Drugs Flashcards
Short acting benzodiazepines
Oxazepam
Triazolam
Alprazolam (Xanax)
Midazolam (Versed)
More likely to lead to dependence and addiction
Rapidly metabolized by the liver (no active metabolites)
Long acting benzodiazepines
Chlordiazepoxide (Librium)
Diazepam (Valium)
Alcohol withdrawal
8-12 hrs: insomnia, tremulousness, anxiety, autonomic instability
12-48 hrs: seizures, alcoholic hallucinosis
48-96 hrs: DT’s (fever, disorientation, severe agitation)
Benzos = first line therapy for psychomotor agitation caused by alc withdrawal and to prevent progession into seizures/delirium
Long acting benzos like chlordiazepoxide and diazepam are preferred due to self tapering effects (active metabolites are formed) –> smoother course of withdrawal
In pts with cirrhosis or alcoholic hepatitis, active metabolites accumulate due to inability to be cleared by the liver –> short acting benzos preferred in cases of hepatic insufficiency
Benzos
Sedative-hypnotic (anxiety + insomnia)
Increases the FREQUENCY of GABA-A channels opening
IV benzos can treat alcohol withdrawal, status epilepticus, and be used in general anesthesia as well as to induce conscious sedation for minor procedures/surgeries
Treats insomnia but not first line due to side effect of physical dependence
Treats parasomnias in children (sleepwalking, night terrors)
Treats spasticity caused by UMN disorders (MS, stroke, spinal cord trauma, tetanus)
Treats GAD and panic disorder although SSRI’s and SNRI’s are first line
Long term use causes tolerance and therefore increases risk of addiction: downregulation of GABA-A receptor complex –> decreased GABA-A sensitivity –> increase dose to produce same pharmacologic effects
Physical dependence develops as well –> withdrawal similar to alcohol withdrawal
Can also cause anterograde amnesia (useful during conscious sedation)
Elderly patients are more sensitive to the side effects of benzos, including central ataxia (increased risk of falls), somnolence, confusion, disorientation, and paradoxical agitation (increased agitation, confusion, aggression, and disinhibition, typically within an hour of administration)
Should not be co-administered with other CNS depressants like alcohol, barbiturates, first-gen antihistamines, and neuroleptics
ANTIDOTE: flumazenil - reverses benzo induced sedation but precipitates seizures; watchout for precipitation of withdrawal sx in ppl who are dependent
Nonbenzo hypnotics
Zolpidem (Ambien), Zaleplon (Sonata), Eszopiclone (Lunesta)- treats insomnia
binds to same allosteric site on GABA-A as benzos do
but are more specific so they create less anxiolytic effects and are mainly used for insomnia
Zolpidem and Zaleplon have rapid onset of action, short duration of action, and are rapidly metabolized by the liver –> treats sleep onset well but not necessarily sleep maintenance
Eszopiclone - longest half-life (5-7 hrs); effective for both sleep onset and sleep maintenance
Elderly pts more sensitive to side effects (eg cognitive impairment, delirium, central ataxia)
Avoid use with other CNS depressants
Less likely to produce tolerance and less likely to produce physical dependence than benzos. Therefore, less likely to cause withdrawal symptoms and less likely to become addicted
ANTIDOTE: flumazenil
Melatonin, Ramelteon
Melatonin receptor agonist - treats insomnia
MT1 and MT2 melatonin receptors are located in the SCN (suprachiasmatic nucleus) of the thalamus
Ramelteon has few side effects; safe in geriatric patients
Barbiturates
Increases the DURATION of GABA-A channel openings
Longer duration of action compared to benzos –> hangover effects are more common
Exception: IV thiopental is short acting, has rapid onset due to rapid accumulation in brain tissue, and a short duration of action due to drug redistribution from CNS to other tissues; can be used for rapid induction anesthesia
Phenobarbital: IV phenobarb can be used to treat seizures; first-line in neonates but not first-line in adults due to slower onset, longer period of sedation, and more apparent side effects like hypoventilation
Primidone: used to treat seizure and essential tremors
Side effects of barbiturates (half life=75-100 hrs):
- hypotension; profound cardiac and respiratory depression
- severe CNS depression eg coma
- tolerance and physical dependence
- potent inducer of cytochrome P450 system
AVOID in elderly
Avoid use with other CNS suppressants
Opiates
Full mu opioid agonist: fentanyl, morphine
Partial mu opioid agonist: tramadol, buprenorphine, nalbuphine, butorphanol
* if someone who has been on a full agonist is switched to partial, it is just like you them an antagonist –> will precipitate withdrawal symptoms
Full opioid antagonist:
Naloxone; used to reverse acute opioid toxicity –> can precipitate withdrawals
Naltrexone; helps maintain abstinence in addicts and helps reduce cravings for alcohol and nicotine and weight loss
Fentanyl - for post-op and chronic pain
Morphine (derivative: Hydromorphone) - for severe and chronic pain
Tramadol - weak agonist at mu opioid receptor; centrally acting properties are due to block of serotonin and norepi reuptake; used for chronic pain; can cause serotonin syndrome
Codeine - antitussive
Dextromethorphan - antagonizes NMDA receptors as well as opioid agonist - antitussive
Opiates can also be used as antidiarrheals ex) loperamide and diphenoxylate = mu opioid agonist that does not cross the BBB –> no analgesic effects
Side effects: constipation, cough suppression, miosis, sedation, resp depression (dose dependent; can be fatal if used in a patient with COPD/asthma), tolerance/dependence, drowsiness and clouding of judgement (more pronounced in the elderly), biliary colic (contraction of biliary smooth muscle/Sphincter of Oddi –> reflux of biliary and pancreatic juices)
*tolerance does not develop for miosis or constipation
Opiate induced hyperalgesia can occur with chronic use
Withdrawal symptoms: start within 6-10 hours after last dose with peak effects in 36 hours
Rhinorrhea, lacrimation, yawning, hyperventilation, hyperthermia, muscle aches, vomiting, diarrhea, anxiety, midriasis
–> Methadone - long acting opioid used to attenuate withdrawal symptoms; has a long half life like Buprenorphine so withdrawal from it in detox is tolerable
Neonatal abstinence syndrome - due to withdrawal of opiates that were transmitted across the placenta from mom (diarrhea, sweating, sneezing, crying, tachypnea, irritability) –> methadone
SSRI’s
Fluoxetine
Paroxetine
Sertraline
Citalopram
1st line agents for: MDD, GAD, panic disorder, PTSD, OCD, bulimia, social anxiety disorder
Not for acute treatment; takes 1-2 months to achieve treatment
Side effects: SIADH (hyponatremia), sexual dysfunction, weight gain, drowsiness, serotonin syndrome
Withdrawal: flu-like symptoms
SNRI’s
Venlafaxine
Duloxetine
1st line agents for: MDD, GAD, panic disorder, PTSD, OCD, diabetic neuropathy, chronic neuropathic pain, fibromyalgia
Not for acute treatment; takes 1-2 months to achieve treatment
Side effects: HTN, tachycardia, CNS activation such as insomnia and irritability; serotonin syndrome and side effects similar to SSRI’s
Withdrawal: flu-like symptoms
Serotonin syndrome
Hypertension, hyperthermia, autonomic instability, agitation, hyperreflexia, myoclonus
Can occur when SSRI/SNRI’s are combined with other drugs that increase serotonin levels like TCAs or MAO inhibitors
Management: discontinuation of all serotonergic drugs, stabilization of vital signs, and possible administration of serotonin antagonist Cyproheptadine
MAO inhibitors
Tranylcypromine
Phenelzine
Isocarboxazid
Selegiline
Monoamines = serotonin, norepinephrine, and dopamine
Breakdown is inhibited by MAOI’s
2 types of monoamine oxidase: MAO-A and MAO-B
MAO-A targets serotonin, norepinephrine, and dopamine
MAO-B targets dopamine
Most MAOI’s are nonselective and irreversible
Exception: Selegiline is selective for MAO-B - useful in Parkinson’s
Clinical use is limited due to potential lethal in overdose, adverse effects, titration
Use: atypical depression, MDD refractory to other drugs
Side effects: similar to SSRI’s like orthostatic hypotension, weight gain, and sexual dysfunction.
MAOI specific side effects: avoid taking MAOI’s with tyramine containing foods like aged meats, alcoholic beverages, and fermented cheeses (tyramine is normally broken down by MAO-A in the GI tract)
In the presence of MAOI’s, tyramine enters the circulation and acts as a sympathomimetic agent –> HTN, tachycardia, HTN crisis leading to stroke or MI (HTN, blurry vision, diaphoresis)
Phentolamine (nonselective alpha blocker) can be used to manage HTN symptoms of tyramine toxicity
Also associated with serotonin syndrome
Atypical depression
Hyperphagia
Hypersomnia
Leaden paralysis
TCA’s
Imipramine (1') Desipramine (2') Clomipramine (2') Amitriptyline Nortriptyline
Inhibit serotonin and norepinephrine reuptake
Potentially lethal in overdose, adverse effects, interactions with other drugs –> used for refractory depression
Off label uses: chronic neuropathic pain, diabetic neuropathy, migraine ppx, OCD
Side effects: sexual dysfunction, anticholinergic toxicity (dry mouth, constipation, blurred vision, urinary retention - more prominent in 1’ than 2’ TCA’s), antihistamine H1 effects (sedation, increased appetite, weight gain), alpha-1 blockade effects (orthostatic hypotension), fatal cardiac arrhythmia (most common cause of death in overdose; due to blockade of cardiac fast Na channels), wide QRS or QT interval –> torsades, seizures, serotonin syndrome
Relatively contraindicated in elderly patients due to severe anticholinergic and antihistamine effects
*3 C’s of TCA toxicity: cardiac, coma (antihistamines), convulsions
Sodium bicarb treats widened QRS and ventricular arrhythmia caused by TCA overdose
Atypical antidepressants
Bupropion
Mirtazapine
Trazodone
Used in refractory MDD or MDD treated with primary med with too many side effects
Bupropion
Inhibits norepinephrine and dopamine reuptake
NO effect on serotonin
Similar in structure to amphetamines –> CNS activating effects (good for depression with low energy or somnolence)
Does not cause sexual dysfunction –> good for depression with sexual dysfunction
Less likely to cause weight gain –> good for depression with weight gain
Can also be used to treat tobacco dependence
Side effects: seizures (risk is higher in ppl with past hx of seizures and ppl with eating disorders –> bupropion is contraindicated in bulimia, anorexia nervosa)
Mirtazapine
alpha-2 blocker, 5HT-2 and 5HT-3 blocker, H1 blocker
Increases presynaptic release of serotonin and norepinephrine
H1 blocker effects cause sedation which can be used in pts with MDD and insomnia
Does not cause sexual dysfunction
Side effects: sedation, weight gain
Trazodone
Serotonin modulator - antagonizes receptors and inhibits reuptake
Alpha-1 blocker - causes vasodilation –> priapism and orthostatic hypotension
H1 blocker - sedation –> good for MDD with insomnia -
Avoid use in elderly
Can cause sexual dysfunction
Serotonin syndrome
1st Gen Antipsychotics (Typical)
Haloperidol - high potency Fluphenazine - high potency Trifluoperazine - high potency Chlorpromazine - low potency Thioridazine - low potency
D2 blockade in the CNS, specifically the mesolimbic and striatofrontal pathways
High potency agents have higher risk of EPS (acute dystonia, akathisia, drug induced Parkinsonism, tardive dyskinesia - due to D2 blockade in nigrostriatal tract) and prolactinemia (due to D2 blockade in tuberoinfundibular tract)
Low potency agents have lower risk of EPS but higher anticholinergic, alpha-adrenergic, and histaminic effects
1st gen antipsychotics have a long half life (highly lipophilic)
Other side effects: neuroleptic malignant syndrome (lead-pipe rigidity, AMS, fever, autonomic instability, rhabdomyolysis), torsades de pointes, can lower the seizure threshold
Chlorpromazine can cause corneal deposits
Thioridazine can cause retinal deposits
–
Many uses:
Schizophrenia - 1st gen antipsychotics are useful for positive sx (hallucinations, delusions, disorganized thinking or behavior) but not negative sx (flat affect, apathy, lack of energy)
Acute psychosis, acute agitation or aggression, Tourette syndrome
2nd Gen Antipsychotics (Atypical)
Quetiapine Olanzapine Risperidone Aripiprazole Ziprasidone Clozapine
D2 blockade in the CNS, specifically the mesolimbic and striatofrontal pathways
Also serotonin blockade (believed this is the reason why there is lower risk of EPS in 2nd gen), H1 blockade (sedation is most prominent with quetiapine and clozapine), alpha-adrenergic blockade, antimuscarinic (most prominent with clozapine although 2nd gen antipsychotics have a lower affinity for muscarinic receptors than first gen)
Other side effects: metabolic syndrome - weight gain, dyslipidemia, hyperglycemia. More prominent in olanzapine and clozapine. Ziprasidone is least associated with these effects
Reduced risk of EPS compared to 1st gen - risperidone has highest risk of EPS
Prolactinemia - risperidone has highest risk
Neuroleptic malignant syndrome
QT prolongation –> torsades
Clozapine can cause neutropenia and agranulocytosis, myocarditis/cardiomyopathy, lower seizure threshold
Many uses:
Schizophrenia - 2nd gen antipsychotics are useful for both positive and negative sx
Treatment resistant MDD, OCD (adjunctive with SSRI’s), Tourette syndrome (risperidone)
Neuroleptic Malignant Syndrome
Tx:
- supportive care and withdrawal of offending medication
- if not responding, give dopaminergic agents that can reverse dopamine blockade (bromocriptine or amantadine)
Dantrolene, a direct-acting muscle relaxant has also been used
MDMA / Ecstasy / Molly
Synthetic amphetamine with mild hallucinogenic properties
Causes an increase in synaptic norepinephrine, dopamine, and serotonin
Enhances euphoria, increases sociability, empathy, and sexual desire
Intoxication: HTN, tachycardia, hyperthermia, serotonin syndrome, hyponatremia, seizure, coma, death, hyperreflexia
Cocaine
Often used in binges, taking the drug repeatedly over a short period to maintain their high
Following abrupt cessation, a crash typically occurs (severe depression with suicidal ideation, psychomotor slowing, fatigue, hypersomnia, increased dreaming, hyperphagia, impaired concentration, intense drug craving)
Acute mania
First-line treatments include antipsychotics, lithium, and anticonvulsant mood stabilizers (eg valproate)
Patients experiencing severe mania with acute agitation commonly receive an antipsychotic alone or in combo with initiation of a mood stabilizer to manage symptoms effectively
Alcohol use disorder
- NALTREXONE (opioid receptor antagonist) - decreases the reinforcing effects of alcohol use; decreases cravings, reduces heavy drinking days, and increases days of abstinence. CAN BE INITIATED WHILE PATIENT IS STILL DRINKING. Contraindicated in patients taking opioids and those with acute hepatitis or liver failure; ok to use in mild liver dysfunction
- ACAMPROSATE (glutamate modulator) - maintains abstinence; INITATED ONCE ABSTINENCE IS ACHIEVED
- DISULFURAM - CANDIDATES MUST BE ABSTINENT AND HIGHLY MOTIVATED
Extrapyramidal symptoms
- Acute dystonia - tx: benztropine or diphenhydramine
- Akathisia - tx: beta blocker or benzodiazepine
- Parkinsonism - tx: benztropine or amantadine
- Tardive dyskinesia - tx: no definitive treatment but clozapine may help
most commonly associated with prolonged use of antipsychotic meds and is typically seen in pts with chronic psychotic disorders. It’s also common for tardive dyskinesia to worsen or first appear following antipsychotic dose reduction or discontinuation. This is due to D2 receptor upregulation supersensitivity resulting from chronic blockade of dopamine receptors. When D2 receptor blockade is reduced, an exaggerated response of the D2 receptor even to low concentrations of dopamine may result in hyperkinetic movements.
