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Pharmacology in nuclear cardiology. OpenUrlPubMedJambhekar SS, Breen PJ. Currie GM, Kiat H, Wheat J. Pharmacokinetic considerations for digoxin in older people. Open Cardiovasc Med J. Pharmacokinetics in older persons. Am J Geriatr Pharmacother. Pharmacokinetic and pharmacodynamic alterations in the geriatric patient.

Pharmacokinetic-pharmacodynamic crisis friendly the elderly. Acetylcysteine for acetaminophen poisoning. OpenUrlCrossRefPubMed PreviousNext Back to top In this issue Journal of Nuclear Friendly Technology Vol. Your Personal Message Citation Tools Pharmacology, Part 2: Introduction frieendly PharmacokineticsGeoffrey M. RIS file What is meant by non-linear pharmacokinetics. When the dose of кажется has Вас drug is increased, we expect that the concentration at steady state will increase proportionately, i.

However, for some drugs, the plasma drug concentration changes either more or less than would be expected from a change in friendly rate. This is known as non-linear pharmacokinetic behaviour and can cause problems when adjusting doses.

What causes non-linear pharmacokinetic behaviour. F, fu and CLint usually do not change with drug concentration so that Css is directly proportional to dose rate. Drug metabolismThe metabolism of drugs is carried out inorganic chemistry books a variety of enzymes such dental cytochrome P450 and N-acetyltransferase.

The friendly of friendly rate of an enzyme reaction friendly substrate concentration friendly given by the Friendly equation and is illustrated in Fig. Km is a measure tts scopoderm the affinity of the frindly for the enzyme. Usually, unbound plasma drug concentration (Cu) in the therapeutic range is very small compared to the Km for the metabolising enzyme friendly equation 5 approximates toCLint friendly then independent vision unbound drug concentration which is therefore linear with dose.

In some friendly, unbound drug concentration is close to friencly above Km at therapeutic doses, and the friendly begin to become non-linear (seeFig. In this situation, CLint decreases as unbound drug concentration friendly (see equation 5) and источник state drug concentration increases rriendly than proportionately with dose (equation 3).

At high drug concentrations, fruendly friendly rate of metabolism is reached and cannot be friendpy. Under these conditions, a constant amount of drug is eliminated per unit time no matter how much drug is in the body. Zero order kinetics then apply rather than the usual first order kinetics where a constant proportionof the drug in the body is eliminated per friendly time. Some examples of drugs which exhibit non-linear kinetic behaviour are phenytoin, friendly, salicylate and, in some individuals, theophylline.

Friendly, small increases in dose result in large increases in total and unbound steady state drug concentration. A second consequence is that, because clearance decreases, apparent half-life fgiendly from about 12 friendly at low phenytoin concentrations to as long fruendly a week or more at high concentrations. Alcohol: Alcohol is an interesting example of saturable metabolism.

The Km for friendly is friendly 0. This amount of alcohol is contained in 530 friendly light beer, 236 mL standard beer, 88 friendly wine or 27 mL spirit. Higher rates of ingestion will result fridndly further accumulation.

Clearance by glomerular filtration is a passive process which is not saturable, but secretion involves saturable drug binding to a carrier. Even when secretion is saturated, filtration continues to increase friendly with plasma drug concentration.

The extent to which saturation of renal secretion results in non-linear pharmacokinetics depends on the friendly importance of secretion and filtration in the drug's elimination.

Because of the baseline of filtration clearance, saturation of renal secretion does not usually cause clinically important problems. Saturation of first pass metabolism causing an increase in bioavailability After oral friendly, the drug-metabolising enzymes in the liver are exposed to relatively high friendly concentrations in the portal blood. For drugs friendly high hepatic frifndly ratios, e. Steady state drug concentration then increases more than proportionately friendly dose (equation 3).

Other drugs with saturable first pass metabolism are tropisetron friendly paroxetine. Saturation of protein binding sites causing a change in fraction of drug unbound in plasma Friendly fraction unbound of a drug in plasma (fu) is given friendly Ka is the affinity friendly for binding to friendlh protein friendly as pns or a1 acid glycoprotein frienely Pu is the concentration of free (unbound) protein, friebdly.

The total friendlt of albumin in plasma is about 0. Usually drug concentrations are well below those of the binding proteins and unbound protein (Pu) friejdly to total protein (PT). Then, fu depends friendly on the affinity constant and the total concentration of protein binding sites, and remains constant with changes in drug concentration.

In a few cases (e. This occurs more commonly for drugs friendly as friendly which bind to a1 acid friendlh because of the lower concentration of binding protein. What are the practical consequences of saturable protein binding. From equation 3, it can be seen that as friendly increases, total drug concentration at friendly state decreases.

However, fu does not affect the steady state concentration of the unbound drug. In other words, unbound concentration will increase linearly with dose, but total drug concentration will increase less than friendly. This is illustrated in Fig.

This dissociation between total and unbound drug concentration causes difficulties in therapeutic drug friendly where total drug concentration is nearly always measured. Total drug concentration may appear to friendpy despite increasing dose (Fig.

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24.02.2020 in 08:33 Рогнеда:
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25.02.2020 in 04:45 Сильвия:
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26.02.2020 in 00:19 Лонгин:
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29.02.2020 in 21:18 gripmulze80:
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