Alcohol Pharm Flashcards
The amounts of ethanol consumed can lead to nutritional and biochemical complications why?
- The shear amount of it you have to drink to get the pharm effects
- 12 oz of Coors Light contains 12k mg of ethanol, and each gram of EtOH has 7.1Kcal with it
- Thus, there can be unbalance of energy and nutrition with the amount of bevarage containing EtOH you take in
Where in the body is alcohol distributed?
• EtOH is water soluble, so it distributes to the whole body “water” compartment (5L of plasma)
• Thus the danger of crossing placenta - fetal alcohol syndrome
• Fatty areas get less alcohol (less water)
○ Big reason why women get drunk faster
Why do people get more drunk from shotgunning a beer than from sipping?
- Absorption, which is greatest in small intestine but quite efficient in the entire GI tract, is concentration dependent.
- Because it is concentration dependent, the bigger the bolus, the faster the absorption
- A heavy meal can decrease peak concentration by 30%, which is why it helps decrease absorption
Describe how EtOH is metabolized
• Metabolism is responsible for 90-98% of disappearance of alcohol from the body
• Liver is primary organ of metabolism but small % is excreted unchanged in expired air (0.05% of BAC) and urine (130% of BAC)
• There is first pass metabolism in gastric mucosa as well
○ Gastric ADH is inhibited by aspirin and cimetidine
• Pathway
○ Ethanol made to acetaldehyde
§ Some by alcohol dehydrogenase (ADH), which is zero-order kinetics and the major metabolic route
§ Some by mixed function oxidase (P450 2EI, which is first order kinetics, induced by ethanol and interferes with metabolism of other drugs)
○ Acetaldehyde is made into acetic acid
§ Partly through aldehyde dehydrogenase
§ Partly through aldehyde oxidase
○ Acetic acid is eliminated through the kidney
Accumulation of what alcohol metabolite is responsible for the adverse “hang over” feeling?
• Acetaldehyde accumulation
○ Remember the liver is fast at converting ethanol to acetaldehyde by alcohol dehydrogenase and the mixed function oxidase
○ There is a constant 7-10g EtOH per hour metabolized
§ 0.015-0.020% BAC reduction
§ But wide variation between people exists
• Causes vasodilation, headache, nausea, vomiting, respiratory difficulties, chest pains, orthostatic hypotension
What is the maximum rate of alcohol metabolism?
• About 220g/day
○ In chronic alcoholics, this can increase by 50-60%
• Remember that a can of Coors Light had 12g of EtOH in it
○ So about 20 cans of Coors Light means that there is NO WAY you metabolize all that EtOH in a full day
○ 10 cans of Coors Light and there’s no way you metabolize that in a night (1/2 day)
○ 6 hours is 1/4 of the day, and if you party from 9pm to 1am that’s only 4 hours.
○ So you can’t metabolize 3-4 cans of coors light fully in that amount of time
What’s the biochemical pathway of metabolism of ethanol?
• CH3 - CH2OH + NAD CH2 - COH + NADH
• Can happen by two enzymes
○ Alcohol dehydrogenase (ADH), in the liver cytosol
○ CYP2E1, can account for 25% maximum of metabolism at higher BACs because of 1st order kinetics and induction by ethanol presence
• CH3-COH + NAD –> CH3-COOH + NADH
○ Aldehyde dehydrogenase (AlDH) in the liver cytosol and mitochondria
○ Inhibited by disulfiram
§ Which is used in alcoholics to make drinking more painful than pleasurable
For the cycle of liver ethanol metabolism to continue there needs to be NADH oxidation to NAD. This can actually lead to hepatic metabolic disturbances how?
• Increased blood lactate
○ Leads to acidosis and behavioral disturbances
• Increased Mg excretion
○ Leads to convulsions
• Decreased uric acid excretion
○ May precipitate gout attacks
• Increased acetyl CoA
○ Increased fatty acid synthesis combined with decreased fat breakdown which leads to fatty liver
• Increased NADH
○ Decrease Krebs cycle, decrease gluconeogenesis which all leads to hypoglycemia
What are the CNS effects of alcohol?
• Sedative and hypnotic effects
• CNS is prime site of ethanol action with the effects proportional to BAC
• Produces dose-dependent CNS depressant effect similar to barbiturates
• Not a stimulant at any dose but depression of inhibitory cortical neurons is seen first, resulting in a relative stimulatory phase prior to depressive actions
• Dose-dependent effects (BAC = g/100mL)
○ BAC of 0 - 0.05
§ Loss of inhibitions, excitement, incoordination, impaired judgment, slurred speech, body sway
○ BAC of 0.05 - 0.08
§ DWAI in colorado
§ Impaired reaction time
§ Further impaired judgment
§ Impaired driving ability
§ ataxia
○ BAC of 0.08 - 0.2
§ DUI in colorado
§ Staggering gait
§ Inability to operate a motor vehicle
○ BAC of 0.2 - 0.3
§ Emesis, stupor, respiratory depression
§ Danger of death in presence of other CNS depressants
§ blackout
○ BAC over 0.3
§ Unconsciousness, severe respiratory and cardiovascular depression
§ death
○ BAC of 2.1
§ Highest known BAC with survival in a chronic alcoholic
§ Normal person this would kill them
Describe the symptoms of different BAC levels
• Dose-dependent effects (BAC = g/100mL)
○ BAC of 0 - 0.05
§ Loss of inhibitions, excitement, incoordination, impaired judgment, slurred speech, body sway
○ BAC of 0.05 - 0.08
§ DWAI in colorado
§ Impaired reaction time
§ Further impaired judgment
§ Impaired driving ability
§ ataxia
○ BAC of 0.08 - 0.2
§ DUI in colorado
§ Staggering gait
§ Inability to operate a motor vehicle
○ BAC of 0.2 - 0.3
§ Emesis, stupor, respiratory depression
§ Danger of death in presence of other CNS depressants
§ blackout
○ BAC over 0.3
§ Unconsciousness, severe respiratory and cardiovascular depression
§ death
○ BAC of 2.1
§ Highest known BAC with survival in a chronic alcoholic
§ Normal person this would kill them
What’s the mechanism of action for CNS depression due to ethanol?
• May include both specific perturbation of membrane proteins and relatively non-specific, non-receptor mediated disruption of neuronal plasma membranes
• Both alter NT function
• Low to moderate doses interact with GABA neurons by potentiating them and also with glutamate NMDA by inhibiting it
• Eventually, at high doses, all sensory modalities are perturbed (overall global effect of ethanol)
Why is ethanol contraindicated in epilepsy?
• It causes withdrawal hyperexcitability (normally produces anticonvulsive effects with high doses)
How does chronic alcohol use affect the liver?
• Reversible damage to liver initially
○ Increased fatty acid and lipid deposition leads to hepatitis, which leads to cell death and replacement by collagen
• Cirrhosis in 20% of chronic alcoholics
• Regeneration and enlargement of the liver lead to pressure on veins resulting in decreased venous return, ascites and esophageal varicosities
• Decreased synthesis of clotting proteins, so increased bleeding time and bleeds
How does chronic alcohol use affect the heart/CV system?
- Alcohol is a direct vasodilator and increases hypothermia risk
- Direct damage to cardiac muscle is possible and can lead to increased BP in heavy drinkers (over 3-5 a day)
- 1-2 drinks a day may be protective of CAD b/c of increased HDL levels and decrease in platelet aggregation
Higher doses of alcohol consumption chronically can mess with the absorption of what important nutrients?
• High doses can decrease absorption of amino acids, glucose, folic acid, thiamine, B12
How does chronic alcohol use affect the GI tract?
- Any beverage with over 15% is an irritant to GI tract which induces gastric secretions
- Gastric ulceration is common if taken with aspirin
- Prolonged use may cause serious ulceration of the gastric mucosa, ranging from gastritis to actual hemorrhage
- Alcohol induced increases in digestive secretions can produce pancreatitis
- High doses can decrease absorption of amino acids, glucose, folic acid, thiamine, B12
Alcohol inhibits the secretion of antidiuretic hormone. What does this result in?
• Diuretic effect when BAC is rising
Heavy drinkers have an increased risk for which cancers?
- Mouth, pharynx, larynx, exophagus, liver, lung
* Either direct or due to common comorbidities
The early withdrawal symptoms of alcohol are more serious than the later ones why?
• Tremor and seizures
• Anxiety/depression and suicide
What is wernicke’s disease?
• Progressive external opthalmoplegia, nystagmus, ataxia of gait, pain, loss of sensation, weakness of arms and legs
• Results from thiamine deficiency that is secondary to alcohol intake
• Responds quickly to thiamine admin
What is korsakoff’s disease?
- Type of psychosis
- Probably an extension of wernicke’s but not completely reversible
- Symptoms include severe amnesia and personality alterations
- Amnesic syndrome may result from interaction of thiamine deficiency with direct neurotoxic effects of alcohol
Alcohol use can alter the liver’s ability to metabolise a whole host of things. But it’s not cut and dry. Describe
• Non-alcoholic person
○ Acute alcohol can inhibit metabolism of other drugs
• In an alcoholic with normal liver function
○ Increased metabolism of other drugs
○ CYP2E1
○ Can potentiate acetaminophen toxicity
• In an alcoholic with mild liver disease
○ Normal drug metabolism
○ The effects cancel eachother out
• In an alcoholic with severe liver disease like hepatitis or cirrhosis
○ Slower metabolism of other drugs because of overall enzyme loss
○ Increases the effect of other drugs
How do you treat alcohol related medical problems?
• Acute
○ Support respiration
○ IV fluids + glucose, thiamine and electrolytes K and Mg
• Alcohol withdrawal syndrome
○ 1st line - Benzos long acting (chlordiazepoxide, lorazepam)
§ Action at GABA receptors prevents emergence of CNS hyperexcitability during withdrawal
○ 2nd line - alpha2 agonist (clonidine)
§ Effective for autonomic hyperactivity
• Reduction of consumption
○ Disulfiram - little clinical evidence that it works
○ Opioid antagonists (naltrexone)
§ reduces craving and consumption
§ Decreases relapse rates if there is concurrent psychotherapy
○ NMDA receptor drugs (acamprosate)
§ Some reduction in craving and relapse rates
If an alcoholic is taking metronidazole or other oral hypoglycemics, what will ingestion of alcohol do?
- It will make them feel like crap
- Works the same as disulfiram
- Inhibits aldehyde dehydrogenase and leads to build-up of metabolite that causes hangover
What is FAS?
- FAS is fetal alcohol syndrome
- There are a spectrum of effects with wide variability
- You MUST have prenatal or postnatal growth retardation AND altered morphogenesis (facial dysmorphology) AND CNS involvement (often mental retardation)
- No safe level of consumption is established, but PEAK BAC is probably the most important variable and is never to exceed 2 drinks/day
