Drug misuse, intoxication and withdrawal: Stimulants: Pathology review

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Case study0:00–1:21

In the middle of the night, a 25 year old female, named Sylvie, comes to the emergency department complaining of retrosternal chest pain that began a couple of hours ago.
Earlier that night, she was at a party, where she and her friends consumed alcohol. Upon further questioning, Sylvie reveals that she also consumed an illicit drug.
She is otherwise healthy, has no history of cardiac disease, and does not take any medications. On physical examination, Sylvie is sweating profusely.
In addition, her pupils are dilated, and the nasal septum is atrophic. Vital signs reveal a temperature of 100 degrees Fahrenheit or 37.7 degrees Celsius, a heart rate of 110 beats per minute, and a blood pressure of 160 over 90 millimeters of mercury.
Some days later, you meet a 36 year old male, named Hunter, who comes in due to recurrent headaches associated with trouble concentrating and irritability.
Hunter adds that he feels like he can’t stop eating, and as a consequence, he’s gained about 3 kilograms, or about 7 pounds, over the last two weeks.
When you ask about his habits, Hunter admits to smoking 2 packs of cigarettes daily for the last 10 years, but stopped smoking about two weeks ago.
Based on the initial presentation, both Sylvie and Hunter seem to have a form of stimulant intoxication or withdrawal. Stimulants are a group of substances that, when consumed, typically lead to increased activity in the body and brain.

Pathology1:21–3:40

Stimulants include legal substances like caffeine, nicotine, and some amphetamines that can be prescribed for medical treatment; as well as illegal substances, such as cocaine and other amphetamines like MDMA.
Now, for your exams, remember that excessive intake of stimulants may result in stimulant intoxication, which can cause several non-specific symptoms, including being more awake, alert, and energetic, having an elevated mood, and a decreased appetite.
However, they also come with some undesirable symptoms like anxiety, psychomotor agitation or restlessness, aggressive behavior, and insomnia.
In addition, stimulants may have physical effects like diaphoresis or excessive sweating, tachycardia or increased heart rate, cardiac arrhythmias, hypertension or elevated blood pressure, and mydriasis or pupillary dilation.
Over time, individuals who regularly use stimulants may develop tolerance, which is the need for increasing doses to achieve the same effect, as well as dependence, which is when the body adapts to that substance and needs it to function normally.
As a result, individuals that stop using it may experience nonspecific withdrawal symptoms, sometimes known as post-use "crash" or wash-out syndrome, which can include depression, increased appetite, psychomotor retardation or slowing down of a person’s thought, emotional reactions, and movements, as well as sleep disturbances like hypersomnia or excessive sleepiness, and miosis or pupillary constriction.
Now, bear in mind that, in addition to these nonspecific symptoms, intoxication or withdrawal from each stimulant can cause its own set of specific symptoms that you must be able to recognize for your exams.Okay, let’s begin with one of the most frequently used stimulants, caffeine!

Caffeine3:40–5:39

Caffeine is present almost everywhere- in coffee of course, but also tea, caffeinated energy drinks, sodas, and even chocolate!
Now, the way this stimulant works is by blocking the adenosine receptors. Normally, adenosine has numerous effects in the nervous system, such as decreasing neuronal activity to trigger sleepiness.
Adenosine can also bind to receptors outside the nervous system, such as in the heart, where it causes heart rate to slow down, and in the kidneys, where it decreases urine output.
Now, when caffeine is consumed in moderate doses, it can have a wide variety of effects, including improved cognitive performance, concentration, alertness, energy, and mood.
What’s important to remember though is that excessive caffeine intake can lead to palpitations, tremor, restlessness, agitation, and can cause insomnia.
In addition, caffeine has a laxative effect that stimulates bowel movement, so excessive consumption can cause gastrointestinal disturbances like diarrhea.
Finally, caffeine also acts as a diuretic, leading to increased frequency and urgency of urination.Now, if an individual regularly consumes caffeine, say to study for their tests, over time they may develop tolerance and dependence.
As a result, if they suddenly quit caffeine, they may experience withdrawal symptoms, such as a depressed mood, irritability, low energy, and difficulty concentrating.
These are typically accompanied by certain physical symptoms, such as a persistent diffuse headache, as well as flu-like symptoms, like nausea and muscle pain.
What’s important to keep in mind is that the higher the consumption of caffeine, the more severe the withdrawal symptoms will typically be.Okay, another very common stimulant is nicotine, which is found in tobacco products, like cigarettes, cigars, or pipes.

Nicotine5:39–10:12

When a person smokes or chews tobacco, nicotine is absorbed, either through the lungs or the oral mucosa, into the bloodstream.
From there, nicotine can travel and bind to nicotinic receptors in postsynaptic neurons throughout the nervous system. In the central nervous system, nicotine triggers the release of neurotransmitters like dopamine, which is involved in the brain’s reward pathway that triggers feelings of pleasure, as well as glutamate, which results in improved cognitive performance and concentration.
On the other hand, in the peripheral nervous system, nicotine triggers the release of neurotransmitters like adrenaline and noradrenaline.
This leads to a variety of effects, such as increased blood pressure, heart rate, and cardiac contractility, as well as a laxative effect.
As a result, excess nicotine consumption and intoxication often cause symptoms like restlessness, agitation, diaphoresis, as well as abdominal pain, nausea, and vomiting.
Now, it’s thought that nicotine is responsible for the addictive qualities of tobacco, but it’s important to keep in mind that tobacco contains thousands of toxic chemicals, which are responsible for its health consequences.
One of these chemicals is formaldehyde, which over time can damage a variety of organs and tissues, increasing the risk for cancers involving the head and neck, lung, stomach, colon, pancreas, kidneys, and bladder.
Formaldehyde can also cause damage to the inner lining of arteries, which increases the risk of myocardial infarction, stroke, and peripheral vascular disease.
Another byproduct of tobacco smoke is carbon monoxide, which makes its way into the bloodstream and binds competitively to hemoglobin, meaning it displaces oxygen to form carboxyhemoglobin.
And that leads to impaired oxygen unloading and delivery to tissues. In addition, exposure to tobacco smoke over time can affect the lung function, causing chronic obstructive pulmonary disease or COPD for short.
Smoking during pregnancy is also associated with various complications, like fetal growth restriction, placental abruption, which is a detachment of the placenta from the uterine wall, and can lead to preterm delivery, or miscarriage.
For your exams, remember that this is because nicotine can induce vasospasm of the placental vessels, resulting in abnormal gas exchange across the placenta.
On top of that, carbon monoxide leads to the formation of carboxyhemoglobin, which results in impaired fetal oxygen delivery.
Okay, now, over time, nicotine use may result in tolerance and dependence. As a consequence, individuals that stop consuming tobacco products may experience withdrawal symptoms, such as craving for nicotine, irritability, anxiety, restlessness, and poor concentration.
In addition, many individuals can experience headaches, sleep disturbances like insomnia, depressed mood, as well as constipation, and increased appetite, which can lead to weight gain.
Withdrawal symptoms can begin within 2 hours after the last use of nicotine, and typically peak within 1 or 2 days. While withdrawal tends to decline over the next few days and weeks, many smokers continue to feel awful for months after their last cigarette.
And this is what makes it so difficult to quit smoking! Symptoms of nicotine withdrawal can be relieved with nicotine replacement therapy in the form of nicotine patch, gum, lozenge, or nasal spray.
These can be used in conjunction with medications that act on nicotinic receptors, like bupropion and varenicline. Keep in mind though that bupropion tends to lower the seizure threshold, so it’s contraindicated in those with a history of seizures or eating disorders.
Finally, let’s move on to illegal stimulants, which include cocaine and amphetamines. Keep in mind that some amphetamines can be prescribed legally for medical purposes, such as for the treatment of attention deficit hyperactivity disorder or ADHD for short and narcolepsy.

Cocaine & amphetamines10:12–17:55

For your exams, remember that both cocaine and amphetamine work on presynaptic neurons by blocking the reuptake of the neurotransmitters dopamine and norepinephrine from the synaptic cleft, while amphetamines also increase the release of these neurotransmitters from the presynaptic neuron.
Both of these actions keep dopamine and norepinephrine in the synaptic cleft longer, increasing their effects. So, in both cocaine and amphetamine intoxication, increased concentrations of dopamine in the brain’s reward pathway produces a number of mental or emotional symptoms, such as an emotional “high” or arousal, and intense feelings of euphoria, which is a state of extreme happiness.
Cocaine and amphetamines also cause an increase in self-confidence, which leads to expansiveness or even grandiosity, where individuals may think that they are more attractive, intelligent, or talented than they are.
But it’s not all happiness! Other classic symptoms of cocaine or amphetamine intoxication include impaired judgement, altered mental status, and confusion, as well as paranoia, so the individual may become accusatory or generally distrustful and suspicious of other people without really having any reason or proof.
Because of this, they are quick to get angry, which might get them into a fight, and are constantly hypervigilant or excessively alert.
And this might cause them to be unable to fall asleep. In addition, individuals may experience hallucinations, but an important difference is that amphetamines mainly cause auditory or visual hallucinations, so individuals may hear or see things that aren’t real.
On the other hand, cocaine intoxication typically causes tactile hallucinations, like delusional parasitosis, also known as “cocaine bugs”, which is a hallucinatory perception of having bugs crawling on or just under the skin.
And that’s a very high yield clue!At the same time, both cocaine and amphetamine intoxication lead to increased norepinephrine concentrations throughout the body.
This produces a variety of physical symptoms, including a physical “high” or feeling of hyper-stimulation and increased energy, as well as mydriasis, diaphoresis, often associated with hyperthermia or increased body temperature, hypertension, and tachycardia or even arrhythmias.
Additionally, cocaine intoxication and, less commonly, amphetamine intoxication can cause angina or retrosternal chest pain.
This can be due to either coronary artery vasospasm, meaning the smooth muscles around the arteries constrict extremely tightly, reducing blood flow to the heart; or the formation of a thrombus that happens because cocaine stimulates platelet aggregation.
Ultimately, this combination can lead to a myocardial infarction and sudden cardiac death. So if a test question mentions a myocardial infarction in a young individual, meaning a male younger than 45 years or a female younger than 55 years, without any cardiac risk factors, such as a family history of coronary artery disease, lipid abnormalities, hypertension, diabetes mellitus, or smoking, the answer is probably cocaine intoxication.
Similarly, keep in mind that cocaine use during pregnancy can cause vasoconstriction of the placental vessels or thrombus formation, which can lead to various complications, such as intrauterine fetal growth restriction, placental abruption, preterm delivery, or even miscarriage.
In contrast, amphetamine intoxication is typically associated with seizures, which are paroxysmal events that occur due to abnormal and excessive electrical discharges in the brain.
Over time, cocaine or amphetamines use can have long-term effects. For cocaine, these include a septal perforation, which happens when repeated snorting of cocaine causes local vasoconstriction, leading to ischemic necrosis and atrophy of the nasal septum.
On physical examination, a common clue for that will be nosebleeds. On the other hand, for amphetamines, look for broken or decaying teeth, which is thought to be due to jaw clenching or teeth grinding, as well as skin excoriations, due to intense itching and picking at one’s skin.For acute intoxication with either cocaine or amphetamines, there’s no specific antidote, so the most important things are keeping a person physically safe, protecting their airway by keeping it open, administering an intravenous sedative like the benzodiazepines diazepam or lorazepam to relax the muscles, and cooling the body using a cold compress or fan.
Individuals with cocaine intoxication that develop hypertension or tachycardia are usually given IV benzodiazepines, and refractory cases may be given IV phentolamine.
What’s extremely important is that beta blockers are contraindicated in the treatment of cocaine- induced hypertension. That’s because cocaine causes a big increase in norepinephrine, and if the beta receptors are blocked by the beta blockers, then that norepinephrine ends up binding to alpha receptors, causing severe coronary vasoconstriction, which can be life-threatening.
On the other hand, individuals with amphetamine intoxication who develop agitation or seizures can also be given IV benzodiazepines.Over time, cocaine and amphetamine use can cause tolerance and dependence, so individuals can experience intense withdrawal symptoms.
Physical symptoms of cocaine or amphetamine withdrawal may include increased appetite, which can lead to unwanted weight gain.
On the other hand, psychological withdrawal symptoms are mainly due to the lack of stimulation and can include depression, fatigue, and difficulty concentrating.
In addition, some individuals may feel anxiety, irritability, and even suicidal ideation. These symptoms can be so intense and persist to the point where a person may relapse, meaning they return to using the drugs just to feel normal and energized once again, further reinforcing the dependence.All right, as a quick recap...

Review17:55–20:24

Stimulants are a group of substances that typically result in increased activity in the body and brain. Some high yield stimulants include caffeine, nicotine, cocaine, and amphetamines.
Excessive caffeine intake or intoxication mainly causes palpitations, tremor, restlessness, agitation, and insomnia; while caffeine withdrawal can manifest with depressed mood, irritability, low energy, difficulty concentrating, headaches, and flu-like symptoms.
Most often, excess nicotine consumption and intoxication presents with restlessness, agitation, diaphoresis, abdominal pain, nausea, and vomiting; while nicotine withdrawal causes symptoms like craving for nicotine, irritability, anxiety, restlessness, poor concentration, depressed mood, as well as constipation, and increased appetite.
Finally, cocaine or amphetamine intoxication results in emotional or mental symptoms, like euphoria, grandiosity, paranoia, hypervigilance and hyperalertness, as well as hallucinations, particularly auditory or visual with amphetamines, and tactile ones with cocaine.
Physical symptoms of cocaine or amphetamines intoxication include increased energy, mydriasis, diaphoresis, hyperthermia, hypertension, tachycardia, and arrhythmias.
Cocaine intoxication, in particular, can also cause angina and myocardial infarction, or pregnancy complications, like placental abruption, whereas amphetamine intoxication can present with seizures.
Long-term complications of cocaine intoxication include septal atrophy or perforation, whereas amphetamine intoxication may lead to teeth damage.
Over time, cocaine and amphetamines may result in dependence and withdrawal symptoms, such as increased appetite, depression, fatigue, difficulty concentrating, anxiety, irritability, and suicidal ideation.Okay, back to our cases.

Summary20:24–21:28

First there’s 25 year old Sylvie, who’s been experiencing angina for the past couple of hours, but she has no cardiac risk factors or history of cardiac disease.
In addition, physical examination reveals mydriasis, diaphoresis, and hyperthermia, associated with tachycardia and hypertension.
These findings, combined with the fact that Sylvie had just consumed an illicit drug at a party should make you think of cocaine or amphetamine intoxication.
The most characteristic clue here is that Sylvie has atrophy of the nasal septum, so she has definitely been consuming cocaine.
Next comes 36 year old Hunter, who’s had recurrent headaches, as well as difficulty concentrating and irritability, which are typical symptoms of stimulant withdrawal.
To help you reach a conclusion, some key findings are increased appetite and weight gain over the past two weeks, which coincide with the fact that he quit smoking two weeks ago.
Putting the pieces together, this is a classic case of