Triptans and Ergot Alkaloids

Overview

Pathophysiology of migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache

• The pathophysiology of migraines is not completely understood.
• Involves:
  • The trigeminovascular system:
    • Neurons Neurons The 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 originate from trigeminal ganglion Trigeminal ganglion The semilunar-shaped ganglion containing the cells of origin of most of the sensory fibers of the trigeminal nerve. It is situated within the dural cleft on the cerebral surface of the petrous portion of the temporal bone and gives off the ophthalmic, maxillary, and part of the mandibular nerves. Trigeminal Neuralgia
    • Innervate cerebral, pial, and dura vessels
  • Vasoactive neuropeptide 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
  • Vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs
  • Plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products protein extravasation
• Serotonin Serotonin A 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 plays a role through 5-hydroxytryptamine 5-hydroxytryptamine A 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-HT 5-HT A 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) 1B and 1D 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 in: 
  • Trigeminal neurons Neurons The 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 
  • Cerebral and meningeal vessels

The role of triptans and ergot alkaloids

• Both medication classes: 
  • Work on 5-HT 5-HT A 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 1B and 1D 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
  • Have similar mechanisms of action
  • Are effective migraine-specific therapies
• Migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache use:
  • Unresponsive to analgesics
  • For moderate-to-severe attacks
• Triptans are preferred over ergot alkaloids because:
  • 5-HT 5-HT A 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 1B and 1D 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 specificity (ergots interact with multiple 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)
  • Better tolerated:
    • Milder side effects
    • Less incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of coronary vasospasm Coronary vasospasm Spasm of the large- or medium-sized coronary arteries. Vasospastic Angina and vasospasm is less prolonged.
• Disadvantages of triptans:
  • Expensive
  • Potential for rebound headaches

Triptans

Chemistry

Triptans and serotonin Serotonin A 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 share a similar core molecule (tryptamine).

Pharmacodynamics Pharmacodynamics Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.” Pharmacokinetics and Pharmacodynamics

• Mechanism of action: Triptans are agonists of 5-HT 5-HT A 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 1B and 1D 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.
• Physiologic effects:
  • Not completely understood
  • Neuron effects: 
    • Inhibited vasoactive neuropeptide 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
    • Inhibited pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways conduction
  • Vascular smooth muscle effect: promotes vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure of intracranial arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology

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

Pharmacokinetic variability exists among the triptan medications.

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:

• Fast GI 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
• Time to achieve peak plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products concentration depends on the route of administration:
  • Subcutaneous: 12 minutes
  • Intranasal: 15 minutes
  • Oral: 1–2 hours

Distribution: 

• 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: 2–6 hours for most triptans
• Sumatriptan does not easily cross the blood-brain barrier Blood-brain barrier Specialized non-fenestrated tightly-joined endothelial cells with tight junctions that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. Systemic and Special Circulations.
• Zolmitriptan and frovatriptan penetrate the blood-brain barrier Blood-brain barrier Specialized non-fenestrated tightly-joined endothelial cells with tight junctions that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. Systemic and Special Circulations more easily.

Metabolism: 

• 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) system 
• Monoamine oxidase Oxidase Neisseria (MAO) system

Excretion:

• Renal (primary)
• Feces

Indications

• Migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache with or without aura Aura Reversible neurological phenomena that often precede or coincide with headache onset. Migraine Headache (1st-line):
  • Sumatriptan is the most commonly used agent:
    • Cheapest
    • Can be used subcutaneously (a benefit in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with 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)
  • Capacity to decrease associated 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 and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Not for prophylaxis Prophylaxis Cephalosporins
• Cluster headaches Cluster headaches Cluster headache is a primary headache disorder characterized by moderate-to-severe unilateral headaches that occur in conjunction with autonomic symptoms. Cluster headache can last from weeks to months, during which the affected individual may experience attacks up to several times a day, followed by a pain-free remission period. Cluster Headaches

Adverse effects and 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

Adverse effects:

• 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
• 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)
• “Triptan sensations”:
  • Paresthesia
  • Flushing
  • Tingling Tingling Posterior Cord Syndrome
  • Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Chest tightness
• Cardiovascular effects:
  • Coronary vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure
  • Rare: atrial and ventricular arrhythmias, myocardial infarction Myocardial infarction MI 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, stroke 
• Serotonin Serotonin A 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
• “Triptan-overuse 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” (rebound 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)

Drug interactions:

• Ergot alkaloids: enhanced vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure
• MAO inhibitors: ↑ serotonin Serotonin A 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 effects, serotonin Serotonin A 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 
• CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers) inhibitors (with eletriptan):
  • Azoles Azoles Azoles are a widely used class of antifungal medications inhibiting the production of ergosterol, a critical component in the fungal cell membrane. The 2 primary subclasses of azoles are the imidazoles, older agents typically only used for topical applications, and the triazoles, newer agents with a wide spectrum of uses. Azoles
  • Macrolides Macrolides Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking transpeptidation. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Macrolides and Ketolides
  • Protease inhibitors Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). Anti-HIV Drugs

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:

• History of coronary artery Coronary Artery Truncus Arteriosus disease, myocardial infarction Myocardial infarction MI 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, or stroke 
• Hemiplegic migraines
• Untreated or uncontrolled hypertension Uncontrolled hypertension Although hypertension is defined as a blood pressure of > 130/80 mm Hg, individuals can present with comorbidities of severe asymptomatic or “uncontrolled” hypertension (≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic) that carries with it a significant risk of morbidity and mortality. Uncontrolled Hypertension
• Ischemic or vasoocclusive cerebrovascular disease
• Bowel ischemia Bowel ischemia Mesenteric ischemia is a rare, life-threatening condition caused by inadequate blood flow through the mesenteric vessels, which results in ischemia and necrosis of the intestinal wall. Mesenteric ischemia can be either acute or chronic. Mesenteric Ischemia
• Peripheral vascular disease
• Severe hepatic or renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome (naratriptan and eletriptan)

Ergot Alkaloids

Chemistry

• Ergot alkaloids are derived from lysergic acid (from tryptophan) and contain a tetracyclic “ergoline” structure.
• 2 families: 
  • Amine alkaloids
  • Peptide alkaloids: ergotamine, dihydroergotamine (DHE), bromocriptine Bromocriptine A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion. Parkinson’s Disease Drugs

Pharmacodynamics Pharmacodynamics Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.” Pharmacokinetics and Pharmacodynamics

• Mechanism of action: 
  • Ergotamine and DHE:
    • 5-HT 5-HT A 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 1B and 1D agonists, and other serotonin Serotonin A 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 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
    • Alpha-adrenergic 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 agonists
  • Bromocriptine Bromocriptine A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion. Parkinson’s Disease Drugs: dopaminergic 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 agonist
• Physiologic effects:
  • Neuron effects: 
    • Inhibited vasoactive neuropeptide 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
    • Inhibited pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways conduction
  • Vascular smooth muscle: vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure
  • Uterine smooth muscle: 
    • Stimulates contraction
    • The effect increases dramatically during 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
  • Suppression Suppression Defense Mechanisms of prolactin Prolactin A lactogenic hormone secreted by the adenohypophysis. It is a polypeptide of approximately 23 kd. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Breasts: Anatomy secretion Secretion Coagulation Studies ( bromocriptine Bromocriptine A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion. Parkinson’s Disease Drugs)

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:

• Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables 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 in the GI tract
• Improved 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 with coadministration of caffeine Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine’s most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. Stimulants

Metabolism: 

• Hepatic
• 1st-pass
• CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers)

Excretion: 

• Feces (primary)
• Renal (minor)

Indications

• Ergotamine and DHE: migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache
• Bromocriptine Bromocriptine A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion. Parkinson’s Disease Drugs: 
  • Hyperprolactinemia Hyperprolactinemia Hyperprolactinemia is defined as a condition of elevated levels of prolactin (PRL) hormone in the blood. The PRL hormone is secreted by the anterior pituitary gland and is responsible for breast development and lactation. The most common cause is PRL-secreting pituitary adenomas (prolactinomas). Hyperprolactinemia
  • Parkinsonism Parkinsonism West Nile Virus
  • Neuroleptic malignant syndrome Neuroleptic malignant syndrome Neuroleptic 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 (off-label)

Adverse effects and 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

Adverse effects:

• 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 and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
• 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
• Prolonged vasospasm, resulting in:
  • Gangrene Gangrene Death and putrefaction of tissue usually due to a loss of blood supply. Small Bowel Obstruction
  • Bowel infarction
• Valvular sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor (with long-term use)
• Arrhythmia

Drug interactions:

• Triptans: Combined use is contraindicated due to vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure.
• Do not combine with other vasoconstrictors.
• CYP3A4 CYP3A4 Class 3 Antiarrhythmic Drugs (Potassium Channel Blockers) inhibitors:
  • Azoles Azoles Azoles are a widely used class of antifungal medications inhibiting the production of ergosterol, a critical component in the fungal cell membrane. The 2 primary subclasses of azoles are the imidazoles, older agents typically only used for topical applications, and the triazoles, newer agents with a wide spectrum of uses. Azoles
  • Macrolides Macrolides Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking transpeptidation. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Macrolides and Ketolides 
  • Protease inhibitors Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). Anti-HIV Drugs

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:

• Cardiovascular and peripheral vascular disease
• Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
• Severe hepatic or renal impairment
• Hemiplegic migraine Hemiplegic Migraine Migraine Headache
• Breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding and 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

Ergotism

Etiology:

• Accidental or intentional medication overdose
• Prolonged ergot use
• Accidental ingestion of grain contaminated by Claviceps purpurea, a rye fungus that synthesizes natural ergot alkaloids

Clinical presentation:

• Initial symptoms:
  • Flu-like
  • 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
  • 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 and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
• Neurologic:
  • Drowsiness
  • Involuntary, spastic movements
  • Hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia
  • Altered mental status Altered Mental Status Sepsis in Children
  • 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
• Ischemic:
  • Claudication
  • Burning sensation of the limbs
  • Diminished distal pulses
  • Peripheral dry gangrene Gangrene Death and putrefaction of tissue usually due to a loss of blood supply. Small Bowel Obstruction
  • Bowel ischemia Bowel ischemia Mesenteric ischemia is a rare, life-threatening condition caused by inadequate blood flow through the mesenteric vessels, which results in ischemia and necrosis of the intestinal wall. Mesenteric ischemia can be either acute or chronic. Mesenteric Ischemia and infarction 

Management:

• Discontinue ergot alkaloid medications.
• Vasospasm is resistant to most vasodilators Vasodilators Drugs used to cause dilation of the blood vessels. Thromboangiitis Obliterans (Buerger’s Disease), but may be responsive to large doses of nitrates Nitrates Nitrates are a class of medications that cause systemic vasodilation (veins > arteries) by smooth muscle relaxation. Nitrates are primarily indicated for the treatment of angina, where preferential venodilation causes pooling of blood, decreased preload, and ultimately decreased myocardial O2 demand. Nitrates (e.g., nitroprusside Nitroprusside A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins. Nitrates, nitroglycerin Nitroglycerin A volatile vasodilator which relieves angina pectoris by stimulating guanylate cyclase and lowering cytosolic calcium. It is also sometimes used for tocolysis and explosives. Nitrates).
• Gangrene Gangrene Death and putrefaction of tissue usually due to a loss of blood supply. Small Bowel Obstruction may require amputation Amputation An amputation is the separation of a portion of the limb or the entire limb from the body, along with the bone. Amputations are generally indicated for conditions that compromise the viability of the limb or promote the spread of a local process that could manifest systemically. Amputation.