CNS drugs Flashcards
chlorpromazine**
→ block D2, α-adrenergic, antihistamine & considerable anticholinergic; Jaundice
neg. ionotrpic on heart
(low potency) →↑-
Thioridazine
retinal deposits
Chorpromazine→ block D2, α-adrenergic, antihistamine & considerable anticholinergic; Jaundice
neg. ionotrpic on heart
(low potency)
Fluphenazine
→ more selective for dopamine, less anticholingeric, ↑ extrapyramidal effects
(high potency)
Perchloroperazine
Phenothiazine
→ nausea & vomiting
Trifluoperazine
→ less anticholinergic: ↑ extrapyramidal, ↓ hypoTN & sedation
Haloperidol**
→ greater potency at D2, some α1 & 5HT2, no anticholinergic; MOST likely to cause pyramidal
- used for acute psychotic situations;
- tourettes
Pimozide
→ binds ONLY to D2; high extrapyramidal, mod. antichol;
Tourettes syn tics
-prolong QT (risperidone, ziprasidone, pimozide)
Loxapine
→ use when others dont work; greater seizure risk than Phenothiazines
Olanzapine**
blocks D2, D4* (+ symp), 5-HT2a (neg. symp); anti-ACh (↓ ↓ extrapyramid); (anti-Hist/ACh/alpha 1)
tx Bipolar
→ WEIGHT GAIN (most likely)
(first line drug)
Risperidone*
→ inhib D2 & esp 5HT2a; block α; +SSRI for resitant depression & autism (↑ DA in basal gang)
- Plaiperidone is metabolite
-prolong QT (risperidone, ziprasidone, pimozide)
(first line drug)
Ziprasidone*
→ similar to risperidone; 5HT1a agonism or inhabit 5HT repute
tx Tourette, acute mania;
-prolong QT (risperidone, ziprasidone, pimozide)
↓ chance weight gain; hyperprolactinemia
-caution w/ pts who have history of seizures
Clozapine
→ binds D4 & 5HT2a > affinity than D2 (↓↓ extrapyramidal) binds α1 & histamine & anti-ACh;
- agranulocytosis; RESERVED;
- psychosis in Parkisons pts
Quetiapine*
→ similar to clozapine; ↑ + & - symp; ↓ ↓ SE;
**-↑ NE via metabolite & 5-HT2c block
-little Prolactin affect
-monotherapy for bipolar
first line drug
Iloperidone
→ block D2 & 5HT2a, α1; no muscarinic
Lurasidone
→ block D2 5HT2a, partial agonist 5HT1a; NO antihistamine or muscarinic; agranulocytosis & neutropenia
Asenapine
→ blocks 5-HT2a & 2c, D3** (not strong D2);
- blocks histamine & α (not muscarinic)
tx: PTSD nightmares
-less metabolic effects
Aripiprazole**
→ dopamine stabilizer;
- partial agonist @ D2 & 5-HT1a;
- blocks 5HT2a, α1, & histamine
- no affect on prolactin, QT;
- less weight gain.
SE- ↓ esophageal motility (aspiration pneumonia)
↑ blood glucose (diabetes may develop or worsen)
Lithium**
→ ↓ release & turnover of NE & DA;
- ↑ ACh;
- ↓ IP3 and DAG
- may uncouple receptors from G-protein (hypothyroid & polyuria)
- SLOW onset of action
- prevent mania and depression
-competes w/ Na in proximal tubule for reabsorption
↓ Lithium clearance:
- -low Na
- -Thiazide diuretics
- -NSAID
SIDE EFFECTS
- TREMOR (tx w/ βB)
- Nausea
- Headache
- ↓ thyroid function (blocks thyroxine)
- Renal effects- nephrogenic diabetes insipidus (tx: amiloride)
- weight gain
Divalproex
Valproic Acid
→ blocks Na, ↓ NMDA receptor stim, ↑ GABA synthesis & lvls
-DOC if both seizure types occur together (can be used for all seizure types except infantile spasm);
-LIVER toxicity, pancreatitis; hair loss
several drug interaction
BIPOLAR
→ anticonvulsant; effect >= Lithium; rapid onset;
pts who dont respont to Li; few SE
category D
Phenytoin**
Fosphenytoin
→ prolong inactivation of Na channel (prevents spread & inhibits glutamate release)
-no general CNS depression, not very sedating
-Zero order metabolism at therapeutic levels
-↑ [warfarin] (↓metabolism)
-↑ metabolism of oral contraceptives
LOTS OF SE & INTERACTIONS
→ water soluble prodrug (IV use)
Carbamazepine**
→ blocks Na & inhibits NTM (glutamate) release; inhib NE release & reuptake; -mood stabilizing (bipolar) -Idosyncratic blod dyscracias: --aplastic anemia --agranulocytosis --mild leukopenia (mainly in elderly for trigem)
DOC for partial seizures;
1st drug for tonic-clonic seizures, Trigeminal nerualgia (↑ doses)
Levatiracetam*
ANTICONVULSANT
→ binds SV2A (↓ glutamate & ↑ GABA); few drug interactions
-Partial & generalized tonic-clonic seizures
-Myoclonic seizures
Lamotrigine*
ANTICONVULSANT
→ inactivates Na, N & P/Q Ca++ channels (absence seizures), ↓ glutamate;
-Dermatitis (life-threatening in children)
–Partial & generalized tonic-clonic seizures
- Atonic seizures
- category C
Topiramate**
ANTICONVULSANT
→ block Na channels, ↑ GABAa current, ↓ glutamate receptor activation;
-inhibits SPREAD not ↑ threshold;
-secreted unchanged in urie
treatment for:
- -bipolar
- -eating disorder & binge eating
- -weight loss aid
- -alcoholics (started in teens)
-SE acute myopia & glaucoma
- Partial & generalized tonic-clonic seizures
- infantile spasm
-helps ↓ craving in recovering alcoholics
category C
Gabapentin
Pregabalin
ANTICONVULSANT
→ GABA analogs, not on receptors, ↑ GABA release; block N-type Ca+ (inhib glutamate release) TMJ
→ fibromyalgia
category C
Vigabatrin
ANTICONVULSANT
→ irreversible inhib of GABA transaminase; ↑ GABA levels & tonic inhib of brain;
Irreversible constriction of visual field and/or retinal damage;
CI pre-exisitng mental illness
Tiagabine*
ANTICONVULSANT
→ inhib. GABA uptake (forebrain & hippo);
–prolong inhib action of GABA
adjunt tx partial seizures
Ethosuximide**
→ DOC for absence seizure; block T-type Ca channels; GI SE; valproic acid ↓ clearance
Carbamazepine ↑ metabolism of
- -phenytoin
- -primidone
- -ethosuximide
- -valproic acid
- -clonazepam
- -haloperidol
- -oral contraceptives
↑ metabolism of Carbamazepine
- -phenobarbital
- -phenytoin
- -valproic acid
- -carbamazepine
↓ Metabolism of Carbamazepine:
- -Cimetidine
- -Fluoxetine
- -Isoniazid
- -erythromycin
Valproic acid ↓ metabolism of:
- Valproic acid
- Phenytoin (& displaces)
- Carbamazepine
- Phenobarbital (coma)
- ↓ elimination of lamotrigine
Baclofen**
GABA-mimetic
→ GABAb agonist brain & spine; ↓ excitatory NTM;
-may ↓ substance P (↓ pain)
-intrathecal administration: better control
tx: chronic spascitiy, back pain, prevent migraines
Diazepam**
→ GABAa in spinal cord; required dose causes significant sedation; spasm w/ trauma
Cyclobenzaprine**
→ similar structure as TCA; sedative @ brain stem; anti-ACh;
- significant sedation, confusion –transient visual hallucination
- spasms from trauma/sprain;
Carisoprodol
→ metabolite (meprobamate) is anxiolytic (acts like barbs); addiction potential; ↑ microsomal enz)
Tizanidine**
→ analogue of clonidine; acts at α2; pre/post synaptic inhib; -inhib pain @ dorsal horn; -SEDATING hypoTN (esp w/ antHTN rx) -dry mouth, muscle weakness (elderly)
Dantrolene**
→ targets excitation contraction coupling not CNS;
-↓ Ca release from SR;
tx: malignant hyperthermia & neuroleptic malignant syndrome (antipsychotics)
Methylphenidate
→ ADHD & narcolepsy; ↑ DA & NE in prefrontal ctx → modulate GABA & glutamate
Amphetamine
→ ADHD & narcolepsy; ↑ DA & NE in prefrontal ctx → modulate GABA & glutamate
Atamoxetine**
→ SNRI, potentiate effects of β-agonists, dont use w/ vasopressors
Tx: ADHD in adolescents and children 6+
possible liver toxicity
Caffeine
→ blocks adenosine receptors & inhib PDE; ↑ contractility dilates coronary aa, constricts cerebral (headache tx) moderate bronchodilation, ↑ gastric acid, diuresis
Levodopa**
→ able to pass BBB; high doses needed b/c peripheral metabolism; nausea & vomitting esp. effective against bradykinesia; arrhythmias, htpoTN & HTN w/ MAOI, dyskinesia
-On/Off phenomenon
Carbidopa
→ dopa decarboxylase inhib, doesnt cross BBB; ↓ DA synthesis in periphery
Carbidopa/levodopa**
→ combo ↑ DA in brain & ↓ in periphery; ↓ nausea & vomiting; food ↓ aborp, taken 3-4x/day; doesnt alter progression of disease; dyskinesa more common
Selegiline**
→ inhib. MAOb (↓ striatal metab of DA); MAOa at ↑ doses;
- may ↓ progession (↓ h2o2);
- amphetamine like metabolite (insomnia)
Rasagiline
→ irreversibe MAO-B inhib; no amphetamine like metabolites, no tyramine restriction
Bromocriptine**
Dopamine Agonist: → D2 agonist; -effectiveness does not ↓ -↓ prolactin; -GI SE, postural hypoTN, arrythmias (same as l-dopa)
-vasospasm SE (erythromelagia, pulmonary fibrosis)
Pergolide
Dopamine Agonist:
→ D1 & D2 agonist; sudden sleep
Pramipexole**
Dopamine Agonist:
→ NO erythromelalgia, vasospasm, fibrosis;
-can cause sudden sleep; well tolerated
-on/off less likely
Ropinirole**
Dopamine Agonist:
→ treatment for RLS
→ NO erythromelalgia, vasospasm, fibrosis; can cause sudden sleep; well tolerated, on/off less likely
Amantadine
→ antiviral for flu; ↑ release of DA (less potent than L-dopa); toxic psycosis & convulsions (OD) spotting of skin & edema; caution w/ history of seizure or CHF
Benztropine**
→ ↓ effects of ACh to balance loss of DA;
-improves rigidity & tremor (not bradykinesia)
Donepezil**
Rivastigmine
Galantamine
Cholinesterase Inhibitors
↓ breakdown of ACh in synaptic cleft
-may slow course of disease
-GI side-effects, ↑ stomach acid & salivation
Memantine
→ NMDA antagonist; ↓ extra-synaptic NMDA glutamate toxicity;
↑ SE of l-dopa & DA agonists;
-SE agitation, urinary incontinence, UTI,
Flumazenil**
→ competes w/ benzo for receptor;
-IV admin slowly in series to ↓ risk of seizures (DoA 30 min)
- reverse effect of: Midazolam, zolpidem, zaleplon, eszopiclone
- can cause seizure in pts w/ barb or TCA overdose; DO NOT use if signs of seizures
Zolpidem**
→ bind BZ1 subtype; 2hr half-life
-minor effect on REM
Zaleplon
→ bind BZ1 subtype; 1hr half-life
-minor effect on REM
Eszopiclone
→ less selective (more like benzo) 6hr half-life; long term treatment of insomnia
-minor effect on REM
Ramelteon**
→ MT1 & MT2; shortens delay to sleep onset;
-extensive 1st pass metab. (caution w/ liver diease, dont use w/ severe liver problems)
SIDE EFFECTS
- ↑ prolactin & ↓ testosterone
- headache, rash
Buspirone**
→ partial agonist 5-HT1; relieves anxiety w/o sedation; 2 wks to take affect
- ↓ serotonin release
- ↑ noradrenergic & DAnergic pathways
- no effect on bento or GABA receptors
- -LOW addiction potential
- -good for ADDICTS & ELDERLY
- no sedation**
- doesnt affect memory**
+ MAOI → severe HTN or serotonin syndrome
Chloral hydrate**
→ converted to trichloroethanol, binds GABAa
- acts similar to barbiturates (low safety)
- -respiratory and vasomotor depression
- -tolerance and dependance
- -liver danage & fatal intoxication
-pediatric dental procedures
Diphenhydramine**
→ blocks H1 receptor, anti-ACh; good choice for insomnia in addicts to alcohol or benzo
Naltrexone**
→ blocks ability of alcohol to simulate reward pathway (B-endorphin)
↓ craving (↓ rate of relapse by 50%); nausea, large dose → liver damage, opioid wont work
Acamprosate
→ structural analogue of GABA; restores normal balance of GABA/Glutamte transmission
(NO LIVER TOXICITY → DOC for pts w/ liver disease)
Disulfiram**
→ blocks ALDEHYDE dehydrogenase; long duration; inhib p450
lots of side-effects and drug interactions; not recommended
Drugs most likely to cause Steve Johnson syndrome
HLA-B*1502
- phenytoin, fosphenytoin
- phenobarbital, primidone
- lamotrigene
- ethosuximide
- valproic acid
Phenobarbital
→ long lasting; anticonvulsant
↑ duration of GABA action
Contraindicated in:
-porphyria (↑ synthesis)
Thiopental
ultra-short acting; induction of anesthesia
↑ duration of GABA action
Benzodiazepines duration of action
Long lasting:
- Diazepam
- Chlordiazepoxide
- flurazepam
- chlorazepate (inactive)
Intermediate:
- oxazepam
- lorazepam
short acting:
- alprazolam
- triazolam
very short acting:
-midazolam
Diazepam**
muscle relax, anticonvulsant (status epilepticus), alcohol/barb withdrawl
-cimetidine ↓ metabolism
-long lasting
↑ actions of GABA
Contraindicated in:
- pregnancy (category D)
- children (elderly confusion)
- sleep apnea
- w/ alcohol use
-Tolerance and dependance can develop
Chlordiazepoxide
alcohol/barb withdrawal
-long lasting
↑ actions of GABA
Contraindicated in:
- pregnancy (category D)
- children (elderly confusion)
- sleep apnea
- w/ alcohol use
-Tolerance and dependance can develop
Lorazepam
anticonvulsant (Status epilepticus)
-alcohol/barb withdrawal
-intermediate action
Contraindicated in:
- pregnancy (category D)
- children (elderly confusion)
- sleep apnea
- w/ alcohol use
-Tolerance and dependance can develop
Oxazepam
alcohol/barb withdrawl if liver damage present
-intermediate action
Contraindicated in:
- pregnancy (category D)
- children (elderly confusion)
- sleep apnea
- w/ alcohol use
-Tolerance and dependance can develop
Clonazepam
anticonvulsant
-prevent absence seizures
Contraindicated in:
- pregnancy (category D)
- children (elderly confusion)
- sleep apnea
- w/ alcohol use
-Tolerance and dependance can develop
Midazolam**
→ anesthesia prep & short procedures
- anterograde amnesia
- very short acting
Contraindicated in:
- pregnancy (category D)
- children (elderly confusion)
- sleep apnea
- w/ alcohol use
-Tolerance and dependance can develop
Flurazepam
treat early morning waking
- long duration of action
- can accumulate if taken daily
Contraindicated in:
- pregnancy (category D)
- children (elderly confusion)
- sleep apnea
- w/ alcohol use
-Tolerance and dependance can develop
Temazepam
Triazolam*
treat insomnia
Triazolam for difficulty falling asleep
-less depression of REM
Contraindicated in:
- pregnancy (category D)
- children (elderly confusion)
- sleep apnea
- w/ alcohol use
-Tolerance and dependance can develop
Anxiety disorders where Benzo are not used
- OCD (SSRI)
- agoraphobia & panic disorders (SSRI or antidepressant)
- PTSD (antidepressants)
- anxiety in children or adolescents (antidepressants)
TCA**
→ inhibit reuptake of NE & 5HT
–analgesic b/c NE ↑ endorphin release which ↓ substance P
- **anti-ACh→ impair memory & cognition, dry mouth, vision problems, ↓ sweating
- **anti-Histamine→ drowsiness & weight gain
- **α1 blockade→ orthostatic hypoTN and ejaculation difficulties
- cardiac depression & ↑ irritability (torsade de pointes)
- -ventricular arryth (flat or inverted T waves)
- -AVOID if previous MI or BBblock
-SIADH → hypoNA
TCA overdose
- cardiac conduction defects & arrhythmias (torsade)
- -Mg & isoproterenol; phenytoin
- hypotension
- respiratory depression
- agitation, delirum, restlessness
- seizures (neuromusc. irratability)
- -phenytoin
- coma w/ shock & metabolic acidosis
Imipramine
TCA
- worst cardiac depression
- enurisis
- metabolized to Desipramine
Clomipramine
only used for OCD
Phenelzine**
Tranylcypromine
→ both irreversibly inhibit MAO-A (NE & 5HT) & MAO-B (DA);
-anti α & ACh
-effects last 1-3 weeks after stopping
-drug of last choice when others have not worked
+ Tyramine or sympathomimetic → HTN crisis
+ OTC cold meds → HTN or serotonin syn
+TCA or SSRI → serotonin syn
+ Busipirone → sever HTN
Fluoxetine**
→ inhibits reuptake of 5HT and NE; has active metabolite (LONG DoA); can cause insomnia
- OCD
- bulimia
- PMS
Fluvoxamine
OCD
Paroxetine
OCD, social anxiety; causes sedation
- more selective for 5HT
- inactive metabolite
- CI in pregnancy due to cardiac effects
Sertraline
OCD, social anxiety; causes insomnia
-more selective for 5HT than fluoxetine → less sexual SE
Citalopram
Escitalopram
- similar SE to fluoxetine & sertraline
- FEWER pharmacokinetic interactions
Vortioxetine
- inhibits serotonin transporters
- -5HT3a & 5HT7 antagonist
- -5HT1b partial agonist
- -5HT1a agonist
Vilazodone
→ SSRI & 5HT1a partial agonist (like busipirone)
Venlafaxine** (longer DOA)
desvenlafaxine (metabolite)
→ inhibts repute of 5HT and NE
–depression, hot flashes, neuropathic pain
-may ↑ BP and hypoNA (SIADH)
Duloxetine (Cymbalta)
SNRI
→ physical symptoms (pain)
-hepatotoxic
-CI in 3rd trimester
Milnacipran
Levomilnacipran
SNRI
→ fibromyalgia
→ major depressive disorder
Bupropion**
→ inhib reuptake of DA and NE
- quit smoking (extended release form), reduce craving for alcohol and weight loss
- ADHD
-combine w/ SSRI to improve effectivness and decrease sexual side-effects
may produce psychosis
CI w/ history of seizures or head trauma
-dont take w/ drugs that may ↓ seizure threshold (TCA and antipsychotics)
Mirtazapine
→ blocks presynaptic α2 ( ↑ NE and 5HT), blocks 5HT2a & 5HT3
- antihistamine
- eliminates normal SE of SSRI b/c of block at 5HT2a & 5HT3
Trazodone**
→ partial agonist at 5HT1a and block 5HT2a
- not good antidepressant
- SLEEP AID
- PRIAPISM
St. John’s Wort
→ block repute of NE, 5HT, and possible DA
-DO NOT USE W/
MAOI, SSRI, TCA, ldopa, selegilline)
Ketamine**
blocks NMDA receptors
- general anesthetic
- rapid and long lasting
-vivid dreams
