Pharm: CNS Drugs Flashcards
Long acting benzodiazepines preferred in treating alcohol withdrawal
Diazepam
Chlordiazepoxide
Triad of Wernicke-Korsakoff syndrome
Ataxia
Confusion
Paralysis of extra ocular muscles
Alcohol blood level associated with:
- Impairment of driving ability
- Gross drunkenness
- Loss of consciousness, coma
- Death
- 60-80 mg/dL
- 120-160
- 300
- 500
Drinking antifreeze leads to severe acidosis and renal damage.
- What is in antifreeze?
- What is its toxic metabolite?
- Initial treatment?
- Ethylene glycol
- Oxalic acid
- Fomepizole, ethanol
Inhibitors of aldehyde dehydrogenase
Disulfiram
Metronidazole
Oral hypoglycemics
Cephalosporins (some)
What are the teratogenic effects caused by
Carbamazepine
Valproic acid
Phenytoin
Carbamazepine: cranio facial abnormalities
Valproic acid: NTD
Phenytoin: Fetal hydantoin syndrome
Most anti seizure drugs are metabolized by hepatic enzymes except:
Gabapentin
Vigabatrin
Levetiracetam
Pregabalin
What is the primary action of Gabapentin?
Blockade of T-type Ca channels.
It is a structural analog of GABA but does NOT act in receptors directly.
Drugs of choice for generalized tonic-clonic seizures
Valproic acid
Carbamazepine
Phenytoin
Drugs of choice for partial seizures
Phenytoin
Carbamazepine
Lamotrigine
Drugs of choice for absence seizures
Ethosuximide
VPA
This antiseizure drug is also a first line drug in the treatment of mania
VPA
Drug of choice for trigeminal neuralgia; also an antiseizure drug
Carbamazepine
What are the MOAs of inhaled anesthetics?
- Facilitate GABA-mediated inhibition
- Block brain NMDA receptors
- Block brain ACh-N receptors
What sedative hypnotic may cause acute intermittent porphyria?
Barbiturates
What NMDA glutamate receptor antagonist is used in the treatment of alcoholism?
Acamprosate
What opioid receptor antagonist is used in the treatment of alcoholism?
Naltrexone
Name two drugs used in the treatment of alcoholism
Naltrexone (opioid antagonist)
Acamprosate (NMDA antagonist)
Name two drugs used in smoking cessation.
Varenicline (partial agonist at Nicotinic acetylcholine receptor)
Rimonabant (cannabinoid receptor agonist)
Sedative with the highest lipid solubility.
Thiopental
What are the drugs used for the treatment of methanol OR ethylene glycol poisoning?
Ethanol - competes for oxidation by alcohol dehydrogenase
Fomepizole: slows or prevents oxalic acid formation
Benzodiazepine used in treating bipolar disorder
Clonazepam
Hematologic complication of barbiturates (e.g. thiopental, pentobarbital, phenobarbital)
Acute intermittent porphyria
Anxiolytic without anticonvulsant activities or muscle relaxant property that has minimal abuse liability and tolerance/withdrawal. Also it does not affect driving skills
Buspirone
Mechanism of ethanol tolerance
Primarily CNS adaptation but also…
Induction of cytochrome p450 enzyme synthesis and increased MEOS activity (MEOS is active at BAL > 100 mg/dl)
Most common neurologic effect of alcohol
Peripheral neuropathy
Chronic alcoholism predisposes to infectious pneumonia, what is the usual causative agent?
K. Pneumoniae
Scale used to monitor/assess delirium tremens?
CIWA scale
Antiseizure drug contraindicated in psychotics as it worsens psychosis.
Leviteracetam
Antiepileptic that blocks GABA reuptake by inhibiting the GAT-1 transporter?
Tiagabine
Antiseizure drug known to have cause fetal hydantoin syndrome. What are the features of this disease?
Phenytoin. Fetal hydantoin syndrome: Upturned nose Mild facial hypoplasia Long upper lip with thin vermillion border
Antiseizure drug that only affects calcium channels (T-type) in the thalamus
Ethosuximide
Drug that blocks glutamate NMDA receptors.
Felbamate
Worst side effects of felbamate
Aplastic anemia, hepatic failure
Long acting benzodiazepine commonly used as a date rape drug
Flunitrazepam
Benzodiazepines used in sleeping disorders
Estazolam, flurazepam, triazolam
MOA of ramelteon
Activates melatonin receptors in the suprachiasmatic nuclei of the CNS decreasing the latency of sleep onset.
Fixed capacity rate for ethanol metabolism
7-10 g / hour
BAL of this level is usually lethal
500mg/dL
What changes in the brain are seen in Wernicke-Korsakoff syndrome
hemorrhagic necrosis of the mamillary bodies
Inhibits alcohol dehydrogenase
fomepizole
Treatment of excessive CNS depression due to alcohol
Thiamine administration before IV dextrose
Treatment of Alcohol withdrawal syndrome if with compromised liver function
short acting benzodiazepines (e.g. lorazepam)
Water soluble form of Phenytoin
Fosphenytoin
Tricyclic antidepressant used in treating GTCS and tic doloreaux
Carbamazepine
What anti-seizure drugs are excreted by the kidney unchanged
Gabapentin, pregabalin, vigabatrin, leviteracetam
Anti-epileptic that irreversibly inhibits GABA-transaminase
Vigabatrin
What are the 4 stages of anesthesia?
A Dominatrix likes S & M (S is the stage we like)
1: Analgesia: decreased awareness of pain
2: Disinhibition: delirous, amnesia occurs, irregular respiration and enhanced reflexes
3: Surgical anesthesia: patient is unconscious, (-) pain reflexes
4: Medullary depression: severe respiratory and cardiovascular depression requiring mechanical and pharmacologic support
What makes Nitrous oxide an incomplete anesthetic?
no muscle relaxant component
Inhaled anesthetic with the lowest partition coefficient
Desflurane
Inhaled anesthetic that causes myocardial depression
Enflurane and halothan
Inhaled anesthetic that causes peripheral vasodilation
Isoflurane, desflurane, and sevoflurane
Inhaled anesthetics that sensitive myocardium to arrhythmogenic effects of myocardium
Halothane and isoflurane
Severe side effects of halothane that prompts its disuse in anesthesia
Postoperative hepatitis
Myocardial depression
Cathecolamine Arryhthmogenicity
Additive CNS depression
IV anesthetic that causes dissociative amnesia
Ketamine
Dissociative anesthesia: conscious but with marked catatonia, analgesia, and amnesia.
Also causes emergence delirium
What combination of anesthetics induce Neurolepthanesia?
fentanyl + droperidol and nitrous oxide
Local anesthetic with the shortest half life
Procaine
1-2 min
Local anesthetic with the longest half life
Ropivacaine
4.2 hours
All local anesthetics are vasodilators EXCEPT
Cocaine
Treatment of cardiotoxicity due to bupivacaine
Intralipid
What drug is known to cause severe post-operative respiratory depression?
Midazolam
Mnemonic to help distinguish made from ester LA.
Esters have one i: tetracaine, procaine, etc
Amides have two i’s: bupivacaine, lidocaine, etc
Expected BP in a patient given propofol during induction.
Marked hypotension via decreased peripheral resistance
Nondepolarizing drug with the most rapid onset
Rocuronium (60-120s)
Phases of Depolarizing blocks
Phase 1: depolarization
Phase 2: desensitization
Pathophysiology of malignant hyperthermia
massive calcium release from the sarcoplasmic reticulum of skeletal muscles
Earliest clinical sign: trismus
Earliest finding: Inc. end tidal CO2 volume
Drugs used in lethal injection
Thiopental 5g
Pancuronium 100mg
KCl 100 mEq
Main drug used for acute muscle spasm
Cyclobenzaprine
Which of the following is not a spasmolytic? Diazepam Baclofen Tizanidine Dantrolene Botulinum Gabapentin Pregabalin
All are spasmolytics
Why is carbidopa given with L-dopa?
To prevent peripheral (carbidopa does not cross BBB) conversion of L-dopa to Dopa by DOPA carboxylase.
COMT inhibitor in the CNS? Periphery?
CNS: Tolcapone
Periphery: Entecapone
Muscle relaxant that can be an antidote to strychnine poisoning
Pancuronium
Causes of drug-induced parkinsonism
Typical antipsychotics
Reserpine
MPTP (meperidine analog)
Parkinsonian phenomenon with alternating periods of improved mobility and akinesia occurring over a few days to weeks
On - Off Phenomenon
Tx: apomorphine
Parkinsonian phenomenon with deterioration of drug effect in between doses
Wearing off Phenomenon
Tx: Entecapone
MAOIs that inhibit MAO-B thereby preventing dopamine from being metabolized
Selegiline and rasagiline
What Antiparkinsonian drug causes livedo reticularis?
Amantadine Others: Hydroxyurea Minocycline Gemcitabine Quinidine
Treatment for tremors caused by SABA, TCA, Lithium
propanolol
Treatment for essential tremors
Gabapentin, topiramate
Botox
Treatment for movement disorder secondary to Huntington’s Disease
Reserpine, haloperidol
Treatment for movement disorder due to tourette’s syndrome
Haloperidol
Treatment for Movement disorder due to Wilson’s disease
penicillamine
Treatment for restless leg syndrome
Ropinirole
Typical antipsychotics act on what receptor
D2 receptor
Atypical Antipsychotics act on what receptor
5-HT2 receptor
Blockade of D2 receptors frequently result in these symptoms
Extrapyramidal symptoms
seen especially in fluphenazine
Only antipsychotic that significantly reduces the risk of suicide
Clozapine
SE: Increased risk of agranulocytosis, and seizures
Only antipsychotic approved for use in young patients
Risperidone
Least sedating atypical antipsychotic
Also used for treating acute mania
Little or no tendency to cause weight gain
Aripiprazole
Compared to Typical antipsychotics, patients on atypical antipsychotics experience 2 symptoms less severely
Extrapyramidal symptoms and Hyperprolactinemia
Atypical antipsychotics that cause prolonged QT
Quetiapine and ziprasidone
Primary mood stabilizer in bi-polar disorder
Lithium
SE: tremor, sedation, Nephrogenic DI, bradycardia, teratogen (Ebstein’s anomaly)
Antidepressant also used to help in smoking cessation
Bupropion
Symptoms of Neuroleptic Malignant Syndrome
Treatment?
FEVER Fever Encephalopathy Vitals unstable Elevated CPK Rigidity
Tx: Dantrolene w/ or w/o diphenhydramine
Serotonin Syndrome = Serotonin + _________ (5 drugs in all)
Treatment?
MAOIs, TCAs, Meperidine, MDMA, St. John’s Wort
Tx: Sedation, intubation, andminsitration of cyproheptadine
First line antidepressant
SSRI: fluoxetine
Antidepressants also used in patients with neuropathic pain and fibromyalgia
SNRIs: Venlafaxine, Duloxetine (for DM neuropathy)
Antidepressant class useful in patients with phobias, anxiety, and hypochondriasis
MAOIs: Phenelzine, Selegiline
Signs of Serotonin Syndrome
FAT CHD Fever Agitation Tremor Clonus Hyperreflexia Diaphoresis
5-HT2 antagonists that are used in depression
Trazodone, Nefazodone
SE: priapism (Tra), hepatotoxicity (Nef)
May cause arrhythmias in patients with cardiac disease
Key features in TCA Overdose
3 C’s of TCA Overdose
Coma
Cardiotoxicity
Convulsions
TCA toxicity:
Excessive sedation, sympathomimetic effects, atropine like effects, orthostatic hypotension, tremor, weight gain
Opioid receptors and their prominent functions
mu: inhibition of respiration
delta: development of tolerance
kappa: sedation & with opioids slowed GI transit
What are the three endogenous opioids?
B-endorphin (mu), enkaphalin (delta), dynorphin (kappa)
Full agonists
morphine, methadone, meperidine, fentanyl, levorphanol, heroin
Systemic antidote for opioid toxicity (except nalbuphine)
Naloxone
Partial Agonists
Codeine, hydrocodone, oxycodone
MOA of tramadol
In what subset of patients is tramadol contraindicated?
Weak agonist of the mu receptor, inhibits neuronal reuptake of serotonin and norepinephrine
CI: epileptics because tramadol decreases seizure threshold.
Triad of opioid overdose
Pupillary constriction, coma, respiratory depression
3 etiologies of tolerance
metabolic, behavioral, functional
Antidote for amphetamine overdose
No specific antidote. :p
control body temp, prevent arrhythmias and seizures
Effects of chronic amphetamine abuse
Necrotizing arteritis, cerebral hemorrhage and renal failure
What is a “crack lung”
Hemorrhagic alveolitis
What is the teratogenic effect of cocaine?
cystic cortical lesions
What is angel dust?
PCP
SE: horizontal and vertical nystagmus, seizures, marked hypertension
Side effects of MJs
impaired mental concentration, vasodilation, tachycardia, reddened conjunctiva, dry mouth
Hallucinogenic that does not cause dependence
LSD
Which canNOT be antagonized by flumazenil?
Barbiturates
Benzodiazepines
Zolpidem
Barbiturates