Systems pharmacology

Drug therapy to achieve the recommended target blood pressure remains the cornerstone of the management of hypertension. Today, there are strong evidences from randomized controlled trials that antihypertensive drugs are more effective than placebo at reducing cardiovascular mortality and morbidity.

8p vifaye 20-09-2024 3 1   Download

We report the cloning, expression, pharmacological char-acterization and tissue distribution of a melanocortin (MC) receptor gene in a shark, the spiny dogfish (Squalus acanth-ias) (Sac). Phylogenetic analysis showed that this receptor is anorthologof theMC4 subtype, sharing71%overall amino acid identity with the human (Hsa) MC4 receptor. When expressedandcharacterizedbyradioligandbindingassay for the natural MSH (melanocyte-stimulating hormone) pep-tides a-, b-, and c-MSH, the SacMC4 receptor showed pharmacological properties very similar to the HsaMC4 receptor. ...

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Regulated gene expression may substantially enhance gene therapy. Corre-lated with structural differences between insect ecdysteroids and mamma-lian steroids, the ecdysteroids appear to have a benign pharmacology without adversely interfering with mammalian signaling systems. Conse-quently, the ecdysone receptor-based gene switches are attractive for appli-cation in medicine.

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Disulfide pairings and active site residues are highly conserved in secretory phospholipases A2 (PLA2s). However, secretory PLA2 s of marine inverte-brates display some distinctive structural features. In this study, we report the isolation and characterization of a PLA2 from the northern Pacific sea anemone,Urticina crassicornis(UcPLA2), containing a C27N substitution and a truncated C-terminal sequence.

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Most evidence suggests that the major efferent limb of the inflammatory reflex is carried in: A. The sympathetic chain B. The phrenic nerve C. The vagus nerve D. Postganglionic sympathetics arising in the stellate ganglia E. The long thoracic nerve Correct Answer: The correct answer is C. Evidence suggests that information leaving the central nervous system regarding regulation of inflammation is carried mainly in the vagus nerve. The sympathetic chain is the origin of postganglionic fibers for sympathetic innervation of visceral organs.

190p ozon_ozon 03-05-2012 58 4   Download

ON MONOTONICITY OF SOLUTIONS OF DISCRETE-TIME NONNEGATIVE AND COMPARTMENTAL DYNAMICAL SYSTEMS VIJAYSEKHAR CHELLABOINA, WASSIM M. HADDAD, JAMES M. BAILEY, AND JAYANTHY RAMAKRISHNAN Received 27 October 2003 Nonnegative and compartmental dynamical system models are widespread in biological, physiological, and pharmacological sciences. Since the state variables of these systems are typically masses or concentrations of a physical process, it is of interest to determine necessary and sufficient conditions under which the system states possess monotonic solutions.

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Delirium: Treatment Management of delirium begins with treatment of the underlying inciting factor (e.g., patients with systemic infections should be given appropriate antibiotics and underlying electrolyte disturbances judiciously corrected). These treatments often lead to prompt resolution of delirium. Blindly targeting the symptoms of delirium pharmacologically only serves to prolong the time patients remain in the confused state and may mask important diagnostic information. Relatively simple methods of supportive care can be highly effective in treating patients with delirium.

5p ongxaemnumber1 29-11-2010 66 4   Download

Harrison's Internal Medicine Chapter 15. Headache Headache: Introduction Headache is among the most common reasons that patients seek medical attention. Diagnosis and management is based on a careful clinical approach that is augmented by an understanding of the anatomy, physiology, and pharmacology of the nervous system pathways that mediate the various headache syndromes. General Principles A classification system developed by the International Headache Society characterizes headache as primary or secondary (Table 15-1).

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Clinical Implications of Altered Bioavailability Some drugs undergo near-complete presystemic metabolism and thus cannot be administered orally. Nitroglycerin cannot be used orally because it is completely extracted prior to reaching the systemic circulation. The drug is therefore used by the sublingual or transdermal routes, which bypass presystemic metabolism. Some drugs with very extensive presystemic metabolism can still be administered by the oral route, using much higher doses than those required intravenously.

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Principles of Pharmacokinetics The processes of absorption, distribution, metabolism, and excretion— collectively termed drug disposition—determine the concentration of drug delivered to target effector molecules. Absorption Bioavailability When a drug is administered orally, subcutaneously, intramuscularly, rectally, sublingually, or directly into desired sites of action, the amount of drug actually entering the systemic circulation may be less than with the intravenous route (Fig. 5-2A ).

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Drugs Acting on Motor Systems spinal disorders. Benzodiazepines enhance the effectiveness of the inhibitory transmitter GABA (p. 226) at GABAA receptors. Baclofen stimulates GABAB receptors. !2-Adrenoceptor agonists such as clonidine and tizanidine probably act presynaptically to inhibit release of excitatory amino acid transmitters. The convulsant toxins, tetanus toxin (cause of wound tetanus) and strychnine diminish the efficacy of interneuronal synaptic inhibition mediated by the amino acid glycine (A).

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Inhibitors of the RAA System lasting effect than does captopril. Indications are hypertension and cardiac failure. Lowering of an elevated blood pressure is predominantly brought about by diminished production of angiotensin II. Impaired degradation of kinins that exert vasodilating actions may contribute to the effect. In heart failure, cardiac output rises again because ventricular afterload diminishes due to a fall in peripheral resistance.

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Drugs Acting on the Sympathetic Nervous System of the sympathetic division can be considered a means by which the body achieves a state of maximal work capacity as required in fight or flight situations. In both cases, there is a need for vigorous activity of skeletal musculature. To ensure adequate supply of oxygen and nutrients, blood flow in skeletal muscle is increased; cardiac rate and contractility are enhanced, resulting in a larger blood volume being pumped into the circulation. Narrowing of splanchnic blood vessels diverts blood into vascular beds in muscle.

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Adverse Drug Effects premature breakdown of red blood cells (hemolysis) in subjects with a glucose6-phosphate dehydrogenase deficiency. The discipline of pharmacogenetics deals with the importance of the genotype for reactions to drugs. The above forms of hypersensitivity must be distinguished from allergies involving the immune system (p. 72). Lack of selectivity (C). Despite appropriate dosing and normal sensitivity, undesired effects can occur because the drug does not specifically act on the targeted (diseased) tissue or organ.

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Adrenocortical steroids and their synthetic analogues Mechanisms of action Actions: mineralocorticoid, glucocorticoid Individual adrenal steroids Pharmacokinetics Dosage schedules Choice of adrenal steroid Adverse effects of systemic pharmacotherapy Adrenal steroids and pregnancy Precautions during chronic therapy: treatment of intercurrent illness Dosage and routes of administration Indications for use Uses: replacement therapy, pharmacotherapy Withdrawal of pharmacotherapy . Inhibition of synthesis of adrenal steroids. Competitive antagonism .

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The liver is the most important organ in which drugs are structurally altered. Some of the resulting metabolites may be biologically inactive, some active and some toxic (see Chapter 7).The liver is exposed to drugs in higher concentrations than are most organs because most are administered orally and are absorbed from the gastrointestinal tract.Thus the whole dose must pass through the liver to reach the systemic circulation.

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Neoplastic disease In most cases, the cause of cancer is multifactorial. About 75% of cancers are due to environmental factors, some of which are within the control of the individual, e.g. tobacco smoking, exposure to sunlight. Growing understanding of cancer genetics and inherited disease suggests that fewer than 10% of cancers are familial.The different systemic modalities used to treat cancer patients are discussed. Immunosuppressive drugs are described here as they share many characteristics with cytotoxics. ...

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Occlusive vascular disease is a major cause of morbidity and mortality.There is now better understanding of the mechanisms by which the haemostatic system ensures blood remains fluid within vessels, yet forms a solid plug when a vessel is breached, and of the ways in which haemostasis may be altered by drugs to prevent or reverse (lyse) pathological thrombosis.

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Overdose, including self-poisoning, causes bradycardia, heart block, hypotension and low output cardiac failure that can proceed to cardiogenic shock; death is more likely with agents having membrane stabilising action (see Table 23.1). Bronchoconstriction can be severe, even fatal, in patients subject to any bronchospastic disease; loss of consciousness may occur with lipid-soluble agents that penetrate the central nervous system. Receptor blockade will outlast the persistence of the drug in the plasma. Rational treatment includes: • Atropine (1-2 mg i.v.

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Acetylcholine is a widespread chemotransmitter in the body, mediating a broad range of physiological effects.There are two distinct classes of receptor for acetylcholine defined on the basis of their preferential activation by the alkaloids, nicotine (from tobacco) and muscarine (from a fungus, Amanita muscaria). Cholinergic drugs (acetylcholine agonists) mimic acetylcholine at all sites although the balance of nicotinic and muscarinic effects is variable.

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