Mechanisms of Action of Different Drugs

Understanding the mechanisms of action of different drugs is crucial for medical professionals. It is a common topic in exams and can earn easy marks if studied well. This article provides a list of drugs and their mechanisms of action in different categories such as antidepressants, anti dementia drugs, mood stabilizers, anxiolytic/hypnotic drugs, antipsychotics, drugs of abuse, and other drugs. For example, mirtazapine is a noradrenaline and serotonin specific antidepressant that works as a 5HT2 antagonist, 5HT3 antagonist, H1 antagonist, alpha 1 and alpha 2 antagonist, and moderate muscarinic antagonist. Similarly, donepezil is a reversible acetylcholinesterase inhibitor used as an anti dementia drug, while valproate is a GABA agonist and NMDA antagonist used as a mood stabilizer. The article also explains the mechanisms of action of drugs such as ketamine, phencyclidine, buprenorphine, naloxone, atomoxetine, varenicline, disulfiram, acamprosate, and sildenafil.

History of Psychiatric Terms

In the exams, it is important to be familiar with the individuals associated with certain psychiatric terms. For example, Kraepelin is associated with dementia praecox and manic depression, while Bleuler is associated with schizophrenia. Other terms and their associated individuals include Hebephrenia (Hecker), Catatonia (Kahlbaum), Schizoaffective (Kasanin), Neurasthenia (Beard), Unipolar and bipolar (Kleist), Hypnosis (Braid), Group dynamics (Lewin), Group psychotherapy (Moreno), Psychopathic inferiority (Koch), Psychiatry (Reil), and Institutional Neurosis (Barton).

It should be noted that there is some debate over the origins of certain terms. While Kraepelin is often credited with coining the term dementia praecox, some sources suggest that it was first used in its Latin form by Arnold Pick in 1891. The original term demence precoce was first used by Morel in 1852. Despite this, the College appears to favor the Kraepelin attribution.

Antidepressant Medications and Ischaemic Heart Disease

The SADHART investigation has shown that sertraline is a safe and effective antidepressant for patients with ischaemic heart disease. However, other medications have not yet been proven safe for this population.

Amitriptyline, a tricyclic antidepressant, is not recommended for patients with comorbid coronary heart disease due to its high relative risk of myocardial infarction and direct cardiac effects. It may also induce weight gain and increase the risk of diabetes, both of which are known risk factors for cardiovascular disease.

Mirtazapine has been studied as a safe second line/alternative treatment to SSRIs in post MI depression, but it can also cause weight gain. Further research is needed to determine the safety and efficacy of other antidepressant medications in patients with ischaemic heart disease.

Temperament is the innate aspect of an individual’s personality that is believed to be influenced by genetics, while character is shaped by learned experiences. Thomas and Chess developed a classification system that assesses children’s behavior based on nine traits, including activity level, adaptability, and emotional response. They found that 65% of children fall into one of three temperament types: easy, difficult, of slow to warm up. Thomas and Chess also introduced the concept of goodness of fit, which refers to the compatibility between a child’s temperament and their environment. When there is a good fit, children are more likely to reach their potential. For example, teachers can provide active learning experiences for children with high activity levels instead of seat work.

The term paramnesia refers to memory disorders where fantasy and reality are confused. There are various types of paramnesias, including déjà vu, jamais vu, confabulation, reduplicative paramnesia, retrospective falsification, and cryptomnesia. Reduplicative paramnesia is a subset of delusional misidentification syndromes, which include Capgras delusion, the Fregoli delusion, and others. A review of reduplicative paramnesia was conducted by Politis in 2012.

Neologism is a symptom of schizophrenia where a person creates new words of uses existing words in a way that only makes sense to them. Alogia is a difficulty in speaking, which can be caused by a lack of thoughts of negative thought disorder. Clang associations occur when words are linked based on their sound rather than their meaning. Logoclonia is a condition where a person gets stuck on a particular word, often repeating syllables of parts of words. Stuttering is a speech disorder characterized by involuntary repetitions, prolongations, and pauses in speech.

Depression rates are elevated among those who are unemployed of divorced. Additionally, the prevalence of major depression is twice as high in women compared to men, although the reasons for this disparity are not fully understood. The mean age of onset for major depression is 27 years, and lifetime rates are estimated to be between 10% and 20%.

Drug-Induced Mania: Evidence and Precipitating Drugs

There is strong evidence that mania can be triggered by certain drugs, according to Peet (1995). These drugs include levodopa, corticosteroids, anabolic-androgenic steroids, and certain classes of antidepressants such as tricyclic and monoamine oxidase inhibitors.

Additionally, Peet (2012) suggests that there is weaker evidence that mania can be induced by dopaminergic anti-Parkinsonian drugs, thyroxine, iproniazid and isoniazid, sympathomimetic drugs, chloroquine, baclofen, alprazolam, captopril, amphetamine, and phencyclidine.

It is important for healthcare professionals to be aware of the potential for drug-induced mania and to monitor patients closely for any signs of symptoms. Patients should also be informed of the risks associated with these medications and advised to report any unusual changes in mood of behavior.

The metabolism of donepezil can be inhibited by CYP3A4 inhibitors like erythromycin and CYP2D6 inhibitors like fluoxetine. Conversely, enzyme inducers of these can decrease donepezil levels.

Pharmacological management of dementia involves the use of acetylcholinesterase inhibitors (AChE inhibitors) and memantine. AChE inhibitors prevent the breakdown of acetylcholine, which is deficient in Alzheimer’s due to the loss of cholinergic neurons. Donepezil, galantamine, and rivastigmine are commonly used AChE inhibitors in the management of Alzheimer’s. However, gastrointestinal side effects such as nausea and vomiting are common with these drugs.

Memantine, on the other hand, is an NMDA receptor antagonist that blocks the effects of pathologically elevated levels of glutamate that may lead to neuronal dysfunction. It has a half-life of 60-100 hours and is primarily renally eliminated. Common adverse effects of memantine include somnolence, dizziness, hypertension, dyspnea, constipation, headache, and elevated liver function tests.

Overall, pharmacological management of dementia aims to improve cognitive function and slow down the progression of the disease. However, it is important to note that these drugs do not cure dementia and may only provide temporary relief of symptoms.

Assessment Tools:

Luria’s Test:
Luria’s test is a motor task designed by Alexander Luria, a Russian neuropsychologist. The test was developed based on his observation that individuals with significant frontal lobe damage were unable to modify their responses to a programmed motor task when the order of actions in the task was changed.

Geriatric Depression Scale:
The Geriatric Depression Scale is a screening tool used to identify depression in older adults. It is not designed to assess cognitive impairment.

Mini-Mental State Examination:
The Mini-Mental State Examination is a brief, 30-question screening tool used to assess cognitive impairment. It does not evaluate frontal lobe functions.

National Adult Reading Test:
The National Adult Reading Test is used to assess the premorbid level of intelligence in English-speaking patients.

Wechsler Adult Intelligence Scale:
The Wechsler Adult Intelligence Scale is a comprehensive assessment tool used to measure intelligence in adults and older adolescents.

It is advisable to maintain the medication and regular monitoring as a QTC of 410 ms is within the normal range.

Amantadine and QTc Prolongation

Amantadine is a medication used to treat Parkinson’s disease and influenza. It has been associated with QTc prolongation, which can increase the risk of Torsades de points. Therefore, caution should be exercised when prescribing amantadine to patients with risk factors for QT prolongation. If a patient is already taking amantadine and develops a prolonged QTc interval, the medication should be discontinued and an alternative treatment considered. It is important to monitor the QTc interval in patients taking amantadine, especially those with risk factors for QT prolongation.

The symptoms observed in the presentation are indicative of serotonin syndrome, which can be caused by various medications such as antidepressants, lithium, opioids, olanzapine, and risperidone. However, benzodiazepines are not associated with serotonin syndrome and are actually used as part of the treatment.

Serotonin Syndrome and Neuroleptic Malignant Syndrome are two conditions that can be difficult to differentiate. Serotonin Syndrome is caused by excess serotonergic activity in the CNS and is characterized by neuromuscular abnormalities, altered mental state, and autonomic dysfunction. On the other hand, Neuroleptic Malignant Syndrome is a rare acute disorder of thermoregulation and neuromotor control that is almost exclusively caused by antipsychotics. The symptoms of both syndromes can overlap, but there are some distinguishing clinical features. Hyper-reflexia, ocular clonus, and tremors are more prominent in Serotonin Syndrome, while Neuroleptic Malignant Syndrome is characterized by uniform ‘lead-pipe’ rigidity and hyporeflexia. Symptoms of Serotonin Syndrome usually resolve within a few days of stopping the medication, while Neuroleptic Malignant Syndrome can take up to 14 days to remit with appropriate treatment. The following table provides a useful guide to the main differentials of Serotonin Syndrome and Neuroleptic Malignant Syndrome.

Alternative Routes of Administration for Antidepressants

While most antidepressants are taken orally, there are a few alternative routes of administration available. However, it is important to note that these non-oral preparations should only be used when absolutely necessary, as they may not have a UK licence.

One effective alternative route is sublingual administration of fluoxetine liquid. Buccal administration of selegiline is also available. Crushed amitriptyline has been shown to be effective when administered via this route.

Intravenous administration is another option, with several antidepressants available in IV preparations, including citalopram, escitalopram, mirtazapine, amitriptyline, clomipramine, and allopregnanolone (which is licensed in the US for postpartum depression). Ketamine has also been shown to be effective when administered intravenously.

Intramuscular administration of flupentixol has been shown to have a mood elevating effect, but amitriptyline was discontinued as an IM preparation due to the high volumes required.

Transdermal administration of selegiline is available, and suppositories containing amitriptyline, clomipramine, imipramine, and trazodone have been manufactured by pharmacies, although there is no clear data on their effectiveness. Sertraline tablets and doxepin capsules have also been given rectally.

Nucleotides: The Building Blocks of DNA and RNA

Nucleotides are the fundamental units of DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). Each nucleotide consists of three components: a sugar molecule (deoxyribose in DNA and ribose in RNA), a phosphate group, and a nitrogenous base. The nitrogenous bases can be classified into two categories: purines and pyrimidines. The purine bases include adenine and guanine, while the pyrimidine bases are cytosine, thymine (in DNA), and uracil (in RNA).

The arrangement of nucleotides in DNA and RNA determines the genetic information that is passed from one generation to the next. The sequence of nitrogenous bases in DNA forms the genetic code that determines the traits of an organism. RNA, on the other hand, plays a crucial role in protein synthesis by carrying the genetic information from DNA to the ribosomes, where proteins are synthesized.

Understanding the structure and function of nucleotides is essential for understanding the molecular basis of life. The discovery of the structure of DNA and the role of nucleotides in genetic information has revolutionized the field of biology and has led to many breakthroughs in medicine, biotechnology, and genetics.

Dementia Pugilistica: A Neurodegenerative Condition Resulting from Neurotrauma

Dementia pugilistica, also known as chronic traumatic encephalopathy (CTE), is a neurodegenerative condition that results from neurotrauma. It is commonly seen in boxers and NFL players, but can also occur in anyone with neurotrauma. The condition is characterized by symptoms such as gait ataxia, slurred speech, impaired hearing, tremors, disequilibrium, neurobehavioral disturbances, and progressive cognitive decline.

Most cases of dementia pugilistica present with early onset cognitive deficits, and behavioral signs exhibited by patients include aggression, suspiciousness, paranoia, childishness, hypersexuality, depression, and restlessness. The progression of the condition leads to more prominent behavioral symptoms such as difficulty with impulse control, irritability, inappropriateness, and explosive outbursts of aggression.

Neuropathological abnormalities have been identified in CTE, with the most unique feature being the abnormal accumulation of tau in neurons and glia in an irregular, focal, perivascular distribution and at the depths of cortical sulci. Abnormalities of the septum pellucidum, such as cavum and fenestration, are also a common feature.

While the condition has become increasingly rare due to the progressive improvement in sports safety, it is important to recognize the potential long-term consequences of repeated head injuries and take steps to prevent them.

Personality Disorder Classification

A personality disorder is a persistent pattern of behavior and inner experience that deviates significantly from cultural expectations, is inflexible and pervasive, and causes distress of impairment. The DSM-5 and ICD-11 have different approaches to classifying personality disorders. DSM-5 divides them into 10 categories, grouped into clusters A, B, and C, while ICD-11 has a general category with six trait domains that can be added. To diagnose a personality disorder, the general diagnostic threshold must be met before determining the subtype(s) present. The criteria for diagnosis include inflexibility and pervasiveness of the pattern, onset in adolescence of early adulthood, stability over time, and significant distress of impairment. The disturbance must not be better explained by another mental disorder, substance misuse, of medical condition.

Course

Borderline and antisocial personality disorders tend to become less evident of remit with age, while others, particularly obsessive-compulsive and schizotypal, may persist.

Classification

The DSM-5 divides personality disorders into separate clusters A, B, and C, with additional groups for medical conditions and unspecified disorders. The ICD-11 dropped the separate categories and instead lists six trait domains that can be added to the general diagnosis.

UK Epidemiology

The prevalence of personality disorders in Great Britain, according to the British National Survey of Psychiatric Morbidity, is 4.4%, with cluster C being the most common at 2.6%, followed by cluster A at 1.6% and cluster B at 1.2%. The most prevalent specific personality disorder is obsessive-compulsive (anankastic) at 1.9%.

The development of tardive dyskinesia is thought to be caused by an increased sensitivity of postsynaptic D2 receptors in the nigrostriatal pathway. Therefore, clozapine is recommended as a treatment option since it has minimal binding affinity for D2 receptors.

Tardive Dyskinesia: Symptoms, Causes, Risk Factors, and Management

Tardive dyskinesia (TD) is a condition that affects the face, limbs, and trunk of individuals who have been on neuroleptics for months to years. The movements fluctuate over time, increase with emotional arousal, decrease with relaxation, and disappear with sleep. The cause of TD remains theoretical, but the postsynaptic dopamine (D2) receptor supersensitivity hypothesis is the most persistent. Other hypotheses include the presynaptic dopaminergic/noradrenergic hyperactivity hypothesis, the cholinergic interneuron burnout hypothesis, the excitatory/oxidative stress hypothesis, and the synaptic plasticity hypothesis. Risk factors for TD include advancing age, female sex, ethnicity, longer illness duration, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, diabetes, smoking, alcohol and substance misuse, FGA vs SGA treatment, higher antipsychotic dose, anticholinergic co-treatment, and akathisia.

Management options for TD include stopping any anticholinergic, reducing antipsychotic dose, changing to an antipsychotic with lower propensity for TD, and using tetrabenazine, vitamin E, of amantadine as add-on options. Clozapine is the antipsychotic most likely to be associated with resolution of symptoms. Vesicular monoamine transporter type 2 (VMAT2) inhibitors are agents that cause a depletion of neuroactive peptides such as dopamine in nerve terminals and are used to treat chorea due to neurodegenerative diseases of dyskinesias due to neuroleptic medications (tardive dyskinesia).

History of Psychiatric Terms

In the exams, it is important to be familiar with the individuals associated with certain psychiatric terms. For example, Kraepelin is associated with dementia praecox and manic depression, while Bleuler is associated with schizophrenia. Other terms and their associated individuals include Hebephrenia (Hecker), Catatonia (Kahlbaum), Schizoaffective (Kasanin), Neurasthenia (Beard), Unipolar and bipolar (Kleist), Hypnosis (Braid), Group dynamics (Lewin), Group psychotherapy (Moreno), Psychopathic inferiority (Koch), Psychiatry (Reil), and Institutional Neurosis (Barton).

It should be noted that there is some debate over the origins of certain terms. While Kraepelin is often credited with coining the term dementia praecox, some sources suggest that it was first used in its Latin form by Arnold Pick in 1891. The original term demence precoce was first used by Morel in 1852. Despite this, the College appears to favor the Kraepelin attribution.

Freud’s Structural Theory: Understanding the Three Areas of the Mind

According to Freud’s structural model, the human mind is divided into three distinct areas: the Id, the Ego, and the Superego. The Id is the part of the mind that contains instinctive drives and operates on the ‘pleasure principle’. It functions without a sense of time and is governed by ‘primary process thinking’. The Ego, on the other hand, attempts to modify the drives from the Id with external reality. It operates on the ‘reality principle’ and has conscious, preconscious, and unconscious aspects. It is also home to the defense mechanisms. Finally, the Superego acts as a critical agency, constantly observing a person’s behavior. Freud believed that it developed from the internalized values of a child’s main caregivers. The Superego contains the ‘ego ideal’, which represents ideal attitudes and behavior. It is often referred to as the conscience. Understanding these three areas of the mind is crucial to understanding Freud’s structural theory.

For the long-term management of mania, NICE (CG185) recommends offering a psychological intervention designed for bipolar disorder to prevent relapse. Additionally, lithium should be offered as the first-line, long-term pharmacological treatment. If lithium is not effective, valproate may be considered as an alternative. If lithium is not well-tolerated of not suitable due to reasons such as the person not agreeing to routine blood monitoring, olanzapine or quetiapine may be considered instead, with quetiapine being a viable option if it has been effective during an episode of mania of bipolar depression. It is important to note that valproate would be the next best option if lithium is contraindicated due to severe renal impairment.

Renal Impairment and Psychotropic Drugs

The following table provides recommendations for drug treatment in patients with renal impairment, based on the Maudsley 14th guidelines. When a new drug treatment is required, the suggestions below should be followed.

Drug Group Recommendation

Antipsychotics: It is recommended to avoid sulpiride and amisulpride. Otherwise, no agent is clearly preferable to another. For first-generation antipsychotics, haloperidol (2-6 mg/day) is the best choice. For second-generation antipsychotics, olanzapine (5mg/day) is the best choice.

Antidepressants: No agent is clearly preferable to another. Reasonable choices include sertraline (although there is poor efficacy data in renal disease), citalopram (with care over QTc prolongation), and fluoxetine (with care over long half-life).

Mood stabilizers: Lithium is nephrotoxic and contraindicated in severe renal impairment. Otherwise, no agent is clearly preferable to another. Valproate of lamotrigine are suggested.

Anxiolytics: No agent is clearly preferable to another. Lorazepam and zopiclone are suggested.

Anti-dementia drugs: No agent is clearly preferable to another. Rivastigmine is suggested.

Anhedonia, a term coined by Théodule-Armand Ribot in 1896, refers to the lack of interest in experiencing pleasure. This condition is commonly linked to depression and is also observed in schizophrenia as a component of the negative symptoms of the disorder.

Lewis’ Views on Mental Illness Diagnosis

Lewis believed that mental illness could be understood by examining the disturbance of part functions of the brain, such as emotion, perception, and memory, as well as a reduction in general efficiency. However, he cautioned against using socially deviant behavior as a means of diagnosis. Instead, he advocated for a multi-axial formulation approach, which was first proposed by Essen-Möller in 1947. Lewis also warned against relying on response to psychotropic medication as a reliable method of diagnosis. Overall, Lewis emphasized the importance of a comprehensive and nuanced approach to diagnosing mental illness.

According to the GMC’s guidance on Financial and Commercial Arrangements and Conflicts of Interest (2013), it is prohibited to encourage patients to give, lend, of bequeath money of gifts that would benefit you directly of indirectly. However, unsolicited gifts from patients of their relatives may be accepted as long as it does not affect of appear to affect the way you prescribe, advise, treat, refer, of commission services for patients, and you have not used your influence to pressure of persuade patients of their relatives to offer you gifts. Nevertheless, if you receive a gift of bequest from a patient of their relative, you should consider the potential damage it could cause to your patients’ trust in you and the public’s trust in the profession. Gifts of bequests that could be perceived as an abuse of trust should be refused. Additionally, it is prohibited to pressure patients of their families to make donations to other people of organizations.

The Wechsler Adult Intelligence Scale (WAIS) is a widely used intelligence test in clinical settings, designed for individuals aged 16 to 90. Its counterpart for children is the Wechsler Intelligence Scale for Children (WISC). The current version of WAIS, WAIS-IV, consists of four index scores, each comprising several subsets. These are the Verbal Comprehension Index, Perceptual Reasoning Index, Working Memory Index, and Processing Speed Index. The results are presented as two scores: Full Scale IQ and General Ability Index. The average score is 100, with a standard deviation of 15. However, the test becomes less accurate at the extremes of IQ (70-130). About 3% of people score below 70, which is the general cut-off for a significant learning disability.

White matter is the cabling that links different parts of the CNS together. There are three types of white matter cables: projection tracts, commissural tracts, and association tracts. Projection tracts connect higher centers of the brain with lower centers, commissural tracts connect the two hemispheres together, and association tracts connect regions of the same hemisphere. Some common tracts include the corticospinal tract, which connects the motor cortex to the brainstem and spinal cord, and the corpus callosum, which is the largest white matter fiber bundle connecting corresponding areas of cortex between the hemispheres. Other tracts include the cingulum, superior and inferior occipitofrontal fasciculi, and the superior and inferior longitudinal fasciculi.

The Basal Ganglia: Functions and Disorders

The basal ganglia are a group of subcortical structures that play a crucial role in controlling movement and some cognitive processes. The components of the basal ganglia include the striatum (caudate, putamen, nucleus accumbens), subthalamic nucleus, globus pallidus, and substantia nigra (divided into pars compacta and pars reticulata). The putamen and globus pallidus are collectively referred to as the lenticular nucleus.

The basal ganglia are connected in a complex loop, with the cortex projecting to the striatum, the striatum to the internal segment of the globus pallidus, the internal segment of the globus pallidus to the thalamus, and the thalamus back to the cortex. This loop is responsible for regulating movement and cognitive processes.

However, problems with the basal ganglia can lead to several conditions. Huntington’s chorea is caused by degeneration of the caudate nucleus, while Wilson’s disease is characterized by copper deposition in the basal ganglia. Parkinson’s disease is associated with degeneration of the substantia nigra, and hemiballism results from damage to the subthalamic nucleus.

In summary, the basal ganglia are a crucial part of the brain that regulate movement and some cognitive processes. Disorders of the basal ganglia can lead to significant neurological conditions that affect movement and other functions.

Extrapyramidal side-effects (EPSE’s) are a group of side effects that affect voluntary motor control, commonly seen in patients taking antipsychotic drugs. EPSE’s include dystonias, parkinsonism, akathisia, and tardive dyskinesia. They can be frightening and uncomfortable, leading to problems with non-compliance and can even be life-threatening in the case of laryngeal dystonia. EPSE’s are thought to be due to antagonism of dopaminergic D2 receptors in the basal ganglia. Symptoms generally occur within the first few days of treatment, with dystonias appearing quickly, within a few hours of administration of the first dose. Newer antipsychotics tend to produce less EPSE’s, with clozapine carrying the lowest risk and haloperidol carrying the highest risk. Akathisia is the most resistant EPSE to treat. EPSE’s can also occur when antipsychotics are discontinued (withdrawal dystonia).

The head injury resulted in anterograde amnesia, which is characterized by memory loss for events that occurred after the injury.

Understanding Amnesia: Types and Causes

Amnesia is a memory deficit that can be categorized into two types: anterograde and retrograde. Anterograde amnesia refers to the inability to create new memories, while retrograde amnesia refers to the loss of memory for information acquired before the onset of amnesia. The damage to the hippocampus and medial temporal lobe is often associated with amnesia. Source amnesia is the inability to remember where of how previously learned information was acquired. Psychogenic amnesia is characterized by sudden retrograde episodic memory loss, while semantic amnesia affects semantic memory and language use. Transient global amnesia is a condition that affects those over 50 and spontaneously resolves within 24 hours, with no clear cause identified. Understanding the types and causes of amnesia can help in its diagnosis and treatment.

The prevention of a disease can be divided into three levels: primary, secondary, and tertiary. Tertiary prevention focuses on minimizing the effects of an existing disease and helping individuals achieve their optimal level of functioning. Primary prevention involves implementing broad changes to decrease the overall risk of a disease in a population, such as promoting healthy nutrition, positive parenting, and smoking cessation. Secondary prevention involves early detection and intervention through screening programs.

Opioid Pharmacology and Treatment Medications

Opioids work by binding to opioid receptors in the brain, specifically the µ, k, and δ receptors. The µ receptor is the main target for opioids and mediates euphoria, respiratory depression, and dependence. Dopaminergic cells in the ventral tegmental area produce dopamine, which is released into the nucleus accumbens upon stimulation of µ receptors, leading to the reward and euphoria that drives repeated use. However, with repeated exposure, µ receptors become less responsive, leading to dysphoria and drug craving.

There are several medications used in opioid treatment. Methadone is a full agonist targeting µ receptors, with some action against k and δ receptors, and has a half-life of 15-22 hours. However, it carries a risk of respiratory depression, especially when used with hypnotics and alcohol. Buprenorphine is a partial agonist targeting µ receptors, as well as a partial k agonist of functional antagonist and a weak δ antagonist. It has a high affinity for µ receptors and a longer half-life of 24-42 hours, making it safer than methadone. Naloxone is an antagonist targeting all opioid receptors and is used to reverse opioid overdose, with a half-life of 30-120 minutes. However, it can cause noncardiogenic pulmonary edema in some cases. Naltrexone is a reversible competitive antagonist at µ and ĸ receptors, with a half-life of 4-6 hours, and is used as an adjunctive prophylactic treatment for detoxified formerly opioid-dependent people.

Alpha2 adrenergic agonists, such as clonidine and lofexidine, can ameliorate opioid withdrawal symptoms associated with the noradrenaline system, including sweating, shivering, and runny nose and eyes. The locus coeruleus, a nucleus in the pons with a high density of noradrenergic neurons possessing µ-opioid receptors, is involved in wakefulness, blood pressure, breathing, and overall alertness. Exposure to opioids results in heightened neuronal activity of the nucleus cells, and if opioids are not present to suppress this activity, increased amounts of norepinephrine are released, leading to withdrawal symptoms. Clonidine was originally developed as an antihypertensive, but its antihypertensive effects are problematic in detox, so lofexidine was developed as an alternative with less hypotensive effects.