Methamphetamine

Mechanism of Action

Methamphetamine affects the central nervous system (CNS)  by enhancing the release of monoamine neurotransmitters such as serotonin, dopamine, and norepinephrine.[4] The use of methamphetamine can lead to many pharmacological effects because of its ability to use various molecular processes. Methamphetamine causes the levels of monoamines to be increased by:

• Discharging the monoamines out of their storage and freeing them into the synaptic space by making reversal action of the dopamine transporters

• Obstructing the reuptake of monoamines by preventing the activity of transporters of monoamine[6]

• Methamphetamine can increase the expression of CRE-Luc by TAAR1 in transfected cells. Methamphetamine interacts with TAAR1, which triggers a definite inhibition in dopamine uptake dependent on TAAR1 in transfected cells. Methamphetamine has a similar effect on brain striatal synaptosomes.[5][6]

• Reducing the dopamine transporters expressions at the cell surface

• The proliferation of the cytosolic levels of monoamines by inhibiting the monoamine oxidase activity

• Enhancing the expression and activity of the dopamine-synthesizing enzyme tyrosine hydroxylase[7]

Methamphetamine is highly lipid-soluble, which helps to be transferred relatively fast across the blood-brain barrier and has an immediate effect on the CNS.[2]

Administration

Methamphetamine can be ingested orally, through intravenous injection, smoked, and snorted.

Adverse Effects

People who use methamphetamine feel an acute, powerful short rush for about 5 to 30 minutes, which varies based on different routes of use. The drug also causes an enhanced energy level, decreases appetite, and creates euphoria for a range of 6 to 12 hours.

 Short-Term Effects

• Decreased appetite
• Nausea
• Psychosis
• Tachycardia
• Hypertension
• Increased body temperature  
• Panic attack
• Mydriasis (dilation of pupils)
• Disturbed sleep patterns
• Violent, bizarre, and erratic behavior
• Hallucinations and irritability
• Seizures, convulsions, and death from high doses

Long-Term Effects

• Long-lasting damage to the blood vessel of the heart and brain
• Lung, liver, and kidney damage
• Hypertension that can lead to heart attacks, strokes, and death
• Severe tooth degeneration
• In cases where the drug was sniffed, destruction of soft tissues in the nose
• In cases where the drug was smoked, respiratory problems
• In cases where the drug was injected, infectious diseases, cellulitis, and abscesses
• Weight loss and malnutrition
• Disorientation, apathy, confusion, and exhaustion
• Severe psychological dependence
• Psychosis
• Depression
• Damage to the brain structure similar to Alzheimer disease, epilepsy, and stroke

Tweaking

The last stage of methamphetamine misuse happens when the person who inappropriately uses methamphetamine becomes paranoid and irritable because of a lack of sleep for about 3 to 15 days. This behavior is called "tweaking," and the person with this behavior is known as the "tweaker." Usually, tweakers continue to require more methamphetamine to get to the original high.[8] This effect is difficult to achieve, which causes frustration and irritability, and unsteady behavior in the tweaker. Because tweakers are unpredictable, they can behave violently, can get involved in domestic arguments, spur-of-the-moment offenses, and become a danger to others or themselves.[9] A tweaker can behave normally and have clear eyes, concise speech, and brisk movements; however, careful observation will indicate that the person's eye movement is much faster than normal (up to 10 times). They have a minor quiver voice and jerky movements. Some tweakers minimize or cover these physical symptoms by using a depressant like alcohol or opioids; however, the use of a depressant by the tweaker increases his or her negative feelings of paranoia, irritability, and frustration significantly. Other people around these users should use extreme caution because of their unpredictable behaviors.[10]

Contraindications

• Having thoughts of suicide
• Tourette syndrome
• Hyperthyroidism
• Bipolar disorder
• Psychotic disorder
• Drug abuse
• Behaving with excessive cheerfulness or activity
• Chronic muscle twitches or movements
• Aggressive behavior
• Increased ophthalmic pressure
• Hypertension
• History of a heart attack
• Coronary artery disease
• Cardiomyopathy
• Arrhythmia
• Chronic heart failure
• Stroke
• Atherosclerosis
• Numbness
• Prickling
• Tingling of fingers and toes
• Seizures
• Loss of appetite
• Weight loss
• Breastfeeding mothers
• Increased cardiovascular event risk
• Structural disorder of the heart
• Chronic kidney disease stage 4 (severe) or 5 (failure)
• Kidney disease with a likely reduction in kidney function
• Allergic reaction to sympathomimetic agents or amphetamine analogs

Monitoring

Methamphetamine users have different recognizable symptoms, for example, lack of sleep (insomnia), acute anxiety, agitation, and psychotic or violent behavior. If these types of behavior develop after using the methamphetamine, the meth use may have developed dependency. Chronic meth users also usually show poor personal hygiene and sores on their bodies from picking at "crank bugs," unhealthy complexion, pallor, and tactile hallucinations that often occur in tweakers. Methamphetamine users may develop cracked teeth because of extreme clenching of their jaw when they are high on methamphetamine.

Toxicity

The use of methamphetamine can cause physical and psychological dependence and increased tolerance. Because of the rapid development of tolerance, methamphetamine users frequently need to increase the dose to get to the satisfying "high," which can be very dangerous because the administration of too much methamphetamine also increases the risk of an overdose.[11] Based on the reports from 2011, more than 102,000 emergency department visits in the United States were related to methamphetamine use, with over 50% of users also using a combination of other drugs such as alcohol and marijuana, thus producing a synergistic effect. Knowing the physical and behavioral symptoms of the methamphetamine overdose and diagnosis of the toxicity is essential for saving the patient's life.[12]

• Acute: When methamphetamine users experience an adverse reaction due to using a large amount of methamphetamine one time, it can be fatal.
• Chronic: Result of many adverse health effects of chronic methamphetamine abuse

Signs and symptoms of methamphetamine toxicity:

• Mydriasis (dilated pupils)
• Bradycardia or tachycardia
• Irregular heart rhythm (arrhythmia)
• Chest pains
• Shortness of breath
• Increased body temperature
• Heart attack
• Hypertension
• Kidney damage
• Altered mental status. 
• Gastrointestinal distress
• Agitation, violent, psychotic behaviors 

Patients who experience methamphetamine toxicity usually present with an altered mental status that can present as psychotic episodes, irritability, suicidal ideation, and rarely coma or seizures.

Some patients present with psychotic symptoms, including tactile hallucinations and severe paranoia.

Chronic long-term methamphetamine use can also cause dental complications, significant weight loss, and skin problems such as sores and abscesses.[3]

Enhancing Healthcare Team Outcomes

Due to the unpredictable behaviors, irritability, and the possibility of psychotic behavior of methamphetamine users, especially during the hospital visit due to the overdose or complication, the safety of medical and security staff is important. Hence, the advice is always to use precautions when dealing with these patients. Another healthcare worker or security personnel should always accompany these patients. The triage nurse should be fully aware of the adverse effects of amphetamine and ensure that the emergency department is fully aware of the individual admitted. This interprofessional team approach to addressing these patients should include clinicians, nurses, and pharmacists, who can collaborate and communicate across interdisciplinary lines to ensure these patients get the care they need, whether misusing the drug or in the rare instances where it has a therapeutic indication. [Level 5]