Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/62

Click to flip

62 Cards in this Set

  • Front
  • Back
What is BAC?
Blood alcohol concentration

Index of consumption and reflects absorption, distribution and metaboliism
How is BAC measured?
measured directly from blood via
-- gas chromatograph analysis OR
-- enzyme analysis
BAC depends on...?
1. quantity of ethanol ingested and consumption rate

2. speed of absorption

3. body weight and percentage of total body water

4. rate of metabolism
Alcohol absorption?
1. simple diffusion largely in PROXIMAL INTESTINE, but also through stomach mucosa (20-30%)

2. delays in gastric emptying slows absorption rate from proximal intestine

3. rate of ethanol absorption is concentration-dependent (20-30% solutions absorbed faster than more dilute solutions)

4. concentrated ethanol can produce gastric irritation and pylorospasm which slows absorption

5. drugs can also decrease gastric absorption
Alcohol distribution?
1. enters systemic circulation to be distributed first to the liver

2. distributes to entire body water

3. typical peak BAC occurs 30-90min after ingestion
Oxidation of alcohol?
Over 90% completely oxidized to CO2 and H2O (98% at lower conc)

Rate of oxidation follows zero-order kinetics
-- independent of time and concentration of ethanol
-- 7-10g of ethanol oxidized per hour
Steps of alcohol metabolism -- general?
1. GASTRIC mucosal alcohol dehydrogenase

2. HEPATIC enzymatic mechanisms
Describe the primary hepatic enzyme mechanism.
Alcohol dehydrogenase (ADH)






-- Availability of nicotinamide adenine dinucleotide (NAD+) is the rate-limiting factor
-- conversion of NAD+ to NADH increases cellular reducing equivalents (H+)
-- acetaldehyde (CH3CHO) is oxidized in the liver via ALDEHYDE DEHYDROGENASE (AIDH)to acetate and subsequently to CO2 and H2O
Describe the secondary hepatic enzyme mechanism.
Microsomal enzyme oxidizing system (MEOS)

-- microsomal ethanol oxidizing system has a high Km for ethanol (>100 mg/dL)
-- does NOT depend on NAD+
-- can be induced by chronic, high levels of ethanol (increased metabolism of other substrates for MEOS)
What is the tertiary enzyme mechanism for alcohol metabolism?
catalase
What are the mbrn effects of alcohol?
1. By virtue of its lipid solubility, ALL tissues and cells can be affected by ethanol, however, organ systems differ in sensitivity

2. Generalized perturbation of MBRN PROTEINS that participate in neuronal signaling
-- enzymes --> Na/K ATPase, adenyl cyclase, protein kinase C
-- voltage-gated ion channels --> Ca++ and K+ voltage-dependent ion channel function
Neurotransmitter effects of alcohol at lower concentrations?
Increased neuronal signaling (stimulant effects) through ethanol-induced:

1. decreased actons of GABA to reduce inhibitory neuron strength (disinhibition)

2. increased release of DOPA in the nucleus accumbens appears to mediate pleasureable effects of EtOH
Neurotransmitter effects of alcohol at higher concentrations?
Decreased neuronal signaling (depressant effects) occurs at higher concentrations through ethanol induced:

1. enhancement of inhibitory signaling via facilitation of effects of GABA

2. inhibition of glutamate effects at the NMDA receptor
CNS acute effects with alcohol use?
1. low concentrations produce disihibition of cortical inhibitory control mechanisms producing impairment of the reticular activating system

2. higher concentrations produce impairment of the reticular activating system leading to generalized depression of neuronal function
CNS chronic effects with alcohol use?
1. directly associated with serious neurologic and mental disorders such as
-- memory loss
-- sleep disturbances
-- psychoses

2. associated deficiency in B vitamins leads to peripheral neuropathies
Acute EtOH effects on cardiovascular and respiratory systems?
1. SMALL doses initially cause cutaneous vasodilation
-- direct smooth muscle relaxant effects

2. TOXIC doses can produce myocardial depression, and central vasomotor and respiratory depression
Chronic EtOH effects on cardiovascular and respiratory systems?
1. HTN, worsening of existing HTN

2. abuse can produce irreversible cardiomyopathy
Acute hepatic system effects of EtOH?
1. excess reducing equivalents (H+) formed from the ADH and AIDH-dependent metabolism increases hepatic NADS/NAD ratio

2. increase in avb H+ leads to number of metabolic consequences, including:
-- transient hyperglycemia or hypoglycemia w/ decreased gluconeogenesis
-- hyperlacticacidemia
-- hyperurucemia
-- hyperlipidemia and ketoacidosis
Chronic hepatic system effects of EtOH?
1. NADH-induced inhibition of glycerophosphate dehydrogenase leads to increased glycerophosphate and esterification of fatty acids (triglycerides)

2. decreased oxidation of fatty acids

3. hepatic accumulation of "neurtral" fat (fatty liver)
Acute effects of EtOH on the GI system?
1. low concentrations increase gastric acid secretion

2. higher concentrations (greater than 40%) produces gastric irritation and possibly pylorospasm (direct effects)
Chronic effects of EtOH on the GI system?
1. erosive gastritis and esophageal and duodenal abnormalities

2. pancreatitis may also occur due to increased pancreatic secretion
Acute effects of EtOH on the endocrine-reproductive system?
1. Pituitary ADH secretion is inhibited causing diuresis of variable intensity and duration

2. inhibition of oxytocin secretion and impaired secretion of LH as well as decreased serum testosterone levels
Chronic effects of EtOH on the endocrine-reproductive system?
1. inhibition of hormone secretion has been assoc w/ testicular atrophy, impotence, sterility, and gynecomastia in males

2. excessive maternal EtOH abuse during pregnancy can produce birth defects and has been characterized as "Fetal Alcohol Syndrome"
Acute alcohol toxicity?
1. effects quantitatively related to blood-ethanol concentration leading to CNS and CV system depression

2. treatment is largely supportive (especially respiratory depression) w/ prevention of aspiration
Chronic alcohol toxicity?
1. assoc w/ increased mortality

2. LIVER DISEASE -- alcoholic fatty liver (reversible) progressing to alcoholic hepatitis and, finally, cirrhosis

3. CNS abnormalities including symmetrical peripheral neuropathies

4. increased risk of development of certain cancers
Types of alcohol tolerance?
1. metabolic

2. pharmacodynamic
Metabolic alcoholic tolerance?
1. occurs as evidenced by increased capacity to metabolize ethanol

2. mechanism involves induction of hepatic cytochrome p450 2E-1 (amt can increse 2-fold)
Pharmacodynamic alcohol tolerance?
1. chronic abuse results in cellular or pharmacodynamic tolerance to ethanol

2. response of mbrn systems affected by ethanol is reduced (mbrn adaptation)

3. behavioral adaptation as well as a significant increas in toxicity threshold
Types of dependence?
1. psychological dependence

2. physical dependence
Describe physical dependence.
Due to chronic abuse and is characterized by adaptive changes in neurotransmitter systems.
1. downregulation of inhibitory GABA receptors
2. upregulation of excitatory glutamate (NMDA) receptors
3. increased central norepi activity
Acute EtOH effects on cardiovascular and respiratory systems?
1. SMALL doses initially cause cutaneous vasodilation
-- direct smooth muscle relaxant effects

2. TOXIC doses can produce myocardial depression, and central vasomotor and respiratory depression
Chronic EtOH effects on cardiovascular and respiratory systems?
1. HTN, worsening of existing HTN

2. abuse can produce irreversible cardiomyopathy
Acute hepatic system effects of EtOH?
1. excess reducing equivalents (H+) formed from the ADH and AIDH-dependent metabolism increases hepatic NADS/NAD ratio

2. increase in avb H+ leads to number of metabolic consequences, including:
-- transient hyperglycemia or hypoglycemia w/ decreased gluconeogenesis
-- hyperlacticacidemia
-- hyperurucemia
-- hyperlipidemia and ketoacidosis
Chronic hepatic system effects of EtOH?
1. NADH-induced inhibition of glycerophosphate dehydrogenase leads to increased glycerophosphate and esterification of fatty acids (triglycerides)

2. decreased oxidation of fatty acids

3. hepatic accumulation of "neurtral" fat (fatty liver)
Acute effects of EtOH on the GI system?
1. low concentrations increase gastric acid secretion

2. higher concentrations (greater than 40%) produces gastric irritation and possibly pylorospasm (direct effects)
Chronic effects of EtOH on the GI system?
1. erosive gastritis and esophageal and duodenal abnormalities

2. pancreatitis may also occur due to increased pancreatic secretion
Acute effects of EtOH on the endocrine-reproductive system?
1. Pituitary ADH secretion is inhibited causing diuresis of variable intensity and duration

2. inhibition of oxytocin secretion and impaired secretion of LH as well as decreased serum testosterone levels
Chronic effects of EtOH on the endocrine-reproductive system?
1. inhibition of hormone secretion has been assoc w/ testicular atrophy, impotence, sterility, and gynecomastia in males

2. excessive maternal EtOH abuse during pregnancy can produce birth defects and has been characterized as "Fetal Alcohol Syndrome"
Acute alcohol toxicity?
1. effects quantitatively related to blood-ethanol concentration leading to CNS and CV system depression

2. treatment is largely supportive (especially respiratory depression) w/ prevention of aspiration
Chronic alcohol toxicity?
1. assoc w/ increased mortality

2. LIVER DISEASE -- alcoholic fatty liver (reversible) progressing to alcoholic hepatitis and, finally, cirrhosis

3. CNS abnormalities including symmetrical peripheral neuropathies

4. increased risk of development of certain cancers
Types of alcohol tolerance?
1. metabolic

2. pharmacodynamic
Metabolic alcoholic tolerance?
1. occurs as evidenced by increased capacity to metabolize ethanol

2. mechanism involves induction of hepatic cytochrome p450 2E-1 (amt can increse 2-fold)
Pharmacodynamic alcohol tolerance?
1. chronic abuse results in cellular or pharmacodynamic tolerance to ethanol

2. response of mbrn systems affected by ethanol is reduced (mbrn adaptation)

3. behavioral adaptation as well as a significant increas in toxicity threshold
Types of dependence?
1. psychological dependence

2. physical dependence
Describe physical dependence.
Due to chronic abuse and is characterized by adaptive changes in neurotransmitter systems.
1. downregulation of inhibitory GABA receptors
2. upregulation of excitatory glutamate (NMDA) receptors
3. increased central norepi activity
Forced reduction or discontinuation of ethanol consumption from physiologic dependence results in…?
Withdrawal symptom
-- hallucinations
-- seizures
-- possible delirium tremors
EtOH addiction treatment?
1. counseling and other behavioral intervention

2. CLONIDINE – alpha2 adrenergic agonist used to decrease W/D symptoms

3. NALREXONE or NALMAFENE – long acting narcotic antagonists help reduce craving

4. DISULFIRAM (Antabuse) – used as aversive deterrent to alcohol ingestion (see further)

5. ACOMPRASE – NMDA receptor antagonist
-- one of number of new agents used in alcoholic treatment programs which have been determined to decreased the relapse rate in alcoholics

6. TIAPRIDE – dopa receptor antagonist that blocks pleasurable effects of alcohol
Ethanol and disease states?
1. precautions in various disease states extend from the properties of ethanol which affect specific organ fxns

2. should be avoided in hepatic and severe renal disease, skeletal or cardiac myopathies, peptic ulcer, pancreatitis and gout

3. disinhibition properties of ethanol on CNS inhibitory pathways predict potential interaction in pts w/ epilepsy or other seizure disorders
How does EtOH affect drug bioavailability?
1. Solubility of diazepam and aminoglycoside antibiotics are increased by low concentrations of ethanol thus increasing bioavailability

2. High concentrations of ethanol can induce pylorospasm and decrease levels and/or delay onset of any drug absorbed preferentially in proximal intestine
How does EtOH affect drug metabolism?
1. DECREASED – acutely high conc of ethanol can interfere w/ hepatic metabolism of drugs such as:
-- pentobarbital
-- phenoparbital
-- phenytoin

2. INCREASED – chronic ethanol can induce hepatic cytochrome P450 microsomal enzyme system to enhance drug metabolism
-- phenytoin
-- morphine
-- benzodiazepines
-- meprobamate

3. ALTERED – disulfiram, metronidazol and the hypoglycemic sulfonylureas inhibit hepatic aldehyde dehydrogenase leading to a buildup of acetaldehyde in the body
-- subsequent “aldehyde syndrome” is assoc w/ cutaneous vasodilation, throbbing headache, respiratory difficulties, nausea, copious vomiting, sweating, chest pain, blurred vision, hypotension, orthostatic syncope and confusion
What kind of potentiation of effects can occur when mixing alcohol with drugs?
1. CNS – enhanced sedation may occur w/ ALL agents which have CNS depressant properties

2. GI – potentiation of gastric irritation due to salicylates

3. ENDOCRINE – potentiation of hypoglycemic response w/ oral sulfonylureas and biguinides

4. CV – potentiation of hypotensive response w nitrates
What is methanol?
“wood alcohol”
-- frequently found in the home as canned heat or in windshield washing solutions
-- used as an adulterant for tax-free ethanol and as an industrial solvent
Pharmacokinetics of methanol?
1. rapidly absorbed from the stomach and distributed to the total body water

2. substrate for alcohol dehydrogenase resulting in formation of formaldehyde which is then converted via aldehyde dehydrogenase to formic acid
Methanol toxicity?
1. Headache, vertigo, vomiting, dyspnea, and blurring vision can be delayed in appearance 8-36 hours following ingestion

2. Profound alterations in respiration and acid-base balance, especially metabolic acidosis

3. formic acid productes destructive inflammation of retinal ganglion cells and can produce bilateral blindness
Treatment of methanol toxicity?
1. largely supportive

2. correction of acidosis is most important step in treatment

3. both ethanol and 4-methylpyrazole can be administered which are substrates for ADH thus blocking metabolism of methanol to its toxic metabolites
What is isopropyl alcohol?
1. described as “rubbing” alcohol

2. used as surface disinfectant (70%) and also in lotions
Isopropyl alcohol pharmacokinetics?
1. initial substrate for alcohol dehydrogenase

2. ultimately oxidized to acetone
Isopropyl alcohol toxicity?
1. fatal dose is 4-8oz, thus more toxic than ethanol

2. signs and symptoms similar to ethanol, though more prominent gastritis, pain, and vomiting (and potential aspiration)

3. intox lasts longer due to slower oxidation to acetone

4. CNS depression proceeds to coma

5. evidence of ketoacidosis and ketones in urine confirms intoxication
What is ethylene glycol?
Polyhedric alcohol

1. ethylene glycol is used primarily in antifreeze

2. may also be used as industrial solvent
Ethylene glycol pharmacokinetics?
Ethylene glycol is converted first via ALCOHOL DEHYDROGENASE to GLYCOALDEHYDE and subsequently by ALDEHYDE DEHYDROGENASE to GLYCOLIC ACID

GLYCOLIC ACID is then metabolized to GLYOXYLIC ACID and subsequently to OXALIC ACID
Ethylene glycol toxicity?
1. Initial sign is CNS depression followed by metabolic acidosis

2. nephrotoxicity can result due to deposition of oxalic acid crystals in the renal tubules
-- crystals of calcium oxalate may be found in the urine
Ethylene glycol treatment?
1. supportive w/ correction of metabolic acidosis

2. formation of toxic metabolites can be reduced by admin of ethanol or 4-methylpyrazole which favorable competes for alcohol dehydrogenase and hence blocks oxalic acid formation