Insulin Clonidine

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

Drugs are administered as a solid in the form of capsules, tablets, and pills (e.g., clonidine), a volatile liquid (e.g., halothane and enflurane), a solution (e.g., chlorpromazine), an aerosol (e.g., beclomethasone), a gas (e.g., oxygen and nitrous oxide), and a crystalline suspension (e.g., insulin). The route of administration is chosen based on the desired onset and duration of action of the drug, the nature of the drug, any special circumstances, and the bioavailability of the drug. 

Figure 10.8. Effect of cAMP on insulin secretion in pancreatic islet cells, a Stracture of the membrane-permeant analog dibutyryl-cAMP. The two butyryl groups and the acetyl group will be cleaved intracellularly, releasing cAMP. b Glucose-de-pendent insulin secretion in the presence or absence of dibutyryl-cAMP. cAMP amplifies glucose-dependent secretion, c Suppression of cAMP-mediated stimulation of insulin secretion by the a2-agonist clonidine. (Data from Life Sci. 32 191-95,1983.)...

MK-912 (L-657,743) (14), an analogue of yohimbine with high in vitro potency and high a,2/ai selectivity [89, 90], lowers FPG and improves glucose tolerance in ob/ob mice and reversed the inhibition of GIR by clonidine [91]. In man, MK-912 attenuated the small elevation in blood glucose caused by clonidine, but had no significant effect on insulin concentration [92]. Healthy volunteers [93] and NIDDM patients [94] treated with MK-912 exhibited a small increase in basal insulin level and a modest decrease in FPG while substantial increases in catecholamines and... 

The insulin-releasing effect of imidazolines would take place selectively via the clonidine-preferring site [109]. 

Somatostatin. Somatostatin is present in numerous tissues including pancreatic D-cells and pituitary cells. Its secretion appears to be mediated via increases in cAMP (Patel et al., 1991). The peptide inhibits insulin and glucagon release in a paracrine or intercellular fashion involving inhibition of cAMP formation (Pipeleers, 1987). Somatostatin, like a2-agonists such as clonidine, stimulates inhibitory Gj-protein in B-cells. Moreover, somatostatin induces repolarization and decreases [Ca2+]j in the B-cell (for a review see Berggren et al., 1992). Previously, Hsu et al. (1991) reported that somatostatin inhibits insulin secretion by a G-protein-mediated decrease in Ca2+ entry via a voltage-dependent Ca2+ channel in the B-cell. 

E>NE I Clonidine Yohimbine Gi AC inhibition P cell Islet of Langerhans NE,E Inhibition of insulin secretion... 

Chan, S. L., Atlas, D., James, R. F., Morgan, N. G. The effect of the putative endogenous imidazoline receptor hgand, clonidine-displacing substance, on insulin secretion from rat and human islets of Langerhans. Br. J. Pharmacol. 1997,120, 926-932. 

Answer A. Back to ANS pharmacology The release of insulin from the pancreas is stimulated by insulinogens (glucose), sulfonylurea hypoglycemics (glipizide), activators of beta, adrenoceptors (e.g., albuterol), and activators of muscarinic receptors (e.g., pilocarpine). The only receptor that, when activated, inhibits insulin release is the alpha2 receptor, which could be stimulated by clonidine or methyldopa. 

Growth hormone deficiency may be present from birth or due to later pituitary-failure. A variety of stimulation tests have been used to evaluate GH deficiency. Seram GH concentrations rise in response to exercise, and this may be u.sed as a preliminary screening test. They also rise during sleep, and high concentrations in a nocturnal sample may exclude GH deficiency. The lack of GH response to clonidine, a potent stimulant of GH secretion, isdiagnostic. Some centres have now abandoned the use of insulin-induced hypoglycaemia as a diagnostic test in children because of its hazards. 

Metz SA, Halter JB, Robertson RP. Induction of defective insulin secretion and impaired glucose tolerance by clonidine. Selective stimulation of metabolic alpha-adrenergic pathways. Diabetes ( 97S) 27, 554-62. 

Okada S, Miyai Y, Sato K, h aki Y, Higuchi T, Ogino Y, Ota Z. Effect of clonidine on insulin secretion a case report. JIntMedRes (198Q 14, 299-302. 

Some alkaloids are active in a- and p-adrenergic receptors (e.g., ephedrine), a receptors (e.g., ergotamine), uterine a2 receptors (e.g., ergometrine), and presynaptic a2 adrenoreceptors (e.g., yohombine). Ephedrine increases blood pressure by elevating cardiac output. It is also known to have some stimulant activity on the respiratory center. Ephedrine may be applied in the treatment of eczema in insulin-dependent diabetics. Clonidine stimulates tt2 receptors in the brain. As the effect of this, the cardiac output is smaller and blood pressure is lowered. Clonidine as an 0(2 adrenergic receptor agonist improves endothelial function and modulates inflammation during reperfusion." ... 

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