Dependence Depression

Keddie, J. L, Jones, R. A. L. and Cory, R. A. (1994) Size-Dependent Depression of the Glass-Transition Temperature in Polymer-Films. Europhys. Lett., 27, 59-64. 

At the cellular level, the major electrophysiological effect appears to be rate-dependent blockade of sodium channels [22]. The onset for this Class I effect (64 + 9% of the final depression of between the first and second beat of the train) was similar to that for Class IB agents [23]. The offset rate (recovery of from rate-dependent depression) for amiodarone was 1.48 s. This value falls between those seen for Class IB agents (200-500 ms) and lA agents (2.3-12.2 s) [23]. Amiodarone inhibited the binding of pH]ba-trochotoxinin A 20a-benzoate to the sodium channel, suggesting that it binds to inactivated sodium channels [24]. 

Quinidine administration results in a dose-dependent depression of membrane responsiveness in atrial muscle fibers. The maximum rate of phase 0 depolarization and the amplitude of phase 0 are depressed equally at all membrane potentials. Quinidine also decreases atrial muscle excitability in such a way that a larger current stimulus is needed for initiation of an active response. These actions of quinidine often are referred to as its local anesthetic properties. 

Most anxiolytic and sedative-hypnotic drugs produce dose-dependent depression of central nervous system function. The ideal anxiolytic drug should calm the patient without causing too much daytime sedation and drowsiness and without producing physical or psycho-... 

All psychostimulants can cause jitteriness, palpitations, and psychic dependence. Depression may arise after their discontinuance, and high doses can produce a florid psychosis. On occasion, even small doses of amphetamine can precipitate psychotic episodes in those with an underlying predisposition (e.g., schizophrenic disorder). 

Isoflurane has a dose-dependent depressant effect on the myocardium. In vitro studies indicate that it reduces myocardial contractility to a similar extent as halothane. In vivo, isoflurane appears to be less of a cardiovascular depressant than other volatile agents. 

Thiopentone has a potent dose-dependent, depressant effect on both respiratory rate and depth and depresses the sensitivity of the respiratory centre to carbon dioxide. A short period of apnoea is common, frequently preceded by a few deep breaths. Respiratory depression is influenced by premedication and is more pronounced in the presence of opioids and in patients with chronic obstructive pulmonary disease. 

Disadvantages of the benzodiazepines include the risk of dependence, depression of central nervous system functions, and amnestic effects. In addition, the benzodiazepines exert additive central nervous system depression when administered with other drugs, including ethanol. The patient should be warned of this possibility to avoid impairment of performance of any task requiring mental alertness and motor coordination. In the treatment of generalized anxiety disorders and certain phobias, newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are now considered by many authorities to be drugs of first choice (see Chapter 30). 

Dose-dependent depressant effects on the CNS including sedation and relief of anxiety, amnesia, hypnosis, anesthesia, coma and respiratory depression... 

Before discussing theoretical approaches let us review some experimental results on the influence of flow on the phase behavior of polymer solutions and blends. Pioneering work on shear-induced phase changes in polymer solutions was carried out by Silberberg and Kuhn [108] on a polymer mixture of polystyrene (PS) and ethyl cellulose dissolved in benzene a system which displays UCST behavior. They observed shear-dependent depressions of the critical point of as much as 13 K under steady-state shear at rates up to 270 s Similar results on shear-induced homogenization were reported on a 50/50 blend solution of PS and poly(butadiene) (PB) with dioctyl phthalate (DOP) as a solvent under steady-state Couette flow [109, 110], A semi-dilute solution of the mixture containing 3 wt% of total polymer was prepared. The quiescent... 

Some perturbation of the reticulocyte numbers was observed, but values at days 3 and 5 did not differ from controls. Absolute numbers of lymphocytes and neutrophils did not differ from controls (no data shown). A slight anemia was observed at 4 and 8 weeks of treatment with 300 and 900 ppm benzene. Results showed minor changes in the stem and progenitor cells. CFU-E depression after 4 days of exposure was significant. There was a dose-dependent depression of colony forming cell numbers present at 4 and 8 weeks of exposure with a maximal effect at the level of CFU-E. Decreased CFU-E and BFU-E were observed in a companion study in which hybrid mice were exposed to 300 or 900 ppm benzene for the same period of time (Plappert et al. 1994b). 

The effect of PPADS on P2ij-purinoceptors was investigated in the rat mesenteric arterial bed at basal tone and at tone raised by methoxamine. These experiments demonstrated the ineffectiveness of PPADS (10 pM) at both vasoconstriction- and vasodilatation-mediating P2XJ-receptors [30]. Similar results were obtained in the rat pulmonary vascular bed [62], In addition, PPADS (10 - 100 pM) was not an antagonist at P2-purinoceptors that mediate UTP-evoked depolarization of the rat superior cervical ganglion, but it produced a concentration-dependent depression of depolarizations evoked by a,3-methylene ATP [59], All these observations substantiate the proposal (see above) that PPADS is a selective antagonist at purine- (P2X receptors) rather than at pyrimidine-nucleotide receptors. 

Sedatives (anxiolytic agents) should reduce anxiety with as little effect on motor or mental functions as possible. However, most of the drugs used for anxiety states cause dose-dependent depression of the CNS that extends to sleep-inducing effects (hypnosis) and possible anesthesia. 

Keddie, R. A.L. Jones, and R. A. Coury, Size dependent depression of the glass transition temp erature in polymer films, Europhys. Lett. 27, 49 (1994). 

Brundage CM, Cartagena CM, Potter EA, Taylor BE. Nicotine elicits a developmentally dependent depression in bullfrog neuroventillatory response to C02. Respir Physiol Neurobiol. 2010 170 226-35. 

Levy W B, Haycock J W, and Cotman C W (1976) Stimulation-dependent depression of readily releasable neurotransmitter pools in brain. Brain Res 115, 243-256... 

Naltrexone 100 mg/day-I-sertraline 200 mg/day was more effective than either drug alone in depression and alcohol abstinence/ delay before relapse. Alcohol-dependent depressed patients (n = 170) were randomly assigned to four groups naltrexone only, sertraline only, naltrexone-I-sertraline, and placebo. All received weekly cognitive behavioral therapy. The rate of adverse events was lower in the combination treatment group (12%) than in the other groups (naltrexone 27%, sertraline 38%, placebo 28%) however, more subjects withdrew seven patients compared with two, four, and one in the naltrexone, sertraline, and placebo groups respectively [213. ... 

Rat alveolar macrophages obtained by bronchoalve-olar lavage showed a concentration- and time-dependent depression of zymosan induced and lu-dgenin enhanced chemiluminescence when exposed to formaldehyde (Schroers and Tilkes 1990). 

Clinical presentation of systemic toxicity is variable, depending on the specific agent. Several agents are so rapidly metabolized that toxicity symptoms are very rarely seen, as with procaine and chloroprocaine. Different drugs present toxic symptoms in different sequence. For example, lidocaine first presents with dizziness or a numb tongue whereas bupivicaine is generally associated with dose-dependent depression of myocardial contractility and conduction and may result in fatal ventricular dysrhythmias. 

May be dose dependent depression, coma, and blindness occur intermittently with excitement or seizures see also Table 7 2... 

Keddie, J.L., Jones, R.A.L., Cory, R.A. Size-dependent depression of the glass transition temperature in pol5oner films. Europhysics 27, 59 (1994)... 

In some experiments, a large but transient depression in the contractility of the preparation was noted in the first 60-90 sec after the addition of the extract. This probably was due to a bolus effect. Responses monitored at 2, 5, 10, and >10 min after the administration of each dose (Fig. 3) showed a dose- and time-dependent depression of developed tension, reaching a plateau at t>10 min (usually 15-25 min) before start of recovery which normally was complete at t=40 min. No initial potentiation of contractility was noted in any of the 5 hearts used. 

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