Ketamine nervous system

Ketamine also can be contrasted to other intravenous drugs in its ability to cause cardiovascular stimulation rather than depression. The observed increases in heart rate and blood pressure appear to be mediated through stimulation of the sympathetic nervous system. In a healthy, normovolemic, unpremedicated patient, the initial induction dose of ketamine maintains or stimulates cardiovascular function. In contrast, patients with... 

Ketamine is the only intravenous anesthetic that possesses analgesic properties and produces cardiovascular stimulation. Heart rate, arterial blood pressure, and cardiac output are usually significantly increased. The peak increases in these variables occur 2-4 minutes after intravenous injection and then slowly decline to normal over the next 10-20 minutes. Ketamine produces its cardiovascular stimulation by excitation of the central sympathetic nervous system and possibly by inhibition of the reuptake of norepinephrine at sympathetic nerve terminals. Increases in plasma epinephrine and norepinephrine levels occur as early as 2 minutes after intravenous ketamine and return to baseline levels 15 minutes later. 

Hartvig P, Valtysson J, Lindner KJ, Kristensen J, Karlsten R, Gustafsson LL, Persson J, Svensson JO, Oye I, Antoni G, et al. 1995. Central nervous system effects of subdisso-ciative doses of (S)-ketamine are related to plasma and brain concentrations measured with positron emission... 

Ketamine exerts its physiological effects at the molecular level by interfering with the actions of excitatory amino acid neurotransmitters, primarily glutamate, the most prevalent excitatory neurotransmitter in the brain. The excitatory neurotransmitters regulate numerous functions of the central nervous system. 

Figure 4.4 This is a schematic representation of the N-methyl-D-aspartate (NMDA) receptor. Both ketamine and phencyclidine block the flow of ions through this receptor, which causes their effects on the central nervous system.

The pharmacological effects of tiletamine plus zolazepam are very similar to the effects produced by ketamine. When used as the sole anesthetic in the horse, tiletamine plus zolazepam can cause excitation and hyperresponsiveness. This combination is only used in the horse after adequate sedation. In general, it produces a dose-related loss of consciousness, characterized as a cataleptic state, and analgesia. Ocular and airway reflexes are well maintained. The combination induces mild cardiovascular stimulation secondary to centrally mediated sympathetic nervous system stimulation. There is minimal respiratory depression. 

At the molecular level intravenous anaesthetics interact mainly with GABAa receptors (thiopental, propofol...) or with other ligand-gated ion channels (ketamine) synthetic opioids (phentanyl congeners) act in a more specific way as agonists of p-opioid receptors. However, all the anaesthetics, in addition to their action at the level of central nervous system, have also a variety of effects at other levels in particular, a temporary impairment of the immune system involving phagocytes can be induced. 

Several investigations have studied the in vivo antidepressant activity of this herb and of compounds isolated from it. For example, a commercially available extract of the aerial parts of Hypericum perforatum LI 160 and hypericin, Fig. (13) showed pronounced activity in selected animal bioassays. These include the forced swimming test and the tail suspension test, used to determine antidepressant activity, and tests indicating activity on the central nervous system, such as body temperature and ketamine-induced sleeping time [231,232],... 

Nervous System Ketamine has indirect sympathomimetic activity and produces distinct behavioral effects. The ketamine-induced cataleptic state is accompanied by nystagmus with pupillary dilation, salivation, lacrimation, and spontaneous limb movements with increased overall muscle tone. Although ketamine does not produce the classic anesthetic state, patients are amnestic and unresponsive to painful stimuli. Ketamine produces profound analgesia, a distinct advantage over other parenteral anesthetics. 

Fig. 18.4. Glutamate or NMDA receptors in the central nervous system. Binding of agonists (glutamate or NMDA) opens the channel, allowing potassium ions to flow outward to extracellular fluid (ECF) and sodium and calcium ions to flow into the nerve cells. Increased intracellular (IGF) calcium ion concentration triggers a cascade that produces a response and liberates the neuronal messenger nitric oxide (NO). Ketamine may produce anesthesia by blocking these NMDA-controlled channels, which are located at excitatory synapses on pyramidal cells (3). Glycine acts as a positive allosteric modulator at the NMDA receptor.

DFP administered to rats produced muscle fiber discharges from the peripheral nerves as well as from the central nervous system (Clinton et al. 1988). This was significantly rednced when the animals were pretreated with atropine methyl nitrate, ketamine, or phenytoin. 

In addition to pharmacokinetic drug-drug interactions, pharmacodynamic effects have been reported as well. Halothane increases the susceptibility to ventricular arrhythmias under theophylline therapy as a result of increased sensitivity of the myocardium to endogenous catecholamine release by theophylUne. Ketamine lowers the theophyUine seizure threshold. Benzodiazepines Uke midazolam, diazepam, lorazepam, and Uurazepam increase the central nervous system concentration of adenosine, a potent central nervous system depressant. As theophyUine also blocks adenosine receptors, it counteracts benzodiazepine-induced sedation, resulting in increased dosage requirements for these compounds. ... 

General effects All the benzodiazepines are cataractogenic. They have a depressant effect on the central nervous system and for this reason they are often used in veterinary medicine associated with ketamine. We have used Diazepam (Valium N.D.) given intramuscularly or intravenously associated with ketamine. The hypnotic effect is much longer than with ketamine alone (dosage 0.25 - 0.5 mg/kg). 

Numerous surgical and anaesthetic factors can affect intraocular pressure (lOP) during ocular operations. All depressants of the central nervous system and all general anaesthetics decrease lOP in proportion to the depth of anaesthesia. Ketamine is the only exception to this rule, but since the ketamine-induced rise of lOP is less than the decrease caused by other general anaesthe-... 

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