Overactivity

Obviously the selection of an EP additive requires great care if it is too active it may give rise to excessive metal removal under normal operating conditions (see the section on corrosion by sulphur additives). Also, if a component is prone to fatigue pitting in service the presence of an overactive EP agent may result in corrosion fatigue. ... 

Another potential complication can occur if the responsiveness of the receptor system changes temporally. This can happen if the receptor (or host system, or both) demonstrates desensitization (tachyphylaxis) to drug stimulation (see Chapter 2). There are numerous systems where constant stimulation with a drug does not lead to a constant steady-state response. Rather, a fade of the response occurs. This can be due to depletion of a cofactor in the system producing the cellular response or a conformational change in the receptor protein. Such phenomena protect against overactive stimulation of... 

At present, no diugs exist that can selectively activate a2-receptor subtypes. Clonidine stimulates all three a2-subtypes with similar potency. Clonidine lowers blood pressure in patients with hypertension and it decreases sympathetic overactivity during opioid withdrawal. In intensive and postoperative care, clonidine is a potent sedative and analgesic and can prevent postoperative shivering. Clonidine and its derivative brimonidine lower... 

COX-2 synthesises PGI2 (prostacyclin) and the high incidence of myocardial infarctions with selective COX-2 inhibitors has been attributed to inhibition of COX-2 in vascular tissues. Prostacyclin, made by blood vessel walls, inhibits aggregation of platelets and maintains a balance with thromboxane. Thromboxane, which is released by platelets, promotes clotting. Prostacyclin is synthesised mostly by COX-1, but in humans selective COX-2 inhibition reduces its biosynthesis in vivo. This reduced synthesis may lead to an overactive thromboxane system and increased risk of thromboembolism. 

SUR2B/Kir6.2 Efforts have also focused on the development of selective KAXP channel openers for vascular and nonvascular indications including angina, airway hyperactivity, bladder overactivity, and erectile... 

BKCa The diversity of BKCa channels can be attributed to the assembly of pore-forming a subunit together with four different auxiliary subunits ((31 -(34). BMS-204352 has been identified as a BKCa channel opener for the treatment of acute ischemic stroke although it has also been shown as an M-channel activator. Therapeutic applications for channel openers include epilepsy, bladder overactivity, asthma, hypertension, and psychosis. Other known BKCa channel openers include NS-8, NS-1619, NS-4, and certain aminoazaindole analogs. 

Orthostatic hypotension is a common adverse reaction seen with the administration of the MAOIs. Other common adverse reactions include dizziness, vertigo, nausea, constipation, dry mouth, diarrhea, headache, and overactivity. 

Discuss the uses, general drug actions, adverse reactions, contraindications, precautions, and interactions of the drugs used to treat infections and symptoms associated with urinary tract infections or an overactive bladder. 

Discuss important preadministration and ongoing assessment activities the nurse should perform on the patient taking a drug for a urinary tract infection or an overactive bladder. 

Discuss ways to promote an optimal response to therapy, how to manage adverse reactions, and important points to keep in mind when educating patients about the use of drugs used to treat a urinary tract infection or symptoms associated with an overactive bladder. 

This chapter discusses drug s used to treat urinary tract infections (UTIs) and certain miscellaneous drag > used to relieve the symptoms associated with an overactive bladder (involuntary contractions of the detrusor or bladder muscle). Structures of the urinary system that may be affected include the bladder (cystitis), prostate gland (prostatitis), the kidney, or the urethra (see Pig. 47-1). These drug s also help control the discomfort associated with irritation of the lower urinary tract mucosa caused by infection, trauma, surgery, and endoscopic procedures. 

The miscellaneous drugp are used to relieve the symptoms associated with an overactive bladder (involuntary contractions of the detrusor or bladder muscle)... 

Figure 7.8 Dopamine and motor function. When nigrostriatal dopamine activity is normal so is motor function. Any reduction in this DA activity, as in Parkinson s disease, results in reduced motor activity, i.e. akinesia. By contrast, too much DA activity, as in Huntington s Chorea, produces abnormal motor function, i.e. dyskinesia. The latter may be controlled by neuroleptic drugs (DA antagonists) but they can swing the balance in DA activity sufficiently to produce akinesia (Parkinsonism). DA agonists (and levodopa) may overcome akinesia but can induce DA overactivity and dyskinesia (peak dose effect) (see Chapter 15)...

From this survey it is clear that just as normal neuronal function requires appropriately balanced inhibitory and excitatory controls so the generation of interictal spikes depends on disturbances in both. Clearly activity cannot spread without the activation of excitatory circuits, in which NMDA receptors play an important role, but it will be much facilitated by reduced inhibition (Masukawa et al. 1989). These observations may help to explain the establishment of a focus and the development of the interictal spike, but why activity can only spread to seizure proportions, at certain times, is less clear. It will, however, again require overactivity of excitatory circuits inadequately controlled by inhibitory processes. Since these controls are mediated by... 

There is no evidence of a general overactivity in DA function in schizophrenic patients. Plasma prolactin is not reduced, so the DA inhibitory control of its release is normal there is no recorded increase in DA turnover as CSF and plasma levels of its major metabolite HVA are normal and dyskinesias, which would reflect increased DA activity, are rare. PM studies have shown no consistent increases in DA brain levels, although some reports show an increase in the left amygdala, or in the activity of enzymes involved in its synthesis (tyrosine hydroxylase) or metabolism (MAO). For a review of the neurochemistry see Reynolds (1995). 

Possibly increased DA function is not the actual cause of schizophrenia and its symptoms are just mediated by normally functioning DA systems that appear overactive because of the loss of some counteracting function or other NT(s). To date there is no evidence to fully implicate any other NT but there is growing interest in 5-HT and glutamate (see below). 

The early stages of bone pathology in rheumatoid disease manifest as periarticular osteoporosis and juxta-articular bone erosion. Osteoclast overactivity is the predominant influence in such bone erosion and NO has a direct inhibitory efiect on osteoclastic bone resorption (MacIntyre et al., 1991). Endothelial cells, present in abundance and in close proximity to the osteoclast may therefore play a role in down-regulating osteoclast activity through the production of NO. Since the osteoclast is of macrophage lineage, it is likely to be... 

The expression of TRPVl in the bladder is, however, not restricted to afferent nerves urothelium, detrusor muscle and fibroblasts also express TRPVl in the human bladder [140]. The implication of these findings for intravesical vanilloid therapy is unclear [141], but the increase in TRPVl immunoreactivity in the urothelium in patients with neurogenic detrusor overactivity (that occurs in concert with increased TRPVl in bladder af-ferents) is a very intriguing finding [142]. In the male urogenital system, TRPVl is also present in testicles, prostate and scrotal skin [143], and it was postulated that TRPVl ligands may be beneficial in the treatment of benign prostatic hyperplasia [144]. 

The pain experienced with headache is likely due to overactivity in the trigeminovascular system of the brain. 

In UUI, the detrusor (bladder) muscle is overactive and contracts inappropriately during the filling phase. The amount of urine lost per episode can be as large as the entire contents of the bladder may empty. Sleep may be disrupted by nocturia and enuresis. 

In most patients, the cause of bladder overactivity is unknown (idiopathic). Clearly-established risk factors for UUI include ... 

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