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.

Agonists and Antagonists in Pharmacology

In pharmacology, an agonist is a substance that binds to a receptor and triggers a biological response. On the other hand, an antagonist is a substance that blocks the effects of an agonist. A partial agonist produces a response but cannot produce the maximum response even at high doses.

Competitive antagonists bind to the receptor in a reversible way without affecting the biological response. They make the agonist appear less potent. Inverse agonists, on the other hand, have opposite effects from those of full agonists. They are not the same as antagonists, which block the effect of both agonists and inverse agonists.

Full agonists display full efficacy at a receptor. Some substances can act as an agonist at certain receptors and as an antagonist at others. Such a substance is called an agonist-antagonist. Understanding the differences between agonists and antagonists is crucial in drug development and treatment.

Elevated levels of creatine phosphokinase (CPK) are observed in NMS.

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.

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).

While varenicline may cause uncommon of rare side effects, abnormal dreams are a frequently reported one.

Varenicline for Smoking Cessation: Safety and Efficacy

Varenicline is a medication used to aid smoking cessation by reducing cravings and pleasurable effects of tobacco products. It has a high affinity for the alpha 4 beta 2 nicotinic receptor and is recommended by NICE for smoking cessation. Varenicline is safe to use in cases of liver dysfunction as it undergoes very little hepatic metabolism. It has been found to be nearly 80% more effective than bupropion and more effective than 24-hour nicotine replacement therapy in two large randomized controlled trials. The initial course of treatment could last 12 weeks, with an additional 12 weeks offered to those who have successfully quit smoking. However, varenicline has been observed to exacerbate underlying psychiatric illness, including depression, and is associated with changes in behavior of thinking, anxiety, psychosis, mood swings, aggressive behavior, suicidal ideation, and behavior. Patients with a psychiatric history should be closely monitored while taking varenicline. One randomized controlled trial has challenged this concern. The FDA has issued a safety announcement that varenicline may be associated with a small, increased risk of certain cardiovascular adverse events in patients with cardiovascular disease. The very common side effects of varenicline include nasopharyngitis, abnormal dreams, insomnia, headache, and nausea.

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.

While the upper limit technically reaches 439, it is evident that 440 is the optimal choice among the options provided.

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.

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).

Bupropion inhibits the reuptake of noradrenaline and dopamine, making it an NDRI.

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.

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.

Lithium – Pharmacology

Pharmacokinetics:
Lithium salts are rapidly absorbed following oral administration and are almost exclusively excreted by the kidneys unchanged. Blood samples for lithium should be taken 12 hours post-dose.

Ebstein’s:
Ebstein’s anomaly is a congenital malformation consisting of a prolapse of the tricuspid valve into the right ventricle. It occurs in 1:20,000 of the general population. Initial data suggested it was more common in those using lithium but this had not held to be true.

Contraindications:
Addison’s disease, Brugada syndrome, cardiac disease associated with rhythm disorders, clinically significant renal impairment, untreated of untreatable hypothyroidism, low sodium levels.

Side-effects:
Common side effects include nausea, tremor, polyuria/polydipsia, rash/dermatitis, blurred vision, dizziness, decreased appetite, drowsiness, metallic taste, and diarrhea. Side-effects are often dose-related.

Long-term use is associated with hypothyroidism, hyperthyroidism, hypercalcemia/hyperparathyroidism, irreversible nephrogenic diabetes insipidus, and reduced GFR.

Lithium-induced diabetes insipidus:
Treatment options include stopping lithium (if feasible), keeping levels within 0.4-0.8 mmol/L, once-daily dose of the drug taken at bedtime, amiloride, thiazide diuretics, indomethacin, and desmopressin.

Toxicity:
Lithium salts have a narrow therapeutic/toxic ratio. Risk factors for lithium toxicity include drugs altering renal function, decreased circulating volume, infections, fever, decreased oral intake of water, renal insufficiency, and nephrogenic diabetes insipidus. Features of lithium toxicity include GI symptoms and neuro symptoms.

Pre-prescribing:
Before prescribing lithium, renal function, cardiac function, thyroid function, FBC, and BMI should be checked. Women of childbearing age should be advised regarding contraception, and information about toxicity should be provided.

Monitoring:
Lithium blood levels should be checked weekly until stable, and then every 3-6 months once stable. Thyroid and renal function should be checked every 6 months. Patients should be issued with an information booklet, alert card, and record book.

, coma, respiratory depression (rare)

The half-life of a drug is the time taken for its concentration to fall to one half of its value. Drugs with long half-lives may require a loading dose to achieve therapeutic plasma concentrations rapidly. It takes about 4.5 half-lives to reach steady state plasma levels. Most drugs follow first order kinetics, where a constant fraction of the drug in the body is eliminated per unit time. However, some drugs may follow zero order kinetics, where the plasma concentration of the drug decreases at a constant rate, despite the concentration of the drug. For drugs with nonlinear kinetics of dose-dependent kinetics, the relationship between the AUC of CSS and dose is not linear, and the kinetic parameters may vary depending on the administered dose.

The question pertains to a classic case of atypical depression, which is best treated with phenelzine, a MAOI. While imipramine and other TCAs have some evidence for treating atypical depression, they are not as effective as MAOIs. Nowadays, SSRIs are commonly used as a first-line treatment, but they have a weaker evidence base compared to MAOIs and TCAs. Vortioxetine is a new antidepressant that has complex effects on the 5HT system, but it has not been studied for its efficacy in treating atypical depression. Similarly, venlafaxine has not been studied for this indication either.

Duloxetine boosts serotonin, norepinephrine, and dopamine levels by functioning as a serotonin and norepinephrine reuptake inhibitor (SNRI). On the other hand, Mirtazapine is a noradrenaline and specific serotonergic agent (NaSSA) that acts as an alpha 2 antagonist, increasing serotonin and norepinephrine levels.

Agonists and Antagonists in Pharmacology

In pharmacology, an agonist is a substance that binds to a receptor and triggers a biological response. On the other hand, an antagonist is a substance that blocks the effects of an agonist. A partial agonist produces a response but cannot produce the maximum response even at high doses.

Competitive antagonists bind to the receptor in a reversible way without affecting the biological response. They make the agonist appear less potent. Inverse agonists, on the other hand, have opposite effects from those of full agonists. They are not the same as antagonists, which block the effect of both agonists and inverse agonists.

Full agonists display full efficacy at a receptor. Some substances can act as an agonist at certain receptors and as an antagonist at others. Such a substance is called an agonist-antagonist. Understanding the differences between agonists and antagonists is crucial in drug development and treatment.

Drug Clearance: Understanding the Rate of Drug Removal from the Body

Drug clearance refers to the efficiency of drug removal from the plasma, and is measured as the volume of plasma cleared of a drug over a specific time period. The unit of measurement for drug clearance is volume per time. Clearance of a drug involves both metabolism and excretion. When drug intake equals clearance, it is referred to as a steady state, which is usually achieved by 4.5 half-lives. The time taken to reach steady state depends on the half-life of the drug.

There are two main types of clearance: hepatic and renal. Hepatic clearance involves the conversion of the parent drug into a different chemical entity by the liver enzymes, while renal clearance involves the removal of the drug from the plasma into the urine. The clearance of a drug can take one of two forms: zero and first-order kinetics. In zero-order reactions, the clearance of a drug is constant and not related to the concentration of the drug in the plasma. This type of reaction is typically found when the material needed for the reaction to proceed (e.g. enzyme) is saturated. Ethanol and Phenytoin are good examples of this.

Most drugs tend to follow first-order reactions, where the clearance is related to the concentration of the drug in the plasma. The half-life of a drug is the time taken for its concentration to fall by half. In first-order reactions, this is constant. In zero-order reactions, it gets progressively shorter.

It is important to note that elimination and clearance are not the same. Elimination is the irreversible removal of the drug from the body, while clearance is a theoretical volume of blood that is cleared of the drug per unit of time, which is independent of the drug dose of concentration. Understanding drug clearance is crucial in determining the appropriate dosing regimen for a drug.

Understanding Bioavailability in Drug Trials

Bioavailability is a crucial factor in drug trials, as it determines the percentage of a drug that reaches the systemic circulation after administration. This can be affected by factors such as absorption and metabolic clearance. For example, if a drug called X is administered orally and only 60% reaches the systemic circulation, its bioavailability is 0.6 of 60%. However, if the same drug is administered intravenously, plasma levels may reach 100%.

One way to potentially increase bioavailability is through the rectal route, which bypasses around two thirds of the first-pass metabolism. This is because the rectum’s venous drainage is two thirds systemic (middle and inferior rectal vein) and one third portal (superior rectal vein). As a result, drugs administered rectally may reach the circulatory system with less alteration and in greater concentrations. Understanding bioavailability and exploring different administration routes can help optimize drug efficacy in clinical trials.

Understanding the Volume of Distribution in Pharmacology

The volume of distribution (Vd) is a crucial concept in pharmacology that helps determine how a drug distributes in the body. It is also known as the apparent volume of distribution, as it is an abstract volume. The Vd indicates whether a drug concentrates in the plasma of spreads out in the body. Drugs that are highly polar tend to stay in central compartments such as the plasma, resulting in a low Vd. Conversely, drugs that are more lipid-soluble are distributed widely, such as in fat, resulting in a high Vd.

The Vd is calculated by dividing the amount of drug in the body by the concentration in the plasma. Clinically, the Vd is used to determine the loading dose of a drug required for a desired blood concentration and to estimate blood concentration in the treatment of overdose. The units of Vd are in volume.

The apparent volume of distribution is dependent on the drug’s lipid of water solubility, plasma protein binding, and tissue binding. Plasma protein binding affects the Vd, as drugs that bind to plasma proteins like albumin have a smaller apparent volume of distribution. This is because they are extracted from plasma and included in drug concentration measurements, which can give a misleading impression of their volume of distribution. Understanding the Vd is essential in pharmacology to ensure the safe and effective use of drugs.

Omega 3 fatty acids, which are found in high amounts in oily fish, have been shown in some studies to improve depressive symptoms and can be safely combined with SSRIs. However, St John’s wort, which inhibits serotonin reuptake at nerve terminals, should not be taken with drugs that have a predominantly serotonergic action. Brewer’s yeast may cause a tyramine reaction with an MAOI, while evening primrose oil and ginkgo biloba have no interaction with SSRIs.

Elevated troponin levels typically manifest within a few hours of myocardial injury and persist for a maximum of two weeks.

Clozapine is an atypical antipsychotic drug that acts as an antagonist at various receptors, including dopamine, histamine, serotonin, adrenergic, and cholinergic receptors. It is mainly metabolized by CYP1A2, and its plasma levels can be affected by inducers and inhibitors of this enzyme. Clozapine is associated with several side effects, including drowsiness, constipation, weight gain, and hypersalivation. Hypersalivation is a paradoxical side effect, and its mechanism is not fully understood, but it may involve clozapine agonist activity at the muscarinic M4 receptor and antagonist activity at the alpha-2 adrenoceptor. Clozapine is also associated with several potentially dangerous adverse events, including agranulocytosis, myocarditis, seizures, severe orthostatic hypotension, increased mortality in elderly patients with dementia-related psychosis, colitis, pancreatitis, thrombocytopenia, thromboembolism, and insulin resistance and diabetes mellitus. The BNF advises caution in using clozapine in patients with prostatic hypertrophy, susceptibility to angle-closure glaucoma, and adults over 60 years. Valproate should be considered when using high doses of clozapine, plasma levels > 0.5 mg/l, of when the patient experiences seizures. Myocarditis is a rare but potentially fatal adverse event associated with clozapine use, and its diagnosis is based on biomarkers and clinical features. The mortality rate of clozapine-induced myocarditis is high, and subsequent use of clozapine in such cases leads to recurrence of myocarditis in most cases.

Antidepressants have varying half lives, with fluoxetine having one of the longest at four to six days. Agomelatine, on the other hand, has a much shorter half life of approximately one to two hours. Citalopram has a half life of approximately 36 hours, while duloxetine has a half life of approximately 12 hours. Paroxetine falls in the middle with a half life of approximately 24 hours. For more information on antidepressant discontinuation syndrome, refer to the article by Warner et al. (2006).

Lithium is known to cause hypercalcemia and hyperparathyroidism, which can lead to various symptoms. These symptoms may include constipation (groans), kidney stones (stones), bone pain (bones), and mental health issues such as depression, lethargy, and confusion (psychic moans).

Lithium – Pharmacology

Pharmacokinetics:
Lithium salts are rapidly absorbed following oral administration and are almost exclusively excreted by the kidneys unchanged. Blood samples for lithium should be taken 12 hours post-dose.

Ebstein’s:
Ebstein’s anomaly is a congenital malformation consisting of a prolapse of the tricuspid valve into the right ventricle. It occurs in 1:20,000 of the general population. Initial data suggested it was more common in those using lithium but this had not held to be true.

Contraindications:
Addison’s disease, Brugada syndrome, cardiac disease associated with rhythm disorders, clinically significant renal impairment, untreated of untreatable hypothyroidism, low sodium levels.

Side-effects:
Common side effects include nausea, tremor, polyuria/polydipsia, rash/dermatitis, blurred vision, dizziness, decreased appetite, drowsiness, metallic taste, and diarrhea. Side-effects are often dose-related.

Long-term use is associated with hypothyroidism, hyperthyroidism, hypercalcemia/hyperparathyroidism, irreversible nephrogenic diabetes insipidus, and reduced GFR.

Lithium-induced diabetes insipidus:
Treatment options include stopping lithium (if feasible), keeping levels within 0.4-0.8 mmol/L, once-daily dose of the drug taken at bedtime, amiloride, thiazide diuretics, indomethacin, and desmopressin.

Toxicity:
Lithium salts have a narrow therapeutic/toxic ratio. Risk factors for lithium toxicity include drugs altering renal function, decreased circulating volume, infections, fever, decreased oral intake of water, renal insufficiency, and nephrogenic diabetes insipidus. Features of lithium toxicity include GI symptoms and neuro symptoms.

Pre-prescribing:
Before prescribing lithium, renal function, cardiac function, thyroid function, FBC, and BMI should be checked. Women of childbearing age should be advised regarding contraception, and information about toxicity should be provided.

Monitoring:
Lithium blood levels should be checked weekly until stable, and then every 3-6 months once stable. Thyroid and renal function should be checked every 6 months. Patients should be issued with an information booklet, alert card, and record book.

Donepezil is a medication that selectively inhibits acetylcholinesterase (AChE) without affecting butyrylcholinesterase (BuChE). It is a long-acting, reversible inhibitor that is commonly used to treat dementia. Other drugs used to treat dementia include Rivastigmine, Galantamine, and Memantine. These medications work by either preventing the breakdown of acetylcholine in the brain of by blocking the chemical messenger glutamate, which can cause further damage to brain cells. By increasing communication between nerve cells of reducing damage, these medications can temporarily improve of stabilize the symptoms of Alzheimer’s disease.

Hyponatremia in Psychiatric Patients

Hyponatremia, of low serum sodium, can occur in psychiatric patients due to the disorder itself, its treatment, of other medical conditions. Symptoms include nausea, confusion, seizures, and muscular cramps. Drug-induced hyponatremia is known as the syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), which results from excessive secretion of ADH and fluid overload. Diagnosis is based on clinically euvolaemic state with low serum sodium and osmolality, raised urine sodium and osmolality. SSRIs, SNRIs, and tricyclics are the most common drugs that can cause SIADH. Risk factors for SIADH include starting a new drug, and treatment usually involves fluid restriction and sometimes demeclocycline.

Priapism: A Painful and Persistent Erection

Priapism is a condition characterized by a prolonged and painful erection, which can occur in males and even in the clitoris. Although rare, certain medications such as antipsychotics and antidepressants have been known to cause priapism. The primary mechanism behind this condition is alpha blockade, although other mechanisms such as serotonin-mediated pathways have also been suggested. Some of the drugs most commonly associated with priapism include Trazodone, Chlorpromazine, and Thioridazine. Treatment involves the use of alpha-adrenergic agonists, which can be administered orally of injected directly into the penis. Priapism is a serious condition that can lead to complications such as penile amputation, although such cases are extremely rare.

Some additional risk factors for QTc prolongation include being female and having a slow heart rate (bradycardia).

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.

ADHD medications can be classified into stimulant and non-stimulant drugs. The therapeutic effects of these drugs are believed to be mediated through the action of noradrenaline in the prefrontal cortex. Common side effects of these drugs include decreased appetite, insomnia, nervousness, headache, and nausea. Stimulant drugs like dexamphetamine, methylphenidate, and lisdexamfetamine inhibit the reuptake of dopamine and noradrenaline. Non-stimulant drugs like atomoxetine, guanfacine, and clonidine work by increasing noradrenaline levels in the synaptic cleft through different mechanisms. The most common side effects of these drugs are decreased appetite, somnolence, headache, and abdominal pain.

ADRs only occur when medications are used at ABNORMAL doses. (FALSE)

Adverse Drug Reactions (ADRs) refer to the harmful effects associated with the use of a medication at a normal dose. These reactions are classified into two types: Type A and Type B. Type A reactions can be predicted from the pharmacology of the drug and are dose-dependent, meaning they can be reversed by withdrawing the drug. On the other hand, Type B reactions cannot be predicted from the known pharmacology of the drug and include allergic reactions.

Type A reactions account for up to 80% of all ADRs, while Type B reactions are less common. Allergic reactions are a type of Type B reaction and are further subdivided by Gell and Coombs into four types: Type I (IgE-mediated) reactions, Type II (cytotoxic) reactions, Type III (immune complex) reactions, and Type IV (cell-mediated) reactions. Proper identification and management of ADRs are crucial in ensuring patient safety and optimizing treatment outcomes.

Lithium – Pharmacology

Pharmacokinetics:
Lithium salts are rapidly absorbed following oral administration and are almost exclusively excreted by the kidneys unchanged. Blood samples for lithium should be taken 12 hours post-dose.

Ebstein’s:
Ebstein’s anomaly is a congenital malformation consisting of a prolapse of the tricuspid valve into the right ventricle. It occurs in 1:20,000 of the general population. Initial data suggested it was more common in those using lithium but this had not held to be true.

Contraindications:
Addison’s disease, Brugada syndrome, cardiac disease associated with rhythm disorders, clinically significant renal impairment, untreated of untreatable hypothyroidism, low sodium levels.

Side-effects:
Common side effects include nausea, tremor, polyuria/polydipsia, rash/dermatitis, blurred vision, dizziness, decreased appetite, drowsiness, metallic taste, and diarrhea. Side-effects are often dose-related.

Long-term use is associated with hypothyroidism, hyperthyroidism, hypercalcemia/hyperparathyroidism, irreversible nephrogenic diabetes insipidus, and reduced GFR.

Lithium-induced diabetes insipidus:
Treatment options include stopping lithium (if feasible), keeping levels within 0.4-0.8 mmol/L, once-daily dose of the drug taken at bedtime, amiloride, thiazide diuretics, indomethacin, and desmopressin.

Toxicity:
Lithium salts have a narrow therapeutic/toxic ratio. Risk factors for lithium toxicity include drugs altering renal function, decreased circulating volume, infections, fever, decreased oral intake of water, renal insufficiency, and nephrogenic diabetes insipidus. Features of lithium toxicity include GI symptoms and neuro symptoms.

Pre-prescribing:
Before prescribing lithium, renal function, cardiac function, thyroid function, FBC, and BMI should be checked. Women of childbearing age should be advised regarding contraception, and information about toxicity should be provided.

Monitoring:
Lithium blood levels should be checked weekly until stable, and then every 3-6 months once stable. Thyroid and renal function should be checked every 6 months. Patients should be issued with an information booklet, alert card, and record book.