CNS and Anesthesia Flashcards
Triptans
5HT agonists Prevent release of 'inflammatory soup' of prostaglandins, substance P and histamine Drugs: Sumatripan - most common Zolmitriptan Rizatriptan - no nasal spray Naratriptan - longer acting, for recurrence Use: - stop migraines
Dihydroergotamine
Rescue medication and for refractory migraines (with metoclopromide)
Barbiturates
IV anesthetics
Mechanism:
- binds to specific sites on GABA A receptors, enhances affinity of GABA, increases Cl influx
Drugs:
- thiopental
- methohexital
Uses:
- induction of anesthesia
- neuroprotection - treat raised ICP and focal cerebral ischemia
Effects:
CNS
- sedation, anesthesia, not analgesic (anti-analgesic), cerebral vasoconstriction, decrease CMRO2 (EEG can flatline)
- methohexital activates epileptic foci
CV
- peripheral vasodilation, decrease in BP
Respiratory
- respiratory depressant
- decrease ventilatory response to hypercapnea and hypoxia
- inadequate suppression of airway and laryngeal reflexes
Other
- precipitation when mixed with acidic drugs
- pain and tissue injury in paravenous tissue
- pain, vasoconstriction, gangrene if arterial injection cuz alkaline pH
- exacerbation of acute intermittent porphyria - stimulates D-ALA synthetase
Desflurane
Inhaled anesthetic
- immobility
- amnesia
- CNS depression - enhance GABA, block NMDA
- not analgesic
Needs highest concentration to achieve MAC
Least soluble - fast onset/offset
Use:
- gastric bypass, obese pts
- peds tonsillectomy
Pros:
- rapid onset/offset
Cons:
- pungent, expensive, tachycardia
Effects:
- decrease MAP due to decreased TPR - vasodilators
- increased HR
- increase RR, decrease tidal volume (maintain minute ventilation)
- decrease FRC, increase dead space
- increase PaCO2, less responsive to it, lead to apnea
- bronchodilation - good for asthma
- depression of pharyngeal and laryngeal reflexes - can intubate
- cerebral vasodilation - increased CBF and ICP
- decrease CMRO2
- dose dependent EEG depression
- dose related skeletal muscle relaxation
- decreased renal blood flow
- decreased hepatic blood flow
Side effects:
- airway irritant - don’t use for mask induction
- expensive
- may prolong QT
Sevoflurane
Inhaled anesthetic - immobility - amnesia - CNS depression - enhance GABA, block NMDA - not analgesic Most commonly used in OR Medium solublity, medium potency Not expensive Use: - inhaled induction in peds - least noxious and least irritating to airways - quicker adult cases - induction agent Pros: - rapid, pleasant Cons: - emergence delirium Effects: - decrease MAP due to decreased TPR - vasodilators - increased HR after 1 MAC - increase RR, decrease tidal volume (maintain minute ventilation) - decrease FRC, increase dead space - increase PaCO2, less responsive to it, lead to apnea - bronchodilation - good for asthma - depression of pharyngeal and laryngeal reflexes - can intubate - cerebral vasodilation - increased CBF and ICP - decrease CMRO2 - dose dependent EEG depression - dose related skeletal muscle relaxation - decreased renal blood flow - decreased hepatic blood flow Side effects: - nephrotoxic effects - keep flow higher - may prolong QT
Isoflurane
Inhaled anesthetic
- immobility
- amnesia
- CNS depression - enhance GABA, block NMDA
- not analgesic
Needs lowest concentration to achieve MAC - most potent
Most soluble - longer emergence
Most economical
Pros:
- inexpensive, hemodynamic stability
Cons:
- long acting
Use:
- longer cases, especially if pt doesn’t get extubated
Effects:
- decrease MAP due to decreased TPR - vasodilators
- increased HR
- increase RR, decrease tidal volume (maintain minute ventilation)
- decrease FRC, increase dead space
- increase PaCO2, less responsive to it, lead to apnea
- bronchodilation - good for asthma
- depression of pharyngeal and laryngeal reflexes - can intubate
- cerebral vasodilation - increased CBF and ICP
- decrease CMRO2
- dose dependent EEG depression
- dose related skeletal muscle relaxation
- decreased renal blood flow
- decreased hepatic blood flow
Side effects:
- may prolong QT
Nitrous Oxide N2O
Inhaled anesthetic
- immobility
- amnesia
- CNS depression - enhance GABA, block NMDA
- mild analgesic
Cannot achieve 1 MAC
Not expensive
Use:
- in combination with volatile anesthetics
- induction agent
- only use alone to calm kids down before inserting IV
- don’t use in surgeries with air cuz diffuses fast into air filled spaces
- labor analgesia
Pros:
- inexpensive, combined with VA, rapid
Cons:
- not used alone, caution with air spaces
Effects:
- little change in MAP or TPR
- bronchodilation - good for asthma
- depression of pharyngeal and laryngeal reflexes - can intubate
- cerebral vasodilation - increased CBF and ICP
- decrease CMRO2
- dose dependent EEG depression
- dose related skeletal muscle relaxation
- decreased renal blood flow
- decreased hepatic blood flow
Side effects:
- increases nausea/vomit
Benzodiazepines
Sedatives/anxiolytics Highly lipid soluble and protein bound, fast BBB penetration Mechanism: - enhance affinity of GABA receptor for GABA, increase Cl flux; BDZ site on GABA receptor Metabolism - midazolam inactive metabolites; diazepam active metabolites so longer duration and hangover effect Drugs: - Midazolam, Diazepam Uses: - pre-medication - sedate pt, anti-anxiety, amnesia - sedation for short procedures (midazolam) - suppression of seizure activity in status epilepticus Effects: CNS - sedation, hypnosis - anterograde amnesia - anticonvulsant - decrease CMRO2 and CBF - not neuroprotective Respiratory - minimal respiratory depression CV - decrease in TPR and BP - CO not affected, so CV stable Other - pain on injection with diazepam
Propofol
Isopropylphenol IV anesthetic - lecithin and soybean oil - need sterile technique Mechanism: - inhibition of neurotransmission via GABA potentiation - increase Cl current Not analgesic Wake up 8-10 mins after induction bolus due to redistribution Uses: - induction agent - maintenance of anesthesia - sedation - flexible use - neuro rooms, seizure, brain tumor, trauma Pros: - rapid onset, short acting - anti-emetic - bronchodilaion - use for asthmatics, smokers - amnesia - neuroprotective Cons: - pain on injection - hypotension - CV and resp depression - allergy to soy, eggs - propofol infusion syndrome - lactic acidosis - not analgesic Effects: CNS - hypnotic, anesthetic, amnesic - decreased CBF, decreased CMRO2, decreased ICP - anticonvulsant - neuroprotective during focal brain ischemia CV - vasodilation, decreased BP, inhibits baroreceptor reflex Respiratory - respiratory depressant - apnea after induction bolus - upper airway reflex suppressed - use for airway instrumentation like bronchoscopy Other - anti-emetic - reduces post op N/V
Etomidate
Imidazole, acidic IV anesthetic Mechanism: - binds GABA A receptor, enhances affinity of GABA for receptor, increases Cl influx Ionized, penetrates brain rapidly Uses: - induction agent for CV unstable Pros: - less respiratory depression/apnea - CV stability - cardiac dysfnx, shock, hypovolemia are good uses Cons: - adrenal suppression - pain on injection - myoclonus Effects: CV - cardiovascular stability after IV bolus - minimal change in BP, HR, TPR, myocardial contractility Respiratory - minimal depressant of ventilation - apnea after IV bolus CNS - cerebral vasoconstrictor, decreased CBF and CMRO2 - myoclonic activity so don't use in seizure disorders Endocrine - adrenocortical suppression - inhibits 11 beta hydroxylase so no cortisol so don't use in critically ill
Ketamine
Phencyclidine
IV anesthetic
Mechanism:
- NMDA receptor antagonist
- binds opioid receptors also
Stimulant and sedative
Highly lipid soluble - rapid onset and short duration of action
Uses:
- induction of anesthesia
- maintenance of anesthesia
- sedation - dressing changes or suturing
- dissociative amnesia
- analgesic affect, post-op pain
- cardiac tamponade
- kids
Pros:
- less respiratory depression
- bronchodilator
- analgesic
- vasoconstrictor
- dissociative state
Cons:
- increase HR and BP
- psychotropic side effects - emergence delirium
- direct cardiac depression in pts with high symp tone - hemorrhage
- increased ICP
- salivation/increased secretions
Effects:
CNS
- dissociative anesthesia
- analgesic
- cerebral vasodilation and increased CBF - increase ICP and CMRO2
- myoclonic and seizure activity so don’t use for neurosurg, brain tumors, seizures, trauma
CV
- symp stimulation centrally - increase HR, BP, CO, myocardial O2 consumption so don’t use in ischemic heart disease
- myocardial depression in pts who can’t raise symp nerve activity - don’t use in shock
Respiratory
- no significant resp depression; apnea if IV bolus
- bronchodilation - use in asthma
- increases salivary and tracheobronchial secretions so treat with glycopyrrolate
Other
- emergence reaction - nightmares, hallucinations, etc. so pretreat with midazolam
Opioids
Mechanism: - bind opioid receptors, decrease Ca influx presynaptically and increase K efflux postsynaptically Drugs: - fentanyl - CV stability, fast acting - alfentanyl - sufentanil - remifentanil - fastest onset, shortest duration - hydromorphone - morphine - methadone - meperidine Pros: - analgesia - minimal cardiac depression - reduces inhalational agents - versatile Cons: - respiratory depression - decrease RR - increase apneic threshold - blunts ventilatory response to hypoxia - bradycardia - skeletal muscle rigidity - nausea, vomit - constipation/ileus - pruritis Effects: - CNS - analagesia, sedation - respiratory system - depression via decreased brainstem ventilation, loss of CO2 responsiveness - antitussive - methorphan, codeine - muscle rigidity - miosis - excitation at E-W nucleus - CV - hypotension due to bradycardia from decreased central symp tone and incrased vagal activity, depressant on SA node, histamine release leads to decreased TPR - GI - decreased peristalsis and increased sphincter tone, constipation, increased biliary pressure from sphincter of Oddi narrowing; nausea and emesis are most common via chemoreceptor trigger zone - GU - urinary retnetion - skin - histamine release, urticaria, cutaneous vasodilation - placenta - neonatal respiratory depression and dependence
Neuromuscular blockade agents
Depolarizing - succinylcholine - rapid onset/short duration, rapid sequence induction Non-depolarizing - rocuronium - fastest onset - cisatracurium - Hoffman elimination - vecuronium - pancuronium - tachycardia - reverse via neostigmine and glycopyrrolate
Dexmedetomidine
Imidazole
IV anesthetic
Mechanism:
- stimulation of alpha 2 receptors in locus coeruleus, inhibits NE release
Uses:
- sedation short term, radiologic procedurs
- general anesthesia, needs loading dose
Pros:
- sedation and analgesia without respiratory depression
Cons:
- hypotension and bradycardia, with bolus
- longer onset and offset
Effects:
CNS
- sedation
- analgesia
- not much on CRMO2 or ICP so good for brain stuff, getting an MRI
CV
- cardiovascular depression - bradycardia, hypotension due to NE decrease
Respiratory
- minimal depressant effects on respiration, no effect on respiratory rate
- response to CO2 unchanged
- so use if no airway experts around
NSAIDs
Mechanism: - block COX - reduce PGE2 and other prostaglandin production Actions: - analgesia - antiinflammatory - anti-pyretic via inhibition of IL1 and IL6 production of prostaglandins in hypothalamus - synergistic with opioids Adverse events: - inhibit platelet aggregation - gastric ulceration - renal dysfnx - hepatocellular injury - allergic rxn - asthma - tinnitus - myocardial infarction
Salicylates
Irreversibly acetylates COX Actions: - analgesic - low intensity pain - anti-pyretic - anti-inflammatory - rapidly absorbed from small intestine - liver metabolism Side effects: - GI upset - dyspesia - bleeding - tinnitus - allergic rxn
Ibuprofen, naproxen
Propionic acid derivatives Actions: - analgesic - anti-pyretic - anti-inflammatory - less GI irritation, dyspepsia compared to aspirin Side effects: - renal toxicity in renal pts Naproxen - longer half-life
Acetaminophen
Actions: - analgesic - anti-pyretic - no interaction with platelets - no GI irritation Side effects: - NAPQI - hepatotoxic - treat with N-acetylcysteine
Ketorolac
Actions: - potent analgesic - moderate anti-inflammatory - potentiates opioid action - absence of ventilatory and cardiac depression Side effects: - inhibits platelet aggregation - bronchospasm in ASA sensitive pts - GI irritation - renal toxicity in renal pts - hepatic toxicity
Celecoxib
COX 2 selective inhibitor Actions: - analgesic - anti-inflammatory - crosses BBB - well absorbed from GI - lacks platelet aggregatoin - decreased GI side effects Uses: - arthritis and post-op pain
Morphine
Delayed onset and peak effect due to poor CNS penetration
- poor lipid solubility and mostly ionized and protein bound
Metabolism:
- most to M3G
- some to M6G - active, analagesia and respiratory depression
- removed in urine, worry about renal pts
Effects:
- analgesia, euphoria, sedation
- histamine release
Worry about renal pts and build up
Meperidine
Less potent than morphine Metabolism: - to normeperidine which can cause seizures and myoclonus - worry about renal pts cuz build up Uses: - post-op shivering Side effects: - decreased cardiac contractility - mydriasis, tachy - like atropine - seziures - histamine release
Fentanyl
Much more potent than morphine
More rapid and shorter duration than morphine - lipophilic
No myocardial depression or histamine release, no active metabolites
Sufentanil
More potent than fentanyl
Rapid onset/offset - lipophilic
Uses:
- big incision with lots of pain
Alfentanil
Less potent than fentanyl
Fastest equilibration and offset
- due to low pK
- readily crosses BBB
Hepatic metabolism, renal failure does not affect clearance
Uses:
- short lived stimuli like nerve block, before putting in big needle
Remifentanil
Similar potency to fentanyl
Very fast onset and offset like alfentanil
Metabolized by tissue plasma esterases so can use in kidney and liver failure
Methadone
Mu agonist and NMDA antagonist 2 half-lives, prolonged and unpredictable - pain is 4-8hrs - negative side effects is 20hrs Dose low and slow Uses: - pain and addiction
Hydromorphone
More potent than morphine - same side effects Safer in renal pts cuz no active metabolite build up Uses: - perioperative pain in renal pts
Buprenorphine, butorphanol
Agonist/antagonist mix Effects: - analgesia - minimal ventilatory depression - low physical dependence potential Uses: - pts who can't tolerate pure agonist, negative side effect profile reduced
Naloxone
Opioid antagonist
Mechanism:
- high affinity for opioid receptor, kicks out agonist
Potently and rapidly reverses agonist effects
Uses:
- treat opiate induced ventilatory depression, neonatal depression and overdose
Short duration
Side effects:
- CV stimulation, increased SNS activity, therefore increased pain perception, tachycardia, HTN, pulmonary edema and dysrhythmia
- can reverse pain/analgesia and lead to withdrawal (especially in neonates)
Phenytoin
Anti-epileptic Mechanism: - slows Na channel recovery rate - keep Na channel block in longer First line for partial/focal seizures 95% protein bound, so saturation kinetics - small dose increases can cause unpredictable changes in plasma concentration and adverse events Induces p450, increases its own metabolism Give IV for status epilepticus Adverse events: - Nystagmus - Ataxia - Lethargy - Gingival hyperplasia - Incoordination, confusion - Hirsutism - Facial coarsening - Systemic skin rash
Carbamazepine
Anti-epileptic Mechanism: - slows rate of Na channel recovery First line for partial/focal seizures - suppression of seizure foci and prevention of spread of activity Inactivated by liver metabolism; induces its own metabolism during first 3-6wks, need larger doses 10-11 epoxy metabolite may contribute to neurotoxicity Side effects: - sedation - drowsiness - headache - dizziness - blurred vision
Oxcarbazepine
Anti-epileptic Mechanism: - slow rate of Na channel recovery - augment K channels and block Ca Metabolized in liver; less p450 induction than carbamazepine Side effects: - sedation - less than carbamazepine - hyponatremia - oral contraceptive interaction
Lacosamide
Anti-epileptic
Mechanism:
- Na channel, unknown, slows transmission
Add on therapy for poorly controlled focal seizures
Side effects:
- dizziness
Eslicarbazepine acetate
Anti-epileptic Mechanism: - blocks voltaged gated Na channels, slows recovery Effective as add on for partial seizures Prodrug, activated in liver Minimal interaction with p450 - does not induce p450 Once daily dosing Decreases bioavailability of oral contraceptives Side effects: - dizziness - somnolence - headache - nausea/vomit
Diazepam
Benzodiazepine Mechanism: - GABA potentiating - enhances GABA mediated inhibition Use: - first line for status epilepticus - parital and tonic clonic seizures - not first line cuz highly sedating Adverse effects: - sedation - dizziness - ataxia - drowsiness - tolerance - loses effectiveness in 6 mo - dependence/addicitive potential
Phenobarbital
Barbiturate Mechanism: - GABA potentiating Use: - focal and tonic clonic seizures - not first line Side effects: - heavily sedating - cognitive effects - tolerance - withdrawal - addictive
Gabapentin, Pregabalin
Mechanism: - act on voltage gated Ca channel a2d1 subunit - prevent release of glutamate Use: - add on for focal and tonic-clonic No interactions with other drugs Well tolerated Limited side effects Less sedating
Lamotrigine
Mechanism: - slows recovery of voltage gated Na channels - inihbits glutamate release - inhibits Ca channels Well tolerated Metabolized by glucuronidation Use: - add on or monotherapy for focal and secondarily generalized tonic-clonic
Valproate
Mechanism:
- inhibits low threshold T type Ca channels
- slows rate of Na channel recovery
- increases the availability of GABA at the synapse - decreases GABA breakdown by reducing GAT activity and increases GABA synthesis through GAD
Uses:
- broad spectrum
- first line for generalized
- also focal and absence
Interactions:
- induces metabolism of carbamazepine and vice versa
- inhibits phenobarbital metabolism
- displaces phenytoin from binding proteins - contributes to phenytoin toxicity
Adverse events:
- sedation
- weight gain
- tremor, hair loss
- elevated liver enzymes - hepatotoxic
- GI disturbances
- teratogenic - autism, spina bifida, sensory deprivation disorders
Topiramate
Mechanism: - glutamate receptor antagonism - AMPA receptors - GABA potentiation - Na and Ca channel blocker - Carbonic Anhydrase inhibitor Minimal drug interactions and side effects Liver enzyme inducer Use: - broad spectrum - focal, generalized, myoclonic - doesn't treat absence Adverse events: - renal stones - cognitive/language difficulties - oral contraceptive interaction
Levetiracetam
Mechanism: - modulates SV2A vesicle that contains GABA - enhances GABA release - increase tonic inhibitory tone Effective at initial dose No known drug interactions Safe, well tolerated Adverse events: - mood irritability/psychosis
Zonisamide
Mechanism: - induces Na channel blockade - reduces voltage dependent T type Ca currents - reduction of glutamate induced synaptic transmission Use: - broad spectrum: focal and generalized - absence maybe Very long half-life Sulfonamide - don't use if allergy Adverse events: - renal stones - anhydrosis
Felbamate
Mechanism: - inhibition of NMDA and AMPA receptors - extremely potent antiepileptic No sedative effects Adverse events: - behavioral effects - aplastic anemia - liver failure Use: - refractory epilepsy - monitor closely
Ethosuximide
Mechanism: - blocks T type Ca channel in thalamus Use: - Absence seizures - first line - no other seizures Less sedating
Haloperidol
Typical anti-psychotic
Mechanism:
- post-synaptic D2 antagonist at mesolimbic pathway
- some alpha 1 block
- no H1 or M1 block
Reduce positive symptoms
Side effects:
- adrenergic: postural hypotension, reflex tachycardia, dizziness
- tardive dyskinesia
- extrapyramidal from nigrostriatal: dystonia, tremor, akinesia, akathesia, TD
- mesocortical: emotional blunting, cognitive problems, negative symptoms
- tuberoinfundibular: hyperprolactinemia, breast secretions, amenorrhea, infertility
Neuroleptic malignant syndrome:
- hyperthermia
- autonomic instability
- rigidity of muscles
- tremor, myoclonus
- confusion/stupor
- rx: stop drug, hydrate, dantrolene and bromocriptine
Chlorpromazine
Typical anti-psychotic
Mechanism:
- post-synaptic D2 antagonist at mesolimbic pathway
- largest H1 antagonism
- largest alpha 1 antagonism
- some M1 block
Reduces positive symptoms
Can reduce extrapyramidal symptoms (not TD) by M1 blockade
Side effects:
- histaminergic: sedation, drowsiness, weight gain, hypotension
- adrenergic: postural hypotension, reflex tachycardia, dizziness
- muscarinic: blurred vision, dry mouth, tachycardia, constipation, urinary retention, memory dysfunction
- tardive dyskinesia
- extrapyramidal from nigrostriatal: dystonia, tremor, akinesia, akathesia, TD
- mesocortical: emotional blunting, cognitive problems, negative symptoms
- tuberoinfundibular: hyperprolactinemia, breast secretions, amenorrhea, infertility
Neuroleptic malignant syndrome:
- hyperthermia
- autonomic instability
- rigidity of muscles
- tremor, myoclonus
- confusion/stupor
- rx: stop drug, hydrate, dantrolene and bromocriptine
Fluphenazine
Typical anti-psychotic
Mechanism:
- post-synaptic D2 antagonist at mesolimbic pathway
- some H1 antagonism
- some alpha 1 antagonism
- some M1 block
Reduces positive symptoms
Can reduce extrapyramidal symptoms (not TD) by M1 blockade
Side effects:
- histaminergic: sedation, drowsiness, weight gain, hypotension
- adrenergic: postural hypotension, reflex tachycardia, dizziness
- muscarinic: blurred vision, dry mouth, tachycardia, constipation, urinary retention, memory dysfunction
- tardive dyskinesia
- extrapyramidal from nigrostriatal: dystonia, tremor, akinesia, akathesia, TD
- mesocortical: emotional blunting, cognitive problems, negative symptoms
- tuberoinfundibular: hyperprolactinemia, breast secretions, amenorrhea, infertility
Neuroleptic malignant syndrome:
- hyperthermia
- autonomic instability
- rigidity of muscles
- tremor, myoclonus
- confusion/stupor
- rx: stop drug, hydrate, dantrolene and bromocriptine
Thioridazine
Typical anti-psychotic
Mechanism:
- post-synaptic D2 antagonist at mesolimbic pathway
- some H1 antagonism
- some alpha 1 antagonism
- largest M1 block
Reduces positive symptoms
Can reduce extrapyramidal symptoms (not TD) by M1 blockade
Side effects:
- histaminergic: sedation, drowsiness, weight gain, hypotension
- adrenergic: postural hypotension, reflex tachycardia, dizziness
- muscarinic: blurred vision, dry mouth, tachycardia, constipation, urinary retention, memory dysfunction
- tardive dyskinesia
- extrapyramidal from nigrostriatal: dystonia, tremor, akinesia, akathesia, TD
- mesocortical: emotional blunting, cognitive problems, negative symptoms
- tuberoinfundibular: hyperprolactinemia, breast secretions, amenorrhea, infertility
Neuroleptic malignant syndrome:
- hyperthermia
- autonomic instability
- rigidity of muscles
- tremor, myoclonus
- confusion/stupor
- rx: stop drug, hydrate, dantrolene and bromocriptine
Risperidone
Atypical anti-psychotic Mechanism: - antagonist at D2 and 5HT2A - therefore increase DA release, but also compete at receptor Lower D2 affinity than typicals Low extrapyramidal side effects Works on negative symptoms - mesocortical has lots of 5HT2A receptors Positive and negative efficacy Mood stabilizer High potency, need less Decreased tardive dyskinesia Side effects: - prolactin elevation - weight gain - dose related EPS (less than typicals)
Olanzapine
Atypical anti-psychotic Mechanism: - antagonist at D2 and 5HT2A - therefore increase DA release, but also compete at receptor Lower D2 affinity than typicals Low extrapyramidal side effects Works on negative symptoms - mesocortical has lots of 5HT2A receptors Positive and negative symptom efficacy Mood stabilizer Decreased tardive dyskinesia Side effects: - big weight gain - associated with diabetes - higher doses related to EPS - prolactin elevation - somewhat sedating
Quetiapine
Atypical anti-psychotic Mechanism: - antagonist at D2 and 5HT2A - therefore increase DA release, but also compete at receptor Lower D2 affinity than typicals Low extrapyramidal side effects Works on negative symptoms - mesocortical has lots of 5HT2A receptors Lower potency - need more Low doses useful for borderline disorders Low EPS Low tardive dyskenia risk Side effects: - some weight gain - sedating - dose titration to decrease dizziness
Ziprasidone
Atypical anti-psychotic Mechanism: - antagonist at D2 and 5HT2A - therefore increase DA release, but also compete at receptor Lower D2 affinity than typicals Low extrapyramidal side effects Works on negative symptoms - mesocortical has lots of 5HT2A receptors High dose more effective No weight gain Low diabetes risk Anti-depressant activty Side effects: - dose related EPS - nausea - sleep disturbance
Aripiprazole
Atypical anti-psychotic Mechanism - partial D2 agonist - 5HT-2A antagonist Lower D2 affinity than typicals Low extrapyramidal side effects Works on negative symptoms - mesocortical has lots of 5HT2A receptors No weight gain Side effects: - little EPS - little sedation - little heart fnx effects
Zotepine
Atypical anti-psychotic Mechanism: - antagonist at DA and 5HT2A - gets D1 and D2 - inhitis NE reuptake Lower D2 affinity than typicals Low extrapyramidal side effects Highly effective for negative symptoms Side effects: - weight gain - somnolence
Other atypical antipsychotics
Amisulpride
Aripiprazole, clozapine, olanzapine, risperidone, ziprasidone, zotepine, quetiapine
Clozapine
Atypical anti-psychotic
Mechanism:
- antagonist at D2 and 5HT2A
- therefore increase DA release, but also compete at receptor
Lower D2 affinity than typicals
Low extrapyramidal side effects
Works on negative symptoms - mesocortical has lots of 5HT2A receptors
Few EPS
No tardive dyskinesia
No elevated prolactin
Greastest efficacy, most side effects - use when typicals fail
Side effects:
- agranulocytosis
- anticholinergic - dry mouth, constipation, blurred vision, drowsiness, memory impairment
- antiadrenergic - low BP, dizziness
- antihistamine - drowsiness, weight gain
- 5HT2C blockade: weight gain
Lithium
Mood stabilizer for bipolar Mechanism: - enhance serotonergic transmision Treatment of choice for BPAD Decreases risk of suicide in pts without bipolar Renal excretion - need good kidneys Don't take with advil/motrin, ACE-I, CBB, thiazide diuretics Hemodialysis for toxicity Pregnancy category D: - Ebstein's anomaly - malformatoin of tricuspid valve, but still 1st line in pregnancy Side effects: - nephrogenic diabetes insipidus - nausea - diarrhea - metallic taste - EKG changes, conduction delay - thyroid abnormalities - hypothyroidism, goiter - tremor - sedation - polydipsia and polyuria - mild leukocytosis - weight gain, edema, dry mouth - cognitive dulling
Valproate
Mood stabilizer Mechanism: - increases GABA More effective for rapid cyclers and mixed states Don't use in liver disease Hemodialysis for toxicity (coma) Side effects: - thrombocytopenia - hepatotoxicity - teratogenic - neural tube defects, liver disease, dysmorphic facies, cardiac abnormalities, reduced IQ in infant - nausea, diarrhea - tremor - sedation - hair loss - weight gain - increased ammonia levels - sedation, altered mental status - pancreatitis
Carbamazepine
Mood stabilizer
Mechanism:
- inhibits voltage gated Na channels - prevents repetitive neuron firing
- inhibits presynaptic Na channels - preents NT release
Good for rapid cyclers and mixed states, not for bipolar depression
Decreases levels of oral contraceptives
Auto-induction - serum levels decrease over time
Side effects:
- SIADH
- aplastic anemia
- agranulocytosis
- teratogenic - spinal malformations, face, heart and head defects
- nausea
- AV block
- A fib
- ataxia
- sedation
- weight gain
- hepatitis
Lamotrigine
Bipolar depression
Side effects:
- Steven’s Johnson
Tricyclic antidepressants
Mechanism: - block reuptake pumps for 5HT and NE, increasing synaptic concentration - non-selective Cross BBB, lipophilic Drugs: - amitriptyline - nortriptyline - desipramine - imipramine - doxepin Use: - pts not responding to SSRIs - depression - panic and GAD Side effects: - anticholinergic - nausea/vomit, anorexia, dry mouth, blurred vision, confusion, constipation, tachycardia, urinary retention - antihistaminic - sedation, weight gain - antiadrenergic - orthostatic hypotension, reflex tachycardia, drowsiness, dizziness - Na channel block - cardiac arrhythmia
MAO-Is
MAO-A - metabolizes 5HT and NE and tyramine MAO-B - metabolize DA Mechanism: - irreversible, non-selective inhibition of MAO Lipophilic, cross BBB Drugs: - isocarboxazid - phenelzine - tranylcypromine Side effects: - hypertensive crisis - blurred vision, dizziness, sleep disturbances, fatigue, weakness, increased sweating - sexual dysfnx - orthostatic hypotension - side effects often disappear in time Don't eat wine/cheese while on an MAO-I Reversible and selective inhibitors of MAO RIMAs: - moclobemide - befloxatone - no hypertensive crisis with tyramine-containing foods
SSRIs
Mechanism: - selectively block 5HT reuptake Drugs: - fluoxetine - sertraline - paroxetine - fluvoxamine - citalopram First line for depression First line for Anxiety Delayed action: 4-6wks Drug-drug interactions - dangerous with MAO-Is Adverse events: - insomnia - nausea - deceased libido - decreased sexual fnx - suicidal thoughts - serotonin syndrome - hyperthermia, muscle rigidity, myoclonus, rapid changes in mental status and vital signs - SSRI and MAOI together
Trazodone
Serotonin 2A antagonist/serotonin reuptake inhibitor SARI
- 5HT2A antagonist - blocks unwanted side effects of agitation/anxiety, sexual dysfnx
- still increases 5HT levels
Side effects:
- antihistamine - sedation
- alpha 1 inhibition - hypotension, dizziness, sedation
Bupropion
NE/DA reuptake inhibitor
- antidepressant if can’t tolerate serotonergic side effects
- no sexual dysfunction
Mirtazapine
Noradrenergic and specific serotonergic antidepressant NaSSA
- alpha 2 receptor antagonist - increase NE and 5HT release
- block 5HT2A and 5HT3 - reduce anxiety and sexual dysfnx
- block 5HT2C and H1 - sedation, weigh gain
Venlafaxine
Serotonin NE reuptake inhibitor
- NE and 5HT selectivity
- very selective, lacks side effect profile cuz no alpha 1, cholinergic, or histamine blocking
Bipolar depression drugs
Lithium
Lamotrigine
Quetiapine
Lurasidone
Bipolar mood stabilizers
Lithium
Valproate
Carbamazepine
Buspirone
Anxiolytic - less effective than SSRIs - 2nd line Mechanism: - 5HT1A agonist No sexual dysfnx No interaction with alcohol No ataxia, confusion, memory disturbances Side effects: - dizziness - headaches - nausea - drowsiness
PTSD first line
SSRIs and SNRIs
Also CBT
Flumazenil
GABA A antagonist
Reverse BZD overdose
Benzos
Act on alpha 2 subunit of GABA A for anxiolysis Metabolism: - oxidized by liver cyp450 Directly conjugated ones: - Oxazepam, Temazepam, Lorazepam - use in elderly Fast elim for hypnotic: - Temazepam Slow elim for anxiolysis: - diazepam Others: - alprazolam - clonazepam
Modafinil
Drug of choice for narcolepsy
Sleeping Drugs
Drugs:
- Zolpidem - alpha 1 GABA agonist; CR 1st line
- Zopiclone - alpha 1 GABA agonist
- Eszopiclone - alpha 1 GABA agonist; 1st line
- Zaleplon - alpha 1 GABA agonist
- Ramelteon - melatonin agonist
- Suvorexant - orexin antagonist
Benzos as sleep drugs
Sedative-Hypnotic Mechanism: - alpha 1 GABA A agonist Tolerance to anti-seizure effects Dependence Additive with EtOH Hip fracture in elderly Side effects: - ataxia - confusion - memory disturbances - hallucinations Drugs: - temazepam - best sleep cycle - estazolam - triazolam
Z Drugs
Drugs: - zolpidem; CR - zaleplon - eszopiclone Side effects: - hallucinations - amnesia - sleepwalking, etc. while sleeping - daytime drowsiness - aggravates depression/anxiety Tapered withdrawal when used chronically
Suvorexant
Orexin antagonist at OX1 and OX2 Side effects: - less severe than Z drugs/BZD - ataxia - confusion - memory disturbances - hallunications
Trazodone for sleep
Small dose
Atypical antidepressant
