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Sedatives

Beschreibung

Doctorate Anaesthesia Mindmap am Sedatives, erstellt von melian.yates am 14/10/2013.
melian.yates
Mindmap von melian.yates, aktualisiert more than 1 year ago
melian.yates
Erstellt von melian.yates vor etwa 11 Jahre
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Zusammenfassung der Ressource

Sedatives
  1. Phenothiazines
    1. Mechanism
      1. Dopamine Antagonism
      2. CNS
        1. Anxiolytic
          1. Neuroleptic
            1. Tranquiliser
              1. Antiemetic
            2. Mild sedative, if dose is increased, will just prolong level of sedation & increase side effects
          2. NO Analgesic properties
            1. Except Methotrimeprazine (small animal immobilon)
            2. Side Effects/ Toxicity
              1. Basal Ganglia
                1. Movement disorders (Chronic use - humans)
                2. Pituitary Gland
                  1. Increases Prolactin release (Chronic use - humans)
                3. CVS
                  1. Blocks alpha 1 - adrenoreceptors
                    1. Vasodilation & Hypotension
                      1. Can promote hypothermia
                        1. Anti-arrhythmic action
                    2. GIT
                      1. Antispasmodic action on gut
                      2. AntiHistamine (receptor blockade)
                        1. AntiMuscarinic (receptor blockade)
                          1. 5 - HT blockade
                        2. Potency of action dependent on the type of side chain attached to the N atom of the Phenothiazide ring
                          1. R1 = Propylamine
                            1. Increases Sedation
                            2. R1 = Piperadine
                              1. Anticholinergic activity
                              2. R1 = Piperazine
                                1. Less Sedative and Less Anticholinergic
                              3. Drugs
                                1. Acepromazine (ACP)
                                  1. Used extensively (Pre-anaesthetic)
                                    1. Oral tablet (Dogs & Cats), Injection (Small & Large animals), Gel (Horses)
                                      1. Absorption
                                        1. Oral bioavailabilty: 20 - 55%
                                          1. Onset: IM: 20 min, I/V: 5 min
                                            1. Lower end of dose range used I/V
                                              1. Combined w/ Opiods (Boxers and small animals w/ CV compromise)
                                              2. IM Preferred
                                                1. I/V: Given slowly to avoid vasodilaton and hypotension
                                              3. Metabolism
                                                1. Liver
                                                2. Distribution
                                                  1. t 1/2 = 4 - 6hrs
                                                  2. Excretion
                                                    1. Conjugated & Non-conjugated metabolites => Urine
                                                    2. Low dose: Behavior; High dose: sedation
                                                      1. Effective on young, anxious animals
                                                      2. Potentiates action of other drugs
                                                        1. Opiods
                                                          1. General Anaesthetics (Barbituates)
                                                            1. Local Anaesthetics
                                                        2. May lower the threshold for epileptiform sezures
                                                          1. Anticonvulsant properties
                                                            1. Potent Spasmolytic
                                                              1. Tx of Laminitis in Horses
                                                        3. Propionylpromazine
                                                          1. Chlorpromazine
                                                            1. Less potent, longer duration, unreliable in horses (excitement)
                                                            2. Promazine
                                                              1. Better sedation, fewer side effects than Chlorpromazine
                                                              2. Methotrimeprazine
                                                                1. Small animal Immobilin
                                                                  1. Potent Analgesic
                                                                2. Promethazine
                                                                  1. Irritant, Deep IM, Potent Antihistamine
                                                              3. Butyrophenoenes
                                                                1. CNS
                                                                  1. Dopamine Antagonism
                                                                    1. Sedative Action
                                                                      1. Potent Antiemetic
                                                                    2. Side Effects
                                                                      1. Hallucinations, Agitation (Humans)
                                                                    3. CVS
                                                                      1. Vasodilation
                                                                        1. Hypotension
                                                                      2. Drugs
                                                                        1. Azaperone
                                                                          1. Sedate/ modify behavior
                                                                            1. Pigs (Licensed)
                                                                              1. Tx of aggression
                                                                                1. Transport stress
                                                                                  1. Obsteric conditions
                                                                                    1. Premed for local and General Anaesthesia
                                                                              2. Potentiates Anaesthetic Agents
                                                                                1. Slight fall in BP
                                                                                2. Absoprtion
                                                                                  1. Deep IM injection
                                                                                    1. Behind ear (Pigs)
                                                                                      1. Leave undisturbed for 20 min
                                                                                    2. Distribution
                                                                                      1. t 1/2: 2-3 hrs
                                                                                    3. Fluanisone
                                                                                      1. Hypnorm: Used in combination w/ Fentanyl
                                                                                        1. Neurolept Anaesthesia
                                                                                          1. Mice, rats, rabbits & guinea pigs
                                                                                      2. Droperidol
                                                                                        1. Potent Neuroleptic
                                                                                          1. t 1/2: 6 - 8 hrs
                                                                                            1. Potent Antiemetic
                                                                                            2. Used in combination w/ Fentanyl
                                                                                              1. Neuroleptanalgesia
                                                                                        2. Benzodiazepines
                                                                                          1. Mechanism
                                                                                            1. Potentiation of GABA mediated Inhibition
                                                                                            2. CNS
                                                                                              1. Primarily Anxiolytic action
                                                                                                1. Muscle relaxation
                                                                                                  1. Anticonvulsant
                                                                                                    1. Little sedation in young, healthy animals
                                                                                                    2. CVS/ Resp.
                                                                                                      1. Minimal depression
                                                                                                      2. Drug interactions
                                                                                                        1. Synergistic effects with other central depressants
                                                                                                          1. Ex. Barbituates, Antihistamines and alcohol
                                                                                                        2. Metabolism
                                                                                                          1. Liver => Active metabolites
                                                                                                          2. Toxicity (Chronic use)
                                                                                                            1. Cognitive impairment
                                                                                                              1. Tolerance
                                                                                                                1. Dependence
                                                                                                                2. Drugs
                                                                                                                  1. Diazepam (Valium)
                                                                                                                    1. Absorption
                                                                                                                      1. Insoluble in H2O
                                                                                                                        1. Dissolved in propylene glycol
                                                                                                                        2. IV or Oral
                                                                                                                          1. Rapid Onset
                                                                                                                            1. Long acting
                                                                                                                            2. Metabolism
                                                                                                                              1. Liver
                                                                                                                                1. Does not induce hepatic enzyme systems
                                                                                                                                  1. Severe hepatic dysfunction, prolonged duration of action possible
                                                                                                                              2. Distribution
                                                                                                                                1. t 1/2: 20 - 40hrs
                                                                                                                                  1. 95% Protein bound
                                                                                                                                  2. Side Effects
                                                                                                                                    1. Pain on injection
                                                                                                                                      1. Thrombophlebitis
                                                                                                                                        1. Cardiac Arrhythmias
                                                                                                                                        2. Uses
                                                                                                                                          1. To control status epilepticus
                                                                                                                                            1. Stimulate appetite
                                                                                                                                              1. + Ketamine (Horses and Small animals): Induce and Maintain Anaesthesia
                                                                                                                                                1. + Hypnorm (small mammals): Anaesthesia w/ muscle relaxation
                                                                                                                                              2. Midazolam
                                                                                                                                                1. Does NOT cause Thrmbophlebitis
                                                                                                                                                  1. Absorption
                                                                                                                                                    1. H2O soluble
                                                                                                                                                      1. IV, IM, Oral
                                                                                                                                                      2. Distribution
                                                                                                                                                        1. Short duration
                                                                                                                                                          1. t 1/2: Cats: 2 hr
                                                                                                                                                      3. Climazolam
                                                                                                                                                        1. Horses: Maintain Anaesthesia + Ketamine
                                                                                                                                                        2. Tolezepam
                                                                                                                                                          1. + Tiletamine (Dissociative Anaesthetic
                                                                                                                                                        3. Benzodiazepine Antagonists
                                                                                                                                                          1. No intrinsic efficacy; Competetive Anatagonist
                                                                                                                                                            1. Flumazenil
                                                                                                                                                              1. Humans
                                                                                                                                                                1. Dogs, Cattle, Sheep: Antagonism of Diazepam/Midazolam sedation
                                                                                                                                                                  1. Has some Inverse Agonist Activity
                                                                                                                                                                  2. Sarmazenil
                                                                                                                                                                    1. Antagonize Midazolam, when used in combination w/ Ketamine to maintain Anaesthesia in Horses
                                                                                                                                                                    2. Inverse Agonists
                                                                                                                                                                      1. Act @ GABA receptor
                                                                                                                                                                        1. CLOSE the Cl- channel
                                                                                                                                                                          1. Causes the neuron to become vulnerable to excitation
                                                                                                                                                                            1. May promote convulsions
                                                                                                                                                                  3. Alpha 2 - Agonists
                                                                                                                                                                    1. Vary in Selectivity for Alpha 1 and Alpha 2 receptors
                                                                                                                                                                      1. Some also bind Nonadrenergic Imidazoline receptors
                                                                                                                                                                        1. Stimulation = Hypotension and Anti-arrhythmic action
                                                                                                                                                                          1. Imidazoles
                                                                                                                                                                            1. Detomidine
                                                                                                                                                                              1. Really expensive
                                                                                                                                                                                1. Really potent
                                                                                                                                                                                  1. Equipotent in Horses and Cattle
                                                                                                                                                                                  2. Absorption
                                                                                                                                                                                    1. IV or IM
                                                                                                                                                                                    2. Distribution
                                                                                                                                                                                      1. Longer duration
                                                                                                                                                                                        1. t 1/2: 1 - 2 hrs (Horses)
                                                                                                                                                                                      2. Urogenital
                                                                                                                                                                                        1. Slows uterine electrical activity
                                                                                                                                                                                          1. Better for pregnant cows
                                                                                                                                                                                      3. Romifidine
                                                                                                                                                                                        1. Distribution
                                                                                                                                                                                          1. Longer duration
                                                                                                                                                                                            1. t 1/2: up to 3 hrs
                                                                                                                                                                                          2. CNS
                                                                                                                                                                                            1. Causes less ataxia in horses
                                                                                                                                                                                          3. Medetomidine
                                                                                                                                                                                            1. Dogs, Cats, Exotics & Horses
                                                                                                                                                                                              1. Absorption
                                                                                                                                                                                                1. IM, IV or S/C
                                                                                                                                                                                                2. Distribution
                                                                                                                                                                                                  1. t 1/2: 3 hrs
                                                                                                                                                                                                  2. Very potent & very selective for Aplha 2 receptors
                                                                                                                                                                                                    1. Profound ANaesthetic sparing effect
                                                                                                                                                                                                      1. Max effect on BP w/ low doses
                                                                                                                                                                                                        1. Equal mixtture of 2 enantiomers
                                                                                                                                                                                                          1. Dexmedetomidine
                                                                                                                                                                                                            1. Levomedetomidine
                                                                                                                                                                                                              1. Pharmacologically inactive
                                                                                                                                                                                                          2. Dexmedetomidine (Dogs)
                                                                                                                                                                                                            1. Very potent
                                                                                                                                                                                                              1. Greater slectivity for Alpha 2 receptors than Alpha 1
                                                                                                                                                                                                                1. CVS
                                                                                                                                                                                                                  1. Antiarrhythmic
                                                                                                                                                                                                                    1. Depresses HR
                                                                                                                                                                                                                      1. Hypotension
                                                                                                                                                                                                                        1. Pale/ blue tinged mucous membranes
                                                                                                                                                                                                                      2. Distribution
                                                                                                                                                                                                                        1. Highly protein bound: 94%
                                                                                                                                                                                                                          1. Doses based on body surface area
                                                                                                                                                                                                                          2. Anaesthetic sparing
                                                                                                                                                                                                                            1. Reduce dose of induction by 30-60%
                                                                                                                                                                                                                            2. Should only be used for procedures < 20 min
                                                                                                                                                                                                                            3. Clodine
                                                                                                                                                                                                                            4. Oxazolines
                                                                                                                                                                                                                              1. Rilmenidine
                                                                                                                                                                                                                              2. (DO NOT BIND to imidazoline receptors) Phenylethylamines
                                                                                                                                                                                                                                1. Xylazine
                                                                                                                                                                                                                                  1. Absorption
                                                                                                                                                                                                                                    1. IM or IV
                                                                                                                                                                                                                                      1. Cows, Horses: 24 hr rule (before 2nd dose)
                                                                                                                                                                                                                                    2. Distribution
                                                                                                                                                                                                                                      1. t 1/2: Species, Route and Dose dependent
                                                                                                                                                                                                                                      2. Metabolism
                                                                                                                                                                                                                                        1. Metabolised to multiple products that are excreted in urine
                                                                                                                                                                                                                                        2. Low selectivity for Alpha 2 receptors
                                                                                                                                                                                                                                          1. Used in Small and Large animals
                                                                                                                                                                                                                                            1. CNS
                                                                                                                                                                                                                                              1. Species differences in sensitivity
                                                                                                                                                                                                                                                1. Ruminant > Horse/Dog > Pig
                                                                                                                                                                                                                                              2. CVS
                                                                                                                                                                                                                                                1. Arrhythmogenic
                                                                                                                                                                                                                                                  1. Unlike modern drugs
                                                                                                                                                                                                                                                2. Urogenital
                                                                                                                                                                                                                                                  1. Contraction of Uterine smooth muscle
                                                                                                                                                                                                                                                    1. Not licensed for Cows in 3rd trimester => Abortion
                                                                                                                                                                                                                                          2. CNS
                                                                                                                                                                                                                                            1. Sedation (Pre-synaptic)
                                                                                                                                                                                                                                              1. Analgesia
                                                                                                                                                                                                                                                1. Muscle Relaxation
                                                                                                                                                                                                                                                  1. + Ketamine
                                                                                                                                                                                                                                                  2. Given intrathecally or Extradurally
                                                                                                                                                                                                                                                2. CVS
                                                                                                                                                                                                                                                  1. Vasoconstriction
                                                                                                                                                                                                                                                    1. Hypertension
                                                                                                                                                                                                                                                      1. Bradycardia
                                                                                                                                                                                                                                                        1. Due to Vagal reflex (feeback mechansims)
                                                                                                                                                                                                                                                    2. Works well w/ Opiods
                                                                                                                                                                                                                                                      1. Anaesthetic sparing effects (50-95%)
                                                                                                                                                                                                                                                      2. RESP.
                                                                                                                                                                                                                                                        1. Respiratory depression
                                                                                                                                                                                                                                                          1. Reduction in airway resistance
                                                                                                                                                                                                                                                            1. Xylozene (Sheep)
                                                                                                                                                                                                                                                          2. GIT
                                                                                                                                                                                                                                                            1. Vomiting (Some species)
                                                                                                                                                                                                                                                              1. GI motility depressed
                                                                                                                                                                                                                                                              2. Endocrine
                                                                                                                                                                                                                                                                1. Inhibition of ADH
                                                                                                                                                                                                                                                                  1. Diuresis
                                                                                                                                                                                                                                                                  2. Inhibition of Insulin release
                                                                                                                                                                                                                                                                    1. Hyperglycemia
                                                                                                                                                                                                                                                                  3. Urogenital
                                                                                                                                                                                                                                                                    1. Uterine contraction (Cows)
                                                                                                                                                                                                                                                                    2. Alpha 2 - Anatagonists
                                                                                                                                                                                                                                                                      1. Atipamezole (Antisedan)
                                                                                                                                                                                                                                                                        1. "Reversal"
                                                                                                                                                                                                                                                                        2. Yohimbine
                                                                                                                                                                                                                                                                          1. Tolazoline
                                                                                                                                                                                                                                                                            1. Sedation induced by Alpha 2 - Agonists may be reversed by specific Alpha 2 - Antagonists
                                                                                                                                                                                                                                                                              1. Going to reverse Analgesic properties too!
                                                                                                                                                                                                                                                                              2. Absorption
                                                                                                                                                                                                                                                                                1. IM

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