2.1 Ethanol Flashcards
Most commonly abused substance in the world is
ethanol
durgs with similar ethanol actions
barbiturates or benzodizepines
Pharmaco dynamics/pharmacological effects of acute ethanol consumption on CNS
like anesthetics, when alcohol is consumed,
cortex and RAS are depressed which are
areas that exhibit control over the body
–> causes apparent excitement, but is NOT a stimulant
–>inhibition of inhibition.
Hyperactivity occurs due to removal of inhibitory effects
Ethanol causes CNS depression by
enhancing GABA stimulated influx of chloride through receptor gated membrane ion channesl (GABAmimetic effect),
inhibits NMDA receptors
Ethanol affects a lare number of membrane proteins that participate in signaling pathways such as
NT receptors for AA and opiodes, enzymes such as Na/K ATPase, adenylcyclae, PLC, ion channels
ethanol causes euphoria by
enhancing endorphin production
ethanol reduces both mental and physical efficiency, and as level in plasma increases, person develps
there are more drunk person effects
high dose ethanol
analgesia,
anesthesia,
sleep
toxic dose ethanol
person becomes unconscious and alcohol depresses medullary center, causing death (due to respiratory depression)
thymine deficiency due to poor diet and dec absorption by acetaldehyde and chronic alcoolism leads to
Wernicke-Korsakoff syndrome
ethanol causes peripheral vasodialation by
depression of VMC (direct), by relaxation of smooth muscle caused by its metabolite (acetaldehyde) feeling of warmth followed by inc in body heat loss
ethanol causes diuretic effect by
inhibiting secretion of ADH
gastric mucosa and small dose of ethanol
stimulates salivary secretions,
gastric secretions,
improves appetite – appetizer
gastric mucosa and high dose of ethanol
produces gastric irritation,
causes back diffusion of acid from the gastric lumen into mucosa causing injury
who should avoid ethanol
peptic ulcer patient
ethanol caues vomiting
by central and local gastric effects,
commonly death occurs due to suffocation from inhaled vomitus
ethanol and sex
stimulates sexual desire and gives false confidence
but impairs the sexual performance
Ethanol chronic ingestion may lead to
impotence,
sterility,
testicular atrophy,
gynecomastia
feminization in alcoholic man has dual origin
alcohol induced hepatic injury leads to hyper estrogenization and decreased production of testosteron, increased metabolic inactivation of testosterone - genital shrinkage may occur in men
ethanol on glucose metabolism
inhibits gluconeogenesis and
hence produces fasting hypoglycemia
ethanol on uterus
relaxes uterus
ethalol and hyperuricemia
may lead to gout (lactate competes with urate for excretion)
ethanol effects on CVS - French Paradox
refers to the fact that people in France suffer relatively low incidence of coronary heart disease, despite having a diet relatively rich in saturated fats
ethanol on coronary diseases with low dose
small dose daily decreases coronary artery disease, alcohol increases level of HDL preventing atherosclrosis, low dose alcohol yields cardio protective effects (decreased risk of CHD compared to abstainer)
ethanol on coronary diseases with high dose
high dose of alcolol causes arrhythmia, cardiomyopathy, hemorrhagic stroke, alcohol has a J-shaped dose mortality curve
consumed at 1-20g/day to 21-40g/day results in
lower rates of angina pectoris, MI and peripheral artery disease
ethanol and hypertention
heavy alcohol use increases both diastolic and systolic BP
ethanol and arrhythmias
both atrial and vetricular arrhythmias
ethanol and cardiomyopathy
depresses cardiac contractility and leads to cardiomyopathy
ethanol effects on liver
fatty liver, alcoholic hepatitis, finally cirrhosis and liver failure
ethanol and cancer
increased risk of canser with chronic use of
mouth,
pharynx,
larynx,
esophagus, and
liver;
also small risk of breast cancer ——>due to the acetaldehyde metabolite!!
ethano absorption
very good and rapid oral absorption withing 5-10 min
– presence of food in gut delays absorption
peak concentration of ethanol reaches withing
30 to 90 minutes form the last drink
ethanol distribution in the body
fairly uniformly distributed throught all tissues and all fluids
ethanol is subject to gastric first pass metabolism by
alcohol dehydrogenase in the gastric wall
female and alcohol dehydrogenase
females have less alcohol dehydrogenase,
alcohol attains higher concentration in systemic blood for the same dose per Kg than in men.
liver and ethanol elimination
liver unusually plays a little role in presystemic elimination although it has a major role in its subsequent metabolism
placenta and alcohol
placenta is permeable to ethanol and henc reach fetus (fetal alcohol syndrome)
more than 90% of ethanol is oxidized in
the liver - micorsomal oxidation
elimination of alcohol follows
zero order kinetics –when the concentration in blood exceeds 10mg/100ml
alcohol leads to tolerance by
enzyme induction
ethanol degradation
ethyl alcohol
- -> acetaldehyde (via alcohol dehydrogenase)
- ->acetic acid (via acealdehyde dehydrogenase)
- ->CO2 and H2O
pathways of ethanol metabolism through two ways
alcohol dehydrogenase path in cytosol,
microsomal ethanol oxidizing system (MEOS) located in the smooth endoplasmic reticulum
fomepizole
inhibits alchol dehydrogenase
–substrate can be ethanol or methanol
drug that inhibits alcohol dehydrogenase
fomepizole
drug that inhibits aldehyde dehydrogenase
disulfiram
disulfiram
inhibits aldehyde dehydrogenase
principle path of alcohol metabolism
alcohol dehydrogenase path
alcohol dehydrogenase path produces
acetaldehyde from alcohol,
NADH is also generated during the proces
rate of ethanol oxidation is determined by
the capacity of the liver to re-oxidize NADH
oxidation of ethanol in the liver
generates an excess of NADH
if the ability of the hepatocytes to meaintain redox homeostasis is overwhlemed
then a number of metabolic distrubances arise including
lactic acidosis,
hyperuricemia, and
abnormalities of hepatic lipid metabolism
MEOS (isoform of cytochrome P450) role in ethanol concentration below 100mg%
small
MEOS induction
chronic alcohol use is associated with an increase in the metabolic rate for ethanol as a result of induction of MEOS system, can account for up to 10% of ethanol oxidation
disulfiram inhibiting aldehyde dehydrogenase
increase acetaldehyde producing unpleasant symptoms so if taking disulfiram or drugs like it you don_t want to consume more
treatment of methanol
ethanol cuts methanol bec alcohol dehydrogenase has higher affinity for ethanol so there is less production of fromaldehyde
ethanol is mainly excreted through
urine, but also through
lungs and
sweat
trigeminal neuralgia
ethanol is a last resort treatment for intractable trigeminal neuralgia
repeated use of alcohol results in
tolerance –> physical dependence
(inc of dopamine release from the mesolimbic reward system)
alcohol give more calories than carbs or protein
7g vs 4 g
addictive cycle of alchohol
alcohol consumption
- ->alcohol high - stimulation of opiod receptors
- ->alcohol high diminishes, increasing desire for more stimualtion of opiod receptors
- -> motivated to consume more alcohol–increased craving and loss of control
- ->leads to more alcohol consumption
cross tolerance with alcohol
benzodiazepines and
other CNS depressants
–>dangerous combination
alcohol withdrawl syndrom
sudden stoppage in chronic consumer leads to alcohol withdrawal syndrome
symptoms of alcohol withdrawl syndrom
alcohol craving, tremors, irritability, nausea, sleep distrubances, tachycardia, inc in BP, sweating, perceptual distortion, hallucinations, seizures, Delirium Tremens, can be fatal
fever and alcohol
vasodialation to dec temperature
delirium tremens (severe)
refers to delirium (mental confusion, agitation, and fluctuation levels of consciousness)
associated with a tremor and autonomic overactivity (eg. Marked increases in pulse, bp, respirations)
–>severe agitation, confusion, visual hallucinations, fever, profuse sweating
rubefacient
vasodialation so produced redness – rubbing it produces counter irritation
Alcoholism
acute and chronic
Acute alcoholism/intoxication
usually occurs in non-tolerant individuals who rapidly consume alcohol in large quantities;
normally the user passes out before a toxic dose of alcohol can be ingested;
the person vomits to rid the stomach of its toxic reservoir;
with rapid dringing the person may fall asleep or pass out without vomiting, allowing continued alcohol absroption form the GIT while the patient sleeps until fatal BAC are achieved
S/S of acute alcoholism
hypotension, tachycardia, hypoglycemia, respiratory depression, and coma
when is alcohol fatal
more than 400mg/dl concentration
treatment goal of acute alcoholism
to prevent severe respiratory depression and aspiration of vomitus
Measures in acute alcoholism
maintenance of ABC,
gastric lavage,
treatment of hypoglycemia and ketsis by administration of IV glucose,
electrolyte balance,
treatment of violent behaviour –by sedatives and antipsychotics in low dose
Chronic alcoholism may cause
malnutrition,
organ failure
Malnutrition related to chronic alcoholism
partidulary def of B group vitamins (esp. thiamine, vit B1),
thiamine supplementation is standard therapy bc it can prevent the development of the Wernicke-Korsakoff Syndrom
(eg. Mental confusion, nystagmus, and ataxia)
which may not be reversible once developed
organ damage related to chronic alcoholism
liver cirrhosis,
deteriorate bain fn (psychotic state, dementia, seizures, loss of memory etc),
peripheral neuropathy,
cardiomyopathy,
cancer of upper alimentary tract and resp tract,
hypertension
abrupt withdrawl of alcohol leads to
a characteristic syndrom of motor agitation, anxiety, insomnia and reduction of the seizure thrshold
management of chronic alcoholism by detoxification
substituting a long-acting sedative hypnotic drugs for alcohol and then gradually reducing (tapering) the dose of the long-acting drug
long acting BZDs include
chlordiazepoxide,
diazepam
what is the advantage of the long acting bzs
less frequent dosing
in pts with liver disease short acting bzds
oxazepam,
lorazepam
fixed schedule therapy
psychological therapy,
aversion therapy
drugs in aversion therapy
disulfiram (antabuse),
naltrexone
disulfiram (antabuse)
aldehyde dehydrogenase inhibitor –renders alcohol unpleasant
naltrexone (opiod antagonist) and Acamprosate (an analog of Gaba)
NMDA antagonist - helps in alcoholism by decreasing relapse and craving
combination of disulfiram and naltrexone should have been avoided bc
both drugs are potential hepatotoxic
disulfiram (antabuse) reactions
facial flushing, throbbing headache, nausea, vomiting, sweating, hypotension, palpitation, tachycardia
usual oral dose of Disulfiram
250mg daily
other drugs producing disulfiram like reactions are
metronidazole, chlorpropamide, griseofulvin, moxalactam, cefoperazone, cefotetan
inhib of Alcohol dehydrogenase
cns depression,
metabolic acidosis,
acetaldehyde toxicity
with increasing ethanol levels you get
inc socialbility, gait disturbances, inc reaction time, ataxia, impaired motor and mental skills, impaired memory, coma, death
inc acetaldehyde you get
N &V, headache, hypotension, combines with folate to inactivate it, combines the thiamine to decrease availability
disulfiram inhibits
acetaldehyde dehydrogenase in the mitochondria
chronic alcoholism will show
hypoglycemia,
fatty liver and lipemia,
muscle wasting (long term alcoholic, poor food intake),
gout (lactate competes with urate for excretion)
ethanol intoxication symptoms
ataxia, nystagmus, sedation, flushed face, mood changes, impaired attention
ethanol withdrawl symptoms
tremors, hallucinations, insomnia, seizures, hyperthermia, nausea/vomitting
Fetal alcohol syndrom
chronic maternal alcohol abuse during pregnancy has teratogenic effects on the offspring like retarded body growth, microcephaly, poor co-ordination, hyperactive behavior
what is a leading cause of mental retardation and congenital malformation in the US
fetal alcohol syndrome
featurs of fetal alcohol syndrome
flattened face, mid facial and mandibular growth deficiencies, mental retardation, minor joint anomalies, malfunction of organ systems like --skeltal, --CVS, --renogenital
what is the vulnerable period for fetal alcohol syndrome
4 to 10 weeks
pregnancy is unlikely to occur in
severly alcoholic women
spontaneous miscarriage rate increases in
2nd trimester
fetal liver alcohol dehydrogenase activity
no/little alcohol dehydrogenase activity
guidelines for safe drinking
less than 2 drinks per day,
not more than 2 drinks on any occasion,
do not engage in hazardous activities after drinkin,
if contraindications do not drink,
do not drink if interacting drug is taken,
women to take less amt per kg
other types of alcohol
ethylene glycol (antifreeze agent, coolant), methanol (wood alcohol)
methanol metabolism produces
formaldehyde and formic acid
S/S accociated with methanol
respiratory failure,
severe anion gap metabolic acidosis,
ocular damage
methanol toxic dose leading to blindness
5-10ml
methanol toxic dose leading to death
30ml
methanol is a major componet of
illicit liquor (moon-shining, boot-legging),
gasoline additive,
industrial solvent xerographic copier solutions
methanol is absorbed from
the reps tract,
gi tract, and
skin
formic acid can convert to
CO2 and water by folate-dependant pathway
clinical features of methanol poisoning
severe malaise, vomiting, abdominal pain, tachypnea, restlessness, headace, acidosis, blindness (like being in a snow storm), coma, circulatory collapse
management of methanol poisoning
put the patient in a dark room, support respiration, gastric lavage, nutrition and electrolytes, correct acidosis (IV NaHCO3), inhibit methanol metabolism, eliminate methanol and its metabolites by dialysis, admin of Ca - luecovorin
what can you give to inhibit methanol metabolism
fomepizole (long acting inhibitor of alcohol dehydrogenase),
IV ethanol
