Question 1: Clinical features associated with amphetamine intoxication
An amphetamine is a Central Nervous System (CNS) stimulant through the sympathetic
nervous system outflow. Amphetamine is a class of “indirect adrenergic agonsists”, which
directly stimulates the adrenergic receptors by facilitating the release of norepinephrine from the
nerve terminals. The adrenergic receptors become stimulated through indirect mechanism
because amphetamines do not bind directly to the receptors (Heal et al., 2013).
There are remarkable series of events that takes 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 causes 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 (enzyme responsible for degrading of ‘biogenic
amine’ neurotransmitters). This causes an increase release of biogenic amines (dopamine,
serotonin and norepinephrine) neurotransmitter into 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 aneroxia 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 the 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 to 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 to 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 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 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 are involved in attention, working memory, associative
learning. In schizophrenic patients, there is lower level of glutamate neurotransmitters. In
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
mesocortical pathway leading to symptoms such as cognitive deficits (Patel, Cherian, Gohil, &
Question 3: Auditory hallucinations mechanisms and brain regions associated with
Auditory hallucinations are most common symptoms of psychosis. The mechanism of
auditory hallucinations is associated to 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,
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 peri-Sylvin region and the
attention to 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 occurs in
the dendrite because 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 neuron or glial cell which indicates that the loss of gray mater 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 hallucinosiques.” When the abnormal neurotransmission of
serotonin and dopamine is included to the glutamate and GABA abnormalities, it causes the “Les
eidolies hallucinosiques” become “Les hallucinations delirantes” (paranoid hallucinations)
Question 4: Medications that may help alleviate Andy’s symptoms and their side
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 antihistamic 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
makes the medication to be effective. The medication side effects include 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 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).
Barnes, T.R., & Paton, C. (2012). Role of the prescribing observatory for mental health. Br J
Calipari, E. S., & Ferris, M. J. (2013). Amphetamine Mechanisms and Actions at the Dopamine
Terminal Revisited. The Journal of Neuroscience : The Official Journal of the Society for
Neuroscience, 33(21), 8923–8925.
Cowen, P., Harrison, P., & Burns, T. (2012). Shorter Oxford textbook of psychiatry. Oxford
Graham, R., Mancher, M., Wolman, D.M. et al. (2011). Clinical practice guidelines we can trust.
National Academies Press, 2011.
Heal, D. J., Smith, S. L., Gosden, J., & Nutt, D. J. (2013). Amphetamine, past and present – a
pharmacological and clinical perspective. Journal of Psychopharmacology (Oxford,
England), 27(6), 479–496.
Keating, D., McWilliams, S., Schneider, I., Hynes, C., Cousins, G., Strawbridge, J., & Clarke,
M. (2017). Pharmacological guidelines for schizophrenia: a systematic review and
comparison of recommendations for the first episode. BMJ Open, 7(1), e013881.
McGorry, P., Bates, T., & Birchwood, M. (2013). Designing youth mental health services for the
21st century: examples from Australia, Ireland and the UK. Br J Psychiatry
National Institute for Health and Care Excellence. (2015). Medicines optimization: the safe and
effective use of medicines to enable the best possible outcomes. NG 5. 2015.
Owen, M.J., Sawa, A., Mortensen, P.B. (2016). Schizophrenia. Lancet;388:86–97.
Paton,C., Adroer, R., Barnes, T.R.(2013). Monitoring lithium therapy: the impact of a quality
improvement programme in the UK. Bipolar Disord 15:865–75.
Patel, K. R., Cherian, J., Gohil, K., & Atkinson, D. (2014). Schizophrenia: Overview and
Treatment Options. Pharmacy and Therapeutics, 39(9), 638–645.
Tandon, R. (2014). Schizophrenia and Other Psychotic Disorders in Diagnostic and Statistical
Manual of Mental Disorders (DSM)-5: Clinical Implications of Revisions from DSM-IV.
Tracy, D.K., and Shergill, S.S. (2013). Mechanisms underlying auditory hallucinations –
understanding perception without stimulus. Brain sciences 3, 642-669.