you feel worse the next day.

When consuming caffeine, epinephrine is released by the adrenal gland. How does this release affect the body?

Epinephrine is a flight or fight hormone, so it overexcites the body causing blood pressure to rise, increase heart rate, blood vessels on surface constrict to slow blood flow from cuts and increase blood flow in muscles, etc.

Why is it that caffeine is sometimes in over the counter medicine for headaches? 

Caffeine constricts blood vessels in the brain because it blocks adenosine’s ability to relax them. 

Caffeine is _____ stimulant and ________

cardiac, mild diuretic

Why is caffeine considered a drug?

It is considered a drug because it affects the CNS and uses the dopamine reward pathway that other hard core drugs use. However, caffeine is a milder drug compared to cocaine.

Ingesting more than 250mg of caffeine in a short period of time causes: 

• restlessness 

• insomnia 

• cardiac arrythmia 

• muscle twitching 

  • GI disturbances

What are the four subtypes of Adenosine receptors?

• A1

• A2A

• A2B

• A3

Where is A1 receptor more abundant and what does it do ?

It is abundant in the cortex, hippocampus, cerebellum, and hypothalamus. When adenosine binds to A1 receptor, firing of the neuron is inhibited as calcium channels are blocked and potassium channels are activated, resulting in hyperpolarized membrane. 

Adenosine is _______ NT in the CNS

Inhibitory 

Adenosine regulates:

drowsiness in the activation of G-protein coupled receptors, increasing the levels of the adenosine in basal forebrain when brain is awake.

Dilation of blood vessels, to increase oxygen supply during sleep

What is the second most important adenosine receptor? Where is it most abundant? 

A2A, is most abundant in the basal ganglia 

When caffeine binds to A2 receptor:

basal ganglia increases motor activity; this is the opposite of adenosine binding to A2 because it would decrease motor activity as the body is preparing to sleep

• it acts similar to DA

Cocaine is a CNS ________.

Stimulant

How does cocaine impact the sympathetic nervous system?

causes fight-or-flight syndrome as norepinephrine is potentiated leading to hypertension, papillary dilation, and peripheral vasoconstriction, etc.

What is the mechanism of action of cocaine?

it inhibits the reuptake of monoamines (norepinephrine, serotonin, and dopamine) causing NT to accumulate in the synapse leading to excessive stimulation of the brain’s reward and arousal pathways

what are some effects of cocaine?

Because cocaine disregulates the CNS, it can cause hallucinations, delusions, increased motor activity, and paranoia. 

What are the three types of alcohol?

Ethanol, methanol, and ethylene glycol

(** ethanol is the one mostly consumed because it is in alcohol/liquor)

Ethanol has ______ pharmacological potency and it is reflected in the range of ______ _____________.

low, plasma concentration

What is the mechanism of action of alcohol? 

It is the least understood but there are theories of ethanol’s actions which are:

enhancing GABA-mediated inhibition, inhibition of calcium entry through VG calcium channels, inhibition of NMDA receptor function, and inhibition of adenosine transport

---

the site of action can hardly be pinpointed because it affects virtually all neurochemical and endocrine systems.

How is ethanol similar to benzodiazepines? 

Ethanol enhances the actions of GABA acting on GABA_A receptors, but the effects are smaller and less consistent than benzodiazepines; inc Cl- influx —> hyperpolarization

Effects of ethanol in the Calcium channel

Inhibits transmitter release in response to nerve terminal depolarization by inhibiting the opening of VG calcium channels

Effect of Ethanol on NMDA receptors

inhibits the excitatory effects of glutamate, and receptor activation of NMDA is inhibited at lower ethanol concentrations

Ethanol and adenosine are similar in what aspects?

In the depressant effects, ethanol resembles those of adenosine A1 receptors. Essentially, ethanol increases extracellular adenosine by inhibiting its uptake, and this inhibition may account for some its CNS effects

Effects of ethanol on serotonin

enhances excitatory effects produced by the activation of nACh receptiors and 5-HT3 receptors

______ reduces the reward associated with ethanol

Naltrexone

How does ethanol affect the CNS?

Affects mood and it can vary between individuals

• can experience euphoria, agression, submission, or melancholy; become outgoing or withdrawn

  • can affect motor performance and sensory discrimination

What BAC constitutes as a legal offense?

alcohol concentration in blood > 80 mg/100ml (0.08%)

• increases intellectual impairment and increases the risks of car accidents

Describe the progressive effects of ethanol

1. 10-30mg/100ml (BAC 0.01%-0.03%) 

   1. normal; subtle effects, only detectable with tests

2. 30-60mg/100ml (BAC 0.03%-0.06%)

   1. mild euphoria/relaxation/talkativeness; impaired alertness/judgment/coordination

3. 60-100mg/100ml (BAC 0.06%-0.1%)

   1. blunted feelings/disinhibition/sexual pleasure; impaired reasoning/depth perception/distance acuity/peripheral vision

4. 100-200mg/100ml (BAC 0.1%-0.2%)

   1. emotional swings/boisterous; slurred speech, staggering

5. 200-300mg/100ml (BAC 0.2%-0.3%)

   1. impaired sensation/loss of understanding; blackout/loss of consciousness

6. 300-400mg/100ml (BAC 0.3%-0.4%)

   1. unconsciousness/severe depression; impaired breathing/heart rate

7. >400mg/100ml (BAC > 0.4%)

   1. unconsciousness/death; impaired breathing/heart rate

What are the effects of ethanol on the liver?

1. increases fat accumulation —> fatty liver

2. causes inflammation of the liver = hepatitis

3. if not treated, can cause liver necrosis and fibrosis (irreversible)

   1. possible as a result of malnutrition since alcohol replaces calorie intake but it does not provide necessary nutritional value —> cellular toxicity

How does alcohol consumption (ethanol) affect fetal development?

Results in FAS = Fetal alcohol syndrome; it is the abnormal facial development with wide set eyes, short periphery fissures and small cheekbones

• retarded growth, mental retardation/behavioral abnormalities, reduced cranial circumference

There is a lesser degree of impairment = ARND- alcohol relates neurodevelopmental disorder; 

• results in behavioral problems, cognitive and motor deficits, which are often associated with reduced brain size

Explain ethanol withdrawal syndrome

physical abstinence syndrome that develops after 8 hours, if severe. It subsides after a few days but there are cravings which can cause relapse.

What are the two stages of withdrawal syndrome?

1st stage: tremor, nauseae, sweating, fever, sometimes hallucination. lasts 24 hrs and can be followed by seizures

2nd stage: delerium tremens that develops after a few days. this is where the patient becomes confuse, agitated and aggressive, and may suffer from sever hallucinations 

What is ethanol tolerance and how does this affect the body?

Tolerance = occurs over 1-3 weeks of continuous consumption

• this causes the body to rapidly recognize drug and breaking it down = rapid elimination; but the most concerning one is tissue tolerance where there is a possible confirmational change where the cells can’t recognize ethanol anymore

• because of this tolerance, the body is also tolerant to anesthetic agent = cross tolerance, meaning if person becomes a patient they will not be as receptive to anesthetia