Flashcards in Pharm list for Neuro Exam 4 Deck (54)
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1
Chlorpromazine
"Typical" First Generation Anti-Psychotic
Schizophrenia
Blockade of D2 receptors explains most significant pharmacological effects of antipsychotics, though these drugs also blocks other Dopamine 5HT, alpha-1, muscarinic, and histamine receptors
D2>5HT = good against POSITIVE symptoms
ADVERSE: ANS symptoms (Dry mouth, tachycardia, constipation, orthostatic hypotension, etc) and Sedation (Musc and Hist block)
High lipid solubility; passes into CNS and will cross placenta and exert effects on fetus
2
Haloperidol
"Typical" First Generation Anti-Psychotic
Schizophrenia
Treat stimulant-induced psychosis
Blockade of D2 receptors explains most significant pharmacological effects of antipsychotics, though these drugs also blocks other Dopamine 5HT, alpha-1, muscarinic, and histamine receptors
D2>5HT = good against POSITIVE symptoms
ADVERSE: Effects associated with D2 block, including acute dystonia, akathisia, Pseudoparkinsonism, and tardive dyskinesia
High lipid solubility; passes into CNS and will cross placenta and exert effects on fetus
3
Clozapine
"Atypical" Second Generation Anti-Psychotic
Schizophrenia
5HT2A> D2= good against
negative symptoms
Causes less psuedoparkinsonism
ADVERSE: Agranulocytosis, Weight gain, Altered thermoregulation, Phtosensitivity, Lowered seizure threshold Neuroleptic malignant syndrome
High lipid solubility; passes into CNS and will cross placenta and exert effects on fetus
4
Quetiapine
"Atypical" Second Generation Anti-Psychotic
Schizophrenia
Bipolar Depression
5HT2A> D2= good against
negative symptoms
ADVERSE: Weight gain, Altered thermoregulation, Phtosensitivity, Lowered seizure threshold Neuroleptic malignant syndrome
High lipid solubility; passes into CNS and will cross placenta and exert effects on fetus
5
Fluoxetine
Selective Serotonin Reuptake Inhibitors (SSRIs)
Blocks SERT, preventing reuptake of 5HT
Safe, multiple indications: GAD, Social anxiety, Panic, OCD, PTSD, PDD
ADVERSE:
*Acute: diarrhea, nausea, jitters/anxiety, dry mouth, P450 inhibition
*Delayed: sexual side effects, weight gain, cognitive blunting
*Death with overdose is rare; withdrawal=flu-like symptoms
*SSRIs+MAOIs = serotonin syndrome (hyperthermia, rigidity, confusion, HTN)
*Note: Olanzapine+fluoxetine used for Bipolar depression
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Paroxetine
Selective Serotonin Reuptake Inhibitors (SSRIs)
Blocks SERT, preventing reuptake of 5HT
Safe, multiple indications: GAD, Social anxiety, Panic, OCD, PTSD, PDD
ADVERSE:
*Acute: diarrhea, nausea, jitters/anxiety, dry mouth, P450 inhibition
*Delayed: sexual side effects, weight gain, cognitive blunting
*Death with overdose is rare; withdrawal=flu-like symptoms
*SSRIs+MAOIs = serotonin syndrome (hyperthermia, rigidity, confusion, HTN)
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Esciralopram
SSRI
8
Bupropion
Aka Wellbutrin
Nicotinic receptor antagonist/DA reuptake inhibitor
Treatment for:
*Nicotine addiction
*Stimulant (cocaine, meth, nicotine, MDMA) withdrawal
*Depression
*ADHD
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Venlafaxine
Serotonin-Norepinephrine Reuptake Inhibitors (SNRI)
Block NET and SERT, preventing reuptake of Norepi and 5HT
Better tolerated than TCADs, multiple indications
ADVERSE: Sexual side effects, seating, increased diastolic blood pressure, withdrawal syndrome (flu-like, “electric shocks”) from missed doses, More rapid appearance of withdrawal than SSRIs
Specific to Venlafaxine: HTN, anxiety
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Trazadone
Mixed Antidepressant
Insomnia treatment (with non-GABA action)
Complex 5HT mech
Can cause drowsiness
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Amitriptyline
Tricyclic Antidepressants
Block NET and SERT, preventing reuptake of Norepi and 5HT
Time tested, very effective esp. in severe depression, can monitor blood levels
Now SECOND line for depression
Can be used in insomnia
ADVERSE: Hypotension, weight gain, sexual side effects, anticholinergic effects (constipation, dry mouth, etc), sedation, dangerous in overdose (arrhymias, seizures)
12
Phenelzine
Monamine Oxidase Inhibitors
Inhibit MAO, which degrades dopamine
Effective in non-responsive patients, especially atypical depression
ADVERSE: Postural hypotension, weight gain, sexual side effects, anticholinergic effects
Hypertensive crisis—Tyramine reaction (eating foods rich in tyramine such as
sausage, aged cheese, wine can provoke HTN attack)
Seizures, shock, hyperthermia in overdose
13
Lithium carbonate
Best studied, best proven drug for MANIA
Anti-mania, some antidepressant and anti-suicidal. BEST preventative agent for mania
Can be used in bipolar depression, but is least affective out of other agents
Thought to interfere with recycling of phosphoinositides= decrease action of GPCRs; may be involved in genes for growth factors/neuronal plasticity
ADVERSE: Tremor, nausea, diarrhea, taste, thirst, cognitive dulling, narrow therapeutic window, renal effects, diabetes insipidus, hypothyroidism. Diuretics can decrease renal clearance=higher plasma levels of Li
NSAIDs can also increase plasma Li
14
Alpraxolam
Benzodiazepine
CYP450 phase I and II >> renal excretion
Uses: Acute anxiety
15
Flurazepam
Benzodiazepine
Insomnia treatment, second line after "Z" drugs.
Anti-anxiety
Bind alpha 1 AND alpha 2/5 GABA receptors >> sleep AND anxiolysis
Facilitate process of GABA opening, but does NOT initiate chloride current (unlike barbs)
(long): half-life=75-90 hrs with active metabolite
ADVERSE: can accumulate due to impaired hepatic clearance, leading to daytime sedation/overdose. BLACK BOX: strange sleep behavior / severe allergic rxns Combined CNS depression (i.e. with EtOH); sedation; tolerance Dependence (Schedule IV)
Rebound insomnia with abrupt discontinuation
Treat toxicity with flumazenil (bdz antagonist)
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Diazepam
Benzodiazepine
Enhance GABA activity
Lipid soluble, can pass into CNS
Metabolized via CYP450, then renal excretion
Treats:
*Seizures; status epilepticus (can develop tolerance)
*Seizures from stimulant overdose
*Anxiety (rapid, can be used prn)
IV anesthesia adjunct for anxiety
Toxicity is common; death from toxicity is NOT
ADDITIVE effects with other CNS depressants
Dependence (Schedule IV)
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Oxazepam
Benzodiazepine
Enhance GABA activity
Lipid soluble, can pass into CNS
NOT P450 metabolized—good for elderly and in liver impairments
Uses:
*Anticonvulsant
*Anxiolytic
*Muscle relaxant
Toxicity is common; death from toxicity is NOT
ADDITIVE effects with other CNS depressants
Dependence (Schedule IV)
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Triazolam
Benzodiazepine
Rapid absorption, can be used prn
Uses:
*Anxiolytic
*Muslce relaxant
Toxicity is common, death from toxicity is NOT. Can have additive effects with other CNS depressants
Dependence (Schedule IV)
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Midazolam
Benzodiazepine
Enhance GABA activity
Lipid soluble, can pass into CNS
CYP450 metabolism then renal excretion
Uses:
*Anticonvulsant
*Anxiolytic
*Muscle relaxant
Toxicity is common; death from toxicity is NOT
ADDITIVE effects with other CNS depressants
Dependence (Schedule IV)
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Lorazepam
Benzodiazepine
Enhance GABA activity
Lipid soluble, can pass into CNS
NOT P450 metabolized—good for elderly and in liver impairments
Uses:
*Anticonvulsant
*Anxiolytic
*Muscle relaxant
Toxicity is common; death from toxicity is NOT
ADDITIVE effects with other CNS depressants
Dependence (Schedule IV)
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Temazepam
Benzodiazepine
Treat insomnia
Bind alpha 1 AND alpha 2/5 GABA receptorssleep AND anxiolysis
Facilitate process of GABA opening, but does NOT initiate chloride current (unlike barbs)
Intermediate half-life=9-13 hrs
BLACK BOX: strange sleep behavior / severe allergic rxns Combined CNS depression (i.e. with EtOH); sedation; tolerance Dependence (Schedule IV)
Rebound insomnia with abrupt discontinuation
Treat toxicity with flumazenil (bdz antagonist)
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Flumazenil
Antagonist at the benzodiazepine binding site, reverses the CNS effects of benzodiazepines
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Zolpidem (Ambien)
"Z drug" of Insomnia treatment; first line treatment!
Bind gamma subunit to facilitate process of GABA opening, but does NOT initiate chloride current (unlike barbs)
Bind alpha 1 GABA receptors >> sleep without anxiolysis
Short half life; good for "I can't fall asleep!"
BLACK BOX warning for all BDZ-site binding GABA agonists >> strange sleep behavior and severe allergic reactions
Schedule IV
Many have some drowsiness, dizziness, headache
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Eszopiclone (Lunesta)
"Z drug" of Insomnia treatment; first line treatment!
Bind gamma subunit to facilitate process of GABA opening, but does NOT initiate chloride current (unlike barbs)
Bind alpha 1 GABA receptors >> sleep without anxiolysis
Longer half life, more for long-term use (little to no tolerance)
BLACK BOX warning for all BDZ-site binding GABA agonists >> strange sleep behavior and severe allergic reactions
Schedule IV
Many have some drowsiness, dizziness, headache
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Zaleplon (Sonata)
"Z drug" of Insomnia treatment; first line treatment!
Bind gamma subunit to facilitate process of GABA opening, but does NOT initiate chloride current (unlike barbs)
Bind alpha 1 GABA receptors >> sleep without anxiolysis
Short half life for duration of 6-8 hours; good for "I can't stay asleep!"
BLACK BOX warning for all BDZ-site binding GABA agonists >> strange sleep behavior and severe allergic reactions
Schedule IV
Many have some drowsiness, dizziness, headache
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Phenobarbital
Barbiturate
Enhance GABA, decrease GLU
Classic CYP450 inducer
Used mostly in neonatal status epilepticus. Sometimes add-on for seizures but sedation limits use
Used to be used as anxiolytic agent, but not really anymore because abuse potential
ADVERSE: CYP450 = DDIs, Sedation, irritability, interferes with learning
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Ramelteon
Insomnia treatment
Non-GABA Action
Agonist at melatonin MT1 (induce sleepiness) and MT2 receptors (regulation
of circadian rhythms) in suprachiasmatic nucleus of hypothalamus. Decreases mean latency to sleep.
ADVERSE: Dizziness, somnolence, fatigue, nausea; 5% incidence or less.
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Diphenhydramine
Antihistamines
H1 histamine and muscarinic antagonist
May be effective in short term treatment of insomnia
Heavily advertised but NOT recommended
Antimuscarinic effects can be troublesome in elderly
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Cocaine
Stimulant
DAT (+SERT, NET)
Toxicity=sympathetic sx (high BP, high temp, sweating)
Treat with supportive measures (ventilation, lavage, etc)
Treat seizures with Diazepam
Treat high BP (DBP>120) with phentolamine DON’T use beta-blockers (unopposed alpha-stimulation)
Treat psychosis with haloperidol
Withdrawal is generally mild (mostly craving, depression, sleepy). Treat with TCADs, bupropion
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Amphetamine
1. Stimulant (think cocaine)
DAT (+SERT, NET)
Can stimulate psychosis
Amphetamine salts = Adderall = ADHD tx
2. "ampehtamine-like" Hallucinogen
5HT-2A receptor (Gq) partial agonist
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Methamphetamine
Stimulant
DAT (+SERT, NET)
Toxicity=sympathetic sx (high BP, high temp, sweating)
Treat with supportive measures (ventilation, lavage, etc)
Treat seizures with Diazepam
Treat high BP (DBP>120) with phentolamine DON’T use beta-blockers (unopposed alpha-stimulation)
Treat psychosis with haloperidol
Withdrawal is mild (craving, depression, sleepy)
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Nicotine
Stimulant
Nicotinic Receptor
Toxicity usually due to accidental ingestion (i.e. of tobacco products (kids), of nicotine insecticides)
Toxicity=nausea, vomiting, stomach pain, salivation, diarrhea, headacheprogress to hypotension, convulsions, resp failure
Treat with supportive measures (ventilation, lavage, etc)
Individual with impaired nicotine metabolism=protection=less likely to become addicted to cigarettes
Increased use in anxiety, VERY common in Schizophrenia
Withdrawal: irritable, anxiety, depression, restless, increased appetite. Treat with nicotine replacement therapy like bupropion
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Alcohol
CNS depressant
Increase GABA-A, decrease NMDA
Withdrawal:
Increased DTR (deep tendon reflex), BP and pulse
Seizures (1-2 days)
Delirium Tremors (2-5 days)
Treatment Meds:
Disulfiram (inhibits acetaldehyde dehydrogenase)
Naltrexone: opioid antagonist
Acamprosate (GABA antagonist)
NADH is produced via ETOH metabolism, which depletes the NAD required for oxidative reactions Leads to increased blood lactate (acidosis), increased Mg excretion (convulsions), decreased uric acid excretion (gout attack), increase acetyl CoA (inc fatty acid synthesis and decrease fat breakdown= fatty liver), decrease krebs=decreased gluconeogenesis (hypoglycemia)
Increased use in anxiety
3rd leading cause of death
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Barbiturates
CNS Depressant
Increase GABA-A, decrease NMDA
Act via prolonging GABA channel chloride effect even in absence of GABA (at high concentrations) and decreasing Glutamate
Toxicity: respiratory depression, hypotension, coma, death
*High tolerance*
Withdrawal carries significant risk of morbidity/mortality: treat with reduced dose or substitution therapy and monitor for seizures
**Classic inducers of CYP450**
Uses: Not often used in anxiety anymore, Insomnia,
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Benzodiazepines
CNS Depressant
Increase GABA-A only
Bind alpha 1 AND alpha 2/5 GABA receptors >> sleep AND anxiolysis
Facilitate process of GABA opening, but does NOT initiate chloride current
Toxicity: respiratory depression, hypotension, coma, death
Benzo antagonist: flumazenil
Withdrawal carries significant risk of morbidity/mortality: treat with reduced dose or substitution therapy and monitor for seizures. Delirium Tremors. Increased DTR, BP and Pulse
Uses:
Panic Disorder, GAD, Social Phobia, Anxiolytic agent, Insomnia medication, Absence seizures
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Heroin
Mu-opioid receptor (Gi/o) agonists
Acute toxicity= coma, respiratory depression, pin-point pupils
Tolerance develops to most opioids (not equally for all systems i.e. develop little tolerance to constipation) Dependence develops rapidly; withdrawal sx can be intense but are not medically dangerous
Withdrawal treatment: clonidine (for symp sx); methadone (to alleviate sx), buprenophine (partial agonist)
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Marijuana
B-1 receptor (Gi/o) agonist
Intoxication: Slowed time, decreased coordination, euphoria.
Toxicity: severe overdose is rare, but can have paranoia, memory impairment, tremors, high HR, dec. strength and coordination>> should not drive
Can exacerbate sx of existing psychotic illness Treat with supportive measures
ADVERSE: Long-term use can cause cognitive impairment, “amotivational syndrome,” pulm problems (COPD, laryngitis, pharyngitis)
Tolerance develops and disappears rapidly; high potential for dependence
Mild withdrawal=sleep issues, anorexia, irritability, cravings
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Methadone
Opiod
Mu-opioid receptor (Gi/o) agonists
Use in opiod withdrawal to alleviate sx
Acute toxicity= coma, respiratory depression, pin-point pupils
Treat toxicity with naloxone
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Buprenorphrine
Treatment for Opiod addiction
Partial agonist at mu opioid receptors that produces minimal withdrawal symptoms, has a low potential for overdose toxicity, a long duration of action, and will block the acute reinforcing effects of heroin. Do not experience the ups and downs of heroin
and drug craving diminishes and may disappear
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Clonidine
Alpha Agonists
Uses:
*ADHD treatment
*Opiod withdrawal
*Alcohol withdrawal
In treating withdrawal: will alleviate symptoms of sympathetic nervous system overactivity (nausea /vomiting, cramps, sweating, tachycardia, and increased blood pressure) that occur during acute
withdrawal
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Disulfiram
Inhibits acetaldehyde dehydrogenase
Results in 5-10 fold increase in acetaldehyde levels (nausea/vomiting, respiratory and cardiovascular collapse, convulsions)
EtOH sensitizing drug
Alcohol addiction treatment
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Naltrexone
Opioid antagonist
Medication for Alcohol and Opiod addiction
Alcohol: Shown to reduce alcohol craving, consumption, and relapse rates when used in combination with psychotherapy
Opiods: block reinforcing actions of
heroin but has no effect on craving or the PWS
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d-Ampethamine
x
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Methylphenidate
Stimulant
Aka Ritalin
Treatment for ADHD
Block reuptake pump and/or increase release of norepinephrine, but these drugs also block dopamine reuptake and/or increase dopamine release, leading to high abuse potential
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Nitrous oxide
Volatile Anesthetics
Only true gas (other are volatile liquids); MAC is 105% so can’t be sued as a sole anesthetic (combine with barb+opioid)
Concentration effect: because of high inspired %, uptake rate is faster than predicted
Diffusion hypoxia: when admin is terminated, large volume of nitrous oxide leaves blood and expands lungsdiutes alveolar O2 >> hypoxia
Second gas effect: if combined with another gas, the huge uptake of rate of nitrous oxide also pulls second gas, so second gas has faster uptake than
expected
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Halothane
Volatile Anesthetics
fluorinated hydrocarbon
Highly potent, poor analgesic (used to be widely used, not so much anymore)
ADVERSE: Respiratory and cardiovascular failure (arrhythmias), Hepatotoxic (1/10,000 have fever/anorexia/nausea 2-5 days later and 50% of these patients die; repeated exposure significantly increases risk)
Malignant hyperthermia (occurs with most volatile GAs): muscle rigidity and fever (due to mutation in RyR)
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Dantrolene
Causes relaxation by blocking Ca2+ release via the ryanodine receptor
Treatment for malignant hypothermia (plus an ice bath)
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Phenytoin
Inhibit VSSC (Na channel) in use-dependent manner; suppress repetitive APs
For partial seizures and gen tonic-clonic
Fosphenytoin (water soluble pro drug) for
active seizures
NO LONGER FIRST LINE b/c of variable
kinetics and availability of better drugs
ADVERSE: Strong P450 inducer!
Nystagmus, diplopia, ataxia, sedation, rash, gingival hyperplasia. Long term=osteomalacia/peripheral neuropath
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Carbamazepine
Inhibit VSSC (Na channel) in use-dependent manner; suppress repetitive APs
Drug of choice for partial seizures
Often tried first for generalized tonic-clonic
ADVERSE: P450 inducer. Can cause Diplopia, ataxia, nausea/vomiting, drowiness, occasionally Hypnatremia, Risk of Steven-Johnson syndrome
50
Levetiracetam
Treats tonic-clonic seizures, Atypical Absence seizures, Atonic or Myoclonic seizures
Binds to and inhibits function of synaptic vesicle protein SV2A in Ca++-
mediated neurotransmitter release. Relation to antiseizure action is uncertain
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Valproate
Treats tonic-clonic seizures and Atypical Absence seizures
Blocks VSCC
Increases levels of other anti-seizure drug, Lamotrigine
Risk of birth defects; mothers need to take higher doses of folic acid
52
Divalproex
Anti-maniac, Anti-seizures
Mechanism of Action: Unclear, but probably involves some potentiation of GABA function (weak effect on GABA-transaminase) and effects on membrane excitability (similar to phenytoin). Limits activity of Ttype
Ca++-channels.
ADVERSE: Not proven as preventative agent, weight gain, sedation, “perming effect”—hair gets frizzy and/or falls out
53
Ethosuximide
Anti-seizure Drug
Inhibit low-threshold T-type Ca channel
Complete oral absorption
CYP3A4 metabolized
Drug of choice for ABSENCE SEIZURES
ADVERSE: CYP3A4 inducing/inhibiting DDIs
GI upset (dose-dependent); some HA, dizziness
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