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Therapeutics P2 Winter Semester > PHRM845-FINAL EXAM > Flashcards

PHRM845-FINAL EXAM Flashcards

Pharmacology and pharmacotherapy of alcohol use/abuse

1
Q

Today’s use for alcohol

A

-Fuel
-Chemical processes
-Disinfectant
-Vehicle (ex: almond extract)
-Recreation/social drinking
~Anxiolytic, euphoria, disinhibition
~Alcoholism (10% of the population)

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2
Q

Absorption of alcohol

A

-10% from stomach; 90% from small intestine
-Peak 30-90 minutes
-Limited by gastric emptying
~Slowed by food (eat before drinking; decreases the amount of alcohol that gets to brain)
-Alcohol increases acid release–>GERD/induce ulcers

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3
Q

Distribution of alcohol

A

-Distributed in total body water
~58% in men; 48% in women
~Men dilute alcohol more

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4
Q

Elimination of alcohol
-What kinetic is the elimination?
-Elimination rate is ____
-What is the rate-limiting step?

A

-Follows a zero-order kinetic
-Elimination is at or above 10-20 mg/dL (metabolizing 1-1.5 drinks/hour)
-ADH is the rate-limiting step

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5
Q

Metabolism of alcohol
**2 important steps

A

-90% in the liver
-ADH
-Microsomal ethanol oxidizing system (MEOS)
~Only at high alcohol concentration
~LOW affinity for alcohol
-Aldehyde dehydrogenase (ALDH)–> toxin (makes people sick)

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6
Q

Glucuronidation of alcohol
-What test is used?
-Who is it best suited for?

A

0.5%-EtG test
-Test used to monitor alcohol consumption for days after–too sensitive
-Ethyl glucuronide has a very long half-life
-Not used for drunk driving
-Mainly for high school athletes

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7
Q
  1. Alcohol is metabolized by ____
    -Where is that enzyme found?
    -Do men or women express higher levels?
A

-ADH
-Found in liver, brain, and stomach
-Men express higher levels of gastric ADH which is why they can drink more than women

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8
Q

Fomepizole (Antizole)

A

-ADH inhibitor
-ONLY used for alcohol poisoning
-Alcohol can be used as well to slow toxin metabolites
~Giving more substrate
-Fomepizole slows metabolism of the toxin so the body has more time to deal with it
-Slow formation of formaldehyde and toxic metabolites
-Liver has more time to further metabolize toxic metabolites

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9
Q

Acetaldehyde is metabolized by ____
-Importance of ALDH2 and the possible mutations

A

-Aldehyde dehydrogenase
-ALDH1B1 and ALDH2 are isoenzymes important for alcohol metabolism (50% of Asians only have ALDH2)
-SNP in ALDH2 reduces activity (ALDH22)
-Heterozygous ALDH22 reduces metabolic activity, causes flushing and increased skin temp, but pts can STILL CONSUME ETHANOL Build up more acetaldehyde
-Homozygous ALDH2*2 causes a deficiency int he ability to metabolize acetaldehyde
~Neurotoxic (Pt CANNOT CONSUME ETHANOL)
~Strong “hangover” from acetaldehyde build up
~Also alcoholic neuropathy

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10
Q

Disulfiram (Antabuse)

A

-Irreversible inhibitor of ADH
-Effects persist up to 14 days
-Must avoid meds with alcohol, such as Nyquil

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11
Q

Is tx with disulfiram effective?

A

NO; pts generally are not adherent because it makes them sick

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12
Q

Alcohol MOA

A

-Really “dirty” drug
-Potentiates opioid receptors
-Possibly works on GABA receptor to control DA release
-Possible works on nucleus accumbens

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13
Q

Ligand-gated ion channels that alcohol targets

A

-GABA-A receptors (allosteric activator of inhibitory neurotransmitters–cells become more negative and hyperpolarize)
-NMDA receptor inhibitor
-Alpha7 nicotinic receptors

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14
Q

Neurotransmitter release from alcohol consumption

A

-Opioids (enkephalin–endogenous opioid peptides)
~DA
-Serotonin and NE
-ACh
-Increases CNS and blood ACTH levels

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15
Q

Alcohol has a concentration that is (small/large) at different targets.

A

SMALL; mM unit

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16
Q

Blood alcohol level can be depicted in different ways

A

0.10% is equal to 100 mg/dL or 22 mmol/L of blood alcohol

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17
Q

What is mg%

A

-Milligrams of ethyl alcohol in 100 millilitres (1 dL) or blood
>0.1% = 100 mg/dL = 100 mg%
>USA 80mg% is the legal driving limit
-Independent of behavior tolerance (even if pt drinks all the time and no longer has a change in behavior from drinking, if they blow over 0.8mg%, they will be arrested.

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18
Q

Pharmacological actions of low alcohol levels

A

-Euphoria (warm feeling)
-Disinhibition (30-60 mg/dl)
-Talkative
-Analgesia (60-90 mg/dl)

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19
Q

Pharmacological actions of intermediate levels of alcohol

A

-CNS stimulation (80-120 mg/dL)
~Mood swings (lose volume control: yelling) & aggression
-CNS depression (100-200 mg/dl)
~Slurred speech, ataxia, sedation, loss of motor control, irrational behavior

20
Q

Pharmacological actions of high/fatal levels of alcohol

A

-Coma/death (300-500 mg/dl)
~Respiratory paralysis
~People have survived 1000-1500 mg/dl

21
Q

Acute CV effects induced by alcohol

A

-Vasodilation
~Warm, flush
~Reduced BP
~Increased HR (decreased at high doses)

22
Q

Moderate use CV effects

A

-Reduced risk of coronary disease (increases HDL)
**primarily red wine

23
Q

CV effects from heavy/chronic alcohol use

A

-Affects heart
~Cardiomyopathy
~Arrhythmias (binge drinking)
~HTN (5% of all cases)
~Homeostasis (change in platelets)

24
Q

Physiological effects of alcohol consumptions

A

-Thermoregulation
~Hypothermia (with higher doses)
>Moderate in man
>Possible lethal with cold temp and large dose
-Gastrointestinal
~Alcohol is a secretagogue
>Increases HCl (acid) secretion
>Chronic gastritis in alcoholics
~Appetite stimulant (low dose)
~Appetite depressant (high dose–lots of carbs&cal)

25
Q

Long-term impact of alcohol consumption on liver

A

-Increases fat metabolism (promotes triglyceride synthesis from FFA)
-Fatty liver leading to cirrhosis is common in abusers
-Vitamin deficiencies; glutathione reduced (small intestine damage–>diarrhea)
-Can cause ascites, edema, and effusions

26
Q

Long-term impact of alcohol consumption on blood

A

-Mild anemia
-Gastritis–>chance of blood loss
-Alcohol related folic acid defiency

27
Q

Long-term impact of alcohol consumption on cancer

A

-Liver
-Along route of ingestion (mouth, larynx, esophagus, stomach)
-Interacts with a lot of other carcinogens (ex: tobacco)

28
Q

CNS depressants that interact with alcohol

A

Opioids
Antipsychotics
Anti-histamine
Sedative hypnotics (Z-hypnotics and benzodiazepines)

29
Q

ALDH inhibitors that interact with alcohol

A

Disulfiram
Antimicrobials (metronidazole, cephalosporin)
Sulfonylureas hypoglycemics (Tolbutamide)

30
Q

What is the issue with acetaminophen (Tylenol) and alcohol?

A

-Increases metabolite (NAPQI)
-Alcohol upregulates CYP2E1
-Tx with n-acetylcysteine to detoxify NAPQI

31
Q

Issue with ASA and alcohol consumption

A

Increases ulcers and GI bleeding

32
Q

Alcohol is toxic and ____

A

Teratogenic

33
Q

Acute intoxication management

A

-Prevent respiratory depression
-Prevent aspiration of vomit

34
Q

Teratology of alcohol

A

Fetal alcohol syndrome (FAS)
-Facial dysmorphology
-Low birth weight
-Decreased brain size
-Mental retardation
*Lower testosterone and sperm quality

35
Q

Alcohol abuse and dependence is widespread

A

-1 in 8 US adults meet alcohol use disorder criteria (12.7%)
-Less than 8% got treatment
-88,000 people die from alcohol-related deaths each year which is a BIG problem

36
Q

Sx of alcohol withdrawal

A

-Anxiety
-Insomnia
-Seizures/tonic clonic convulsions
-N/V
-Tactile hallucinations/delirium tremens

37
Q

Tx for alcohol withdrawal

A

-Benzodiazepines
-Phenytoin for seizures (excitatory is more active because GABA is no longer stimulated)
-Electrolytes
-Alpha-2 adrenergic partial agonists
~Clonidine, guanfacine
~Alcohol desensitizes alpha-2 adrengeric receptors
~Withdrawal increases NE response

38
Q

Relapse from alcohol cessation

A

-Cue triggered
~Seeing a glass of alcohol
~Favorite bar
~Mood (stress, anxiety, depression)

39
Q

Disulfiram (Antabuse)

A

-FDA-approved tx for alcoholism
-ALDH inhibitor
-Causes flushing, throbbing, HA, N/V, sweating, hypotension, and confusion
-Pts should be alcohol-free for 24 h before use (Some OTC contain alcohol)
-Aversive tx (build up acetaldehyde and get sick)

40
Q

Acamprosate (Campral)

A

-FDA-approved tx for alcoholism
-NMDA receptor antagonist/GABA agonist
-Reduced relapse and prolong abstinence
-Some of the same activity as alcohol
-Replacement tx

41
Q

Naltrexone (Revia)

A

-FDA-approved tx for alcoholism
-Opioid receptor antagonist
-Prevents relapse and ppl who do relapse are in better control
-Blocks enkephalin binding (drinking does not feel as rewarding)

42
Q

____ is more effective in patients with a SNP in the mu opioid receptor gene

A

Naltrexone
-Alanine118glycine mutation (allows enkephalins to bind more tightly; decreases rewarding effect if their binding is blocked)
~N-terminal tail of mu opioid receptor
~Changes asparagine amino acid–>aspartate (N40D)
~3x higher potency for beta-endorphins
-118G patients respond better to naltrexone
-Highest prevalence in Asians
-Clear indication for precision/personalized medicine

43
Q

Topiramate (Topamax)

A

-Off-label tx for alcoholism
-Inhibits glutamate signaling; enhances GABA signaling
-Similar in MOA to Acamprosate
-Approved for epilepsy and migraine
-Encouraging results in 2 trials for alcoholism

44
Q

Baclofen

A

-Off-label tx for alcoholism
-Stimulates GABA-B receptors
-Approved for tx spasticity
-Reduces anxiety and craving
-High doses reduced drinking in several small trials for alcoholism
-Not better than placebo in double blind trial

45
Q

Varenicline (Chantix)

A

-Nicotinic acetylcholine receptor partial agonist
-Approved for smoking cessation (rewarding behavior)
-Human tests for alcoholism are underway–based on mechanism that alcohol can hit nicotinic receptors

46
Q

Alcoholics anonymous

A

-Originated in 1935
-12-step program
-Spiritual
-Sponser-sponsee
-around 2 million members
-1 yr retention rate is about 33%
-Meds and psychotx

Therapeutics P2 Winter Semester (29 decks)

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