Alcohol MBBS 2014

(1)

Alcohol

Beer Beer Cider Cider Wine Wine Whiskey Whiskey Brandy Brandy Rum Rum

(2)

Ethyl alcohol

•• Alcohol is im Alcohol is important in portant in medicine -medicine -misuse/abuse

misuse/abuse

•• Present in beverages/used as drugPresent in beverages/used as drug

•• Alcoholism Alcoholism is a compis a complex disordlex disorder with er with aa genetic and environmental component genetic and environmental component

(3)

Pharmacological actions Pharmacological actions

-Local

Local

•• Mild rubefacient - Cutaneous vasodilationMild rubefacient - Cutaneous vasodilation •• Promotes heat lossPromotes heat loss

•• Astringent; Astringent; antiseptic antiseptic ((↑↑20-70%=90%20-70%=90%↓↓)) •• Injected to nerveInjected to nerve – – permanent damage permanent damage

(sclerosant) (sclerosant)

(4)

William Shakespeare (1564

William Shakespeare (1564 – –1616). 1616). The The Tragedy Tragedy ofof Macbeth.

Macbeth.

•• Lechery, sir, it provokes, and unprovokes;Lechery, sir, it provokes, and unprovokes; •• It provokes the desire, but it takes awayIt provokes the desire, but it takes away

the

the performanceperformance;;

•• It makes him, and it mars him;It makes him, and it mars him;

•• It sets him on, and it takes him off;It sets him on, and it takes him off;

•• It persuades him, and disheartens him;It persuades him, and disheartens him; •• Giveth redness of nose, sleep and urineGiveth redness of nose, sleep and urine

(5)

CNS effects

•

• CNS depressantCNS depressant

•

• Inhibition is lostInhibition is lost

•

• At higher concentrations - slurred speech, ataxia, impaired judgment, motorAt higher concentrations - slurred speech, ataxia, impaired judgment, motor

incoordination, increased self-confidence & disinhibited behavior

•

• Induces sleep-not dependableInduces sleep-not dependable

•• Chronic: dementia,Chronic: dementia, wernick’swernick’s, cognition disorders, cognition disorders •• Mechanism of CNS action involves:Mechanism of CNS action involves:

–

– potentiation of GABA receptor potentiation of GABA receptor –

– inhibition of Glutamate receptor neurotransmissioninhibition of Glutamate receptor neurotransmission

(6)

CVS

•• Small dosesSmall doses – – cutaneous vasodilatation cutaneous vasodilatation

•• Moderate dose -Moderate dose - ↑ BP central sympathetic stimulation↑ BP central sympathetic stimulation

•• High dose -High dose - ↓BP –↓BP – Myocardial + vasomotor center depression Myocardial + vasomotor center depression

•• Chronic alcoholismChronic alcoholism – – cardiomyopathy, cardiomyopathy, conduction defect,

conduction defect, ventricular hypertrophy,ventricular hypertrophy, atrial &

(7)

Blood

•• Low doses-Low doses- ↑ HDL↑ HDL && ↓ CHD risk ↓ CHD risk

•• Do not advice non drinkers to drinkDo not advice non drinkers to drink

Body temperature

•• Combats cold??Combats cold??——feeling of warmthfeeling of warmth •• Heat loss is increased-vasodilationHeat loss is increased-vasodilation

(8)

•• Gastric mucosaGastric mucosa

–

– disrupt the gastric mucosal barrier and cause acute anddisrupt the gastric mucosal barrier and cause acute and chronic gastritis

chronic gastritis –

– Promotes the release of gastrin and histaminePromotes the release of gastrin and histamine –

– ↑ gastric ac↑ gastric acid secretionid secretion –

– act synergistically withact synergistically with H. pylori H. pylori to delay healing to delay healing –

– Inflammation and bleeding by ulceration of the stomachInflammation and bleeding by ulceration of the stomach lining

lining

Acute pancreatitis Acute pancreatitis

(9)

Liver

•• Small to moderate-safeSmall to moderate-safe

•• Chronic-CirrhosisChronic-Cirrhosis

•• Chronic alcohol consumptionChronic alcohol consumption – – osteoporosiosteoporosiss

–

– reasons - unclear, reasons - unclear, impaired osteoblasimpaired osteoblastic activity hastic activity has been implicated

been implicated

Endocrine

 Small doses-hyperglycemia-AdrenalineSmall doses-hyperglycemia-Adrenaline release

release

 Large- Large- Hypoglycemia[gHypoglycemia[gluconeogenesis luconeogenesis isis inhibited]

(10)

Kidney

•• Diuresis -Diuresis - ↓ Antidiuretic↓ Antidiuretic hormonehormone

Uterus

(11)

Pharmacokinetics

•• Orally - rapidly absorbed from stomach and small intestineOrally - rapidly absorbed from stomach and small intestine

•• Depends on the presence of foodDepends on the presence of food

•• Vol.of distribution wideVol.of distribution wide

(12)

Ethanol Metabolism

o

o Oxidation - AlcoholOxidation - Alcohol

dehydrogenase (Al.DH) dehydrogenase (Al.DH) [[F o m e p i z o l e F o m e p i z o l e inhibits] inhibits]

o Ald.DH - mainly in liver, o Ald.DH - mainly in liver,

stomach and brain stomach and brain [[D is u l fi r a m Di s u lfi r am inhibits] inhibits]

Sulfonylurea, cefoperazone,

metronidazole]

Microsomal Ethanol-Oxidizin

Microsomal Ethanol-Oxidizing System g System (MEOS)(MEOS)

Another minor pathway of metabolism

(13)

Ethanol-metabolism

•• Genetic factorsGenetic factors

•• In 50% of Asian people, an inactive geneticIn 50% of Asian people, an inactive genetic variant of one of the aldehyde

variant of one of the aldehyde dehydrogen

dehydrogenase isoforms (ALDH-2) ase isoforms (ALDH-2) isis expressed;

expressed;

•• These individuals experience a disulfiram-These individuals experience a disulfiram-like reaction after alcohol, and the

like reaction after alcohol, and the incidenceincidence of alcoholism in this group is extremely low of alcoholism in this group is extremely low

(14)

Adverse hea

Adverse health effects

lth effects

•• >3 drinks/day is associated with adverse health effects>3 drinks/day is associated with adverse health effects

•• 1 drink =18 ml of alcohol1 drink =18 ml of alcohol

•• 350ml of beer or 150 ml of wine or 45 ml of spirit350ml of beer or 150 ml of wine or 45 ml of spirit

1. GIT

1. GIT – – peptic ulcer, hyperacidity, nutritional deficiency, peptic ulcer, hyperacidity, nutritional deficiency, pancreatitis

pancreatitis

2. Lowers seizure threshold 2. Lowers seizure threshold 3. Liver disease

(15)

Adverse health

Adverse health effects

effects

•• Abuse Abuse

•• Fetal alcohol syndromeFetal alcohol syndrome •• HTN, HTN, cardiomyopcardiomyopathyathy

•• CNSCNS – – impaired mental and physical impaired mental and physical performance

performance

•• WerWerninickecke’s ’s encencephephaloalopatpathy, hy, KorKorsasakofkoff’sf’s psychosis

(16)

Teratogenic effects Teratogenic effects Fetal alcohol syndrome Fetal alcohol syndrome

Characteristics of fetal alcohol syndrome include: Characteristics of fetal alcohol syndrome include: (1) intrauterine growth retardation,

(1) intrauterine growth retardation, (2)

(2) microcephalymicrocephaly,,

(3) poor coordination, (3) poor coordination,

(4) underdevelopment of mid-facial region (4) underdevelopment of mid-facial region (appearing as a flattened face),

(appearing as a flattened face), (5) minor joint anomalies

(5) minor joint anomalies

(17)

Interactions

•• Anxiolytics, Anxiolytics, antihistamantihistaminics, hyinics, hypnotics- pnotics-marked CNS

marked CNS depressiondepression

•• Sulfonylurea, cefoperazone,Sulfonylurea, cefoperazone,

metronidazole-Disulfiram like reaction metronidazole-Disulfiram like reaction

•• Acute[Enzyme Acute[Enzyme inhibitor][Chinhibitor][Chronic induronic inducer- cer-Pmol?]

(18)

Therapeutic Uses

TOPICAL TOPICAL • • AntisepticAntiseptic •• CounterirritantCounterirritant

•• Prevent bedsoresPrevent bedsores

•• To reduce body temp???To reduce body temp???

SYSTEMIC SYSTEMIC

•

• Trigeminal neuralgia (to destroy painful nerves)Trigeminal neuralgia (to destroy painful nerves)

•• Carminative and appetizerCarminative and appetizer •

• Treat Methanol poisoningTreat Methanol poisoning

(19)

Contraindication

•• Peptic ulcerPeptic ulcer •• EpilepticsEpileptics

•• Liver diseaseLiver disease •• Pregnancy-

Pregnancy-a.

a. MoModederarate te drdrininkiking-ng-fefetatal l sysyndndroromemess b.

(20)

Acute Ethanol In

Acute Ethanol Intoxication

toxication

•• Occurs from consumption of large quantities by naive individualsOccurs from consumption of large quantities by naive individuals Degree of intoxication depends on:

Degree of intoxication depends on:

1.

1. BloBlood ethod ethanoanol concel concentrntratiation (BAon (BAC)C) 2.

2. How fHow fast tast the blhe blood ood ethanethanol lol level evel risesrises 3.

3. How lHow long ong the Bthe BAC iAC is mas maintintainaineded

Other factors are:

Drinking patterns, Absorptive surface, other medications Drinking patterns, Absorptive surface, other medications

(21)

Acute Etha

Acute Ethanol

nol Intoxication…..

Intoxication…..

•

• Acute Effects: Acute Effects: Vasodilation, TachycardiaVasodilation, Tachycardia G.I. Irritation, respiratory depression

G.I. Irritation, respiratory depression •

• Management:Management: Prevention of respiratory depression;Prevention of respiratory depression; aspiration of vomitus

aspiration of vomitus

•• Treatment of: Hypoglycemia & ketosis with glucoseTreatment of: Hypoglycemia & ketosis with glucose •• Treatment of dehydration with electrolytesTreatment of dehydration with electrolytes

(22)

Alcoholis

Alcoholism & Treatme

m & Treatment

nt

•• Chronic alcohol use (alcoholism) results in CNS adaptations calledChronic alcohol use (alcoholism) results in CNS adaptations called Tolerance and Physical dependence

Tolerance and Physical dependence

•• Withdrawal symptoms during abstinence from alcohol includeWithdrawal symptoms during abstinence from alcohol include delirium tremens, convulsion, seizure, tremors and nausea delirium tremens, convulsion, seizure, tremors and nausea

TREATMENT / DETOXIFICATION

•• Substitution of a long acting sedative/hypnotic drug for ethanol, i.e.Substitution of a long acting sedative/hypnotic drug for ethanol, i.e. Benzodiazepine or Oxazepam

Benzodiazepine or Oxazepam

•• I.V. infusion of Phenytoin to stop SeizuresI.V. infusion of Phenytoin to stop Seizures •• Disulfiram (250 mg daily)Disulfiram (250 mg daily)

(23)

Treatment of alcoholism

1 1..

Motivated alcoholic and complete abstinence Motivated alcoholic and complete abstinence 2.

2. DisulfiramDisulfiram – – used as a aversion technique in chronic used as a aversion technique in chronic alcoholics

alcoholics 3.

3. NaltrexoneNaltrexone – – long acting opioid antagonist - long acting opioid antagonist - ↓↓ craving for craving for alcohol and prevent relapse

alcohol and prevent relapse 4.

4. Acamprosate Acamprosate ; Complex receptor action[GABA & NMDA] ; Complex receptor action[GABA & NMDA]

–

(24)

Disulfiram

•• Inhibits ALDH activity - blood acetaldehyde concentration rise to 5Inhibits ALDH activity - blood acetaldehyde concentration rise to 5 to 10 times

to 10 times

•• Ingestion of alcohol by individuals pretreated with disulfiram - riseIngestion of alcohol by individuals pretreated with disulfiram - rise to marked signs and symptoms of acetaldehyde poisoning.

to marked signs and symptoms of acetaldehyde poisoning. •• Face feels hot , flushingFace feels hot , flushing

•• Throbbing ache in the head and neck, Respiratory difficulties, Throbbing ache in the head and neck, Respiratory difficulties, nausea, copious vomiting, sweating, thirst, chest pain,

nausea, copious vomiting, sweating, thirst, chest pain,

hypotension, marked uneasiness, weakness, vertigo, blurred hypotension, marked uneasiness, weakness, vertigo, blurred vision, and confusion

vision, and confusion A/E

(25)

Methyl alcohol

(Methanol/Wood alcohol)

•• Metabolized to formaldehyde and formic acidMetabolized to formaldehyde and formic acid •• CNS depressantCNS depressant

•• Formic acid is responsible for toxic effectFormic acid is responsible for toxic effect •• ManifestationManifestation – – vomiting, headache, vomiting, headache,

epigastric pain, dyspnoea, hypotension, epigastric pain, dyspnoea, hypotension, acidosis,

acidosis, retinal damageretinal damage, death, death

Leucovorin Leucovorin

(26)

Methanol-poisoning

Leucovorin Leucovorin

(27)

Treatment

•• Protect the eyes from lightProtect the eyes from light

•• Gastric lavage with sodium bicarbonateGastric lavage with sodium bicarbonate

•• IV sodium bicarbonate -IV sodium bicarbonate - ↓retinal damage by↓retinal damage by decreasing acidosis.

decreasing acidosis.

•• Ethanol to saturate alcohol dehydrogenaseEthanol to saturate alcohol dehydrogenase enzyme

enzyme

•• FomepizoleFomepizole – – specific inhibitor of alcohol specific inhibitor of alcohol dehydrogenase

dehydrogenase – – retards methanol metabolism retards methanol metabolism [Also used in ethylene glycol poisoning]

(28)

Summary

•• Actions-CNS,CVS,LOC Actions-CNS,CVS,LOCAL,AL, KIDNEY,STOMACH

KIDNEY,STOMACH

•• PK-Zero order and metabolismPK-Zero order and metabolism •• ADEs-peptic ADEs-peptic ulcer,ulcer,

cirrhosis,CNS,cardiomyopathy, psychosis cirrhosis,CNS,cardiomyopathy, psychosis •• DIs---Disulfiram like DIs---Disulfiram like reactionsreactions

•• UsesUses