Pharmacokinetics A and D Flashcards
Quantitative description of the time course of drug distribution in the body
Absorption
o Distribution
o Biotransformation [metabolism]
o Excretion
Ethyl alcohol absorption
Small intenstine most 75-80%
stomach 20-25%
colon negibile
How is ethyl alcohol absorbed
through mucosal surfaces of the GI tract
-simple difussion
Ficks Law
Rate is proportional to the concentration gradient of alcohol across a membrane and to a diffusion coefficient that is constant for ethyl alcohol and specific membrane
Factors Affecting absorption
Food, concentration and dose, physiology and drugs
How does food affect absoprtio
reduced efficiency of absorption due to prolonged gastric emptying time
Reduces and shifts the right
Isn’t released into small intestine since small intestine is closed to absorbed food
Time to peak Alcohol concetration
Fasting .5-2 hours
nonfasting 1-3 hrs
What has impact with food on alcohol
Directly proportional to size of meal
Indirectly proportion to elapsed time from food intake and alcohol consumption
reduction in Cpmax 9-23%
Time to peak alcohol concetration
Peak generally occurring in less than 30 minutes
Winek et al
Variation in BAC after last drink
Gullberg and Predmore
Mean time to reach peak BAC, with and without food was 19 minutes
Breen et al (1998)
Avg time to peak after one for the road: 16 – 20 minutes
Concentration and dose
Alcohol is most rapidly absorbed when the concentration is between 10 – 30%
Concentration dilute solutions
Result in a lower concertation gradient across the absorbing membrane
Larger volume may delay gastric emptying
concentration solution grater
irritating to the gastric mucosa and pyloric sphincter
Causing increased secretion of mucosa and delayed gastric emptying
Tripling the dose from 0.4 to 1.2 g/kg of alcohol, produces a 79% increase in time required to achieve peak BAC in fasting subjects and a 61% increase in non-fasting subjects
Physiology and drug
Changes in motility, blood supply, or morphology of the GI tract
Whether induced by internal or external factors, may result in a significant change in the rate of absorption of ethyl alcohol
Physiologoy increasing abosrption
Increased GI motility
Chronic gastritis or ulcers
Cholinergic
Increase GI blood flow
Chronic gastritis
Ingestion of warm liquids/food
Accelerated emptying
Ingestion of carbonated liquids
Chronic alcoholism
Gastrectomy (gastric by-pass)
Physiology decreasing absorption
Decreased GI motility
Nausea (exclusive of vomiting)
Shock
Anticholinergics
Decreased GI blood flow
Fear, pain
Sympathomimetics
Delayed gastric emptying
Gastric fibrosis
Carcinomatosis
Smoking cigarettes
Bariatric Surghery-gastric by pass
Most efficient method to tx morbid obesity
Complaints of increased sensitivity of reduced tolerance to EtOH as compared to pre-surgical state
Reduction in body weight [20 – 40% within 1-2 years]
Increased dose per Kg of body weight
Rapid absorption of EtOH
Higher Cmax
Earlier Tmax
Is alcohol hydrophilic or hydrophobic
hydrophilic–
Volume of Distribution
Volume of distribution is and expression of the total body water
Variability due to adiposity
Vd of alcohol decreases with age
Volume of Distribution
Males: 0.7 L/kg avg. 0.62-0.70 (.59-.9)
Females: 0.6 L/kg avg. .55-.66(.46-.86)
Blood-tissue ratio
Whole blood consists mainly of water with red/white cells, proteins, lipids
DUI-whole blood
Hospital test on serum/plasma which runs higher
