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PDA Block 3 > Intro to Neuropsychopharmacology Part 2 > Flashcards

Intro to Neuropsychopharmacology Part 2 Flashcards

1
Q

Antimanic Drugs

A

Lithium

Valproic Acid

Divalproex

Carbamazepine

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2
Q

Antianxiety agents, Hypnotics, and Muscle Relaxants

A
  • Alprazolam
  • Buspirone
  • Chloral Hydrate
  • Diazepam
  • Flumanzenil
  • Flurazepam
  • Lorazepam
  • Pentobarbital
  • Zolpidem

Muscle Relaxants

  • Baclofen
  • Tizanidine
  • (Diazepam)
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3
Q

Lithium Mechanism of Action

A

Inhibits the recycling of inositol - Impacts IP3 and DAG second messenger system

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4
Q

Lithium Pharmacokinetics

A

Readily Absorbed after oral administration

Eliminated in urine approximately 95%

Sodium levels effect lithium excretion and retention

Narrow therapeutic window (.6 - 1.2 m Eq/l)

Interactions with ACE inhibitors and angiotensin II receptor blockers

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5
Q

Toxic Reactions and side Effects to Lithium

A
  1. Fatigue
  2. Tremor
  3. GI symptoms
  4. Goiter
  5. Slurred Speech and Ataxia
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6
Q

Lithium should be used with caution in ______ _______

A

Pregnant women

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7
Q

Serious toxicity to Lithium

A

Plasma levels about 2mEq/L

  1. Impaired consiousness
  2. Rigidity and hyperactive deep reflexes
  3. Coma
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8
Q

Therapeutic uses of lithium

A

Manic episodes and to prevent recurrences of bipolar depression and mania

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9
Q

Alternatives to Lithium and their mechanism of action

A

Carbamazepine, divaloproex (Valproic acid)

  • Alters ion conductances. Use dependent effect on Na+ channels
  • Inhibits the generation of repetitive action potentials
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10
Q

Carbamazepine

Mechanism of Action:

Pharmacokinetics:

A

Mechanism of Action: Blocks sodium channels at therapeutic concentration.

Pharmacokinetics: Unpredictable absorption; hepatic enzyme induction; toxicity is dose-related

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11
Q

Carbamazepine Toxicity

A
  1. Diplopia and ataxia
  2. G.I. upset
  3. Drowsiness
  4. Rare Blood dyscrasias
  5. Teratogen - increased incidence of spinal bifida
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12
Q

Valproic Acid and Divalproex

Mechanism of Action:

Pharmacokinetics:

A
  • Mechanism of Action
    • Blocks repetitive neuronal firing
    • May reduce T-type Ca++ currents
    • Increases GABA concentration
  • Pharmacokinetics
    • Well absorbed orally
    • Bound to plasma protein
    • Distributes in extracellular fluid
    • Inhibits metabolism of Phenyoin and Carbamazepine
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13
Q

Side Effects and Toxicity of Valproic Acid

A
  1. GI upset
  2. Weight gain, hair loss
  3. Idiosyncratic hepatotoxicity
  4. Teratogenicity - Spina Bifida
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14
Q

What is Anxiety?

A

Anxiety symptoms are among the most common that are presented to family doctors and specialists. It has been estimated that from 4 - 8% of the general population has at some time had an anxiety disorder

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15
Q

Sleep and Insomnia

A

Sleep is a normal and reversible physiological state. Insomnia is a term for disorders of initiating and maintaing sleep

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16
Q

Neurochemistry of Sleep

A
  1. Slow wave sleep - Serotonin
  2. REM sleep - Norepinephrine
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17
Q

Benzodiazepines and barbituates: Mechanism of Action

A

Act at sites on the GABA receptor-chloride ion channel complex

GABA localization - Substantia Niagra, Globus Pallidus, Hippocampus

Limbic Structures - Amygdala, Hypothalamus, Spinal Cord

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18
Q

On the GABA receptor, GABA binding increases ________ conductance

19
Q

Benzodiazapine Receptor

A

Found on GABA receptor-chloride channel complex

  1. Enhances action of GABA
  2. Increases frequency of GABA induced chloride channel openings
  3. Separate from barbiturate site
  4. There are also pure antagonists (Flumazenil) and inverse agonist compoundst active at receptor
20
Q

Buspirone

A
  1. Partial agonist at 5-HT1A receptors - opens K+ channel
  2. Also binds to dopamine-D2 receptors
21
Q

Alprazolam

CNS Effects:

Mechanism:

Uses:

Duration:

A

CNS Effects: Forebrain depression; Dependence

Mechanism: GABA enhancement

Uses: Anxiolytic, antipanic

Duration: Short

22
Q

Diazepam

CNS Effects:

Mechanism:

Uses:

Duration:

A

CNS Effects: Broad CNS Depression; Dependence

Mechanism: GABA enhancement

Uses: Anxiolytic, sedative, muscle relaxant

Duration: Long

23
Q

Buspirone

CNS Effects:

Mechanism:

Uses:

Duration:

A

CNS Effects: Little Sedation; No dependence

Mechanism: 5-HT effect

Uses: Amxiolytic

Duration: Delayed Onset

24
Q

What drugs are used as hypnotics

A

Flurazepam (primarily)

Lorazepam

25
Benzodiazapines - Pharmacokinetcs and Metabolism
1. Relative lipophilicity 2. Rate of absorption is variable between compounds 3. Plasma protein binding - 70-97% 4. Lipophilicity determines rate of entry into CNS 5. The duration of action of a single dose is related to redistribution from CNS 6. Lorazpam does not form an active metbolite
26
Benzodiazapines pharmacological effects
1. Decrease of anxiety 2. Sedation 3. Hypnosis 4. Muscle Relaxation (**Diazapam)** 5. Anterograde amnesia - IV administration 6. Anticonvulsant action 7. Cardiovascular and respiratory actions - minimal at therapeutic doses
27
Drug Interactions with Benzodiazepines
1. Produce additive CNS depression with most other depressant drugs such as ethanol, other sedative hypnotics and sedating antihistamiens 2. Drugs that affect hepatic metabolism
28
Clinical uses of Benzodiazepines
* Anxiety states * Generalized anxiety disorder * Panic disorder - **alprazolam** * **​**​Sleep disorders * Muscle relaxant * Seizure treatment * Intravenous sedation and anesthesia * Alcohol withdrawal * Acute manic episodes
29
Benzodiazepine tolerance, depndence and abuse
Dependence and withdrawal - signs include anxiety, insomnia, irritability, headache, hallucinations and seizures Treatment of abuse - Gradual dose reduction. Switch to longer acting drugs
30
Buspirone
An azaspirodecanedione compound that is neither chemically nor pharmacologically related to benzodiazepines
31
Buspirone characteristics
1. High affinity for 5-HT1A receptors - partial agonist 2. Elimination half life - 2-11 hours 3. Less sedating than benzodiazepines 4. No cross tolerance with benzodiazepines 5. Does not potentiate other sedative hypnotics and depressants 6. Used in the treatment of generalized anxiety syndrome
32
Other treatments of anxiety
SSRIs ß-blockers - performance anxiety Rarely - other sedatives
33
Treatment of sleep disorders
Sedatice Hypnotic drugs are an effective short-term treatment for insomnia - long term effectiveness is questionable
34
Effects of benzodiazepines on sleep and adverse effects
* Effects on sleep * Decreased latency to sleep * Increases in stage 1 and 2 sleep; decreased time in stagge 3 and 4 and REM sleep * Rebound insomnia upon withdrawal * Adverse effects * Daytime sedation * Ataxia * Rebound insomnia * Tolerance and dependence * Occaisonal idiosyncratic excitement and stimulation
35
**Zolpidem** characteristics
Imidazopyridine derivative that binds to benzodiazepine receptors. Less disruption of sleep architecture 1. Binds to Omega-1 BDZ receptor 2. Antagonized by Flumazenil 3. Relative lack of muscle relaxant or anxiolytic effects 4. A longer acting controlled release form is now available 5. Dose reduction to prevent daytime drowsiness is now required by FDA
36
Barbituates
Among the earliest sedative hypnotic pharmaceuticals used. Currently their use has been supplanted by the much safer benzodiazepines except in some special situations
37
Barbiturates: Chemistry and Pharmacokinetics
* Derivatives of barbituric acid * They are weak acids and salts of the compounds are formed * Readily absorbed and distributed into all tissues and body fluids * Highly lipid soluble compounds - distribute rapidly to the brain and redistribute to depot fat to terminate their action * Can induce their own metabolism and that of other drugs
38
Barbiturates adverse effects
1. General CNS depression (Sedation, hypnotic action, anesthesia) 2. Anticonvulsant 3. Respiratory Depression 4. Tolerance 5. Physical Dependence 6. Acute poisoning
39
Barbiturates Drug Interactions: Clinical Uses:
Drug Interactions: Additive with other CNS depressants; Drugs that affect microsomal drug metabolism Clinical Uses: Hypnotic (**Pentobarbital)**; Anticonvulsant; Induction of Anesthesia
40
**Chloral Hydrate**
Aldehyde hydrate with pungent taste and somewhat caustic taste 1. Metabolized to trichloroethanol which is the active form of the drug 2. Pharmacology similar to barbiturates 3. Less effects on stages of sleep than benzodiazepines and barbiturates
41
Drugs used to reduce muscle tone associated with spasticity related to multiple sclerosis injuries and other muscular skeletal disorders:
Baclofen Tizanidine Diazepam
42
Baclofen
* GABA - mimetic agent that works at GABAB receptors. This results in hyperpolarization causing presynaptic inhibition. * Decreased release of excitatory transmitters such as glutamate * At least as effective as diazepam in reducing spasticity and produces much less sedation
43
Tizanidine
An α2 adrenergic agonist that is related to clonidine * May have simila efficacy to diazepam and baclofen in relieving muscle spasm * Side effects include drowsiness, hypotension, dry mouth and asthenia
44
Generalized Anxiety Disorder
* Generalized persistent anxiety for at least 1 month duration * Absence of symptoms and patterns that characterize other anxiety disorders such as phobias, panic attacks, or OCD * Apprehensive expectation with worry and fear and anticipation of misfortune to self and others

PDA Block 3 (16 decks)

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