Inhaled Halothane: [Flurothane] Overview: Halothane (Fluothane) o Halothane (Fluothane), a nonflammable liquid at room temperature is a halogenated alkane derivative. o Halothane (Fluothane) vapor has been described as having a sweet, non-pungent odor which made it and agent of choice among the older inhalational agents for pediatric anesthesia. Other inhalational agents are effective in anesthesia maintenance both for infants and children; however, most of these agents have sufficiently unpleasant, pungent odor that they should not be used for inhaled induction. [isoflurane (Forane) and desflurane (Suprane) are examples of agents which may be used in pediatric cases for anesthesia maintenance, but because of their odor they really cannot be used for mask induction. Concerns about halothane (Fluothane)'s use in children have to do with the following hemodynamic characteristics: Halothane (Fluothane) is a myocardial depressant, an effect which is particularly apparent in children, especially in hypovolemic patients.
Transcript
Inhaled
Halothane: [Flurothane]
Overview: Halothane (Fluothane)o Halothane (Fluothane), a nonflammable liquid at room
temperature is a halogenated alkane derivative. o Halothane (Fluothane) vapor has been described as having a
sweet, non-pungent odor which made it and agent of choice among the older inhalational agents for pediatric anesthesia.
Other inhalational agents are effective in anesthesia maintenance both for infants and children; however, most of these agents have sufficiently unpleasant, pungent odor that they should not be used for inhaled induction. [isoflurane (Forane) and desflurane (Suprane) are examples of agents which may be used in pediatric cases for anesthesia maintenance, but because of their odor they really cannot be used for mask induction.
Concerns about halothane (Fluothane)'s use in children have to do with the following hemodynamic characteristics:
Halothane (Fluothane) is a myocardial depressant, an effect which is particularly apparent in children, especially in hypovolemic patients.
The extent of cardiac depression can be reduced if halothane (Fluothane) requirements are reduced by concurrent administration of other agents such as opioids or muscle relaxants.
Halothane (Fluothane) can sensitize the myocardium to catecholamines, thus predisposing towards arrhythmias. This effect is more likely to occur during "light" anesthesia or in the presence of hypercarbia. When epinephrine is required, up to 10
ug/kg may be given in the normocarbic pediatric patients without incurring significant risk.
Alternatives to halothane (Fluothane) for mask induction in pediatric patients: Sevoflurane (Sevorane, Ultane), an inhalational agent with a non-pungent odor, is probably the agent of choice for pediatric patients.
Sevoflurane (Sevorane, Ultane) combines both rapid induction and emergence, secondary to its low lipid solubility, with very low myocardial depression -- even at high vaporizer output.
Furthermore, there probably is a reduced likelihood of cardiac arrhythmias with sevoflurane (Sevorane, Ultane) compared halothane (Fluothane) in this patient group.
o Halothane (Fluothane), a nonflammable relatively potent inhalational agent exhibits a low blood:gas partition coefficient, predicting relatively rapid induction and recovery
o This agent can be used to provide controlled hypotension bleeding control
o Intermediate solubility (blood) + high-potency result in rapid onset/recovery from anesthesia (either alone or in combination with nitrous oxide or injected opioids)
Chemical Considerations: (see structure above)o Consequences of halogenated structure:
Thymol: remaining in vaporizers, following halothane (Fluothane) vaporization leading to malfunction of temperature-compensating devices or vaporizer turnstiles
o Cardiovascular: Halothane (Fluothane) causes a slight decrease in heart
rate, a decrease in mean arterial pressure (MAP)-- both associated with its well-documented cardiac depressant property.
Halothane (Fluothane) may also sensitize the myocardium to circulating catecholamines, explaining the pro-arrhythmogenic property.
o Pulmonary: Halothane (Fluothane) causes decreasing tidal volume with
increasing MAC, increasing respiratory rate with increasing MAC
Halothane (Fluothane) also promote significant bronchodilation
o Hepatic: fulminant hepatic failure (halothane hepatitis): Case history for slides below: "Forty four year old lady had uterine curettage for metrorrhagia. Eight weeks later she had hysterectomy. Three days after hysterectomy she became jaundiced. Seven days later she died in liver failure. Halothane was used as anesthetic in both surgical procedures. The autopsy showed massive liver necrosis. It appears that the liver damage was mediated by an immunoreactive mechanism. Multiple exposures increase the incidence of liver damage." DRUG-INDUCED LIVER INJURY by Dr. Emilio Orfei
Musculoskeletal: relaxation
Contraindications:o Trigger to malignant hyperpyrexia o Recent halothane (Fluothane) exposure
Drug-drug interactions:o Muscle relaxants potentiation o Reduced MAC with opioids, nitrous oxide & benzodiazepines
Concerns:o Inadequate analgesia o May not provide adequate muscle relaxation o May not provide adequate suppression of visceral reflexes o Reversible reduction of GFR
Halothane Disadvantages
unpredictable occurrence of hepatitis
Status: infrequently used due to the availability of isoflurane (Forane), enflurane (Ethrane) and desflurane (Suprane).
Nitrous Oxide
Overview: Low-molecular weighto Oderless to sweet smelling o Nonflammable o Low-potency gas o Poor blood solubility (0.46)
Low blood solubility allows rapid attainment of alveolar and brain partial pressure
Most commonly administered in combination with opioids or volatile anesthetics.
With a MAC value of 105%, nitrous oxide, by itself is not suitable or safe as a sole anesthetic agent.
Effective analgesic. Minimal skeletal muscle relaxation Effective: Nitrous oxide in combination with thiopental for induction, a
skeletal muscle relaxant, and hyperventilation to reduce CO2 Nitrous oxide can be used as an adjunct to other agents: For example,
using 70% nitrous oxide + oxygen significantly reduces MAC for halothane, enflurane, and isoflurane.
Despite the relative insolubility of nitrous oxide, large quantitities of gas are rapidly absorbed due to its high inhaled concentration.
o This concentration effect speeds induction as fresh gas is literally drawn into the lung from the breathing circuit.
Since nitrous oxide is often administered with a second gas, the second gas effect also enhances the rate of induction
If administration of nitrous oxide is abruptly discontinued, rapid transfer of NO from blood and tissues to the alveoli decreases arterial tension of oxygen. This process is diffusional hypoxia.
Nitrous Oxide Disadvantages
No skeletal muscle relaxation Weak anesthetic Air pockets in closed spaces expand Post-anesthesia hypoxia (diffusion hypoxia) Not suitable as a sole anesthetic agent
Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, p 319 - 321.
Stoelting, R.K., "Inhaled Anesthetics", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 36-76
Desflurane (Suprane)
Desflurane (Suprane) Overview: o Fluorinated methyl ethyl ether and, similar to isoflurane (Forane).
Substitution of a fluorine atom for chlorine (isoflurane) o Fluorination (compared to chlorination) results in:
High vapor pressure would result in boiling at operating room temperatures requires:
implementation of new vaporizer technology converts desflurane (Suprane) to a gas (heated & pressurized electric vaporizer) which is blended with fresh gas flow
o Pungent odor --desflurane (Suprane) less likely to be used for inhalation induction compared to halothane (Fluothane) or sevoflurane (Sevorane, Ultane).
Airway irritation, breath-holding, coughing, laryngospasm is greater than 6% desflurane (Suprane) administered to an awake patient.
Significant salivation o Carbon monoxide:
Secondary to desflurane (Suprane) degradation by strong base present in carbon dioxide absorbants.
Carbon monoxide concentration: desflurane (Suprane) > enflurane (Ethrane) > isoflurane (Forane) {carbon monoxide produced by halothane (Fluothane) or sevoflurane (Sevorane, Ultane): extremely small)
o Solubility (blood: gas partition coefficient = 0.45) and potency (MAC 6%):
Rapid achievement of alveolar partial pressures required for anesthesia along with rapid awakening
Distinguishing features of desflurane (Suprane) and sevoflurane (Sevorane, Ultane) compared to earlier volatile anesthetics:
Lower blood-gas solubility More rapid recovery from anesthesia
(Suprane); these agents, metabolized to reactive acyl halide intermediates may produce:
hepatoxicity cross-sensitivity between agents
o Sevoflurane (Sevorane, Ultane) no carbon monoxide formation following exposure to carbon dioxide and absorbants
o Level of major sevoflurane (Sevorane, Ultane) metabolite, a vinyl-ether derivative (Compound A) is significantly below possible toxic levels, even with gas flows > 1 liter per minute
Clinical Use:sevoflurane (Sevorane, Ultane)o First-line, excellent induction agent o Rapid emergence o Allows excellent anesthetic depth control
Systems Physiology: sevoflurane (Sevorane, Ultane)o CNS:
o Cardiovascular: reduced vascular resistance decreased MAP (mean arterial pressure)
o Pulmonary: Nonirritant Respiratory depression
o Musculoskeletal: Muscle relaxation
Contraindications/Issues: o Trigger to malignant hyperpyrexia o Long cases (fluoride accumulation) o Closed-circuit anesthesia
Drug-drug interactionso Muscle relaxants effect potentiation o MAC decreases when sevoflurane is combined with opioids,
benzodiazepines, nitrous oxide
1. Propofol (INN, marketed as Diprivan by AstraZeneca) is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine. Propofol is approved for use in more than 50 countries, and generic versions are available.
Pharmacology
Propofol is highly protein-bound in vivo and is metabolised by conjugation in the liver.[4] Its rate of clearance exceeds hepatic blood flow, suggesting an extrahepatic site of elimination as well. It has several mechanisms of action,[5][6][7] both through potentiation of GABA-A receptor activity, thereby slowing the channel closing time,[8][9][10] and also acting as a sodium channel blocker.[11][12] Recent research has also suggested the endocannabinoid system may contribute significantly to propofol's anesthetic action and to its unique properties.[13]
The elimination half-life of propofol has been estimated to be between 2 and 24 hours. However, its duration of clinical effect is much shorter, because propofol is rapidly distributed into peripheral tissues. When used for IV sedation, propofol typically wears off in minutes. Propofol is versatile; the drug can be given for short or prolonged sedation as well as for general anesthesia. Its use is not associated with nausea as is often seen with opioid medications. These characteristics of rapid onset and recovery along with its amnestic effects[14] have led to its widespread use for sedation and anesthesia.
EEG research upon those undergoing general anesthesia with propofol finds that its effect upon the loss of consciousness links to its causing a prominent reduction in the brain's information integration capacity at gamma wave band frequencies.[15]
Contraindications and interactions
The respiratory effects of propofol are potentiated by other respiratory depressants, including benzodiazepines.[16]
Adverse effects
Aside from low blood pressure (mainly through vasodilatation) and transient apnea following induction doses, one of propofol's most frequent side effects is pain on injection, especially in smaller veins. This pain can be mitigated by pretreatment with lidocaine.[17] Patients show great variability in their response to propofol, at times showing profound sedation with small doses. A more serious but rare side effect is dystonia.[18] Mild myoclonic movements
are common, as with other intravenous hypnotic agents. Propofol appears to be safe for use in porphyria, and has not been known to trigger malignant hyperpyrexia.
It has been reported that the euphoria caused by propofol is unlike other sedation agents, "I even remember my first experience using propofol: a young woman who was emerging from a MAC anesthesia looked at me as though I were a masked Brad Pitt and told me that she felt simply wonderful" —C.F. Ward, M.D.[19]
Propofol has reportedly induced priapism in some individuals.[20][21]
Propofol infusion syndrome
Another recently described rare, but serious, side effect is propofol infusion syndrome. This potentially lethal metabolic derangement has been reported in critically-ill patients after a prolonged infusion of high-dose propofol in combination with catecholamines and/or corticosteroids
2. Sodium thiopental, better known as Sodium Pentothal (a trademark of Abbott Laboratories), thiopental, thiopentone sodium, or trapanal, is a rapid-onset short-acting barbiturate general anaesthetic. It is an intravenous ultra-short-acting barbiturate. Sodium thiopental is a depressant and is sometimes used during interrogations—not to cause pain (in fact, it may have just the opposite effect), but to weaken the resolve of the subject and make him or her more compliant to pressure.[3] Thiopental is a core medicine in the World Health Organization's "Essential Drugs List", which is a list of minimum medical needs for a basic health care system.[
Uses
Anesthesia
Thiopental is an ultra-short-acting barbiturate and has been used commonly in the induction phase of general anesthesia. Its use in the United States and elsewhere has been largely replaced with that of propofol. Following intravenous injection the drug rapidly reaches the brain and causes unconsciousness within 30–45 seconds. At one minute, the drug attains a peak concentration of about 60% of the total dose in the brain. Thereafter, the drug distributes to the rest of the body and in about 5–10 minutes the concentration is low enough in the brain such that consciousness returns.
A normal dose of thiopental (usually 4–6 mg/kg) given to a pregnant woman for operative delivery (caesarian section) rapidly makes her unconscious, but the baby in her uterus remains conscious. However, larger or repeated doses can depress the baby.
Thiopental is not used to maintain anesthesia in surgical procedures because, in infusion, it displays zero-order elimination kinetics, leading to a long period before consciousness is regained. Instead, anesthesia is usually maintained with an inhaled anesthetic (gas) agent. Inhaled anesthetics are eliminated relatively quickly, so that stopping the inhaled anesthetic will allow rapid return of consciousness. Thiopental would have to be given in large amounts to maintain an anesthetic plane, and because of its 11.5–26 hour half-life, consciousness would take a long time to return.[6]
In veterinary medicine, thiopental is also used to induce anesthesia in animals. Since thiopental is redistributed to fat, certain breeds of dogs, primarily the sight hounds can have prolonged recoveries from thiopental due to their lack of body fat and lean body mass. Thiopental is always administered intravenously, as it can be fairly irritating; severe tissue necrosis and sloughing can occur if it is injected incorrectly into the tissue around a vein.
Medically induced coma
In addition to anesthesia induction, thiopental was historically used to induce medical comas. It has now been superseded by drugs such as propofol.
Thiopental has a long Context Sensitive Half Time (CSHT) meaning infusions saturate peripheral compartments (fat, muscle etc). When the infusion is stopped, the drug re-distributes from the peripheral tissues back into the blood, prolonging the effect.
Thiopental also exhibits zero order kinetics at higher doses. The rate of clearance becomes fixed which slows elimination from the body.
Patients with brain swelling, causing elevation of the intracranial pressure, either secondary to trauma or following surgery may benefit from this drug. Thiopental, and the barbiturate class of drugs, decrease neuronal activity and therefore decrease the production of osmotically active metabolites which in turn decreases swelling. Patients with significant swelling have improved outcomes following the induction of coma. Reportedly, thiopental has been shown to be superior to pentobarbital [7] in reducing intracranial pressure.
Euthanasia
Thiopental is used intravenously for the purposes of euthanasia. The Belgians and the Dutch have created a protocol that recommends sodium thiopental as the ideal agent to induce coma followed by pancuronium bromide.[8]
Intravenous administration is the most reliable and rapid way to accomplish euthanasia and therefore can be safely recommended. A coma is first induced by intravenous administration of 20 mg/kg thiopental sodium (Nesdonal) in a small volume (10 ml physiological saline). Then a triple intravenous dose of a non-depolarizing neuromuscular muscle relaxant is given, such as 20 mg pancuronium dibromide (Pavulon) or 20 mg vecuronium bromide (Norcuron). The muscle relaxant should preferably be given intravenously, in order to ensure optimal availability. Only for pancuronium dibromide (Pavulon) are there substantial indications that the agent may also be given intramuscularly in a dosage of 40 mg.[8]
Lethal injection
Along with pancuronium bromide and potassium chloride, thiopental is used in 35 states of the U.S. to execute prisoners by lethal injection. A very large dose is given which places the subject into a rapidly induced coma. Executions using the three drug combination are usually effective in approximately 10 minutes, but have been known to take several times this length. The use of thiopental alone is hypothesized to cause death in approximately 45 minutes.[citation needed] The use of sodium thiopental has been the cause of current Supreme Court challenges to the lethal injection protocol, after a study in the medical journal the Lancet, where autopsy studies on executed inmates revealed that there was not a high enough concentration of thiopental in their blood to have caused unconsciousness. The exclusion of physicians participating in executions is partly to blame for inept administration of the drugs.[citation needed]
Truth serum
Thiopental is still used in some places as a truth serum.[3] The barbiturates as a class decrease higher cortical brain functioning. Some psychiatrists hypothesize that because lying is more complex than telling the truth, suppression of the higher cortical functions may lead to the uncovering of the "truth". However, the reliability of confessions made under thiopental is dubious; the drug tends to make subjects chatty and cooperative with interrogators, but a practiced liar or someone who has a false story firmly established would still be quite able to lie while under the influence of the drug.[9]
Psychiatry
Psychiatrists have used thiopental to desensitize patients with phobias,[10] and to "facilitate the recall of painful repressed memories."[11] One psychiatrist who worked with thiopental is Professor Jan Bastiaans, who used this procedure to help release trauma in victims of the Nazis.[12]
Metabolism
As with all lipid soluble anaesthetic drugs, the short duration of action of STP is almost entirely due to its redistribution away from central circulation towards muscle and fat tissue. Once redistributed the free fraction in the blood is metabolised in the liver. Sodium thiopental is mainly metabolized to pentobarbital,[13] 5-ethyl-5-(1'-methyl-3'-hydroxybutyl)-2-thiobarbituric acid, and 5-ethyl-5-(1'-methyl-3'-carboxypropyl)-2-thiobarbituric acid.[14]
Dosage
The usual dose range for induction of anesthesia using thiopental is from 3 to 7 mg/kg; however, there are many factors that can alter this. Premedication with sedatives such as benzodiazepines or clonidine will reduce requirements, as do specific disease states and other patient factors.
Side effects
As with nearly all anesthetic drugs, thiopental causes cardiovascular and respiratory depression resulting in hypotension, apnea and airway obstruction. For these reasons, only suitably trained medical personnel should give thiopental in an environment suitably equipped to deal with these effects. Side effects include headache, emergence delirium, prolonged somnolence and nausea. Intravenous administration of sodium thiopental is followed instantly by an odor sensation, sometimes described as being similar to rotting onions. The hangover effects may last up to 36 hours.
Although molecules of thiopental contain one sulfur atom, it is not a sulfonamide, and does not show allergic reactions of sulfa/sulpha drugs.
Drug interaction
Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats. This pulmonary oedema was not mediated by cardiac failure or by pulmonary hypertension but was due to increased pulmonary vascular permeability.[15]
Ketamine is a drug used in human and veterinary medicine developed by Parke-Davis (today a part of Pfizer) in 1962. Its hydrochloride salt is sold as
Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist [2] . At high, fully anesthetic level doses, ketamine has also been found to bind to opioid μ receptors and sigma receptors.[citation needed] Like other drugs of this class such as tiletamine and phencyclidine (PCP), it induces a state referred to as "dissociative anesthesia"[3] and is used as a recreational drug.
Ketamine has a wide range of effects in humans, including analgesia, anesthesia, hallucinations, elevated blood pressure, and bronchodilation.[citation needed] Ketamine is primarily used for the induction and maintenance of general anesthesia, usually in combination with some sedative drug. Other uses include sedation in intensive care, analgesia (particularly in emergency medicine), and treatment of bronchospasm. It is also a popular anesthetic in veterinary medicine.
3. Ketamine is a chiral compound. Most pharmaceutical preparations of ketamine are racemic; however, some brands reportedly have (mostly undocumented) differences in enantiomeric proportions. The more active enantiomer, (S)-ketamine, is also available for medical use under the brand name Ketanest S.[4] Ketamine is a core medicine in the World Health Organization's "Essential Drugs List", which is a list of minimum medical needs for a basic health care system.
Medical use
Indications for use as an anaesthetic:
Paediatric anaesthesia (as the sole anaesthetic for minor procedures or as an induction agent followed by muscle relaxant and endotracheal intubation)
Asthmatics or patients with chronic obstructive airway disease Emergency surgery in field conditions in war zones To supplement spinal / epidural anaesthesia / analgesia utilizing low
In medical settings, ketamine is usually injected intravenously or intramuscularly,[17] but it is also effective when insufflated, smoked, or taken orally.[18]
Since it suppresses breathing much less than most other available anaesthetics,[19] ketamine is still used in human medicine as an anesthetic, however, due to the hallucinations which may be caused by ketamine, it is not typically used as a primary anesthetic, although it is the anaesthetic of choice when reliable ventilation equipment is not available. Ketamine tends to increase heart rate and blood pressure. Because ketamine tends to increase or maintain cardiac output, it is sometimes used in anesthesia for emergency surgery when the patient's state of fluid volume status is unknown (e.g., from traffic accidents). Ketamine can be used in podiatry and other minor surgery, and occasionally for the treatment of migraine. There is ongoing research in France, the Netherlands, Russia, Australia and the US into the drug's usefulness in pain therapy, depression suppression, and for the treatment of alcoholism [20] and heroin addiction.[21]
In veterinary anesthesia, ketamine is often used for its anesthetic and analgesic effects on cats, dogs, rabbits, rats, and other small animals. Veterinarians often use ketamine with sedative drugs to produce balanced anesthesia and analgesia, and as a constant rate infusion to help prevent
pain wind-up. Ketamine is used to manage pain among large animals, though it has less effect on bovines. It is the primary intravenous anesthetic agent used in equine surgery, often in conjunction with detomidine and thiopental, or sometimes guaifenesin.
Ketamine may be used in small doses (0.1–0.5 mg/kg·h) as a local anesthetic, particularly for the treatment of pain associated with movement and neuropathic pain.[22] It may also be used as an intravenous co-analgesic together with opiates to manage otherwise intractable pain, particularly if this pain is neuropathic (pain due to vascular insufficiency or shingles are good examples). It has the added benefit of counter-acting spinal sensitization or wind-up phenomena experienced with chronic pain. At these doses, the psychotropic side effects are less apparent and well managed with benzodiazepines.[23] Ketamine is a co-analgesic, and so is most effective when used alongside a low-dose opioid; while it does have analgesic effects by itself, the higher doses required can cause disorienting side effects.[23] The combination of ketamine with an opioid is, however, particularly useful for pain caused by cancer.[24]
The effect of ketamine on the respiratory and circulatory systems is different from that of other anesthetics. When used at anesthetic doses, it will usually stimulate rather than depress the circulatory system.[25] It is sometimes possible to perform ketamine anesthesia without protective measures to the airways. Ketamine is also a potent analgesic and can be used in sub-anesthetic doses to relieve acute pain; however, its psychotropic properties must be taken into account. Patients have reported vivid hallucinations, "going into other worlds" or "seeing God" while anesthetized, and these unwanted psychological side-effects have reduced the use of ketamine in human medicine. They can, however, usually be avoided by concomitant application of a sedative such as a benzodiazepine.[23]
Low-dose ketamine is recognized for its potential effectiveness in the treatment of complex regional pain syndrome (CRPS), according to a retrospective review published in the October 2004 issue of Pain Medicine.[26]
Although low-dose ketamine therapy is established as a generally safe procedure, reported side effects in some patients have included hallucinations, dizziness, lightheadedness and nausea. Therefore nurses administering ketamine to patients with CRPS should only do so in a setting where a trained physician is available if needed to assess potential adverse effects on patients.[27]
Examples of epidural anesthesia
Clexane - General Information:
Clexane, a highly sulfated glycosaminoglycan is widely used as an injectable anticoagulant. It has the highest negative charge density of any known biological molecule. Clexane acts as an anticoagulant, preventing the formation of clots and extension of existing clots within the blood. While heparin does not break down clots that have already formed, it allows the body's natural clot lysis mechanisms to work normally to break down clots that have already formed. Clexane binds to and accelerates the activity of antithrombin III. By activating antithrombin III, heparin preferentially potentiates the inhibition of coagulation factors Xa and IIa. Factor Xa catalyzes the conversion of prothrombin to thrombin, so heparins inhibition of this process results in decreased thrombin and ultimately the prevention of fibrin clot formation.
Pharmacology:
Clexane is a highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Clexane occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Clexane is a well known and commonly used anticoagulant which has antithrombotic properties. Clexane is indicated for the prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism, and also for the prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin. Clexane inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo. Clexane acts at multiple sites in the normal coagulation system. Small amounts of Clexane in combination with antithrombin III (Clexane cofactor) can inhibit thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin. Once active thrombosis has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Clexane also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor.
Clexane for patients
Clexane Interactions
Drug Interactions:
a. Drugs Enhancing Heparin Effect:Oral anticoagulants: Heparin sodium may prolong the one-stage prothrombin time. Therefore, when heparin sodium is given with dicumarol or warfarin sodium, a period of at least 5 hours after the last intravenous dose or 24 hours after the last subcutaneous dose should elapse before blood is drawn if a valid prothrombin time is to be obtained.
Platelet inhibitors: Drugs such as acetylsalicylic acid, dextran, phenylbutazone, ibuprofen, indomethacin, dipyridamole, hydroxychloroquine and others that interfere with platelet-
aggregation reactions (the main hemostatic defense of heparinized patients) may induce bleeding and should be used with caution in patients receiving heparin sodium.
The anticoagulant effect of heparin is enhanced by concurrent treatment with antithrombin III (human) in patients with hereditary antithrombin III deficiency. Thus in order to avoid bleeding, reduced dosage of heparin is recommended during treatment with antithrombin III (human).
b. Drugs Decreasing Heparin Effect:Digitalis, tetracyclines, nicotine, or antihistamines may partially counteract the anticoagulant action of heparin sodium. Heparin Sodium Injection should not be mixed with doxorubicin, droperidol, ciprofloxacin, or mitoxantrone, since it has been reported that these drugs are incompatible with heparin and a precipitate may form.
Drug/ Laboratory Tests Interactions
Hyperaminotransferasemia: Significant elevations of aminotransferase (SGOT [S-AST] and SGPT [S-ALT]) levels have occurred in a high percentage of patients (and healthy subjects) who have received heparin sodium. Since aminotransferase determinations are important in the differential diagnosis of myocardial infarction, liver disease and pulmonary emboli, rises that might be caused by drugs (heparin sodium) should be interpreted with caution.
Clexane Contraindications
Heparin sodium should not be used in patients:
With severe thrombocytopenia. In whom suitable blood coagulation tests e.g. the whole-blood clotting time, partial
thromboplastin time, etc. cannot be performed at appropriate intervals (this contraindication refers to full-dose heparin; there is usually no need to monitor coagulation parameters in patients receiving low-dose heparin sodium).
With an uncontrollable active bleeding state, except when this is due to disseminated intravascular coagulation.
Additional information about Clexane
Clexane Indication: For anticoagulant therapy in prophylaxis and treatment of venous thrombosis and its extension, for prevention of post-operative deep venous thrombosis and pulmonary embolism and for the prevention of clotting in arterial and cardiac surgery.Mechanism Of Action: The mechanism of action of heparin is antithrombin-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Clexane interacts with antithrombin III, prothrombin and factor X.Drug Interactions: Aspirin Association of ASA/Clexane increases risk of bleedingDrospirenone Increased risk of hyperkaliemia
Food Interactions: Adequate calcium intake is recommended, needs increased with long term use, supplement recommended.Generic Name: HeparinSynonyms: Alpha-Heparin; Heparin sodium; Heparin sodium preservative Free; Heparin sodium salt; Heparin sulfate; Heparinate; Heparinic acid; Low molecular weight heparin sodium; Sodium heparinDrug Category: Fibrinolytic Agents; Anticoagulants; HeparinsDrug Type: Small Molecule; Approved; InvestigationalOther Brand Names containing Heparin: Ariven; Arteven; Bemiparin; Calcilean; Calciparine; Certoparin; Clexane; Clivarin; Clivarine; Dalteparin; Depo-Heparin; Eparina [DCIT]; Fluxum; Fragmin A; Fragmin B; Fraxiparin; Hed-Heparin; Hepalean; Heparin Cy 216; Heparin Leo; Heparin Lock Flush; Hepathrom; Leparan; Lipo-Hepin; Liquaemin; Liquaemin Sodium; Liquemin; Multiparin; Novoheparin; Pabyrin; Parnaparin; Parvoparin; Pularin; Reviparin; Sandoparin; Sublingula; Thromboliquine; Vetren; Vitrum AB; Absorption: Some oral absorption but lack of anticoagulant effect. Rapidly taken up by endothelial cells with remainder bound to plasma proteins.Toxicity (Overdose): Heparin sodium - Mouse, median lethal dose greater than 5000 mg/kg. Another side effect is heparin induced thrombocytopenia (HIT syndrome). HIT is caused by an immunological reaction that makes platelets form clots within the blood vessels, thereby using up coagulation factorsProtein Binding: Very high, mostly to low-density lipoproteinsBiotransformation: Liver and the reticulo-endothelial system are the sites of biotransformation.Half Life: 1.5 hoursDosage Forms of Clexane: Solution IntravenousLiquid IrrigationSolution SubcutaneousLiquid IntravenousSolution IntraperitonealChemical IUPAC Name: 6-[5-acetamido-4,6-dihydroxy-2-(sulfooxymethyl)oxan-3-yl]oxy-3-[5-(6-carboxy-4,5-dihydroxy-3-sulfooxyoxan-2-yl)oxy-6-(hydroxymethyl)-3-(sulfoamino)-4-sulfooxyoxan-2-yl]oxy-4-hydroxy-5-sulfooxyoxane-2-carboxylic acidChemical Formula: C26H42N2O37S5Heparin on Wikipedia: http://en.wikipedia.org/wiki/HeparinOrganisms Affected: Humans and other mammals
Levophed - General Information:
Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Levophed is the principal transmitter of most postganglionic
sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [PubChem]
Pharmacology:
Noradrenaline acts on both alpha-1 and alpha-2 adrenergic receptors to cause vasoconstriction. Its effect in-vitro is often limited to the increasing of blood pressure through antagonising alpha-1 and alpha-2 receptors and causing a resultant increase in systemic vascular resistance.
Additional information about Levophed
Levophed Indication: Mainly used to treat patients in vasodilatory shock states such as septic shock and neurogenic shock and has shown a survival benefit over dopamine. Also used as a vasopressor medication for patients with critical hypotension.Mechanism Of Action: Levophed functions as a peripheral vasoconstrictor (alpha-adrenergic action) and as an inotropic stimulator of the heart and dilator of coronary arteries (beta-adrenergic action).Drug Interactions: Not AvailableFood Interactions: Not AvailableGeneric Name: NorepinephrineSynonyms: L-noradrenaline; Arterenol; L-Norepinephrine; Norepinephrine; NoradrenalineDrug Category: Adrenergic alpha-Agonists; Sympathomimetics; Vasoconstrictor AgentsDrug Type: Small Molecule; ApprovedOther Brand Names containing Norepinephrine: Levophed; Absorption: Not AvailableToxicity (Overdose): In high dose and especially when it is combined with other vasopressors, it can lead to limb ischemia and limb death.Protein Binding: Not AvailableBiotransformation: Not AvailableHalf Life: Not AvailableDosage Forms of Levophed: Solution IntravenousLiquid IntravenousInsert, extended release IntrauterineTablet OralChemical IUPAC Name: 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diolChemical Formula: C8H11NO3Norepinephrine on Wikipedia: http://en.wikipedia.org/wiki/NorepinephrineOrganisms Affected: Humans and other mammals
Isocaine HCL - General Information:
A local anesthetic that is chemically related to bupivacaine but pharmacologically related to lidocaine. It is indicated for infiltration, nerve block, and epidural anesthesia. Isocaine HCL is effective topically only in large doses and therefore should not be used by this route. (From AMA Drug Evaluations, 1994, p168)
Pharmacology:
Mepivicaine is a local anesthetic of the amide type. Mepivicaine as a reasonably rapid onset and medium duration and is known by the proprietary names as Carbocaine and Polocaine. Mepivicaine is used in local infiltration and regional anesthesia. Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with normal therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal.
Isocaine HCL for patients
When appropriate, patients should be informed in advance that they may experience temporary loss of sensation and motor activity, usually in the lower half of the body, following proper administration of caudal or epidural anesthesia. Also, when appropriate, the physician should discuss other information including adverse reactions listed in this package insert.
Isocaine HCL Interactions
Isocaine HCL Contraindications
Mepivacaine is contraindicated in patients with a known hypersensitivity to it or to any local anesthetic agent of the amide-type or to other components of mepivacaine solutions.
Additional information about Isocaine HCL
Isocaine HCL Indication: For production of local or regional analgesia and anesthesia by local infiltration, peripheral nerve block techniques, and central neural techniques including epidural and caudal blocks.Mechanism Of Action: Local anesthetics block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. In general, the progression of anesthesia is related to the diameter, myelination, and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: pain, temperature, touch, proprioception, and skeletal muscle tone.Drug Interactions: Not AvailableFood Interactions: Not AvailableGeneric Name: Mepivacaine
Synonyms: Mepivacaina [INN-Spanish]; DL-Mepivacaine; Mepivacaine HCL; mepivacaine hydrochloride; Mepivacainum [INN-Latin]; Mepivicaine; S-Ropivacaine MesylateDrug Category: Anesthetics, LocalDrug Type: Small Molecule; ApprovedOther Brand Names containing Mepivacaine: Arestocaine HCL; Carbocain; Carbocaine; Isocaine HCL; Polocaine; Polocaine-MPF; Scandicain; Scandicaine; Scandicane; Scandonest Plain; Absorption: Absorbed locally. The rate of systemic absorption of local anesthetics is dependent upon the total dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic solution.Toxicity (Overdose): The mean seizure dosage of mepivacaine in rhesus monkeys was found to be 18.8 mg/kg with mean arterial plasma concentration of 24.4 µg/mL. The intravenous and subcutaneous LD 50 in mice is 23 mg/kg to 35 mg/kg and 280 mg/kg respectively.Protein Binding: Mepivacaine is approximately 75% bound to plasma proteins. Generally, the lower the plasma concentration of drug, the higher the percentage of drug bound to plasma.Biotransformation: Rapidly metabolized, with only a small percentage of the anesthetic (5 percent to 10 percent) being excreted unchanged in the urine. The liver is the principal site of metabolism, with over 50% of the administered dose being excreted into the bile as metabolites.Half Life: The half-life of mepivacaine in adults is 1.9 to 3.2 hours and in neonates 8.7 to 9 hours.Dosage Forms of Isocaine HCL: Solution SubcutaneousSolution InfiltrationLiquid InfiltrationChemical IUPAC Name: N-(2,6-dimethylphenyl)-1-methylpiperidine-2-carboxamideChemical Formula: C15H22N2OMepivacaine on Wikipedia: http://en.wikipedia.org/wiki/MepivacaineOrganisms Affected: Humans and other mammals
