Spasmolytics are skeletal muscle relaxants that reduce forceful, involuntary muscle contractions. Spasmolytics have several mechanisms and can either act centrally to inhibit somaticmotorMotorNeurons which send impulses peripherally to activate muscles or secretory cells.Nervous System: Histology neuron signals, or peripherally to preventCaCACondylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding.Condylomata Acuminata (Genital Warts)+2 release from thesarcoplasmic reticulumSarcoplasmic ReticulumA network of tubules and sacs in the cytoplasm of skeletal muscle fibers that assist with muscle contraction and relaxation by releasing and storing calcium ions.Muscle Tissue: Histology. Spasmolytics are often used as temporary adjunctive treatment to alleviate musclespasmsSpasmsAn involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle.Ion Channel Myopathy or musculoskeletalpainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways. Spasmolytics may also be used in the management ofspasticitySpasticitySpinal Disk Herniation due to uppermotorMotorNeurons which send impulses peripherally to activate muscles or secretory cells.Nervous System: Histology neuron disorders. Most medications readily cross theblood–brain barrierBlood–Brain BarrierMeningitis in Children; thus, CNS depression is a common side effect. It is also important to be aware of dependence and withdrawal symptoms (particularly with CNS depressants andGABAGABAThe most common inhibitory neurotransmitter in the central nervous system.Receptors and Neurotransmitters of the CNS agonists).
Skeletal muscle cell contraction requires stimulation by anaction potentialAction PotentialAbrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli.Membrane Potential (AP) from somaticmotorMotorNeurons which send impulses peripherally to activate muscles or secretory cells.Nervous System: HistologyneuronsNeuronsThe basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system.Nervous System: Histology.
The AP propagates in all directions throughout thesarcolemmaSarcolemmaThe excitable plasma membrane of a muscle cell.Muscle Tissue: Histology.
Excitation-contraction couplingExcitation-contraction couplingA process fundamental to muscle physiology whereby an electrical stimulus or action potential triggers a myocyte to depolarize and contract. This mechanical muscle contraction response is regulated by entry of calcium ions into the cell.Skeletal Muscle Contraction:
The AP stimulates voltage-dependentdihydropyridineDihydropyridinePyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers) (DHP)receptorsReceptorsReceptors 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:
Mechanically tethered toryanodine receptorsRyanodine ReceptorsMalignant Hyperthermia present on (and remain closed) theCaCACondylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding.Condylomata Acuminata (Genital Warts)+2-releasechannelsChannelsThe Cell: Cell Membrane in thesarcoplasmic reticulumSarcoplasmic ReticulumA network of tubules and sacs in the cytoplasm of skeletal muscle fibers that assist with muscle contraction and relaxation by releasing and storing calcium ions.Muscle Tissue: Histology (SR)
CaCACondylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding.Condylomata Acuminata (Genital Warts)2+ floods out of the SR into thesarcoplasmSarcoplasmMuscle Tissue: Histology → binds to troponin on the thin filaments (actinActinFilamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or f-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or g-actin. In conjunction with myosins, actin is responsible for the contraction and relaxation of muscle.Skeletal Muscle Contraction)
Troponin-tropomyosin complex changes shape → allows binding ofactinActinFilamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or f-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or g-actin. In conjunction with myosins, actin is responsible for the contraction and relaxation of muscle.Skeletal Muscle Contraction andmyosinMyosinA diverse superfamily of proteins that function as translocating proteins. They share the common characteristics of being able to bind actins and hydrolyze mgATP. Myosins generally consist of heavy chains which are involved in locomotion, and light chains which are involved in regulation. Within the structure of myosin heavy chain are three domains: the head, the neck and the tail. The head region of the heavy chain contains the actin binding domain and mgATPase domain which provides energy for locomotion. The neck region is involved in binding the light-chains. The tail region provides the anchoring point that maintains the position of the heavy chain. The superfamily of myosins is organized into structural classes based upon the type and arrangement of the subunits they contain.Skeletal Muscle Contraction
Spasmolytics can be divided based on where and how they exert their effects:
Centrally acting:
Function: prevent nerve signal transmission from thebrainBrainThe 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 orspinal cordSpinal cordThe spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons).Spinal Cord: Anatomy via:
CNS depression results in skeletal muscle relaxation.
No direct effect on the contractile mechanism of skeletal muscle
PharmacokineticsPharmacokineticsPharmacokinetics 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
AbsorptionAbsorptionAbsorption 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
Cross theplacentaPlacentaA highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones).Placenta, Umbilical Cord, and Amniotic Cavity
Metabolism: hepatic
Carisoprodol: viacytochrome P450Cytochrome P450A 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)2C19 to the active metabolite
Methocarbamol: via dealkylation and hydroxylation
Excretion: urine
Indications
Relief ofpainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways associated with acute musculoskeletal conditions (musclespasmsSpasmsAn involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle.Ion Channel Myopathy)
For short-term use
Usually used as an adjunct to otherpainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways relievers (e.g.,acetaminophenAcetaminophenAcetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood.Acetaminophen,NSAIDsNSAIDSPrimary vs Secondary Headaches)
SeizuresSeizuresA 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
Drug dependency and withdrawal symptoms (carisoprodol)
ContraindicationsContraindicationsA 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 and precautions
Carisoprodol should not be taken if there is a history ofacute intermittent porphyriaAcute intermittent porphyriaAn autosomal dominant porphyria that is due to a deficiency of hydroxymethylbilane synthase in the liver, the third enzyme in the 8-enzyme biosynthetic pathway of heme. Clinical features are recurrent and life-threatening neurologic disturbances, abdominal pain, and elevated level of aminolevulinic acid and porphobilinogen in the urine.Porphyrias.
Use with caution in individuals with hepatic or renal impairment.
Drug interactions
Enhanced CNS depression can occur with (list is not exhaustive):
Alcohol
BarbituratesBarbituratesA 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
Cannabinoid products
OpioidsOpioidsOpiates 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
AntihistaminesAntihistaminesAntihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation.Antihistamines
BenzodiazepinesBenzodiazepinesBenzodiazepines 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 (such asdiazepamDiazepamA benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of gamma-aminobutyric acid activity.Benzodiazepines)
Mechanism of action
Baclofen:
GABAGABAThe most common inhibitory neurotransmitter in the central nervous system.Receptors and Neurotransmitters of the CNSBreceptorReceptorReceptors 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 agonist:
Closes presynapticCaCACondylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding.Condylomata Acuminata (Genital Warts)2+channelsChannelsThe Cell: Cell Membrane
Inhibits adenylyl cyclase
↓ Excitatory neurotransmitter release and inhibition of spinalmotorMotorNeurons which send impulses peripherally to activate muscles or secretory cells.Nervous System: HistologyneuronsNeuronsThe basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system.Nervous System: Histology
Mechanism of action of baclofen: Baclofen binds to presynaptic GABABreceptors and modulates Ca2+ and K+ channels, ultimately blocking excitatory neurotransmitter release.
Image by Lecturio.
DiazepamDiazepamA benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of gamma-aminobutyric acid activity.Benzodiazepines:
Binds to the γ subunit of theGABAGABAThe most common inhibitory neurotransmitter in the central nervous system.Receptors and Neurotransmitters of the CNSAreceptorReceptorReceptors 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 → enhances the binding ofGABAGABAThe most common inhibitory neurotransmitter in the central nervous system.Receptors and Neurotransmitters of the CNS in the pocket between the α and β subunits of thereceptorReceptorReceptors 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
↑ Frequency ofchlorideChlorideInorganic compounds derived from hydrochloric acid that contain the Cl- ion.Electrolytes channel opening → ↑chlorideChlorideInorganic compounds derived from hydrochloric acid that contain the Cl- ion.Electrolytes influx → inhibits AP
Mechanism of action of diazepam: Diazepam binds to the γ subunit of the GABAA receptor and enhances GABA binding to the pocket between the α and β subunits, increasing the frequency of opening of the chloride (Cl–) channels. The subsequent increase in Cl– influx blunts depolarization of the neuron and decreases action potentials.
Image by Lecturio.
PharmacokineticsPharmacokineticsPharmacokinetics 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
PharmacokineticsPharmacokineticsPharmacokinetics 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 of baclofen:
AbsorptionAbsorptionAbsorption 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:
Rapid, oralabsorptionAbsorptionAbsorption 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
Crosses theplacentaPlacentaA highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones).Placenta, Umbilical Cord, and Amniotic Cavity
Spinal cordSpinal cordThe spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons).Spinal Cord: Anatomy injury (e.g., multiplesclerosisSclerosisA pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve.Wilms Tumor)
Cerebral injury (e.g, cerebralpalsyPalsyparalysis of an area of the body, thus incapable of voluntary movementCranial Nerve Palsies,traumatic brain injuryTraumatic brain injuryA form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.Le Fort Fractures)
Temporary adjunctive therapy for musclespasmsSpasmsAn involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle.Ion Channel Myopathy or musculoskeletalpainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways
DiazepamDiazepamA benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of gamma-aminobutyric acid activity.Benzodiazepines:
Temporary adjunctive therapy for:
MusclespasmsSpasmsAn involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle.Ion Channel Myopathy
Neuroleptic malignant syndromeNeuroleptic malignant syndromeNeuroleptic malignant syndrome (NMS) is a rare, idiosyncratic, and potentially life-threatening reaction to antipsychotic drugs. Neuroleptic malignant syndrome presents with ≥ 2 of the following cardinal symptoms: fever, altered mental status, muscle rigidity, and autonomic dysfunction.Neuroleptic Malignant Syndrome (adjunctive therapy)
SeizuresSeizuresA 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 (acute management)
Adverse effects
Urinary retentionUrinary retentionInability to empty the urinary bladder with voiding (urination).Delirium
NauseaNauseaAn 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 andvomitingVomitingThe forcible expulsion of the contents of the stomach through the mouth.Hypokalemia
ConstipationConstipationConstipation 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
CNS depression
HypotensionHypotensionHypotension is defined as low blood pressure, specifically< 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause.Hypotension
Respiratory depression (more likely withdiazepamDiazepamA benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of gamma-aminobutyric acid activity.Benzodiazepines)
Seizure (baclofen)
Withdrawal effects with abrupt discontinuation
ContraindicationsContraindicationsA 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 and precautions
Baclofen should be used with caution in individuals with:
Urinary retentionUrinary retentionInability to empty the urinary bladder with voiding (urination).Delirium
Psychiatric disorders (e.g., psychotic disorders,schizophreniaSchizophreniaSchizophrenia is a chronic mental health disorder characterized by the presence of psychotic symptoms such as delusions or hallucinations. The signs and symptoms of schizophrenia are traditionally separated into 2 groups: positive (delusions, hallucinations, and disorganized speech or behavior) and negative (flat affect, avolition, anhedonia, poor attention, and alogia).Schizophrenia)
Renal impairment
Seizure disorder
DiazepamDiazepamA benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of gamma-aminobutyric acid activity.Benzodiazepines:
ContraindicationsContraindicationsA 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:
Untreated open-angleglaucomaGlaucomaGlaucoma 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
Myasthenia gravisMyasthenia GravisMyasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement.Myasthenia Gravis
Severe respiratory impairment
Severe hepatic impairment
Use with caution:
Psychiatric conditions (e.g., depression,anxietyAnxietyFeelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders.Generalized Anxiety Disorder)
Renal impairment
Respiratory conditions
Drug interactions
Enhanced CNS depression can occur with (list is not exhaustive):
Alcohol
BarbituratesBarbituratesA 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
Cannabinoid products
OpioidsOpioidsOpiates 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
AntihistaminesAntihistaminesAntihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation.Antihistamines
ClonidineClonidineAn imidazoline sympatholytic agent that stimulates alpha-2 adrenergic receptors and central imidazoline receptors. It is commonly used in the management of hypertension.Sympathomimetic Drugs (also an alpha-1 agonist)
Mechanism of action
Stimulate presynaptic alpha-2 adrenergicreceptorsReceptorsReceptors 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 → ↓norepinephrineNorepinephrinePrecursor 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 release
Inhibit spinalmotorMotorNeurons which send impulses peripherally to activate muscles or secretory cells.Nervous System: HistologyneuronsNeuronsThe basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system.Nervous System: Histology → ↓muscle toneMuscle toneThe state of activity or tension of a muscle beyond that related to its physical properties, that is, its active resistance to stretch. In skeletal muscle, tonus is dependent upon efferent innervation.Skeletal Muscle Contraction andspasticitySpasticitySpinal Disk Herniation
PharmacokineticsPharmacokineticsPharmacokinetics 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
PharmacokineticsPharmacokineticsPharmacokinetics 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 of tizanidine:
AbsorptionAbsorptionAbsorption 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:
Tablets: Food increases peakplasmaPlasmaThe residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation.Transfusion Products concentrations and the extent ofabsorptionAbsorptionAbsorption 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.
Capsules: Food decreases peak concentration but increases the extent ofabsorptionAbsorptionAbsorption 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.
Management ofspasticitySpasticitySpinal Disk Herniation (includingspasticitySpasticitySpinal Disk Herniation associated with multiplesclerosisSclerosisA pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve.Wilms Tumor, stroke, orspinal cordSpinal cordThe spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons).Spinal Cord: Anatomy injury)
Can be used as temporary adjunctive therapy for muscle spasm or musculoskeletalpainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways
Adverse effects
HypotensionHypotensionHypotension is defined as low blood pressure, specifically< 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause.Hypotension
BradycardiaBradycardiaBradyarrhythmia 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
ConstipationConstipationConstipation 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
↑LiverLiverThe 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: AnatomyenzymesEnzymesEnzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules.Basics of Enzymes
Rebound symptoms after abrupt discontinuation
ContraindicationsContraindicationsA 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 and precautions
ContraindicationsContraindicationsA 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: concurrent therapy with potent CYP1A2 inhibitors (tizanidine)
Use with caution in individuals with:
Severe renal or hepatic impairment
Cardiovascular disease (clonidineClonidineAn imidazoline sympatholytic agent that stimulates alpha-2 adrenergic receptors and central imidazoline receptors. It is commonly used in the management of hypertension.Sympathomimetic Drugs)
HypotensionHypotensionHypotension is defined as low blood pressure, specifically< 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause.Hypotension
Drug interactions
CYP1A2 inhibitors ↑ tizanidine concentration (and risk of adverse effects):
CimetidineCimetidineA histamine congener, it competitively inhibits histamine binding to histamine h2 receptors. Cimetidine has a range of pharmacological actions. It inhibits gastric acid secretion, as well as pepsin and gastrin output.Antihistamines
Enhanced CNS depression can occur with (list is not exhaustive):
Alcohol
BarbituratesBarbituratesA 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
Cannabinoid products
OpioidsOpioidsOpiates 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
AntihistaminesAntihistaminesAntihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation.Antihistamines
↑ Risk ofhypotensionHypotensionHypotension is defined as low blood pressure, specifically< 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause.Hypotension:
Beta-blockersBeta-blockersDrugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.Class 2 Antiarrhythmic Drugs (Beta Blockers)
OtherantihypertensivesAntihypertensivesThe 1st-line medication classes for hypertension include thiazide-like diuretics, angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers (ARBs), and calcium channel blockers (CCBS). Contraindications, adverse effects, and drug-to-drug interactions are agent specific.Hypertension Drugs
↑ Risk ofbradycardiaBradycardiaBradyarrhythmia 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:
Beta-blockersBeta-blockersDrugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.Class 2 Antiarrhythmic Drugs (Beta Blockers)
MidodrineMidodrineAn ethanolamine derivative that is an adrenergic alpha-1 agonist. It is used as a vasoconstrictor agent in the treatment of hypotension.Sympathomimetic Drugs
Terlipressin
Cyclic Antidepressants
Medications in this group
Cyclobenzaprine is the main drug in this group.
Mechanism of action
Similar structure as that oftricyclic antidepressantsTricyclic antidepressantsTricyclic 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
Acts centrally within the brainstem to inhibit somaticmotorMotorNeurons which send impulses peripherally to activate muscles or secretory cells.Nervous System: Histology activity
The exact mechanism is unclear but may include the inhibition ofserotoninSerotoninA biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity.Receptors and Neurotransmitters of the CNS (5-HT2)receptorsReceptorsReceptors 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.
Also hasanticholinergicAnticholinergicAnticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes.Anticholinergic Drugs properties
PharmacokineticsPharmacokineticsPharmacokinetics 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
AbsorptionAbsorptionAbsorption 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: orally absorbed
Cyclobenzaprine can be used as a temporary adjunctive therapy for:
MusclespasmsSpasmsAn involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle.Ion Channel Myopathy and musculoskeletalpainPainAn unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons.Pain: Types and Pathways
Temporomandibular joint dysfunction
Note: Cyclobenzaprine is ineffective inspasticitySpasticitySpinal Disk Herniation due to cerebral orspinal cordSpinal cordThe spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons).Spinal Cord: Anatomy pathologies.
Adverse effects
AnticholinergicAnticholinergicAnticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes.Anticholinergic Drugs effects:
MydriasisMydriasisDilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome.Glaucoma
TachycardiaTachycardiaAbnormally 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
ConstipationConstipationConstipation 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
Urinary retentionUrinary retentionInability to empty the urinary bladder with voiding (urination).Delirium
CNS depression
SerotoninSerotoninA biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity.Receptors and Neurotransmitters of the CNS syndrome
Muscle weakness
ContraindicationsContraindicationsA 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
Concurrent therapy with monoamineoxidaseOxidaseNeisseria (MAO) inhibitors → ↑ risk ofserotoninSerotoninA biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity.Receptors and Neurotransmitters of the CNS syndrome
Heart block or arrhythmias → cyclobenzaprine slows cardiac conduction via blockade of fast Na+channelsChannelsThe Cell: Cell Membrane
AcuteMIMIMI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms.Myocardial Infarction
Acuteheart failureHeart FailureA heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction.Total Anomalous Pulmonary Venous Return (TAPVR)
Drug interactions
Serotonergic medications → ↑ risk ofserotoninSerotoninA biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity.Receptors and Neurotransmitters of the CNS syndrome
Enhanced CNS depression can occur with (list is not exhaustive):
Alcohol
BarbituratesBarbituratesA 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
Cannabinoid products
OpioidsOpioidsOpiates 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
AntihistaminesAntihistaminesAntihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation.Antihistamines
Acts directly on skeletal muscle (does not affect cardiac orsmooth musclesSmooth musclesUnstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant.Muscle Tissue: Histology)
Binds toryanodine receptorsRyanodine ReceptorsMalignant Hyperthermia in the SR → blocksCaCACondylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding.Condylomata Acuminata (Genital Warts)2+ release
↓ Concentration of intracellularCaCACondylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding.Condylomata Acuminata (Genital Warts)2+ → ↓excitation-contraction couplingExcitation-contraction couplingA process fundamental to muscle physiology whereby an electrical stimulus or action potential triggers a myocyte to depolarize and contract. This mechanical muscle contraction response is regulated by entry of calcium ions into the cell.Skeletal Muscle Contraction → ↓skeletal muscle contractionSkeletal muscle contractionSkeletal muscle is striated muscle containing organized contractile structures known as sarcomeres that are made up of overlapping myofilaments: actin and myosin. When a nerve impulse arrives from a motor neuron, the signal triggers an action potential (AP) in the sarcolemma (muscle cell membrane), resulting in the release of Ca ions from the sarcoplasmic reticulum (SR) within the muscle cell.Skeletal Muscle Contraction
Physiology of Ca2+ release from the sarcoplasmic reticulum in response to an action potential: A wave of depolarization (i.e., the action potential) travels down the T-tubules and triggers the voltage-dependent dihydropyridine (DHP) receptors. These DHP receptors are mechanically tethered to ryanodine receptors, which normally keep the Ca2+-release channels closed. When DHP receptors are stimulated by an action potential, they remove the ryanodine receptors from the Ca2+-release channels, allowing Ca2+ to spill out of the sarcoplasmic reticulum and into the sarcoplasm, where they can bind to troponin and stimulate muscle contraction. Dantrolene binds to ryanodine receptors, preventing Ca2+ release and muscle contraction.
Image by Lecturio.
PharmacokineticsPharmacokineticsPharmacokinetics 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
AbsorptionAbsorptionAbsorption 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: well absorbed orally
Crosses theplacentaPlacentaA highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones).Placenta, Umbilical Cord, and Amniotic Cavity
Malignant hyperthermiaMalignant hyperthermiaAn important complication of anesthesia is malignant hyperthermia, an autosomal dominant disorder of the regulation of calcium transport in the skeletal muscles resulting in a hypermetabolic crisis. Malignant hyperthermia is marked by high fever, muscle rigidity, rhabdomyolysis, and respiratory and metabolic acidosis.Malignant Hyperthermia
Neuroleptic malignant syndromeNeuroleptic malignant syndromeNeuroleptic malignant syndrome (NMS) is a rare, idiosyncratic, and potentially life-threatening reaction to antipsychotic drugs. Neuroleptic malignant syndrome presents with ≥ 2 of the following cardinal symptoms: fever, altered mental status, muscle rigidity, and autonomic dysfunction.Neuroleptic Malignant Syndrome
PhlebitisPhlebitisInflammation of a vein, often a vein in the leg. Phlebitis associated with a blood clot is called (thrombophlebitis).Glycopeptides (at the site of IV administration)
ContraindicationsContraindicationsA 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 and precautions
ContraindicationsContraindicationsA 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: activeliverLiverThe 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 disease
Use with caution: individuals with impaired respiratory function
Drug interactions
Enhanced CNS depression can occur with:
Alcohol
Antidepressants
BarbituratesBarbituratesA 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
Cannabinoid products
OpioidsOpioidsOpiates 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
AntihistaminesAntihistaminesAntihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation.Antihistamines
USMLE™ is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). MCAT is a registered trademark of the Association of American Medical Colleges (AAMC). NCLEX®, NCLEX-RN®, and NCLEX-PN® are registered trademarks of the National Council of State Boards of Nursing, Inc (NCSBN®). None of the trademark holders are endorsed by nor affiliated with Lecturio.
Create your free account or log in to continue reading!
