Dopaminergic agents Flashcards
Levodopa
Class: Dopamine precursor
Mech: Crosses the BBB and converted to dopamine
Thera: Parkinson’s Disease (used late in the course of treatment because get densensitization over time called on-off phenomenon which ends up giving side effects)
Tox: Dyskinesia, psychosis, mania, hypervigilant, nausea, dizziness, anxiety, hypotension, syncope, fatigue
Misc: Given with Carbidopa
Carbidopa
Class: N/A
Mech: Inactivates dopamine activity in periphery (does not cross the BBB)
Thera: Parkinson’s Disease (given with levodopa in order to lower peripheral dopamine activity)- helps reduce fatigue, dizziness, nausea
Tox: N/A
L-Methylfolate/S-adenosyl methionine (SAM)
Class: 1 Carbon metabolism intermediates
Mech: Increases 1-carbon cycle which ultimately increases the amount of tyrosine converted to dopamine
Thera: Depression (less aggressive than L-DOPA)
Tox: Rare maybe GI upset
Misc: Considered complimentary alternative medicine
Bupropion
Class: N/A
Mech: Blocks both dopamine and NE transporters blocking their reuptake into the presynaptic neuron and causing their accumulation within the synapse
Thera: Depression
Tox: DA: Hypervigilence, seizures, nausea, agitation
Insomnia, NE poisoning (dry mouth, sweating, palpitations, hypertension)
Dextroamphetamine
Mixed Amphetamine Salts
Lisdexamfetamine
Class: Amphetamines (Lisdexamfetamine is a prodrug to amphetamine)
Mech: 1: Blocks DAT
2: Reverses DAT
3: Increases VMAT2 activity causing even more DA to be dumped into synapse via vesicles
Thera: ADHD
Tox: Strong propensity for addiction (mesolimbic pathway)
High doses may see psychosis
Appetite and subsequent weightloss
Typical DA and NE overdose SEs
DA: Hypervigilence, seizures, nausea, agitation
Insomnia, NE poisoning (dry mouth, sweating, palpitations, hypertension)
Methylphenidate
Class: N/A
Mech: Blocks DAT
Thera: ADHD
Tox: See amphetamines although less severe addiction
DA: Hypervigilence, seizures, nausea, agitation
Insomnia, NE poisoning (dry mouth, sweating, palpitations, hypertension)
Modafinil/Armodafinil
Class: Stimulant (pseudostimulant actually)
Mech: 1: Increases histamine activity in the tuberomammilary nucleus causing alertness in frontal cortex
2: Increases orexin activity
3: Blocks DAT
4: Manipulate NE receptors postsynaptically
Thera: Fatigue due to narcolepsy, apnea, shiftwork
NOT used for ADHD
Tox: Less addictive than amphetamines or Methylphenidate
DA: Hypervigilence, seizures, nausea, agitation
Insomnia, NE poisoning (dry mouth, sweating, palpitations, hypertension)
Selegiline (low dose)
Rasagiline
Class: MAO-B inhibitor
Mech: MAO-B is responsible for breaking down DA primarily. These inhibitors are irreversible
Thera: Parkinson’s Disease
Tox: Hypotension, dizziness, insomnia, weight gain
Isocarboxazid
Phenelzine
Tranylcypromine
Selegine (high doses)
Class: MAO-A and B inhibitor
Mech: Responsible for breaking down monoamines DA, NE, 5-HT. Irreversible inhibitor
Thera: Depression
Tox: Hypotension, dizziness, insomnia, weight gain
Hypertensive Crisis
Serotonin Syndrome (antidepressants, narcotics, antihistamines)-tremor, muscle spasm, increased/decreased vitals, hyperthermia, delirium, coma, death
Entacapone
Tolcapone
Class: COMTi
Mech: Will cause elevations in DA or NE or other monoamines
Thera: Parkinson’s
Tox: Nausea, fatigue, liver failure (tolcapone)
Bromocriptine
Pramipexole
Ropinerole
Apomorphine injections
Class: DA2 receptor agonist
Mech: DA2 receptor is a phasic receptor
Thera: PD, RLS
Tox: Nausea, fatigue, dizziness, mania
Aripiprazole
Class: DA3 receptor agonist, also DA2 agonist
Mech: DA3 receptor is a static receptor
Thera: Antipsychotic or depression
Amantadine
Class: Antiviral
Mech: 1: Release DA
2: Block DAT
3: Stimulate D2 receptors
Thera: PD, influenza
Tox: Nausea, dizziness, psychosis, insomnia, seizures
Reserpine
Class: VMATi
Mech: Vesicles cannot be loaded and released decreasing DA and NE in the synaptic space
Thera: HTN, psychosis
Tox: Less DA increases depression while less NE decreases depression
Tetrabenzamine
Class: VMATi
Mech: Vesicles cannot be loaded and released decreasing DA and NE in the synaptic space
Thera: HD
Haloperidol
Fluphenazine
Thiothixine
Class: High potency FGA
Mech: High affinity for D2 receptor antagonism however nonselective in that it can occur in any DA pathway
Thera: Psychosis in Schiz
Tox: Extrapyramidal side effects (EPS)-akathisia (restlessness), dystonia(muscle spasm), parkinsonism, Neuroleptic Malignant Syndrome (hyperthermia, muscle rigidity, vital sign instability, rhabdo) Tarditive Dyskinesia (permanent choreic or athetotic movements (slow, writhing) due to new D2 receptors being created
Chloropromazine
Thioridazine
Class: Low potency FGA
Mech: D2 receptor, H1 receptor, Muscarinic, Alpha 1 receptor antagonists
Thera: Psychosis associated with schizo
Tox: D2-EPS
H1-fatigue, increased weight and appetite
Anticholinergic
Anti-alpha1-orthostasis
Benztropine
Trihexyphenadyl
Diphenhydramine
Class: Anticholinergics
Mech: Inhibiting cholinergic tone in the basal ganglia improves dopaminergic flow in the nigrostriatal pathway
Thera: EPS associated with FGA
Tox: Dry mouth, blurred vision, tachycardia, constipation, confusion, delirium, hallucinations
Risperidone Paliperidone Ziprasidone Iloperidone Lurasidone
Class: “Dones” SGA
Mech: D2 receptor antagonism, 5-HT2a antagonism which allows for greater blocking of DA in the mesolimbic system while allowing better transmission in all other DA pathways
Thera: D2: Antipsychosis, aggression in autism, mania
5-HT: Lessens EPS, anxiety, depression
Tox: Possibly more EPS (distinguish from pines)
Anti-serotonin-headache, GI problems, insomnia, anxiety, suicide risk, Metabolic syndrome (diabetes, hyperlipidemia, HTN, obesity), Stroke in dementia patients
Olanzapine
Quetiapine
Asenapine
Clozapine
Class: “Pines” SGA
Mech: D2 receptor antagonism, 5-HT2a antagonism which allows for greater blocking of DA in the mesolimbic system while allowing better transmission in all other DA pathways
Thera: D2: Antipsychosis, aggression in autism, mania
5-HT: Lessens EPS, anxiety, depression
Tox: More sedating (H1 antag) and more metabolic syndrome distinguishing from pines
Anti-serotonin-headache, GI problems, insomnia, anxiety, suicide risk, Metabolic syndrome (diabetes, hyperlipidemia, HTN, obesity), Stroke in dementia patients
Aripiprazole
Class: “Rips” SGA
Mech: Partial agonist of D2 and D3
Clozapine
Class: Pines SGA
Mech: Antagonizes D2 and 5HT-2a as well as D1, D4
Thera: Most effective anti-psychotic
Tox: Little to no chance of EPS but huge metabolic syndromes
Also may see agranulocytosis
