Pharmacology-Alcohols-Intoxication-CNS- MADE EASY!

0:01 alcohol's as we know them to be our organic compounds in which a hydroxyl group is bound to a carbon but that's not how we'll approach to study it fir in pharmacology in pharmacology we are mostly concerned with the overdose toxicity of alcohols chronic alcoholism and drugs and measures used to overcome it in order to better understand alcohol toxicity first let's have a look at the different actions of alcohol on the different body systems firstly on the CNS it causes dose dependent CNS depression it causes stimulation initially and then later depression the stimulation is because we don't know if it is inhibiting an inhibitory neuron that can lead to excitation it has a facilitate

0:48 reaction on gaba-a receptors leading to depression it inhibits glutamate action on NMDA receptors which are basically excited receptors thus leading to depression in GI T it causes irritation gastric acid secretion is increased gastritis and peptic ulcer aggravation locally it destroys lipid and proteins of bacterial membranes that's why it is used as an antiseptic and as an astringent it can cause fall in the body temperature causing sweating and alcohol sponges etc used in fever to lower the body temperature on CVS acetaldehyde is a product of alcohol metabolism which is

1:34 a potent vasodilator it causes cutaneous vasodilation leading to flushing it can also cause myocardial depression and vasomotor Center depression alcohol causes serious respiratory depression as well in the liver when alcohol is metabolized into acetaldehyde by the enzyme and cobalt dehydrogenase it usually the acetaldehyde increasing level of acetaldehyde causes consumption of the antioxidants and also leads to production of reactive oxygen species this leads to a parricide inflammation and apoptosis leading to cirrhosis and five roses that's why alcoholics have a cirrhotic liver on the kidney it

2:19 inhibits antidiuretic release leading to die races now let's see how different types of alcohols are metabolized after they're ingested they can be methanol ethylene glycol and ethanol first enzyme they see is alcohol dehydrogenase it will convert methanol into formaldehyde ethylene glycol into like Oh aldehyde and ethanol into acetaldehyde with the next enzyme that will act on these aldehydes will be aldehyde dehydrogenase specifically acetaldehyde dehydrogenase

3:04 for acetaldehyde it will convert formaldehyde into formic acid black will be hired into Claire colic acid and then ultimately into oxalic acid and acetaldehyde into acetic acid now we'll see how these assets or their products cause toxicity in the body one thing you need to remember is that alcohol dehydrogenase is a NAD+ dependent enzyme hence it follows zero order kinetics that is a fixed amount of alcohol is metabolized in a fixed amount of time now we'll look at the presentation of toxicity of all of these metabolic products of alcohols firstly formic acid

3:50 will cause severe respiratory depression and thus respiratory failure it causes metabolic acidosis it's an acid it causes ocular damage due to neurotoxicity and a typical sign of methanol methanol poisoning is standing out in snowstorm or flickering white spots before the eyes are seen by the patient and formaldehyde breath can also be perceived now when ethylene glycol or antifreeze causes toxicity it will be converted into ultima into oxalic acid which will cause respiratory failure and metabolic acidosis as all alcohols - and a special feature of this type of poisoning will

4:37 be the formation of oxalic crystals and they will cause acute tubular necrosis this is reversible now ethanol toxicity can present as acute toxicity due to acute intake of large amounts of ethanol and as well as chronic alcoholism the Q toxicity will present as CNS depression metabolic acidosis acute hepatitis and acute pancreatitis now the increased amounts of acetaldehyde formed by the action of alcohol dehydrogenase on ethanol will cause some symptoms which will cause severe irritation to the patient such as

5:22 nausea vomiting headache hypotension etc and this feature is basically used in alcohol aversion to make people not drink ethanol we will discuss more about it when we are discussing the management of chronic alcoholics acute toxicity also involves decreased availability of folic acid and thymine because acetaldehyde will bind to folic acid and inactivated and thymine is deficient because of in absorption and decreased intake chronic alcoholism is manifested as fasting hypoglycemia fatty liver muscle wasting because there is proteolysis and the alcoholics basically don't eat very well

6:08 they depend upon alcohol for their energy intakes there is included increased glucagon and decreased gluconeogenesis there is also a out because we know that lactate in order to be converted into pyruvate needs NAD+ but in alcoholics the NAD+ is all of it is basically used up by the alcohol dehydrogenase to get rid of the alcohol so there is increased lactic acid which will compete with uric acid for excretion by the kidneys and thus increased uric acid will cost out another important feature of chronic alcoholism is Wernicke's Korsakoff syndrome we know that chronic alcoholics have decreased thymine in their bodies so when a hypoglycemic alcoholic is given IV glucose what

6:53 happens is that the glucose cannot be metabolized because the enzymes need timing for their activity so there will be hypo hyper or small or calm which can be because of the glucose administered so whenever you need to administer glucose to a chronic alcoholic you need to administer thymine with it as well one thing to remember about chronic alcoholism is that the high levels of plasma ethanol in a chronic alcoholics body cannot be handled alone by alcohol dehydrogenase what happens is that the microsomal ethanol oxidizing system of the liver comes into play and thus it converts the ethanol into acetaldehyde we know that chronic alcohol is an enzyme inducer so it will increase p450 enzyme activity and as well as the enzyme synthesis will

7:41 also be increased so due to these two activities what will happen is that tolerance to alcohol will be developed and the same amount of alcohol which will cause toxicity in a normal patient will not cause a toxicity in a chronic alcoholic there will also be some drug interactions such as increased conversion of acetaminophen - it's a petro toxic metabolite because that is also done by the liver conjugation so we need to adjust the dose of these drugs and because increased conversion of hepatotoxic metabolites will cause Pharma and hepatitis coming to the treatment of alcohol associated problems such as withdrawal symptoms alcohol dependence and acute intoxication with methanol or ethylene glycol to treat the

8:28 withdrawal symptoms we need to give time in because we know that chronic alcoholics are deficient in thiamine we also need to administer benzodiazepines such as diazepam and chlordiazepoxide we give these two drugs when we know that the liver function is normal because these need a lot of metabolism and have active metabolites while if we know that the company liver function is compromised then we need to give Laura's a pump which is a short-acting benzodiazepine and has less complex metabolism so it is safe in compensated liver function next to treat alcohol dependence we primarily use three drugs first is disulfiram second is naltrexone and thirdly a can

9:14 proceed now the disulfiram as I previously mentioned will inhibit aldehyde dehydrogenase now what will happen that aldehyde dehydrogenase when is inhibited will cause accumulation of acetaldehyde and all those bad symptoms that I mentioned before such as headache nausea vomiting hypertension will be associated with disulfiram use so naturally the alcoholic will not want to drink alcohol while he is taking this drug so it will cause a version from alcohol other drugs which act like disulfiram are metronidazole Joseph 11 and several Paris zone they should not be administered in alcoholics secondly

9:59 we can use naltrexone which will decrease the effects of endogenous opioids in the brain and a can proceed is NMDA automate receptor antagonist and a GABA a receptor and activator just like alcohol now in the management of acute intoxication of methanol or ethylene glycol what we do is that we can give ethanol or FMF is all ethanol is given because it has more affinity for alcohol dehydrogenase than others and acetaldehyde will not be as toxic as the other two metabolites which were formic acid and oxalic acid while this practice is now very obsolete from episode can be given because it is a long-acting inhibitor of alcohol

10:45 dehydrogenase and thus the alcohol will not be converted into its toxic metabolites that's all about alcohols