205

Anästhesie (Subject) / Pharmakologie (Lesson)

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• Salmeterol   long acting beta-2 receptor agonist (duration of action is up to 12 hours) > Seretide = Salmeterol + Fluti­casoni-17-propionas long onset time >  unsuitable for treating acute asthma. may have some degree of anti-inflammatory activity Potenz highly selective for the ß2 receptor  at least equipotent to isoprenaline as a bronchodilator.  It is 15 times more potent than salbutamol at the ß2 receptor at the cardiac ß1 receptor, it is four times less potent than salbutamol and 10,000 times less potent than isoprenaline. Tachyphylaxis (Toleranzentwicklung) to the unwanted side effects (Tremor oder Kopfschmerzen) commonly occurs, but not to bronchodilation.  
• NaCl 0,9% Natrium 154 mmol/l  Chlorid 154 mmol/l  pH 5.5
• ADH nonapeptid Plasma half life is approximately 18 minutes Vasopressin and oxytocin differ in respect of only two out of their nine amino acids.  For this reason, each of them has some of the activity of the other.  ADH-Ausschüttung     Gauer-Aury-Reflex: Abnahme Füllungsdruck in Vorhöfe Osmorezeptoren im Hypothalamus (zB nach 1l 5% dextrose)     Wirkungen:   ACTH-Freisetzung aus Hypophysenvorderlappen (V3).  V2 > cAMP > Einbau Aquaporine im Sammelrohr renal vasoconstriction, especially cortical vasoconstriction hepatic glucogenesis in hoher Konzentration: systemische Vasokonstriktion (V1)   Antidiuretic hormone (ADH) secretion is inhibited by: Dilution Cold Hypertension Alcohol Tetracyclines. Atriopeptin Secretion is increased by: Barbiturates Selective serotonin reuptake inhibitors (SSRIs)  Sulphonylureas.    
• Phenytoin  Natrium-, Calciumkanalblocker Ind:   Digitalis induzierte Rhythmusstörungen  breites antiepileptisches Wirkspektrum, aber keine Wirksamkeit gegen Absencen.  Second line treatment for status epilepticus.   Pharmacokinetik Unzuverlässigkeit des Wirkspiegels (hohe Plasmaeiweissbindung, zwischen Serum-Konzentration von Phenytoin und seiner Abbaugeschwindigkeit besteht keine lineare Abhängigkeit, so dass eine Dosissteigerung zu einem überproportionalen Anstieg des Serumspiegels führen kann) > geringe therapeutische Breite   first-order elimination kinetics in the therapeutic range:  The rate of elimination is proportional to plasma concentration.  Change in Plasma concentration is not linear.  log of plasma concentration plottet against time is linear plasma concentration plottet against time is exponential Rate of elimination can be described by the following equation: C = C0e−Kt C = drug concentration C0 = drug concentration at time zero (extrapolated) k = rate constant t = time   zero-order elimination just above the therapeutic range (wie ASS oder Alkohol), as a result of saturation of liver enzymes, so that toxicity can occur with a small increase in dose. plasma concentration plottet against time is linear 70% to 100% bioavailability following oral administration   It is a highly protein bound drug (70 to 95%), which is metabolised by the liver (non-linear) and genetic variation in the gene controlling metabolism occurs (CYP2C9 and CYP2C19). elimination half life of 22 hours and is excreted primarily through the bile (<5% in the urine) but its metabolites undergo reabsorption and then secretion in urine.     UEW:  Osteomalacia Hirsutism Gingival hyperplasia  Ataxia Vitamin-D-Stoffwechsel beeinträchtigt enterale Calcium-Resorption vermindert megaloblastäre Anämie Teratogen psychische Beeinträchtigung gastrointestinale Störungen Lupus erythematodes-Syndrom Lymphadenopathie Hyperkinesen Rapid intravenous infusion may cause hypotension, heart block, ventricular fibrillation or asystole skin rashes    
• Phentolamin, Regitin® Wirkungen:  kompetitiver nichtselektiver Alpha1- und Alpha2-Alphablocker. Es ist gefässerweiternd, antihypertensiv, positiv inotrop und chronotrop.   Indikationen Blutdruckkrisen bei Phäochromozytom Regitin-Test bei Verdacht auf Phäochromozytom Akzidentelle intravenöse oder paravasale Verabreichung von Noradrenalin Presented in a 5 mg/ml solution, often stored at 4°C, it is typically given as a 0.5-5 mg bolus or as an infusion. Onset of action is at two minutes with a bolus dose typically lasting 10-15 minutes.  
• Trizyklische Antidepressiva   Leitsubstanzen: Imipramin und Amitriptylin  Hemmung der neuronalen Rückaufnahme von biogenen Aminen (Serotonin und Noradrenalin) und Blockade von Rezeptoren im ZNS und in der Peripherie (Histamin-, Serotonin-, M-Acetylcholin- und Noradrenalin-Rezeptoren > buntes Nebenwirkungsbild.) Die antidepressive Wirkung mag auf adaptiven Vorgängen im ZNS beruhen. hydrophobes dreigliedriges (trizyklisches) Ringsystem Metabolisiert in Leber > Metaboliten mit Urin ausgeschieden Bei Überdosierung v.a. anticholinerge NW: Tachykardie, Urinretention, unscharfes Sehen Weitere UEW:  ECG changes (widening of the QRS complex, heart block, AF and VF) and are recognised to potentiate the effects of warfarin. Weight gain is a recognised side effect as are anticholinergic side effects such as dry mouth and tachycardia. !! TCA cause increased sensitivity to catecholamines. Hypertension and arrhythmias may result from the use of sympathomimetic drugs (e.g. noradrenaline and adrenaline), and indirectly acting sympathomimetics (e.g. ephedrine, metaraminol) should not be used. Anaesthetics known to increase circulating catecholamines should be used with caution e.g. ketamine and pancuronium.    
• NA-+ Serotonin-Wideraufnahmehemmstoffe Duloxetin, Venlafaxin
• Theophyllin unspezifischer Phosphodiesterasehemmer > weniger Abbau von cAMP (sc messanger; aktivierung Phosphokinase u.a.) relaxierung glatter Mm. Erregung Gehirn ++, Medulla oblongata ++, Kardiale Stimulierung +++, Bronchodilatation +++, Vasokonstriktion der Hirngefäße +++, Diurese  +++  Überdosierung Respiratorische Alkalose (Hyperventilation) Metabolische Azidose (wegen Hypotension und Krämpfen)   Convulsions Supraventricular tachycardia (SVT)  Ventricular tachyarrhythmia (VT)
• Nephrotoxizität, Antibiotika Tetracyclin Cephalosporin Vasculär: NSAID, ACE-I, Cyklosporin A, Amphotericin B, Mytomicin Tubulotoxisch: NSAID, Aminoglykosid (Gentamicin), Cyklosporin A, Amphotericin B, Cisplatin, Forscarnet, Jodhaltige KM, Lithium Tubulo-obstruktiv: MTX, Aciclovir, Sulfonamid Immunologisch-interstitiell: NSAID, Aciclovir, Sulfonamide, Rifampicin, Methocillin, Penicillin G, Ampicillin, Allopurinol, Thiazide, Interferon  
• Alfentanil, Rapifen Vergleich mit Fentanyl Alfentanil ist 10 x weniger Potent Fentanyl und Alfentanil sind synthetische Phenylpiperidin-Komponenten Fentanyl ist lipidlöslicher. Trotzdem schlägt Alfentanil wegen dem geringeren pKa-Wert schneller an (89%  unionisiert im Ggs zu 9% bei Fentanyl) Alfentanil hat eine geringere Clearance, aber seine Elimination ist trotzdem höher wegen dem geringeren Verteilungsvolumen. Geringeres Verteilungsvolumen von Alfentanil wegen hoher Proteinbindung. Fentanyl is 83% plasma protein bound Alfentanil is 90% plasma protein bound. Alfentanil is extensively metabolised in the liver and its clearance is affected by liver disease, but its clearance is almost completely independent of renal function.    
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• Phosphodiesterase-3-Hemmer Amrinon, Cilostazol, Milrinon und Enoximon Therapie der akuten Herzinsuffizienz  Erhöhung cAMP  > Proteinkinasen werden phosphoryliert und Calciumkanäle aktiviert > Calcium-Einwärtsstrom während der Plateauphase nimmt zu + vermehrte Freisetzung von Calcium aus Sarkoplasmatischem Retikulum > positiv inotrop Wiederaufnahme von Calcium in intrazelluläre Speicher (sarkoplasmatisches Retikulum) beschleunigt > positiv lusitrop (erhöhen Erschlaffungsgeschwindigkeit, erleichtern Muskelrelaxation)  vasodilatatorisch Side effects include Arrhythmias Deranged liver function tests  Thrombocytopenia.  
• cannabis 9-tetrahydrocannabinol: wichtigster Wirkstoff  Cannabis sativa: Hartz; Marihuana: getrocknete Blätter Eliminationshalbwertszeit: 50 Stunden (hohes Verteilungsvolumen wg. Fettlöslichkeit). Akute Wirkung klingt nach einigen Stunden wieder ab   Bioavailability nach oraler Aufnahme: 6% metabolisiert > wasserlöslich > Auscheidung renal  Cannabis-Rezeptoren: ZNS, Milz. Agonist: verringert an spannungsabhängigen Calcium-Kanälen den Einstrom Agonist an Opioidrezeptoren Naloxon antagonisiert antinozeptiven, aber nicht psychiatrischen Effekt.   Wirkungen: psychotrop, analgetisch, antiemetisch Vermindert Augeninnendruck vermindert Arachidonsäure induzierte Entzündungsantwort durch Hemmung der Eicosanoidproduktion somatische UEW: gehäuftes Auftreten von Neoplasien im Säuglingsalter ( bei Konsumin SS), Hemmung der Testosteron-Inkretion und Leukopenien (erhöhte Infekt-Anfälligkeit), Assoziation mit Schizophrenieo der beim weiblichen Geschlecht Depression  
• Enzym -Induktoren   Barbiturates Carbamzepine Griseofulvin Phenytoin Rifampicin Alcohol Tobacco Chloral derivatives. Cimetidine binds to microsomal cytochrome P450 and retards (not induces) oxidative hepatic drug metabolism. Allopurinol interferes with warfarin but is not an enzyme inducer.
• Xenon   Xenon is an inert gas (due to a complete outer electron shell). It is not negatively inotropic and does not cause vasodilatation. Xenon gives rapid induction and recovery, due to its low blood/gas solubility coefficient (0.115).  Its oil/water solubility coefficient is 20, which implies that it has relatively low potency, as reflected by a MAC of 60-70%. Its boiling point is −108°C and it has an oil/gas solubility coefficient of 1.9. Its low blood solubility can cause diffusion hypoxia if supplementary oxygen is not provided at the end of anesthesia. It Has a low toxicity Is not teratogenic Is not metabolised within the body and Is not a trigger for malignant hyperpyrexia. Several studies have shown that xenon exhibits neuroprotective properties without co-existing neurotoxicity by protecting neural cells against ischaemic injury. Xenon is produced as a by-product of the fractional distillation of liquid air and is an expensive process and is thus delivered in closed circuit breathing systems. Xenon-133, unlike elemental xenon, is a radioactive gas produced by fission of uranium-235, which is used in diagnostic inhalational tests. causes: dose related respiratory depression and increases the work of breathing  
• Sugammadex (Bridion) Cyclo-dextrin; ringförmiges Molekül aus 8 Zucker-Einheiten, die negativ geladene Seitenketten tragen. Vecuronium und Rocuronium (positiv geladen) werden in dem röhrenförmigen Sugammadex-Molekül komplexiert und verlieren sofort ihre pharmakologoische Wirksamkeit. Pancuronium möglich, aber NICHT untersucht und empfohlen! EU-Empfehlung: Antagonisierung von Rocuronium- oder Vecuronium-bei Erwachsenen oder Rocuronium bei Kindern.  Dosis:  Noch kein Twich:  16 mg/kg 1-2 post-tetanic counts: 4 mg/kg 2 Twich: 2 mg/kg  häufige Nebenwirkung: Dysgeusie (abnorme Geschmacksempfindungen) Überempfindlichkeitsreaktionen (inkl. 3 Anaphylaxie-Reaktionen) traten mit 16 mg/kg Sugammadex häufig (4,7%) und mit 4 mg/kg Sugammadex gelegentlich (0,7%) auf bei schwerer Niereninsuffizienz einschliesslich Dialysepatienten (CrCl <30 ml/min) wird nicht empfohlen
• Chlorpromazin - dopamine antagonist of the typical antipsychotic class of medications possessing additional antiadrenergic, antiserotonergic, anticholinergic and antihistaminergic properties - used to treat schizophrenia -  local anaesthetic effect by stabilising cell membranes and reducing the tendency of nerves to depolarise - extensively metabolised in the liver and many metabolites may be detected in the urine up to 18 months after administration. - Chlorpromazine undergoes extensive first-pass hepatic metabolism and has an oral bioavailability of 30%.
• Agonisten, partielle Agonisten, Inverse Agonisten Full Agonist   Compounds that are able to elicit a maximal response following receptor occupation and activation. The dose response curves are sigmoid in shape. Examples of full opioid agonists include: Morphine Methadone Oxycodone Heroin Codeine Meperidine Fentanyl Alfentanil, and Remifentanil. Partial agonists: A full agonist has both a high affinity and high intrinsic activity, whereas a partial agonist has significant affinity but submaximal intrinsic activity.The shape of the curve is hyperbolic. Examples of opioids that are partial agonists include: Pentazocine Buprenorphine Nalbuphine. An example of an agonist/antagonist is buprenorphine. It is a partial agonist and the mu opioid receptor and an antagonist at the kappa receptor. The log-dose response curve will not reach the ceiling of response (100% efficacy) and when higher doses are administered this response may decline producing a bell-shaped curve. It is sometimes referred to as a partial agonist. Inverse agonist: An agent that binds to the same receptor binding-site as an agonist for that receptor and reverses constitutive activity of receptors. Inverse agonists exert the opposite pharmacological effect of a receptor agonist. An example of an inverse agonist is flumazenil that has affinity for the GABAA receptor. Naloxone is sometime regarded as a weak inverse agonist. Naloxone and naltrexone are mu receptor antagonists that have affinity for the receptor but no intrinsic activity.  
• CO2 (O=C=O) Produktion: Oxidation kohlehaltiger Substanzen oder Erhitzen von calcium (oder magnesium) carbonat. 1,5x dichter als Luft wenig reaktiv und nicht entflammbar (vollständig oxigeniert)  boiling point -79°C,  critical temperature of + 31.2°C   The carbon dioxide dissociation curve is steeper and more linear than the oxygen dissociation curve.
• Bacterizid: penicillins, aminoglycosides (amoxicillin and gentamicin) 
• Helium schlecht entflammbar (> In Zeppelinen benutzt) brown cylinder at 137 bar. All gases have low viscosities which are independent of their other physical properties but the viscosity of helium is less than that of oxygen (though very similar): At atmospheric pressure and 15°C the viscosity of oxygen is 0.0001909 poise and that of helium is 0.0001863 poise. Helium is less dense than nitrogen and as turbulent flow depends on fluid density, helium/oxygen mixtures are used to reduce the work of breathing and increase the supply of oxygen to the alveoli in upper airway obstruction. It is of no use in lower airway obstruction, for example, asthma, because flow is largely laminar already and depends on viscosity.  
• Carbimazol (Néo-Mercazole®) Struktur: Thioharnstoff-Derivat. Prodrug. Wirkform Thiamazol. Wirkung: Thyreostatisch. volle Wirkung erst nach einer Woche. Behandlungdauer: 6 bis 24 Monaten. Allerdings erneute Thyriotoxicose nach Absetzen bei 70% Therapie auch in Schwangerschaft möglich KI: Stillzeit,  Thyreotropin-abhängigen Schilddrüsenkarzinom, Leberinsuffizienz, schwere Blutkrankheiten UEW: Die am häufigsten auftretenden Nebenwirkungen sind Übelkeit, Kopf-, Gelenkschmerzen, Magenverstimmung, Hautausschlag und Juckreiz. Lymphadenopathie. Schwerwiegend: Agranulozytose  (< 0,5%), Leberentzündung, Cholestase.   
• Glukagon Polypeptidhormon sezerniert von Alpha-Zellen der Langerhans-Zellen des Pankreas Gegenspieler des Insulin > erhöht BZ-Spiegel durch Mobilisation der Glucogen-Speicher
• Diazoxid (Proglicem®) Wirkungen hyperglykämisch, antihypertensiv und antidiuretisch. Hemmung der Freisetzung von Insulin Indikationen Endokrin-aktive Tumoren (Inselzell-Adenom/Karzinom oder extrapankreatische maligne Tumoren) mitHypoglykämie.  Leucin-Sensibilität mit Hypoglykämie Therapierefraktäre maligne Hypertonie bei Niereninsuffizienz
• Entonox   Entonox is a 50:50 mixture, formed by oxygen dissolving into nitrous oxide. The Poynting effect: change in the vapor pressure of a liquid when a non-condensable gas is mixed with the vapor at saturated conditions.   >  involves the dissolution of gaseous O2 when bubbled through liquid N2O, with vaporisation of the liquid to form a gaseous O2/N2O mixture. Flasche: blauer Zylinder (frensh blue) mit weiss geviertelten Schultern, 137 bar, 2 stufiges Ventil. pseudo-kritische Temperatur −7°C: kann unterhalb dieser Temperatur in seine Komponenten zerfallen. Anfänglich v.a. O2-Inhalation, mit andauernden Gebrauch mehr und mehr N2O.       
• Phenothiazin Ausgangsverbindung für eine Reihe von Neuroleptika, Sedativa > chlorpromazin, promethazin, etc They have numerous other properties including Antiemetic Antimuscarinic Antihistamine Antidopaminergic and Alpha adrenergic receptor antagonist (not alpha agonist). Some drugs may potentiate the effects of opioid analgesic drugs  
• Dobutamin Dobutamine is a synthetic catecholamine with a similar structure to isoprenaline. Plasma-HWZ: 2 Minuten Dosis 2.5-10 µg/kg/min   Wirkung sympathomimetisch > Aktivierung der Adenylatcyclase relative selective at beta-1 adrenoceptor agonist   weak agonism at beta-2 and indirect at alpha adrenoceptors (preventing noradrenaline uptake at adrenergic nerve terminals, but this is offset by slightly more potent beta-2 adrenergic receptor stimulation) no action at the dopamine receptor, so has no direct effect on the renal vasculature. Any increase in renal perfusion with the use of dobutamine is only due to the increase in cardiac output and perfusion pressure.     effects  Increased inotropy Increased cardiac output (which may be responsible for the increased renal perfusion and urine output) Minimal or modest decreases in systemic and pulmonary vascular resistance. minimal effect on heart rate (chronotropy)      
• Phenoxybenzamin ist ein irreversibler Blocker von α1- (und α2-Rezeptoren) Ind: Phäochromozytom, Blasenentleerungsstörung
• Prazosin spezifischer alpha 1 Blocker Blutdrucksenkung  keine relevante Steigerung der Herzfrequenz, Abnahme der Auswurffraktion des Herzens oder Steigerung der Reninfreisetzung HWZ 3h hohe Proteinbindung > Ausscheidung mit Galle und Stuhl    
• Tachyphylaxie Wirkungsabschwächung eines Pharmakons in kurzer Zeit bei wiederholter Gabe; v.a. bei indir. Sympathomimetika (infolge Erschöpfung der Noradrenalin-Speicher) Bsp: Ephedrin, präsynaptische alpha 2 blockade> NA-Freisetzung > kardiale NW über beta1-Stimulation, Nitro
• Benzodiazepine Benzodiazepines have sedative, anxiolytic and anticonvulsant properties, and also cause muscle relaxation and amnesia. They act by enhancing gamma-aminobutyric acid (GABA) mediated inhibition in the central nervous system, which enhances the chloride ion flux associated with the GABA receptor complex. Short acting compounds are associated with more dependency problems than long acting compounds. Lorazepam has a half life of 12 hours Midazolam has a half life of one to three hours Temazepam has a half life of six to eight hours Diazepam has a half life of 24 to 48 hours. Rebound anxiety can occur within two days following withdrawal Convulsions may occur on withdrawing benzodiazepines but they are usually associated with rapid withdrawal.
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• beta-blockers with intrinsic sympathomimetic activity Pindolol, Labetalol Beta-blockers that are partial agonists may have agonistic activity leading to sympathomimetic effects when the endogenous catecholamine levels are low but act as antagonists when levels are high.
• Opioide Morphine is a strong agonist at the mu and delta receptors. Codeine is a weak agonist at mu and delta receptors. Fentanyl and sufentanil are strong agonists at mu. Tramadol is a weak agonist at mu receptors. Naloxone and naltrexone are both antagonists at the mu, delta and kappa receptors. Naltexon ist länger wirksam. NW: Lungenödem, Arrythmie, Hypertension Buprenorphine is a partial agonist at the mu and delta. Dynorphin has a high affinity for the kappa receptor Enkephalin has highest affinity for the delta receptor Pentazocine and Nalorphin are examples of agonist/antagonist (agonist activity at kappa receptors and antagonist activity at the mu receptors) There are four opioid receptors: Mu - is present in the brain, spinal cord and the periaqueductal grey, produces analgesia, meiosis, euphoria, respiratory depression, bradycardia, constipation Kappa - produces analgesia, sedation, miosis Delta - produces analgesia, respiratory depression Nociceptin opioid receptor The action of opioids on the cell is mediated by the G protein (that is, cGMP), the effect of which is to reduce cell excitability. This is done by reducing the permeability of voltage gated calcium channels and increasing intracellular potassium concentrations  
• Antibiotika, Wirkmechanismus     Erythromycin inhibiert die Proteinsynthese durch blockade der Ribosomen. Sulphonamide inhibieren die Synthese von Purin und Thymidin durch Hemmung der bakteriellen Folsäuresynthese    Antibiotic action can be categorised into: Inhibition of protein synthesis: tetracyclines (Doxycyclin), macrolides (Erythromycin), aminoglycosides (Gentamycin), chloramphenicol Inhibition of cell membrane synthesis: lincomycins Inhibtion of DNA formation: sulphonamides (Hemmung Folsäuresynthese), trimethoprim (Cotrimoxazol), quinolones, metronidazole Inhibition of cell wall synthesis: penicillins, vancomycin, cephalosporins, macrolides (Erythromycin)  
• SSRI (fluoxetin, paroxetin, sertralin)   Wirkmechanismus: selectively inhibiting the neuronal reuptake of 5-HT from the synaptic cleft. Nebenwirkungen: weniger im Vgl. zu trizyklischen Antidepressiva: Less sedative Have fewer anticholinergic effects Very rarely cause cardiovascular side effects (occasionally can cause bradycardia) Are much safer in overdose than TCAs. They are associated with: Gastrointestinal side effects (nausea, vomiting and diarrhoea or constipation) Central effects (sleep disturbance, agitation, tremor, headache and sexual dysfunction) However, most effects are mild and transient in hoher Dosis   decrease platelet aggregation inhibit cytochrome p450 enzymes  Syndrome of inappropriate ADH, more of a problem in the elderly population.   Serotonin syndrome is a toxic crisis caused by increased synaptic levels of serotonin (5-HT) in the brainstem and spinal cord. It presents as: An alteration in behavior (agitation and confusion) Motor activity (muscle rigidity, hyperreflexia and clonus) Autonomic instability (hyperthermia, tachycardia, diarrhoea and labile BP) It may progress to: Seizures Oculogyric crises DIC Rhabdomyolysis Myoglobinuria Acute renal failure Arrhythmias Coma Death It is most commonly due to overdose of SSRIs, or interactions between drugs that increase serotonin activity:   monoamine oxidase inhibitor trizyklische Antidepressiva pethidine  tramadol    Management is supportive, usually requiring intensive care and typically resolves within 24 hours. Examples of selective serotonin re-uptake inhibitors (SSRIs) include: Citalopram Fluoxetine Paroxetine Sertraline Fluvoxamine Escitalopram. Venlafaxine is a serotonin and noradrenaline re-uptake inhibitor. Imipramine is a tricyclic antidepressant and their mechanism of action is central inhibition of biogenic amine reuptake, predominantly affecting norepinephrine and serotonin. It is also a competitive antagonist at histamine H1 and H2 receptors. Reboxetine is an antidepressant but selectively inhibits noradrenaline re-uptake.  
• Neuromuskuläre Blockade, Potenzierung The clinical conditions which are known to prolong or potentiate non-depolarising neuromuscular blockade include Hypokalaemia Hypocalcaemia Hypermagnesaemia Metabolic alkalosis Respiratory acidosis and Hypothermia. Numerous drugs are also associated with prolonged neuromuscular blockade Antibiotics such as streptomycin, polymyxin and neomycin Cocaine, procaine and lidocaine and Lithium due to its hypokalaemic effect. The features of hypercalcaemia on skeletal muscles is to cause muscle weakness, but this is not commonly associated with a prolongation of the neuromuscular block. Conversely the features of hypocalcaemia include muscle cramps, spasm and tetany and these patients may have a shorter block, but this is rarely seen in practice.
• Schwangerschaft: sichere und schädliche Medikamente   Schädlich:   Enalapril  (adversely affect neonatal blood pressure control and renal function. Skull defects and oligohydramnios) Warfarin (congenital malformations) Phenytoin Isotretinoid   Sicher   Cyclizine (Antihistaminikum) methyldopa  amoxicillin     
• Papaveretum Papaveretum is an opioid analgesic preparation that contains the following opium alkaloids: Morphine Codeine Papaverine Thebaine (1,5%) It is less potent than morphine (20 mg of papaveretum being equivalent to 12.5 mg of morphine), and has more sedative effects. Papaverine has a relaxant effect on vascular smooth muscle and is used in the management of an intra-arterial injection of thiopentone.
• Diazepam      highly protein bound insoluble in water (emulsion with soya bean oil) oral bioavailability of 85 - 100%  Intramuscular injection is painful and its absorption is unreliable half life 20-70 hours active metabolites, for example, nordiazepam (desmethyldiazepam) have an even longer half life (120 hours). volume of distribution in paediatric patients is similar to adult values but with a greatly prolonged half life. in renal disease diazepam may have a more marked effect owing to reduced protein binding and a dose reduction is appropriate. Due to impaired phase I metabolism in liver disease, there is increased sensitivity to diazepam and midazolam.    
• Thrombolyse Plasminogen is an inactive precursor and it is converted into the active plasmin through the action of endogenous tissue plasminogen activator and thrombin. It lyses fibrin and fibrinogen resulting in the formation of fibrin degredation products (FDP) that inhibit thrombin. Epsilon-aminocaproic acid inhibits thrombolysis by antagonising plasminogen activation. Streptokinase is produced by Lancefield group C beta-haemolytic Streptococci. It binds to plasminogen forming a streptokinase-plasminogen complex which converts additional circulating plasminogen and fibrin-bound plasminogen into plasmin. It is associated with allergic and anaphylactic reactions and has a plasma half life of approximately 20 minutes. However, studies with radioactive streptokinase indicate two disappearance rates: A fast half life of approximately 18 minutes due to the action of antibodies, and A slow half life, operative in the absence of antibodies, of approximately 83 minutes. Urokinase activates plasminogen directly and may cause anaphylaxis
• Magensäure- Reduktion Aluminium hydroxide is a simple antacid, which neutralises acid but does not reduce gastric acid production. Omeprazole is a proton pump inhibitor.  Cimetidine is a H2 receptor antagonist which are powerful gastric acid suppressants.  Misoprostol is a prostaglandin E1 analogue that increases mucosal protection and has some antisecretory properties, which reduces acid and gastrin secretion.
• Cerebraler Blutfluss- Medikamentöse Einflüsse   Thiopentone, propofol and etomidate decrease cerebral metabolism and blood flow. Ketamine causes pronounced cerebral vasodilatation, increasing blood flow and cerebral metabolism. Opiates have only moderate effects on cerebral haemodynamics in the presence of normocapnia. Sufentanil (not morphine) can cause cerebral vasodilatation. Isoflurane does not cause cerebral vasodilatation or an increase CBF if inspired concentrations are kept below 1 MAC. The same applies to enflurane and halothane if the inspired concentrations are kept below 0.6 MAC.  
• hyoscin hydrobromid Scopolamin antiemetisch sedierend Anticholinerg überquert die Bluthirnschranke NW: zentral anticholinerg, selten Tachykardie
• Nitroprusside The plasma half life is about two minutes It is presented as a powder which is reconstituted to form a solution unstable in light. The solutions should be protected from light to prevent breakdown into coloured products.   It is active within 30 seconds of administration and initially dilates the venous system and as the dose increases the arterial smooth muscle is affected. Thus the systemic vascular resistance is reduced and a compensatory tachycardia is common.   Nitroprusside is an organic nitrate that produces nitric oxide, which activates the enzyme guanylate cyclase and increases the concentrations of cyclic guanosine monophosphate that relaxes vascular smooth muscle. The metabolism of nitroprusside begins with the transfer of an electron from the iron of oxyhaemoglobin to nitroprusside, yelding methaemoglobin and an unstable nitroprusside radical. This unstable radical breaks down to release all five cyanide ions forming cyanmethaemoglobin and thiocyanate. Cyanide toxicity may occur as a side effect of its use, especially in vitamin B12 deficiency. Cave: metabolische Azidose. The appearance of tachyphylaxis with a metabolic acidosis and an elevated mixed venous PO2 is suggestive of cyanide toxicity. The increased mixed venous PO2 is due to paralysis of cytochrome oxidase and inability of the tissues to utilise oxygen and the metabolic acidosis is due to tissue anaerobic metabolism. A coronary steal of blood flow away from ischaemic areas may occur because nitroprusside dilates resistance vessels in nonischaemic myocardium, causing diversion of blood flow from ischaemic areas where vessels are maximally dilated. Attenuation of hypoxic pulmonary vasoconstriction may accompany infusions of nitroprusside with an associated decrease in the arterial PO2. Positive end-expiratory pressure (PEEP) may reverse vasodilator induced reductions in the arterial PO2. Infusions of nitroprusside delivering more than 16 mg may result in dose-related decreases in platelet aggregation and an increase in bleeding time. The release of rennin may accompany the reduction in blood pressure induced by nitroprusside and may contribute to the overshoot in blood pressure when the drug is discontinued. This overshoot may be prevented by administering an infusion of an angiotensin II inhibitor (for example, saralasin).  
• NO Nitric oxide is produced from l-arginine by nitric oxide synthase and is produced by the vascular endothelium in response to haemodynamic stress and produces smooth muscle relaxation and reduced vascular resistance. Nitric oxide is a free radical and may be inactivated through interaction with other oxygen free radicals e.g. oxidised LDL. It causes the production of cGMP as a second messenger. The formation of methionine from homocysteine by methionine synthase is involved in folic acid metabolism, and thymidine and DNA synthesis. Methionine synthase is inhibited by nitrous oxide.
• Desfluran- Tec 6 plenum vaporiser Desflurane is pressurised and heated in a Tec 6 plenum vaporiser. Which single physical property of desflurane necessitates the requirement for a specialised vaporiser? - The saturated vapour pressure (SVP), defined as the pressure exerted by the vapour in equilibrium with the liquid phase.  Desflurane is extremely volatile: at 22.8℃. Its boiling point is only slightly above normal room temperature. This precludes the use of a normal variable-bypass type vaporiser. If desflurane were used in a standard plenum vaporiser, at 1 atm and 20oC, a bypass flow of 100 ml though it would pick up 735 ml of desflurane (compared with 46 ml isoflurane). Under these same conditions to produce 1% vapour concentration it would require a bypass flow of 73 l/minute (compared with 5 l/minute of isoflurane). The amount of vapour produced would be limited by the specific heat capacity of the vaporiser itself. The MAC of desflurane is 7% and has a heat of vaporisation similar to that of the other agents. To produce a vapour concentration of 2 MAC there would be significant cooling of the vaporiser and temperature compenstation woud be impossible in the conventional way. To maintain constant and reliable vapour pressure and temperature, the vaporiser is heated The Tec 6 vaporiser avoids this problem by heating the desflurane liquid to above its boiling point in a sealed chamber and mixing pure desflurane gas with the carrier gas. Desflurane liquid is heated to 39℃ by a heating element at which temperature its SVP is approximately 1300 mmHg. The carrier gas flow is restricted by an orifice so that the pressure of the carrier gas within the vaporiser is proportional to gas flow. The pressure is sensed by a differential pressure transducer that adjusts a resistor so that the flow of desflurane out of the vaporising chamber is proportional to the carrier gas flow. This enables the output concentration to be made independent of carrier gas flow rate. The control dial adjusts a second resistor that controls the output of desflurane gas, and thus the output concentration. The Tec 6 is electrically powered and electronically controlled and so requires a mains power supply. Since the vaporising chamber is sealed from the atmosphere, a special filler arrangement is required.
• Desfluran  Presentation: Clear colourless liquid that should be protected from light. Mode of action: mechanism of general anaesthesia remains unclear.  Routes: Administered by inhalation. Because of the high saturated vapour pressure, Desflurane is administered by a specific pressurised and heated vaporiser. Induction dose, 4-11%; maintenance, 2-6%.  Tec 6 Desflurane vaporiser:  Because of the volatility of this agent, it requires a different vaporiser to contain, transfer and vaporise it. The saturated vapour pressure at room temperature (20 degrees C) is 88.5 kPa -87% of one atmosphere. This means that desflurane is nearly boiling at room temperature. The vaporiser is a gas/vapour blender, not a variable bypass type.   Classification of vaporiser  Electrically heated, dual circuit gas/vapour blender, constant- temperature, agent specific and out-of-circuit.   Function: Heats the agent to 39 degrees C, which produces a vapour pressure of around 1550 mmHg. Electronic controls inject pure vapour into the fresh gas flow stream from the flowmeters, controlled by the concentration control dial, and a transducer (which senses the fresh gas flow rate and adjusts the vapour output accordingly). Requires electrical power and has alarms. In use, it is similar to variable bypass vaporisers: it fits in the interlocks, and is mounted on the back bar in a similar way. It is accurate at low flows (i.e. considerably less than 1 L/min total fresh gas flow). It may be filled during use. A mark on a liquid crystal display indicates when the liquid level is one bottle low (250 ml). There is an alarm for low liquid level. The unit requires a warm-up period. Internal switches cut out the system if temperature increases above 57 degrees C or if the vaporiser is tilted or becomes empty.  Effects  Cardiovascular system: Causes a decrease in myocardial contractility, but sympathetic tone is well preserved. Does not sensitise the myocardium to circulating catecholamines. Causes a dose-dependent decrease in systemic vascular resistance, thus leading to a decrease in mean arterial pressure. Heart rate may increase via an indirect autonomic effect. Does not cause ‘coronary steal’.  Respiratory system: Respiratory depressant. Decreases tidal volume, although may increase respiratory rate. Decreases response to hypoxia and hypercapnia. Irritant to the respiratory tract at concentrations greater than 6%.  Cental nervous system: Principal effect is general anaesthesia; little analgesic effect. Causes cerebral vasodilatation, leading to increased cerebral blood flow. Decreases cerebral oxygen consumption and is not associated with epileptiform activity. Causes a centrally mediated decrease in skeletal muscle tone.  Abdominal system: Does not decrease hepatic blood flow.  Genitourinary system: Decreases renal cortical blood flow.  Toxicity: Trigger agent for malignant hyperthermia. Unsuitable for use during gaseous induction.  Absorption: Coefficients: blood/gas:0.42, oil/gas: 19; minimum alveolar concentration: 5-10 Desflurane is exceptionally insoluble in blood; the alveolar concentration therefore reaches the inspired concentration very rapidly, resulting in a rapid induction of anaesthesia.  Distribution: Initially to areas of high blood flow (brain, heart, liver and kidney). Later to less well-perfused organs.  Metabolism: 0.02% is metabolised, predominantly to trifluoroacetic acid.  Excretion: Via the lungs, predominantly unchanged. Elimination is rapid due to its low solubility.  Special points: Potentiates action of depolarising and non-depolarising muscle relaxants
• Drug interactions   Additive interaction (summation) (1+1=2) The actions of combinations of intravenous agents such as ketamine and thiopentone or ketamine and midazolam are described as additive. They have different mechanisms of action. Ketamine is an NMDA receptor antagonist whereas thiopentone and midazolam are GABAA receptor agonists. Another example is nitrous oxide and halothane. Synergism (supra-additive interaction) (1+1>2) Refers to the administration of two drugs with similar pharmacological properties and closely related sites of action that produces an effect in combination that is greater than would be expected from the summation of the contribution of each component. These can be interpreted and understood by construction of an isobologram. The hypnotic effect of benzodiazepines and intravenous induction agents such as propofol is the best example. Midazolam is often administered prior to propofol as part of a co-induction technique. Potentiation Volatile agents potentiate the effects of neuromuscular blocking agents in a dose dependent manner. Effects of the neuromuscular blocking agents can be increased by electrolyte disturbance (hypomagnesaemia), Penicillin and probenecid (the latter has no similar pharmacological activity). Infra-additive interaction (antagonism) (1+1<2) This can be subclassified as: Pharmacokinetic interference, for example, one drug affecting the absorption of another by the gastrointestinal tract or influencing metabolism by hepatic microsomal enzyme induction Chemical antagonism, for example, heparin and protamine or heavy metals and chelating agents Competitive reversible, for example, opioids and naloxone, and irreversible antagonism of receptors  
• Antihistaminika   H2-Bocker: reduzieren Säureproduktion, erhöhen Pankreas -Sekretion. H1-Antihistaminika: sedativ-hypnotisch, Antiemetisch, NICHT teratogen, antiallergisch „ersten Generation“: Clemastin, Dimetinden, Diphenhydramin, Fenistil: wenig spezifisch > antimuscarinerge NW Promethazin: neuroleptische NW  Cimetidin; hemmt Cytochrom P450  
• Metoclopramid zentraler Dopaminantagonist (Chemorezeptortriggerzone) in hoher Dosierung ausserdem: kompetetive Hemmung des 5-HT3 Rezeptors. The peripheral effects of metoclopramide inhibiting the action of dopamine are illustrated by its enhancement of antral and fundal contractility and relaxation of the pylorus. The net effect is to increase the rate of gastric emptying. The lower oesophageal sphincter pressure is increased and this leads to an increase in barrier pressure.
• Verapamil (Isoptin) Calciumkanalblocker, der gefäßerweiternd und im AV-Knoten des Herzens leitungsverzögernd wirkt. Verlängert Refraktärzeit. Klasse IV der Vaughan/Williams-Klassifikation der Antiarrhythmika  Indikationen  koronaren Herzkrankheit, Arrhythmie: vorbeugend gegen paroxysmale supraventrikuläre Tachykardien, zur Verlangsamung der Pulsfrequenz bei Vorhofflimmern und Vorhofflattern  Hoher Bluthochdruck Cluster-Kopfschmerz hypertrophe Kardiomyopathie mit dynamischer Obstruktion (HOCM). Kontraindikationen:  Schock akuter Herzinfarkt mit Komplikationen wie Bradykardie, Hypotonie oder Linksherzinsuffizienz SA- oder AV-Block II. und III. Grades Sinusknotensyndrom manifeste Herzinsuffizienz WPW-Syndrom  erste sechs Monaten der Schwangerschaft, Stillzeit gleichzeitige Betablockertherapie hoher hepatischer first pass Effekt  

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