The MHRA categorizes adverse drug reactions into five types. Type A reactions occur when a drug’s normal pharmacological actions are exaggerated at the usual therapeutic dose, and are typically dose-dependent. Type B reactions are unexpected responses that do not align with the drug’s known pharmacological actions. Type C reactions persist for an extended period of time, while Type D reactions become apparent after some time has passed since the medication was used. Finally, Type E reactions are linked to the discontinuation of a medication.

Antipsychotics can be classified in different ways, with the most common being typical (first generation) and atypical (second generation) types. Typical antipsychotics block dopamine (D2) receptors and have varying degrees of M1, Alpha-1, and H1 receptor blockade. Atypical antipsychotics have a lower propensity for extrapyramidal side-effects and are attributed to the combination of relatively lower D2 antagonism with 5HT2A antagonism. They are also classified by structure, with examples including phenothiazines, butyrophenones, thioxanthenes, diphenylbutylpiperidine, dibenzodiazepines, benzoxazoles, thienobenzodiazepine, substituted benzamides, and arylpiperidylindole (quinolone). Studies have found little evidence to support the superiority of atypicals over typicals in terms of efficacy, discontinuation rates, of adherence, with the main difference being the side-effect profile. The Royal College also favors classification by structure.

Plasma concentrations of lithium may be decreased by both sodium bicarbonate and aminophylline.

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.

According to Gillman (1998), it is recommended to avoid using the antihistamines brompheniramine and chlorpheniramine as they act as serotonin reuptake inhibitors (SRIs). However, all other antihistamines are considered safe for use. Gillman’s study focused on the history and risk of serotonin syndrome.

MAOIs: A Guide to Mechanism of Action, Adverse Effects, and Dietary Restrictions

First introduced in the 1950s, MAOIs were the first antidepressants introduced. However, they are not the first choice in treating mental health disorders due to several dietary restrictions and safety concerns. They are only a treatment option when all other medications are unsuccessful. MAOIs may be particularly useful in atypical depression (over eating / over sleeping, mood reactivity).

MAOIs block the monoamine oxidase enzyme, which breaks down different types of neurotransmitters from the brain: norepinephrine, serotonin, dopamine, as well as tyramine. There are two types of monoamine oxidase, A and B. The MOA A are mostly distributed in the placenta, gut, and liver, but MOA B is present in the brain, liver, and platelets. Selegiline and rasagiline are irreversible and selective inhibitors of MAO type B, but safinamide is a reversible and selective MAO B inhibitor.

The most common adverse effects of MAOIs occurring early in treatment are orthostatic hypotension, daytime sleepiness, insomnia, and nausea; later common effects include weight gain, muscle pain, myoclonus, paraesthesia, and sexual dysfunction.

Pharmacodynamic interactions with MAOIs can cause two types of problem: serotonin syndrome (mainly due to SSRIs) and elevated blood pressure (caused by indirectly acting sympathomimetic amines releasers, like pseudoephedrine and phenylephrine). The combination of MAOIs and some TCAs appears safe. Only those TCAs with significant serotonin reuptake inhibition (clomipramine and imipramine) are likely to increase the risk of serotonin syndrome.

Tyramine is a monoamine found in various foods, and is an indirect sympathomimetic that can cause a hypertensive reaction in patients receiving MAOI therapy. For this reason, dietary restrictions are required for patients receiving MAOIs. These restrictions include avoiding matured/aged cheese, fermented sausage, improperly stored meat, fava of broad bean pods, and certain drinks such as on-tap beer. Allowed foods include fresh cottage cheese, processed cheese slices, fresh packaged of processed meat, and other alcohol (no more than two bottled or canned beers of two standard glasses of wine, per day).

Antidepressants: Minimum Effective Doses

According to the Maudsley 13th, the following are the minimum effective doses for various antidepressants:

– Citalopram: 20 mg/day
– Fluoxetine: 20 mg/day
– Fluvoxamine: 50 mg/day
– Paroxetine: 20 mg/day
– Sertraline: 50 mg/day
– Mirtazapine: 30 mg/day
– Venlafaxine: 75 mg/day
– Duloxetine: 60 mg/day
– Agomelatine: 25 mg/day
– Moclobemide: 300 mg/day
– Trazodone: 150 mg/day

Note that these are minimum effective doses and may vary depending on individual factors and response to treatment. It is important to consult with a healthcare professional before starting of changing any medication regimen.

The initial antidepressants were imipramine and iproniazid.

A Historical Note on the Development of Zimelidine, the First Selective Serotonin Reuptake Inhibitor

In 1960s, evidence began to emerge suggesting a significant role of serotonin in depression. This led to the development of zimelidine, the first selective serotonin reuptake inhibitor (SSRI). Zimelidine was derived from pheniramine and was marketed in Europe in 1982. However, it was removed from the market in 1983 due to severe side effects such as hypersensitivity reactions and Guillain-Barre syndrome.

Despite its short-lived availability, zimelidine paved the way for the development of other SSRIs such as fluoxetine, which was approved by the FDA in 1987 and launched in the US market in 1988 under the trade name Prozac. The development of SSRIs revolutionized the treatment of depression and other mood disorders, providing a safer and more effective alternative to earlier antidepressants such as the tricyclics and MAO inhibitors.

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.

Aripiprazole does not affect the QTc interval and has minimal risk of extrapyramidal side effects, sedation, of weight gain. Amisulpride, citalopram, and quetiapine have a moderate effect on the QTc interval, which requires ECG monitoring due to a prolongation of >10 msec. Haloperidol has a high effect on the QTc interval, which mandates ECG monitoring due to a prolongation of >20 msec.

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.

Stevens-Johnson syndrome, a condition that can be triggered by various anticonvulsants including lamotrigine, appears to align with the patient’s medical history.

Stevens-Johnson syndrome is a severe skin condition that can be caused by medication use of infection. Anticonvulsants, particularly lamotrigine, are often the cause. Symptoms include fever, sore throat, fatigue, and the appearance of ulcers and lesions in the mucous membranes. A rash of round lesions also appears on the face, trunk, arms, legs, and soles of the feet. It is a life-threatening condition that requires immediate medical attention.