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Therapeutics > Exam 5 lecture 8 > Flashcards

Exam 5 lecture 8 Flashcards

1
Q

What are delusions

A

Delusions are fixed false beliefs unresponsive to logic. Paranoia is a common manifestation. Paranoia is a common manifestation.

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2
Q

Whar are hallucinations

A

False perception arising from internal stimuli
Creates false reality

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3
Q

What are illusions

A

Misperception of external stimuli
Distorts reality

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4
Q

What are the different typs of psychadelics?

A

Classical psychadelics (derivatives of tyramine and phenethylamine)
Dissociative psychadelics (Phencycladine, ketamine, muscimol)

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5
Q

What are some drugs that are derivatives of phenethylamine

A

MDMA
Mescaline
MDA

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6
Q

What are some drugs that are derivatives of tryptamine

A

LSD, DMT, Ibogaine, 5-MeO- DiPT

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7
Q

What are some naturally occuring psychadelic drugs

A
  • dimethyl triptamine (DMT)
    ayahuasca leaves

-5-me ODMT
colorado river toad

-Psilocybin
Mushrooms

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8
Q

Mescaline combines mechanism of what two drugs

A

MDMA and LSD

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9
Q

Phenethylamine MOA

A

Amphetamine like (increases release of 5HT> Da)

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10
Q

Most classical psychadelics are agonists of

A

5HT-2A receptor

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11
Q

pre treatment of 5HT-2A antagonists has what effect on hallucinogen

A

blocks psychadelic effects (except MDMA)

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12
Q

global integration and psychadelics?

A

psychadelics increase global integration in CNS, increasing interconnectedness of different sites on brain

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13
Q

What are the 3 components of an LSD trip

A
  1. visionary restructuralization (hallucinations)
  2. Oceanic boundlessness (Highly pleaserable state of self dissolution)
  3. anxious-ego dissolution- though disorder leading to unpleasant state (bad trip)
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14
Q

what are the classes of adverse effects associated with psychadelics

A

short term physiologic
acute dysphoric reaction
psychotic reaction

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15
Q

short term physiologic adverse effects of psychadelics

A

tachycardia
hypertension
tremors
dry mouth
nausea
hyperthermia

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16
Q

acute dysphoric reaction adverse effects of psychadelics

A

Terrifying thoughts
Fear of insanity
Fear of losing control
Fear of death

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17
Q

Psychotic reaction adverse effects of psychadelic use

A
  • flashbacks
    -enduring changes in personality
    -exacerbate underlying psychotic disorder
  • instigate psychotic disorder
    -rate of psychosis after LSD
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18
Q

What are some potential uses of psychadelics? What are some short comings of clinical trials?

A

Depression, PTSD, alcohol use disorder, substance use disodrder

potential short comings include- small sample size, lack of inadequate controls, what is proper control group, selection bias

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19
Q

Difference in MOA of classic psychadelics and dissociative psychadelics

A

Dissociative psychadelics act as antagonists of NMDA receptors

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20
Q

What are the two types of glutamate receptors?

A

Ionotropic (iGluR)
Metabotropic (MgluR

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21
Q

What are the names of the ions in ionotropi can metabotropic glutamate receptors

A

Ionotropic- NMDA, AMPA, Kainate (fast acting and excitatory)
Metabotropic- group 1 (slow excitatory), Group 2 and 3 (slow and inhibitory)

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22
Q

are NMDAR pre or post synaptic?

A

post (can also bind glycine)

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23
Q

What are some prominent NMDA receptor antagonists

A

ionotropic glutamate receptor
Ketamine (special K)
Dextromethorphan (DXM)

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24
Q

What are ionotropic glutamate receptors used for?

A

NMDA receptor antagonist used for anesthetic and analgesic effects

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25
Q

Which variant of ketamine is more active (racemic)

A

S

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26
Q

What is dextromethorphan usually abused by? doses for cough suppression vs dosing for high

A

4% of highschoolers

<60 mg are doses for cough suppression
100-600 mg induce hugh

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27
Q

How does phencycladine (PCP) act? side effects?

A

NMDA antagonist more potent than ketamine
also a dopamine D2 receptor agonist

self mutilation could be a side effect

28
Q

Describe the pharmacology of muscimol

A

Agonist of GABAa channels and can also induce dissociative psychadelic effects

29
Q

What are the different ways inhalants can be misused

A

volatile solvents (toulene, glue, kerosene, gasoline)
Aerosol, gases, spray
Nitrates and nitrous oxide
Hydrocarbons and ketones

30
Q

How do alkyl nitrates work and why are they abused?

A

Nitric oxide results in smooth muscle relaxation, commonly sold as poppers

Relaxes anal sphincter and lead to prolonged erections

Highest abuse among gay men

31
Q

State the volatile solvents, what they are and who is more likely to abuse them

A

volatile solvents are liquid at RT and evaporate when exposed to air

Toluene- glue, spray paont
acetone- nail polish remover, rubber cement, model glue
Benzene- clwaning fluids, rubber cements, tire tube repair kit
Butane- hair spray, spray paint, lighters

Highest frequency of use amont adolescents living in isolated communities

32
Q

What is the most characterized of the volatile solvents

A

Toluene

33
Q

List the risks of inhalant abuse

A

asphyxiations- from repeated inhalation, displaces oxygen in lungs
suffocation- from blocking air from re entering lungs
convulsions/seizures- from abnormal electric discharges in brain
coma- brain shutting down almost all vital functions
choking- on vomit
fatal injuries- from operating machinery

34
Q

explain sudden sniffing death syndrome

A

development of fatal arrythmias within minutes of inhalation

35
Q

Where is Alcohol absorbed? When does it peak in body? What does this absorption cause?

A

10% stomach, rest in intestine
peaks in 30-90 minutes (slowed by food)
Alcohol increases acid release (GERD, Ulcers)

36
Q

Why can men handle alc better than women

A

skill diff
(58% water content for men, 48% in women so we dilute it better)

37
Q

Alcohol elimination follows what order kinetics

A

Zero order

38
Q

What are the two enzymes involved in alcohol metabolism

A

Alcohol dehydrogenase (ADH)
Aldehyde dehydrogenase (ALDH)

39
Q

Where is alcohol metabolized? when does microsomal ethanol oxidizing system occur?

A

90% liver

MEOS only at high alcohol concentration

40
Q

What enzyme is involved in MEOS oxidizing alcohol

A

CYP2E1

41
Q

Where is ADH found? What antagonizes ADH? What effect does this antagonization have?

A

ADH is found in liver, brain and stomach (men express higher levels)

Fomepizol (antizol) is an ADH inhibitor
It slows formation of formaldehyde and toxic metabolites so liver has more time to metabolize toxic effects

42
Q

What is aldehyde metabolized by>

A

aldehyde dehydrogenase (ALDH)

43
Q

what are the isoenzymes under ALDH? What are the important for?

A

ALDH1B1 and ALDH2

44
Q

What effect do we see in the real world regarding ALDH2?

A

50% of asians only have ALDH2.

45
Q

Describe heterozygous and homozygous ALDH2

A

heterozygous- reduced metabolic activity, flushing and increased skin temp, CAN STILL CONSUME ALC

homozygous- Deficient in ability to metabolize acetaldehyde, neurotoxic, strong hangover

46
Q

What is an irreversible inhibitor targetting ALDS

A

Disulfram (antabuse)

47
Q

What are some places alcohol acts on in the body?

A

Ligand gated ion channels
Neurotransmitter release

48
Q

What are some ligand gated ion channels that are affected by alcohol

A

GABA a receptors (allosteric activator of inhibitory mechanisms)
NMDA receptor (inhibitor)

49
Q

What are some neurotransmitters released by alcohol

A

Opioids (enkephalins)
increase CNS and blood ACTH levels
Serotonin, norepinephrine

50
Q

What are the pharmacological actions of different levels of alcohol

A

low- CNS stimulation
intermediate- CNS depression
High- coma-death

51
Q

what are the cardiovascular effects induced by alcohol

A

acute use- vasodilation, reduced BP, increased HR
Moderate use- reduced risk of coronary heart disease (increases HDL)
Heavy/chronic use- cardiomyopathy

52
Q

What are some physiological effects of alcohol consumption

A

Thermoregulation- hypothermia
GI effects- EtOH is a secretagogue (increases HCL secretion)

53
Q

Long term adverse effects of alcohol consumption

A

Liver- fatty liver leading to cirrhosis is common among abusers
Cancer- along route of ingestion (mouth, larynx, esophagus, stomach)

54
Q

What are some important drug drug interactions with alcohol

A

CNS depressants
aldehyde dehydrogenase inhibitors
Acetaminophen
Aspirin

55
Q

What are some CNS depressants to be wary of with alcohol

A

Opioids
antipsychotics
sedative/hypnotics

56
Q

What are aldehyde dehydrogenase inhibitors that could interact with alcohol

A

Disulfram
Antimicrobials (metronidazole)
sulfonylureas

57
Q

Why is alcohol use with acetaminophen bad?

A

Increases toxic metabolite (NAPQI)
alcohol upregulates CYP2E1

58
Q

Why is aspirin contraindicated with alcohol

A

Increased GI bleeding risk

59
Q

What to do for acute intoxication management of alcohol

A

Prevent respiratory depression

60
Q

Withdrawal symptoms of alcohol

A

Anxiety, insomnia, seizures (tonic-clonic), delirium tremens

61
Q

What are the FDA approved treatments for alcohol withdrawal

A

Disulfram (antabuse)
Acamprosate
Naltrexone

62
Q

What receptors does disulfram act on? what does it cause

A

Acts as Aldehyde dehydrogenase inhibitor

causes flushing, throbbing headache, N/V, sweating

patients should be alcohol free for 24 hours before starting

63
Q

What receptor does acamprosate act on?

A

NMDA receptor antagonist/GABA agonist

64
Q

What receptor does naltrexone act on

A

Opioid receptor

65
Q

What patients is naltrexone most useful in?

A

patients with an SNP in Mu opioid receptor gene

118G patients respond better to
naltrexone

66
Q

prevalence of 188G

A

most in asians, least in Aa and latino

67
Q

Three important off-label drugs used for treatment of alcoholism? What enzyme do they act on?

A

-Topiramate (Topamax): Inhibits glutamate signaling, enhances
GABA signaling

-Baclofen (Baclofen): Stimulates GABA B receptors

-Varenicline (Chantix): nicotinic acetylcholine receptor partial
agonist

Therapeutics (38 decks)

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