In obese patients, thiopental has an increased Vd and a longer elimination half life (t1/2), but Cl values are unchanged. It was stated in as long ago as 1969 that thiopental dosage should be based on LBM.
How can a high BMI affect the distribution of aminoglycosides?
Morbid obesity alters aminoglycosides pharmacokinetics, as both Vd and clearance are increased in morbidly obese patients compared to patients with normal weight , but most published data in obesity refer to drug distribution.
How does body fat affect drug distribution?
Increased volume of distribution for lipid-soluble drugs
Obese individuals are also likely to have a degree of heart failure which further decreases blood flow. This makes their fat a large compartment of potential distribution for lipophilic drugs which fills gradually, and then becomes a slowly emptying reservoir.
How does obesity affect volume of distribution?
In obese compared with normal weight individuals, the total volume of distribution (Vd) is moderately increased (aminoglycosides, caffeine) or similar (H2-blockers, neuromuscular blockers), but the Vd corrected by kilogram of actual bodyweight is significantly smaller.
How does body weight affect pharmacokinetics?
Pharmacokinetic changes in obese patients. Effect on absorption: Gastric emptying may be increased OR decreased (and it is unpredictable). Absorption from the subcutaneous compartment will be slowed due to poor blood flow to subcutaneous fat.
What do aminoglycosides treat?
Aminoglycosides are used in the treatment of severe infections of the abdomen and urinary tract, as well as bacteremia and endocarditis. They are also used for prophylaxis, especially against endocarditis.
Does gentamicin distribute easily into fat tissue?
Gentamicin is highly hydrophilic, i.e. not distributed into body fat and minimally distributed into tissue fluids.
What are the factors affecting drug distribution?
Drug distribution is affected by many factors, including plasma or tissue protein binding, body weight, body composition, and body fluid spaces (8). Of these, total body weight, muscle mass, and fat composition are the major determinants of drug distribution, and women may differ from men in both of these factors.
How does protein binding affect drug distribution?
Protein-binding may affect drug activity in one of two ways: either by changing the effective concentration of the drug at its site of action or by changing the rate at which the drug is eliminated, thus affecting the length of time for which effective concentrations are maintained.
Which drug has the highest volume of distribution?
Some drugs (e.g. tolbutamide, phenytoin, gentamicin, warfarin) are known to have small volumes of distribution (0.1–1 L/kg) while others (e.g. meperidine, propranolol, digoxin) are known to have large volumes of distribution (1–10 L/kg).
What is considered a high volume of distribution?
If the volume of distribution is larger than 42, the drug is thought to be distributed to all tissues in the body, especially the fatty tissue. Some drugs have volume of distribution values greater than 10,000 L! This means that most of the drug is in the tissue, and very little is in the plasma circulating.
Does body weight affect drug absorption?
The distribution of a drug between fat and lean tissues may influence its pharmacokinetics in obese patients. Thus, the loading dose should be adjusted to the TBW or IBW, according to data from studies carried out in obese individuals.
Which drugs are dosed by ideal body weight?
In general, lean body weight is the most appropriate dose for most anesthetic drugs, with the exception of NDMB, where ideal body weight may be more appropriate. Succinylcholine should be dosed to total body weight.
How does weight affect drug effectiveness?
Changes in body weight can influence the amount of medicine you need to take and how long it stays in your body. The circulatory system may slow down, which can affect how fast drugs get to the liver and kidneys.
How does body weight affect absorption?
Physiological changes due to obesity that affect this route generally include increases in gastrointestinal blood perfusion, higher cardiac output, increased splanchnic blood flow, changes in enterohepatic recirculation, accelerated gastric emptying, and increased gut permeability, all of which can alter both the rate …
How does disease affect drug action?
The absorption, distribution, metabolism, and elimination (ADME) of drugs can be influenced by the physiological and biochemical changes that occur due to various diseases. These changes can have dramatic influence on the exposure of drugs and lead to drug toxicity or lack of drug efficacy.