Clinical Features with Amphetamine Intoxication Order Instructions: Andy is a 20-year-old male who has recently presented to the emergency department
experiencing distressing auditory hallucinations and paranoid delusions after taking
amphetamines.
Andy’s previous psychiatric history reveals that Andy began taking amphetamines when he
was 15 years old. When taking amphetamines he experienced auditory hallucinations,
delusions and paranoid ideas along with long periods of wakefulness. These symptoms
appeared to be related to the physiological effect of the amphetamine use, as when the
effects of the amphetamine wore off then so did the psychotic symptoms. However, when
Andy was 17 years old he began using amphetamines on a daily basis resulting in an
increase in auditory hallucinations and paranoid delusions. He was admitted to a mental
health facility for the first time and a DSM V diagnosis of ‘Substance/Medication-Induced
Psychotic Disorder’ was made. By the age of 18, Andy had stopped taking amphetamines
but continued to experience prominent paranoid delusions and auditory hallucinations.
Following several admissions to hospital with increasing psychotic symptoms the DSM V
diagnosis of ‘Schizophrenia’ was made.
Answer the following questions (max 1500 words)
Clinical Features with Amphetamine Intoxication Sample Answer
Question 1: Clinical features associated with amphetamine intoxication
Amphetamine is a Central Nervous System (CNS) stimulant through the sympathetic nervous system outflow. Amphetamine is a class of “indirect adrenergic agonists”, which directly stimulates the adrenergic receptors by facilitating the release of norepinephrine from the nerve terminals. The adrenergic receptors become stimulated through an indirect mechanism because amphetamines do not bind directly to the receptors (Heal et al., 2013).
There are remarkable series of events that take place in the human brain. The brains cells consist of neurons transmit signals to one another and consist of many junctions known as synapses. The central control of this system is the brain. The first neuron receives information, creates electrical impulse that triggers secretion of neurotransmitters. The chemicals move across the gap to the next neuron where they bind to the receptors (different for each neurotransmitter). This takes place with incredible precision and the sequence over and over until the signal is passed. The Amphetamines enhance the effects of three main neurotransmitters. To start with is dopamine neurotransmitter which when secreted; it causes the brain to elicit feelings of pleasure and excitement. The second neurotransmitter is the serotonin which is responsible for appetite, mood, and anger. This neurotransmitter affects key functions of the body including blood pressure, temperature and sleeping cycles. The other neurotransmitter is the norepinephrine, responsible for fight/flight response (Cowen, Harrison, & Burns, 2012).
Amphetamines lead to secretion of norepinephrine (dopamine) in the nerve terminals of the adrenergic neuron in the synaptic cleft. Amphetamine compounds cause efflux of biogenic amines in the neural synaptic terminals. The efflux inhibits biogenic amines specific transporters from up taking the biogenic amines at pre-synaptic vesicles and synaptic nerve endings. Amphetamines also hinder monoamine oxidase (the enzyme responsible for degrading of ‘biogenic amine’ neurotransmitters). This causes an increased release of biogenic amines (dopamine, serotonin, and norepinephrine) neurotransmitter into the synapse. The increased catecholamine levels cause the state of increased arousal and reduced fatigue. The high levels of dopamine at synapse are responsible for movement issues, euphoria, and schizophrenia. Hallucinogenic and anorexia is associated with serotonergic signals (Calipari & Ferris, 2013).
The pharmacological effects of amphetamines lie in the central effect, which also affects the peripheral adrenergic neurons of the sympathetic nervous system. It is these autonomic effects that make up some of the adverse effects and toxicity of this drug. In the central effects, amphetamines increase wakefulness, euphoria, agitation, bruxism, reduce appetite, fatigue and reduce appetite. The main autonomic effect of amphetamines affects cardiovascular effects. The amphetamines cause the activation of ‘Alpha 1 receptor’ which leads to significant vasoconstriction, and has higher does activation of beta 1 receptors increases contractility and heart rate. These effects cause prominent diastolic and systolic hypertension. At high or toxic dosage can make individuals feel palpitations that can lead to arrhythmias. If a person takes amphetamines for a long period of time, they develop tolerance to the drug, making them use higher dosage so as to achieve the desired effects. As the dosage increases, the higher the risk of developing physiologic amphetamine drug dependence. The clinical manifestation of drug overdose includes shaking, weakness, nausea, aggression, heart rhythm disturbances, seizures or coma (Calipari & Ferris, 2013).
Question 2: dopamine Schizophrenia of hypothesis
This hypothesis argues that the experiences and unusual behavior associated with schizophrenia can be described through changes of dopamine function in the brain. The hypothesis argues that schizophrenia occurs due to excessive transmission in dopaminergic neuronal pathways at the synapse. This creates abnormal functioning of dopamine-dependent brain systems which causes schizophrenic symptoms. Dopamine is a neurotransmitter responsible for transporting signals between one nerve ending of the brain and another. It is believed that the brains of people with psychotic disorders and schizophrenia secrete too much dopamine which causes delusions and hallucinations. The support of this theory is the fact that the medications used to manage schizophrenia works by blocking dopamine receptors. The medications bind to the dopamine receptors (Owen, Sawa, & Mortensen, 2016).
- b) Neurotransmitters linked schizophrenia
Recent studies indicate that other neurotransmitters such as serotonin and glutamate play a great role in the symptoms of schizophrenia. Glutamate transmitter is responsible for excitatory neurotransmitter substance in the CNS. Glutamate acts in the N-methyl-D-aspartate (NMDA) receptor, present at brain region that is involved in attention, working memory, associative learning. In schizophrenic patients, there is the lower level of glutamate neurotransmitters. In the mesolimbic pathway, the glutamate activity inhibits dopamine activity. The serotonin hypothesis suggests that serotonin neurotransmitter plays role in schizophrenia. Serotonin activity is caused by the knock effect due to glutamate activity, which leads to the inhibition of dopamine in the mesocortical pathway leading to symptoms such as cognitive deficits (Patel, Cherian, Gohil, & Atkinson, 2014).
Question 3: Auditory hallucinations mechanisms and brain regions associated with auditory hallucinations.
Auditory hallucinations are the most common symptoms of psychosis. The mechanism of auditory hallucinations is associated with aberrant activity in primary auditory cortex known as Heschl’s gyrus, often triggered by charged or stressful situations. The hallucinations are believed from altered monitoring systems of inner speech. Auditory hallucinations can be caused by failures in synaptic connectivity. It can also be caused by disturbances in the spines due to temporal abnormal excitations of the neurons (Tracy & Shergill, 2013; Paton, Adroer, & Barnes, 2013).
Based on Hugdahl’s hypothesis, the peri- Sylvian part in the cortical network connects with the temporal lobe anterior parts thereby generating auditory hallucinations due to perceptual misrepresentations. Therefore, in schizophrenic patients, the superior function of the prefrontal cortex responsible for up-down inhibitory system becomes impaired. This causes the auditory hallucinations due to perceptual misrepresentations in the left side of the peri-Sylvin region and the attention to the voice in the parietal cortex. Excitatory neurons in the cerebral cortex represent about 80% of the cerebral cortex neurons. This implies that most of the excitatory synapses occur in the dendrite because of the spines (Barnes & Paton, 2012).
The connective strength in the spinal cord varies and is influenced by the synaptic transmission efficiencies and stimulus. Therefore, it is possible that abnormal neural circuits lead to Schizophrenia. This is associated with the loss of gray matter volume in the cerebral cortex, especially in the frontal as well as the temporal area. However, there is no change in the number of neurons or glial cell which indicates that the loss of gray matter volume is due to reduced synaptic neuritis and density. Therefore, the extent of synaptic connectivity failure indicates the degree of aggravation. The abnormal neurotransmission of glutamic acid and GABA leads to amplitude attenuation of MMN and abnormal Y oscillations. This causes musical hallucinations, auditory awareness, and “Les eidolies hallucinosis.” When the abnormal neurotransmission of serotonin and dopamine is included to the glutamate and GABA abnormalities, it causes the “Les eidolies hallucinosis” become “Les hallucinations delirantes” (paranoid hallucinations) (Tandon, 2014).
Question 4: Medications that may help alleviate Andy’s symptoms and their side effects
Schizophrenia is a chronic mental illness, and can be arbitrarily divided into three main categories namely a) acute, b) stabilizing phase and 3) maintenance of the disorder (McGorry, Bates, & Birchwood, 2013). The patient needs stabilizing and management medication. The best treatment approach for Andy’s symptoms is antipsychotic drugs because they provide the calming effect. The first line treatment is Chlorpromazine (CPZ) in the range of 300-1000 which works by inhibiting dopamine activity by blocking the D2 receptors. This helps in reducing delusions and hallucinations. The medication also has antiserotonin and antihistaminic activity. The second antipsychotic medication is haloperidol. Similar to Clorpromazine, Haloperidol works by blocking dopamine activity, but its exact mechanism is unknown. These two medication side effects include confusion, nervousness, nausea, sleep disturbance restlessness among others. However, the biological mechanism for these side effects is still unclear (Keating et al., 2017).
The clozapine antipsychotic drugs help in blocking serotonin and dopamine activity. The 5-HT2A antagonist property and D4 receptor antagonist properties and D2 blocking activity make the medication to be effective. The medication side effects include a reduction in the levels of white blood cells, weight gain, postural, as well as motor impairment, headache, tachycardia, and dizziness. There is little research on the biological mechanism associated with the drug’s side effects, but it can be associated with the alteration of the circulatory system, leading to rapid or slow blood circulation (National Institute for Health and Care Excellence, 2015; Graham, Mancher, & Wolman, D.M. et al., 2011).
Clinical Features with Amphetamine Intoxication References
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