Term
| A patient presents with methanol poisoning. What drug do you give him as treatment? |
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Definition
| Fomepizole is a new drug used to treat methanol or ethylene glycol consumption. If not available, use a bolus of ethanol, which will also competetively displace methanol/ethylene glycol from alcohol dehydrogenase. |
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Term
| What effects does alcohol have on the kidney, liver, vasculature, and sexual function? |
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Definition
Kidneys: Alcohol acts as a diuretic
Liver: Fatty liver because the triglyceride secretory system of the liver is impaired. Fatty acids taken up in the liver cannot be oxidized, because the oxidation of alcohol has used up the available NAD+. Chronic alcoholism leads to liver cirrhosis!
Vasculature: Alcohol causes cutaneous vasodilation, increasing heat loss.
Sexual Function: Increases desire but decreases performance. Failure of liver to break down estrogen may result in gynecomastia. |
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Term
| Where is alcohol absorbed? |
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Definition
| Alcohol is absorbed in the stomach and small intestine. |
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Term
| How is alcohol metabolized? |
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Definition
In the cytosol, the enzymes Alcohol dehydrogenase and aldehyde dehydrogenase convert alcohol to acetic acid. This process follows zero order kinetics and uses up the available NAD+. This is the main pathway of metabolism (75%).
Alcohol is also metabolized by microsomal enzymes of the SER. Alcohol induces these enzymes. |
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Term
| How can alcoholism lead to gout? |
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Definition
| Because the metabolism of alcohol uses up NAD+, glycolosis favors the lactic acid pathway to renew NAD+. There is a build-up of lactate. Lactate competes with uric acid for renal excretion. Therefore, less uric acid is excreted, leading to hyperuricemia and gout! |
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Term
| How does the drug disulfiram work? |
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Definition
| Disulfiram acts by blocking aldehyde dehydrogenase. This leads to a build up of acetaldehyde with even small amounts of alcohol. Acetaldehyde is responsible for the nausea and sickness associated with alcohol consumptions. It is toxic. This causes nausea in patients taking the drug even when consuming minimal amounts of alcohol. It is used in recovering alcoholics after they have undergone detox and are committed to recovery. |
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Term
| How does binge drinking affect other drugs? |
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Definition
Binge drinking is the acute consumption of excessive amounts of alcohol. It utilizes most of the NAD+ for the metabolism of alcohol. This decreases the breakdown of other drugs, which can lead to toxicity! Other such drugs are:
Benzodiazepines, barbiturates, phenothiazines, TCADs, phenytoin, warfarin, MAOIs, and hypoglycemic agents. Increased action of this last one can lead to hypoglycemic coma! Recall that barbiturates are linearly toxic and can result in death, so this is also a great danger. Increased warfarin effect may lead to bleeding. |
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Term
| What effects does chronic alcoholism have on other drugs? |
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Definition
| Chronic alcoholism results in an increase in the CYP450 microsomal enzyme activity. This stimulation of CYP450 enzymes causes a decreased activity of other drugs that are metabolized by them. Such drugs are barbiturates, benzodiazepines, phenytoin, warfarin, etc. This can lead to therapeutic failure. |
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Term
| What is the difference in alcohol-drug interaction between chronic alcoholism and binge-drinking? |
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Definition
| Binge drinking will decrease drug metabolism, leading to toxicities. Chronic alcoholism stimulates the CYP450 system, potentially leading to therapeutic failure of other drugs. |
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Term
| Why does simultaneous taking of cocaine and alcohol lead to dependence on both drugs? |
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Definition
| When cocaine is consumed with alcohol, it is converted to cocaethylene, an intermediate with equipotent effects at blocking DA reuptake, thus amplifying the effects of cocaine! |
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Term
| Describe alcohol withdrawal |
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Definition
| Alcohol is a CNS depressant. Therefore, when it is removed after chronic, heavy use, there is an 'overcompensation' in the opposite direction. This leads to heavy stimulation and you will see gross tremors, perspiration, hyperreflexia. In people that have become heavily habituated to alcohol, hypertension, seizures, visual hallucinations can result. Delerium tremens is the term used for the disorientation, visual hallucination, and coarse tremors seen in alcohol withdrawal. Treatment is with benzodiazepines! |
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Term
| What drugs are used to treat patients in alcohol withdrawal? |
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Definition
Use benzodiazepines to treat alcohol withdrawal!
Ex: diazepam, oxazepam... (long half-life benzos)
remember: treatment for withdrawal involves drugs that are cross-tolerant with the offending drug but don't have the same toxic effects. Alcohol acts on the GABA receptor, benzos act on this same receptor, but at a different binding site. |
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Term
| What drug is given to patients in alcohol rehabilitation? |
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Definition
Disulfiram (ANTABUSE) is given to patients on rehab. It cannot be given to patients that are still taking alcohol, as this could kill them. It is therefore crucial that they've already been through detox.
Do not give disulfiram to patients with a history of psychoses! this is because disulfiram also blocks dopamine b-hydroxylase, causing DA accumulation. Remember that the theory behind many psychoses is increased DA levels... thus disulfiram administration would worsen their condition! |
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Term
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Definition
Methanol is metabolized to toxic intermediates: formaldehyde and formic acid.
Formaldehyde can cause blindness. Formic acid disturbs the body's acid-base balance.
Tx is with ethanol or fomepizole
Also give sodium bicarbonate to restore the acid base balance. |
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Term
| What is the drug fomepizole used for? |
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Definition
| Fomepizole is the drug given to patients that have overdosed on methanol or ethylene glycol. It is a competetive inhibitor of alcohol dehydrogenase, the enzyme responsible for the first step in the metabolism of methanol and ethylene glycol. |
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Term
| What products would you see in the urine of someone with ethylene glycol poisoning? |
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Definition
Ethylene glycol poisoning can be confirmed by finding glycolic acid, glycoxylic acid, or oxalic acid in the urine. Ethylene glycol is sequentially metabolized into glycolaldehyde then these three excretable products.
Oxalic acid in the urine is a definitive finding in ethylene glycol overdose. Ethylene glycol (antifreeze) is used as a coolant and industrial solvent. |
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Term
| A patient enters the ER with metabolic acidosis, large anion gap, and oxalate crystals in the urine. They are on the verge of renal failure. What drug do you give them? |
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Definition
| This patient is suffering from ethylene glycol poisoning. Oxalic acid in the urine is a definitive sign of ethylene glycol poisoning. Treatment is with ethanol, or if available Fomepizole. Fomepizole and ethanol will both competetively displace ethylene glycol from alcohol dehydrogenase. Also give sodium bicarbonate to counter the metabolic acidosis! |
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