Other Antidepressants

Overview

• Depression is a unipolar Unipolar Nervous System: Histology mood disorder characterized by persistent low mood and loss of interest in association with somatic symptoms Somatic symptoms Major Depressive Disorder for a duration of at least 2 weeks.
• Depression is managed via pharmacotherapy, psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy, and neuromodulation.

Bupropion

Chemistry

Mechanism of action

Norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS reuptake inhibitor (NDRI):

• Heterocyclic structure
• Inhibits norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS (NE) transporter (NET) and dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS (DA) transporter (DAT) in the presynaptic terminal → ↑ NE and DA levels in the synaptic cleft Synaptic cleft Synapses and Neurotransmission
• Stimulates vesicular monoamine transporter (VMAT) activity → ↑ DA release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology into the synaptic cleft Synaptic cleft Synapses and Neurotransmission

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

• Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption: Oral absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption is rapid.
• Distribution:
  • Protein binding is 84%.
  • Elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy half-life Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics is 13–30 hours.
• Metabolism:
  • 1st-pass metabolism extensively in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
  • Converted to hydroxybupropion by cytochrome P450 Cytochrome P450 A superfamily of hundreds of closely related hemeproteins found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (mixed function oxygenases). In animals, these p450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (biotransformation). They are classified, according to their sequence similarities rather than functions, into cyp gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the cyp1, cyp2, and cyp3 gene families are responsible for most drug metabolism. Drug-Induced Liver Injury (CYP)2B6
• Elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy:
  • Mainly via urine
  • Also in the feces, but to a lesser extent

Indications

• Major depressive disorder Major depressive disorder Major depressive disorder (MDD), commonly called depression, is a unipolar mood disorder characterized by persistent low mood and loss of interest in association with somatic symptoms for a duration of ≥ 2 weeks. Major depressive disorder has the highest lifetime prevalence among all psychiatric disorders. Major Depressive Disorder
• Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation
• Seasonal affective disorder
• Off-label use:
  • ADHD ADHD Attention deficit hyperactivity disorder is a neurodevelopmental disorder characterized by a pattern of inattention and/or hyperactivity-impulsivity that occurs in at least 2 different settings for more than 6 months. Although the patient has normal intelligence, the disease causes functional decline. Attention Deficit Hyperactivity Disorder
  • Bipolar Bipolar Nervous System: Histology depression
  • Sexual dysfunction Sexual dysfunction Physiological disturbances in normal sexual performance in either the male or the female. Sexual Physiology

Adverse effects

• Cardiovascular:
  • Most common: tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
  • Chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Arrhythmia
• GI:
  • Most common: dry mouth
  • Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
• Endocrine/metabolic:
  • Most common: weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
  • Weight gain
  • Menstrual irregularities
• CNS:
  • Most common: insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia
  • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
  • Agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus
• Ophthalmic:
  • Most common: blurred vision Blurred Vision Retinal Detachment
  • Diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis
  • ↑ Risk of angle-closure glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma
• Respiratory:
  • Most common: nasopharyngitis
  • Rhinitis Rhinitis Inflammation of the nasal mucosa, the mucous membrane lining the nasal cavities. Rhinitis
• Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care:
  • Category C
  • ↑ Risk of congenital Congenital Chorioretinitis heart disorders

Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation/warnings

• Monoamine oxidase Oxidase Neisseria (MAO) inhibitors: 14-day washout period between initiation of other antidepressants and vice versa
• Seizure disorder: Bupropion lowers the seizure threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction.
• Eating disorder:
  • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa nervosa
  • Bulimia Bulimia Eating an excess amount of food in a short period of time, as seen in the disorder of bulimia nervosa. It is caused by an abnormal craving for food, or insatiable hunger also known as ‘ox hunger’. Bulimia Nervosa nervosa
• Abrupt discontinuation of sedatives:
  • Ethanol Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. Ethanol Metabolism
  • Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines
  • Barbiturates Barbiturates A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are gaba modulators used as hypnotics and sedatives, as anesthetics, or as anticonvulsants. Intravenous Anesthetics

Drug-drug interactions

• Agents lowering seizure threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction:
  • Tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants ( TCAs TCAs Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants)
  • Clozapine Clozapine A tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2a/2c receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. Second-Generation Antipsychotics
  • Phenothiazines
  • Tramadol Tramadol A narcotic analgesic proposed for severe pain. It may be habituating. Opioid Analgesics
• Sympathomimetics Sympathomimetics Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (î±, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs: ↑ hypertensive effects
• CYP2D6 substrates:
  • Bupropion is a strong CYP2D6 inhibitor.
  • ↑ 2D6 substrate Substrate A substance upon which the enzyme acts. Basics of Enzymes levels
  • ↓ Active metabolite levels of 2D6 prodrugs
• Bupropion ↓ active metabolite levels of:
  • Codeine Codeine An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. Opioid Analgesics
  • Tamoxifen Tamoxifen One of the selective estrogen receptor modulators with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the endometrium. Antiestrogens
  • Tramadol Tramadol A narcotic analgesic proposed for severe pain. It may be habituating. Opioid Analgesics

Brexanolone

Chemistry

• Also known as allopregnanolone and is a C21 steroid
• Naturally occurring neurosteroid biosynthesized from the hormone progesterone Progesterone The major progestational steroid that is secreted primarily by the corpus luteum and the placenta. Progesterone acts on the uterus, the mammary glands and the brain. It is required in embryo implantation; pregnancy maintenance, and the development of mammary tissue for milk production. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Gonadal Hormones

Mechanism of action

• GABA GABA The most common inhibitory neurotransmitter in the central nervous system. Receptors and Neurotransmitters of the CNS_A receptor-positive modulator
• Complete mechanism unknown
• Brexanolone is an allopregnanolone analog that allosterically modulates synaptic (phasic inhibition of action potentials) and extrasynaptic (tonic) inhibition of GABA GABA The most common inhibitory neurotransmitter in the central nervous system. Receptors and Neurotransmitters of the CNS_A receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors. 
• Endogeneous allopregnanolone levels ↑ in the peripartum period and dramatically ↓ during the postpartum period Postpartum period In females, the period that is shortly after giving birth (parturition). Postpartum Complications → low levels blunt the inhibitory effects of GABA GABA The most common inhibitory neurotransmitter in the central nervous system. Receptors and Neurotransmitters of the CNS during stress. Administration of exogenous synthetic allopregnanolone (brexanolone) helps restore levels.

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

• Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption:
  • Oral bioavailability Bioavailability Pharmacokinetics and Pharmacodynamics is poor.
  • Given as an IV formulation
• Distribution:
  • Volume of distribution is 3 L/kg.
  • Protein binding is 99%.
• Metabolism:
  • Not mediated by CYP
  • Ketoreduction via aldo-keto reductases
  • Glucuronidation
  • Sulfation
  • Elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy half-life Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics is 9 hours.
• Excretion:
  • Feces
  • Urine

Indications

Brexanolone is indicated in postpartum depression Postpartum depression Depression in postpartum women, usually within four weeks after giving birth (parturition). The degree of depression ranges from mild transient depression to neurotic or psychotic depressive disorders. Postpartum Psychiatric Disorders.

Adverse effects

• Cardiovascular:
  • Most common: presyncope Presyncope Syncope
  • Flushing
  • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
• CNS:
  • Most common: drowsiness/sedation
  • Dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome)
  • Vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo
• GI:
  • Most common: xerostomia Xerostomia Decreased salivary flow. Sjögren’s Syndrome
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Dyspepsia Dyspepsia Impaired digestion, especially after eating. Lactose Intolerance
• BLACK BOX WARNING: excessive sedation and sudden loss of consciousness

Drug interactions

• Other CNS depressants
• Sedatives (e.g., opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics, benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines, barbiturates Barbiturates A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are gaba modulators used as hypnotics and sedatives, as anesthetics, or as anticonvulsants. Intravenous Anesthetics, ethanol Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. Ethanol Metabolism, esketamine)

Ketamine

Chemistry

• Arylcyclohexylamine derivative
• Chiral compound
• Pharmacologically related to phencyclidine

Mechanism of action

• Mechanism of antidepressant Antidepressant Antidepressants encompass several drug classes and are used to treat individuals with depression, anxiety, and psychiatric conditions, as well as those with chronic pain and symptoms of menopause. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and many other drugs in a class of their own. Serotonin Reuptake Inhibitors and Similar Antidepressants action is unclear.
• N-methyl-D-aspartate (NMDA) receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonist
• Acts directly on the cortex and limbic system Limbic system The limbic system is a neuronal network that mediates emotion and motivation, while also playing a role in learning and memory. The extended neural network is vital to numerous basic psychological functions and plays an invaluable role in processing and responding to environmental stimuli. Limbic System: Anatomy
• Increases the activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors, which modulates a few signaling pathways to influence neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission in the limbic system Limbic system The limbic system is a neuronal network that mediates emotion and motivation, while also playing a role in learning and memory. The extended neural network is vital to numerous basic psychological functions and plays an invaluable role in processing and responding to environmental stimuli. Limbic System: Anatomy:
  • Upregulation of brain-derived neurotrophic factor (BDNF)
  • Activation of tropomyosin Tropomyosin A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. Skeletal Muscle Contraction receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors kinase B
  • Activation of mammalian target of rapamycin ( mTOR mTOR Peutz-Jeghers Syndrome) pathway
  • Deactivation of glycogen synthase Glycogen synthase An enzyme that catalyzes the transfer of d-glucose from udp glucose into 1, 4-alpha-d-glucosyl chains. Glycogen Metabolism kinase 3
  • Inhibits phosphorylation Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Post-translational Protein Processing of eukaryotic Eukaryotic Eukaryotes can be single-celled or multicellular organisms and include plants, animals, fungi, and protozoa. Eukaryotic cells contain a well-organized nucleus contained by a membrane, along with other membrane-bound organelles. Cell Types: Eukaryotic versus Prokaryotic elongation factor 2 Elongation factor 2 Peptide elongation factor 2 catalyzes the translocation of peptidyl-tRNA from the a site to the p site of eukaryotic ribosomes by a process linked to the hydrolysis of GTP to GDP. Diphtheria (eEF2)

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

• Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption:
  • Good absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption, as it is both water and lipid soluble Lipid Soluble Chloramphenicol
  • Low oral bioavailability Bioavailability Pharmacokinetics and Pharmacodynamics due to 1st-pass metabolism
  • IV bioavailability Bioavailability Pharmacokinetics and Pharmacodynamics is 100%.
• Distribution:
  • Rapidly distributed to the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and other tissues
  • Plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products protein binding is approximately 27%.
• Metabolism:
  • Extensive metabolism via CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers) and CYP2B6
  • Elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy half-life Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics is around 2.5–3 hours.
• Excretion:
  • Urine (90%)
  • Feces (3%)

Indications

• Ketamine Ketamine A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (n-methyl-d-aspartate receptors) and may interact with sigma receptors. Intravenous Anesthetics is the anesthetic of choice for short day procedures.
• Management of treatment-resistant depression
• Maintenance therapy for depression

Adverse effects

• Cardiovascular:
  • Blood pressure changes
  • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
  • Bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias
• CNS:
  • Drug dependence
  • Hypertonia Hypertonia Abnormal increase in skeletal or smooth muscle tone. Skeletal muscle hypertonicity may be associated with pyramidal tract lesions or basal ganglia diseases. Neurological Examination/tonic-clonic movements
  • Increased intracranial pressure Increased Intracranial Pressure Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP)
• GI:
  • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
  • Sialorrhea
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
• Ophthalmic:
  • Diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis
  • Nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism
  • Increased intraocular pressure Intraocular Pressure The pressure of the fluids in the eye. Ophthalmic Exam

Drug interactions

• Potentiates the action of:
  • Opiates Opiates Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics
  • Barbiturates Barbiturates A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are gaba modulators used as hypnotics and sedatives, as anesthetics, or as anticonvulsants. Intravenous Anesthetics
  • Alcohol
• Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines may diminish the antidepressant Antidepressant Antidepressants encompass several drug classes and are used to treat individuals with depression, anxiety, and psychiatric conditions, as well as those with chronic pain and symptoms of menopause. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and many other drugs in a class of their own. Serotonin Reuptake Inhibitors and Similar Antidepressants effect.
• May cause seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures with theophylline Theophylline A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3. Asthma Drugs