Drug misuse, intoxication and withdrawal: Other depressants: Pathology review

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Case study0:00–1:02

A 28-year-old male named Frank is brought to the emergency department unconscious after being found by his roommate in their apartment.
On physical examination, Frank is unresponsive, his breathing is slow, and he has pinpoint pupils. In addition, both his arms are covered in what looks like multiple needle tracks.
Vital signs reveal a heart rate of 60 beats per minute, a respiratory rate of 7 breaths per minute, and a blood pressure of 90 over 60 millimeters of mercury.
A few days later, a 14-year-old female named Sarah is brought to your office by her worried mother. Sarah has been experiencing headaches that have increased in frequency over the past 6 months.
Upon further questioning, the mother reveals that Sarah sometimes appears confused, with a clumsy gait, and has been sleeping less lately.
On physical examination, you notice that Sarah's skin is dry and irritated around the mouth, and she has sores on the lips.
You ask to have a private talk with Sarah, during which she admits to having sniffed glue and spray paint once or twice with a friend over the past few months.Based on their initial presentation, both Frank and Sarah seem to have some form of depressant drug abuse, which specifically has led Frank to intoxication, while Sarah is experiencing withdrawal from it.

Depressants1:02–2:21

Now, depressants are a class of drugs that depress bodily functions by reducing the activity of various excitatory neuronal pathways in the brain.
Some high yield depressants include alcohol, as well as opioids, barbiturates, benzodiazepines, and inhalants like spray paints and glue.For your exams, remember that intoxication with a depressant can result in various symptoms, including mood elevation, a decrease in anxiety, and behavioral disinhibition, which refers to a disregard for social rules that leads to inappropriate, impulsive, or even aggressive behavior.
Another high yield fact is that depressants can lead to sedation, and even central nervous system or CNS and respiratory depression, which is when the respiratory center in the medulla is suppressed, to the point where a person may simply stop breathing.
Over time, the body gets used to the depressant and develops dependence on it. As a result, when the individual suddenly stops using it, they may experience withdrawal symptoms, which include anxiety, tremors, seizures, and insomnia.
Okay, let’s begin with opioids, which are frequently tested in your exams! Now, opioids can be endogenous, meaning they’re naturally produced by the body, such as endorphin, which is short for endogenous morphine.

Opioid intoxication2:21–4:56

Or, they can be exogenous, meaning that they are derived from an external source. Exogenous opioids can further be divided into naturally occurring ones that come from the opium poppy, such as morphine, which is used for severe pain relief, and heroine, which is an illicit drug; as well as synthetic opioid produced in a laboratory, such as fentanyl, which is used for anesthesia during surgery.Now, exogenous opioids can be taken in through multiple routes, including ingestion, inhalation, and directly injecting them into the blood.
Once in the body, opioids bind to three major opioid receptors called the mu, kappa, and delta, which are found in the brain, spinal cord, and gastrointestinal tract, and respectively regulate reward, pain transmission, and gastrointestinal motility.
As a result, symptoms of opioid intoxication include a feeling of euphoria or ‘the rush’, which is usually followed by a period of sedation or apathy.
Additionally, there can be other behavioral changes like dysphoria, which is a feeling of being dissatisfied with life; as well as psychomotor retardation; and impaired attention, memory, or judgment.
Opioids also cause physical symptoms, and the most characteristic ones you must remember are constricted, or pinpoint pupils, as well as constipation due to decreased gastrointestinal motility.
In addition, individuals may present with slurred speech; bradycardia or decreased heart rate, hypotension or low blood pressure, and hypothermia or reduced body temperature.
Another high yield fact is that opioid intoxication has the potential to cause seizures. Worst of all, opioid overdose leads to severe central nervous system and respiratory depression, And that’s why opioid intoxication is the most common cause of drug-related deaths worldwide.In case of an opioid overdose, the most important thing to administer is the antidote naloxone.
Remember that naloxone is a short-acting opioid antagonist, which competes with the drug for binding at the opioid receptors and prevents the drug from acting.
As a result, it can reverse the effects of opioids. Naloxone is usually administered slowly to prevent withdrawal symptoms, and discontinued once there’s an improvement in respiration and dilation of the pupils.Now, overtime, opioid use can result in dependence and tolerance to its effects.

Opioid withdrawal4:56–6:18

So, upon discontinuation, individuals may experience withdrawal symptoms, including anxiety, tremors, increased sweating, and piloerection or goosebumps, as well as dilated pupils, rhinorrhea or runny nose, and for some reason, yawning!
In addition, opioid withdrawal may result in an increased heart rate and blood pressure, as well as gastrointestinal symptoms like nausea, diarrhea, and abdominal cramps.Treatment of opioid withdrawal includes symptomatic management with medications like clonidine, which is an alpha-2 adrenergic agonist; and opioid substitution therapy with opioid agonists like methadone and buprenorphine.
The principle behind opioid substitution therapy is that these medications competitively bind to the opioid receptor without producing the same level of euphoria as the replaced opioids, so they can be safely tapered off.
Methadone is a complete opioid agonist with a long half-life, so it can be used as long-term maintenance therapy. On the other hand, buprenorphine is a partial opioid agonist that is used to prevent relapse.
In addition, individuals may also be given naltrexone, a long-acting opioid antagonist, to block the effects of opioids and prevent relapse.Now, maternal use of opioids during pregnancy can cause dependence in the baby.

Neonatal abstinence syndrome6:18–7:08

After birth, the drug starts to clear out of the baby’s system, and withdrawal symptoms can occur, which is called neonatal abstinence syndrome.
Usually, the infant's central nervous system, autonomic nervous system, and gastrointestinal system are the ones affected the most.
As a result, in a test question, think of neonatal abstinence syndrome if the infant presents with symptoms of irritability, a high-pitched cry, and uncoordinated sucking reflexes, as well as tachypnea, sneezing, diarrhea, tremors, and even seizures.
Now, treatment of neonatal abstinence syndrome involves trying to calm the neonates by placing them in a dark and quiet environment and administering morphine, methadone, or buprenorphine to improve their withdrawal symptoms.
All right, moving on to barbiturates, these are a group of drugs that include phenobarbital, pentobarbital, thiopental, and secobarbital.

Barbiturate intoxication7:08–8:52

These medications can be used in the treatment of seizure disorders, anxiety, insomnia, and to induce anesthesia in surgical procedures.
Barbiturates act by enhancing the effect of the inhibitory neurotransmitter GABA by binding to a specific site on the GABAA receptors, which are ligand-gated ion channels that open up to let chloride ions into the cell.
What barbiturates do is they increase the duration of their opening, thereby increasing the influx of chloride ions. As a result, the neuron becomes less responsive to stimuli, and it becomes much more difficult for the neuron to depolarize and fire off an action potential.
This is known as membrane hyperpolarization. Through this mechanism of action, barbiturates produce a drowsy, calm feeling, reduce anxiety and tension, and they are often abused for these effects.
However, barbiturate intoxication can also produce symptoms of sluggishness, slurred speech, impaired attention and memory, nystagmus, and behavioral changes.
What’s high yield for your exams is that barbiturates have a low safety margin, which means an individual can overdose with even small amounts of the drug, and they have a very high risk of developing respiratory depression.
Symptoms can get especially dangerous when barbiturates are taken along with other nervous system depressants like alcohol or benzodiazepines.
This can lead to marked respiratory depression, coma, and even death. Treatment of barbiturate overdose involves symptomatic management with supportive care, focusing on the individual’s respiration and blood pressure.
Over time, using barbiturates can lead to dependence and tolerance, so individuals can experience intense withdrawal symptoms, ranging from anxiety, agitation, tremors, and tachycardia, to delirium, life-threatening seizures, and cardiovascular collapse.

Barbiturate withdrawal8:52–9:25

Management of withdrawal symptoms involve symptomatic care and replacement therapy with a benzodiazepine, so they can be safely tapered off.
Once the withdrawal period is complete, the individual is usually started on psychotherapy to prevent relapses.Speaking of which, benzodiazepines are a class of drugs that can be used in a wide variety of conditions including anxiety, panic disorder, seizure disorders, spasticity, detoxification of other depressant drugs, insomnia, night terrors, and general anesthesia.

Benzodiazepine intoxication9:25–11:13

For your exams, remember that some commonly used benzodiazepines include diazepam, lorazepam, alprazolam, oxazepam, midazolam, and chlordiazepoxide.
An important fact to keep in mind is that the addiction potential is especially higher with short-acting benzodiazepines like alprazolam, oxazepam, and midazolam, since they have a shorter half-life!
Now, benzodiazepines act by a mechanism similar to barbiturates, but they bind to a different site on the GABAA receptor and increase the opening frequency rather than the duration of these chloride channels.
Ultimately, the result is pretty much the same, as the influx of negatively charged chloride ions makes the neuron less responsive to stimuli.
Acute intoxication with benzodiazepines usually produces symptoms like loss of coordination, ataxia, and anterograde amnesia, which is defined as an inability to form new memories after the administration of the medication.
The good news is that benzodiazepines have a greater safety margin when compared to barbiturates, so they require higher doses to cause respiratory depression and coma.
And that’s a high yield fact! However, the risk can increase when benzodiazepines are combined with other CNS depressants, as their depressive effects add up.
Treatment of benzodiazepine intoxication involves supportive care and administering its antidote flumazenil, which acts as a competitive antagonist by binding to the same site as benzodiazepines, preventing their action.
Keep in mind that flumazenil should be used with caution, as it may induce seizures.Now, when benzodiazepines are used chronically, individuals can develop dependence and tolerance.

Benzodiazepine withdrawal11:13–11:37

Withdrawal symptoms of benzodiazepines are milder when compared to barbiturates and include insomnia, depression, and most importantly but less commonly, seizures.
Treatment involves symptomatic care and tapering off, followed by psychotherapy.Our final depressants are inhalants, which are volatile chemical substances that produce vapors that can be inhaled.

Inhalant intoxication and withdrawal11:37–13:00

Inhalants include toluene, which is a major component found in glues and spray paints, as well as butane, which is found in solvents.
A high yield fact here is that inhalants are commonly misused by teenagers, due to their easy availability. Now, the exact mechanism by which inhalants cause CNS depression isn't fully understood, but it's thought to be through stimulation of the GABA receptors.
Acute intoxication with an inhalant can produce a feeling of euphoria and disinhibition, associated with disorientation and drowsiness.
Inhalants may also lead to impaired judgment and violent behavior. Finally, individuals may present with physical symptoms like slurring of speech and unsteady gait.
The effects of inhalant intoxication are extremely short-lasting and resolve on their own. However, individuals who use inhalants repeatedly may develop a perinasal and perioral skin rash and sores, and that’s very high yield!
Over time, inhalants can lead to dependence and tolerance. Withdrawal symptoms most often include headaches; mood changes like irritability and dysphoria; and sleep disturbances like insomnia.
Treatment of inhalant use mainly involves symptomatic care, followed by individual and group psychotherapy.All right, as a quick recap...

Recap13:00–15:30

Depressants are a class of drugs that result in reduced brain and bodily functions. Intoxication can result in various symptoms, including mood elevation, decreased anxiety, behavioral disinhibition, sedation, and even CNS and respiratory depression.
Using depressants over time can lead to dependence and tolerance, so when the individual suddenly stops using it, they may experience withdrawal symptoms, which include anxiety, tremors, seizures, and insomnia.
Some important depressants include opioids, barbiturates, benzodiazepines, and inhalants. Opioid intoxication typically presents with symptoms like euphoria, pinpoint pupils, and constipation, while severe cases can lead to an overdose, resulting in CNS and respiratory depression, and it’s the most common cause of death from drug overdose.
Using opioids over time can cause dependence and tolerance, resulting in withdrawal symptoms like increased sweating, and piloerection, as well as dilated pupils, rhinorrhea, yawning, and gastrointestinal symptoms like nausea, diarrhea, and abdominal cramps.
Also, opioid use during pregnancy may result in neonatal abstinence syndrome in the baby. Next, barbiturates are a group of drugs with a low safety margin, which can produce intoxication and overdose even at low doses, posing a very high risk of developing severe respiratory depression, coma, and even death.
In case of barbiturates withdrawal, individuals can experience delirium, seizures, and cardiovascular collapse. Benzodiazepines can also result in acute intoxication, but they have a greater safety margin.
Symptoms of intoxication include loss of coordination, ataxia, and anterograde amnesia, and rarely respiratory depression and coma.
With chronic use, individuals can develop tolerance and dependence, presenting with withdrawal symptoms like insomnia, depression, and seizures.
Finally, inhalant intoxication is extremely short-lasting, and presents with euphoria, disinhibition, disorientation, and drowsiness, as well as slurred speech and unsteady gait.
individuals who use inhalants repeatedly may develop a perinasal and perioral skin rash; and over time, inhalants can lead to dependence and tolerance.
Withdrawal symptoms most often include headaches; mood changes like irritability and dysphoria; and sleep disturbances like insomnia.

Summary15:30–16:22

Okay, back to our cases. First, there’s 28-year-old Frank, who's unconscious and unresponsive.
Physical examination reveals a low respiratory rate, bradycardia, and hypotension. This should already point you towards a depressant intoxication.
Now, the most important clue here is that Frank has pinpoint pupils, which combined with the fact that he has multiple needle tracks on his arms, would indicate that he has injected heroin, so he’s experiencing an opioid overdose.
Next comes 14-year-old Sarah, who’s had recurrent headaches over the past 6 months, as well as disorientation, unsteady gait, and insomnia, which are typical symptoms of depressant withdrawal.
The biggest hint here is the fact that Sarah presents with a perioral skin rash and sores, which is a telltale sign of recurrent inhalant use, and a history of sniffing glue and spray paint confirms