By K. Zuben. Virginia Commonwealth University.

In- sulin (administered with glucose) is also used in the emer- gency treatment of hyperkalemia discount 25 mg promethazine visa latex allergy symptoms underwear. In chronic renal failure purchase promethazine 25 mg line allergy fatigue, hyperkalemia usually does shrink and raises intracellular [K ], which then favors out- not develop until GFR falls below 15 to 20 mL/min because ward diffusion of K into the ECF. The major cause of renal K wasting is iatro- pseudohyperkalemia, results if blood has been mishandled genic, an unwanted side effect of diuretic drug therapy. In un- The plasma [K ] is sometimes taken as an approximate controlled diabetes mellitus, K loss is increased because of guide to total body K stores. For example, if a condition the osmotic diuresis caused by glucosuria and an elevated is known to produce an excessive loss of K (such as taking rate of fluid flow in the cortical collecting ducts. Several a diuretic drug), a decrease in plasma [K ] of 1 mEq/L may rare inherited defects in tubular transport, including Bart- correspond to a loss of 200 to 300 mEq K. Clearly, how- ter, Gitelman, and Liddle syndromes also lead to excessive ever, many factors affect the distribution of K between renal K excretion and hypokalemia (see Table 23. As was discussed in Chapter 23, K is filtered, reabsorbed, and secreted in the kidneys. Most of the filtered K is reabsorbed in the prox- The Kidneys Normally Maintain K Balance imal convoluted tubule (70%) and the loop of Henle Figure 24. K intake (50 to 150 ally the result of secretion by cortical collecting duct prin- mEq/day) and absorption by the small intestine are unreg- cipal cells. On the output side, gastrointestinal losses are nor- urine is typically about 15% (Fig. With prolonged mally small, but they can be large, especially with diarrhea. K depletion, the kidneys may excrete only 1% of the fil- Diarrheal fluid may contain as much as 80 mEq K /L. However, excessive K intake may result in the loss in sweat is clinically unimportant. Normally, 90% of excretion of an amount of K that exceeds the amount fil- the ingested K is excreted by the kidneys. The kidneys are tered; in this case, there is greatly increased K secretion the major sites of control of K balance; they increase K by cortical collecting ducts. An important site for this adaptive change is the cortical collecting duct. The kidneys may excrete too little K ; if the dietary intake of K con- [K ] leads to increased K uptake by the basolateral tinues, hyperkalemia can result. For example, in Addison’s plasma membrane Na /K -ATPase in collecting duct prin- disease, a low plasma aldosterone level leads to deficient cipal cells, resulting in increased intracellular [K ], K se- K excretion. Second, elevated plasma [K ] with acute renal failure; the hyperkalemia caused by inade- has a direct effect (i. K directly stimulates aldosterone secretion and leads to an increase in cell [K ] in collecting duct principal cells. With K loading, this secretion is so vigorous that the amount of Another puzzling question is: Why is it that K ex- K excreted may actually exceed the filtered load. AVP, in addition to its effects on water permeabil- ity, stimulates K secretion by increasing the activity of giotensin) on the adrenal cortex to stimulate the synthesis luminal membrane K channels in cortical collecting and release of aldosterone. Since plasma AVP levels are low dur- duct principal cells to (1) increase the Na permeability of ing water diuresis, this will reduce K secretion, oppos- the luminal plasma membrane, (2) increase the number and activity of basolateral plasma membrane Na /K -ATPase pumps, (3) increase the luminal plasma membrane K per- meability, and (4) increase cell metabolism. In cases of decreased dietary K intake or K depletion, the activity of the luminal plasma membrane H /K -AT- Aldosterone secretion GFR and proximal Pase found in -intercalated cells is increased. This pro- Na+ reabsorption motes K reabsorption by the collecting ducts. The col- lecting ducts can greatly diminish K excretion, but it takes Fluid delivery to a couple of weeks for K loss to reach minimal levels. Plasma aldosterone cortical collecting ducts Counterbalancing Influences on K Excretion. Consid- K+ secretion + ering that aldosterone stimulates both Na reabsorption K secretion and K secretion, why is it that Na deprivation, a stimu- lus that raises plasma aldosterone levels, does not lead to + enhanced K excretion? The explanation is related to the Unchanged K excretion fact that Na deprivation tends to lower GFR and increase proximal Na reabsorption (Fig. Proximal convoluted convoluted tubule tubule 100% 40% CALCIUM BALANCE 10% The kidneys play an important role in the maintenance of 2 2 Ca balance.

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The amount If individuals experience a seizure in pub- of disability experienced order 25 mg promethazine allergy shots gluten, if any discount 25mg promethazine with mastercard allergy vaccine uk, after this lic, they risk feelings of embarrassment type of surgery depends on individual cir- and onlookers’ potential misperception of cumstances. Alcohol can lower the seizure threshold At times, even when seizures are adequate- and therefore precipitate seizures. Alcohol ly controlled, anxiety over the possibility and antiepileptic medications may also of having a seizure or other psychosocial interact and cause untoward effects. Con- dysfunction may be the most disabling sequently, individuals with epilepsy should factor associated with the condition. A medical ment and emotional development depend identification bracelet should be worn by on when the diagnosis of epilepsy is made individuals with epilepsy at all times. When epilepsy is diagnosed in child- with epilepsy depends on the type of hood, parental feelings of fear, anxiety, seizure, the underlying cause, the admin- guilt, overprotectiveness, or mourning istration of appropriate treatment, and the can affect not only the child’s ability to individual’s willingness and ability to fol- accept his or her disability but also his or low the prescribed treatment regimen. Children may learn als with epilepsy can live active, produc- to use their condition as an excuse for in- tive lives. When medical intervention can greatly improve they are teenagers, concerns related to the ability to control seizures and enhance whether they will drive a car, participate in the general quality of life for the individ- sports, or engage in dating may cause addi- ual with epilepsy. Diagnosis of epilepsy in adulthood can Psychosocial Issues in Epilepsy also disrupt interpersonal and family rela- tionships. The impact on individuals’ Individuals with epilepsy may face social identity may be threatened, so that many psychological and psychosocial they go to great lengths to conceal their challenges. They must learn to deal with disability in order to avoid potential the uncertainty of whether and when rejection. No matter how lepsy may be fearful of observing a seizure Conditions Affecting the Brain 65 or may be concerned that the disorder is out a disability because of anticipated hereditary. Because of anxiety and misin- rejection due to real or perceived public formation, they may be unwilling to learn attitudes. Inability to drive can limit social Sexual activity, in most cases, need not interaction, educational experiences, and be affected by epilepsy (Frazer & Gumnit, employment opportunities. Although some medications used stances, individuals with epilepsy can to treat seizures may have some effect on drive without significant risk of accident libido, most do not. Psychological issues if their seizures are controlled with med- of low self-esteem or poorly developed ication. Individuals may be reluctant to were restricted from driving motor vehi- form intimate relationships because of the cles because of concerns for public safety fear of having a seizure. Although today be necessary to help them overcome this most states permit individuals with epilep- fear so that appropriate intimate relation- sy to obtain driver’s licenses, the length of ships can be established. State laws do not always take into ing a seizure, there are no outward signs account individual differences; some make of disability. Although considerable effort blanket rules that apply to all individuals has been devoted to educate the public with epilepsy regardless of their personal about the condition, misinformation and circumstances. In some cultures, historical with epilepsy should always consult their misconceptions about epilepsy have physician about alcohol consumption, es- linked it to demonic possession and insan- pecially in regard to taking alcohol when ity. In other instances people with epilep- they are also taking anticonvulsant med- sy were not permitted to participate in ication; however, each individual situation various events because of their diagnosis. Attitudes have changed in recent years as Sports activities are also an important the result of public education programs, means of socializing as well as helping in- improved placement of individuals with dividuals build self-confidence and self- epilepsy into the world of work, and in- esteem. In some situations, restrictions on creased ability to control seizures. In many participation in various activities are placed instances, however, individuals with on individuals with epilepsy even though epilepsy may still experience unjust re- no basis for limiting the activities exists. The stigma be precipitated by fatigue or other sports- and shame associated with epilepsy may related circumstances, others may have a cause individuals and/or their family to reduced incidence of seizures with exercise. Indi- Consequently, authorities should consider viduals may try to pass as someone with- the individual’s specific circumstances 66 CHAPTER 2 CONDITIONS OF THE NERVOUS SYSTEM: PART I rather than issuing blanket restrictions; reducing stress are other self-management each case should be considered individu- issues individuals with epilepsy must ally. The stress, uncertainty, restric- cific activities that present a hazard should tions, isolation, and difficulty with em- a seizure that involves loss of consciousness ployment all require adjustment and take place.

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Common physical effects include dry mouth generic 25 mg promethazine free shipping allergy shots jacksonville fl, sweating cheap promethazine 25 mg on-line allergy symptoms cold symptoms, loss of appetite and increased heart and pulse rate. The effects from snorting cocaine start quickly but only last for up to 30 min without repeating the dose. The effects are felt even quicker when smoking crack but are even more short-lived. Large or quickly repeating doses over a period of hours can led to extreme anxiety, paranoia and even hallucinations. These effects usually disappear as the drug is eliminated from the body. The after-effects of cocaine and crack use may include fatigue and depression as people come down from the high. Excessive doses can cause death from respiratory or heart failure but this is rare. Neither tolerance nor heroin-like withdrawal symptoms occur with regular use of cocaine. However, regular users may develop a strong psychological dependence on the feelings of physical and mental well-being and may be tempted to keep taking cocaine to avoid feeling tired and depressed. Dependence may be more likely and more severe from smoking crack compared to snorting cocaine. The fact that cocaine and crack are expensive means that people who become dependent may spend vast amounts of money. Those who are not wealthy may find themselves involved in crime or prosti- tution to fund a habit. With everyday use restlessness, nausea, hyperactivity, insomnia and weight loss may develop. Lack of sleep and weight loss may lead to exhaustion and being very run down. Repeated smoking of crack may cause breathing problems and partial loss of 516 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION voice. Pregnant women who heavily use cocaine or crack may experience complications and find that their babies are adversely affected. Mode of action Cocaine, a stimulant, blocks the reuptake of NA (and DA) and so has similar actions to those of the amphetamines which have a number of actions that include the release of NA and DA, and a block of reuptake and metabolism. BASIS FOR DEPENDENCE The production of dependence (physical) by the depressant drugs is thought to result from an adaptation of the CNS to the altered environment due to chronic drug use. In the case of the depressant drugs the CNS is believed to establish a new homeostatic state by supersensitivity of the pathways involved, counteracting the drug depression. When the drug is discontinued the depressive effect is removed and dramatic withdrawal symptoms result from this supersensitivity. Since opiates act on specific opiate receptors the withdrawal symptoms are relatively specific, whereas withdrawal from a general depressant such as alcohol produces more marked and generalised symptoms. The supersensitivity has been proposed to result from a number of changes in the depressed pathways that are not mutually exclusive: (1) Receptor supersensitivity (2) Unmasking of other neuronal pathways (3) Synthetic enzyme induction, increasing transmitter levels (4) Nucleotide changes or coupling to receptor increasing receptor sensitivity (5) Membrane depolarisation None of these are mutually exclusive and they may all relate to a common mechanism. There is an extensive literature showing that physical withdrawal can be reduced or prevented by drugs acting on related inhibitory systems (e. Furthermore, withdrawal can be reduced by a large range of drugs that block excitatory systems such as excitatory amino-acid receptor antagonists, calcium channel blockers, etc. Most of the work has been based on opioids since it is the easiest system to manipulate as administration of the antagonist, naloxone, precipitates withdrawal. Here, the idea that physical dependence results from opposing changes in the neuronal systems depressed by the drug of dependence is borne out by consideration of the acute effects of an opioid and the withdrawal symptoms. They are mirror images of each other: DRUG DEPENDENCE AND ABUSE 517 Figure 23. These excitatory compensations produce symptoms opposite to the acute effects of the drug 518 NEUROTRANSMITTERS, DRUGS AND BRAIN FUNCTION Acute effects Symptoms of withdrawal Analgesia Spontaneous aches and pains Depressed reflexes Spontaneous twitches (kick the habit) Feeling of warmth Feeling of cold (cold turkey) Anxiolysis Anxiety and paranoia Constipation Diarrhoea Drying up of secretions Lacrimation, runny nose, salivation Although these symptoms last for several days and are not pleasant, they are not that different from a bad cold with influenza yet clearly will be a deterrent to discontinuing the use of a drug. However, a number of people go through withdrawal and yet then go back to the drug. Thus, it is felt that the psychological effects of drugs are critical aspects as are the social issues that interact with continued drug use. The psychological effects of drugs are poorly understood but involve dopamine systems in the CNS.

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