Pharmacology Flashcards
Entacapone
- COMT inhibitor (catechol-o-methyltransferase)
- Dopamine is metabolized by COMT –> 3-o-methyldopa
- by inhibiting conversion, it extends plasma half-life of dopamine
- administered concomitantly with levodopa
- increase duration of action of levodopa, reduce off periods
Levodopa
- dopamine precursor
- after ingestion, it is converted in the brain and peripherally to dopamine by dopa-decaroboxylase
- peripheral conversion –> SE (nausea & dyskinesias due to dose and duration of therapy); carbidopa inhibits peripheral conversion (that is why it is adminsitered with levodopa)
Pramipexole & Ropinirole
- dopamine agonists at D2 and D3 receptors
Rasagiline, Selegiline
- selective MAOB inhibitors (involved in dopamine metabolism)
- SE selegiline: insomnia (converted into methamphetamine)
Trihexyphenidyl
- anticholinergic
- treatment of tremor (thought to result from excess Ach)
- SE: cognitive dysfunction (esp older), constipation, dry eyes/mouth, urinary retention
Amantadine
- antiglutamatergic
- also used in treatment of PD
- increases presynaptic dopamine release, inhibits reuptake of synaptic dopmaine
Barbiturates
- phenobarb, pentobarb, thiopental, secobarbital
- facilitate GABAa action by increasing duration of Cl- channel opening, thus decreasing neuron firing
- OD can cause CNS depression, respiratory and cardiovascular depression, induces CYP 450
Benzodiazepines
- Diazepam, lorazepam, midazolam
- facilitate GABAa action by increasing frequency of Cl- channel opening
- most have long T1/2 (except midazolam)
- CNS depression, less risk of resp depression and coma than with barbiturates
- tx OD with flumazenil
Memantine
NMDA receptor antagonist; used for tx of alzheimers dementia (moderate-severe disease in adjunct to a AchE inhibitor, usually donepezil)
AchE inhibitors
Donepezil, galantamine, rivastigmine
- rivastigmine can also be used in Parkinson’s dementia
Pimavanserin
new 5-HT2A receptor inverse agonist that has been shown to reduce psychosis in Parkinson’s disease without worsening motor symptoms
Fingolimod
- acts on sphingosine-1 phosphate receptors (S1P1 receptor) –> decrease in release of lymphocytes
- first oral agent for treatment of MS
- side effects: macular edema, bradycardia
Antipsychotics associated with TD
fluphenazine and haldol
Drugs used to tx essential tremor
- combo of primidone and propranolol shown to be more effective than either alone (each reduces tremor by 50%)
- can also use topiramate, gabapentin, and benzo (clomazepam)
- in severely resistant cases, can consider DBS to ventra intermediate nucleus of thalamus
Tysabri (Natazulimab)
Monoclonal AB for relapsing MS
- MOA: selectively binds to alpha-4 subunit of integrin (cell adhesion molecule)
- reduces ability to inflammatory cells to cross BBB into CNS –> decreased inflammation
- need to screen for JC virus
Teriflunomide (Aubagio)
For RRMS
- selectively and reversibly inhibits DHOD (dihydroorate dehydrogenase) which is mitochondrial enz necessary for pyrimidine synthesis
- immunomodulatory effects which is useful in MS
- may cause transaminitis
Alemtuzumab (Lemtrada)
monoclonal AB useful for relapsing MS
- binds to CD52 (T and B lymphocytes)
- has serious side effects (emergency of 2/2 autoimmune dx)
- only approved to pts who have failed 2 other MS medications
Ocrelizumab (Ocrevus)
- target of action is CD20 (B cell marker); same as rituximab
- ## approved to relapsing and progressive MS
Antidepressants to be avoided in epilepsy
bupropion, TCAs, clomipramine, amoxapine
Antidepressants which precipitate and exacerbate RLS
TCAs, SSRIs, and lithium
Dalfampridine (Ampyra)
- potassium channel blocker, increases conduction of action potential in demyelinated axons (MS)
- improves gait function in 1/3 of MS patients
- SE: seizures and anxiety
Risperidone
- se: orthostatic hypotension, dizziness (alpha 1 blockade), headaches
- more likely to cause TD at higher doses than other atypical antipsychotics
Galantamine
- used in tx of AD
- acetylcholinesterase inhibition and modulation of nicotinic Ach R to increase presynaptic Ach
dextromethorphan-quinidine
used for tx of pseudobulbar affect
OCD treatment
First line: SSRI (fluoxetine, fluvoxamine, sertraline, paroxetine, escitalopram, citalopram)
Triptans
- work on the 5-HT 1D, 1B, and 1F receptors (agonist)
- used as migraine abortives
- use contraindicated in those with severe liver disease, pregnancy, cerebro-vascular disease, uncontrolled HTN, and CAD/PVD
Ergots (DHE)
- used as migraine abortive
- act on 5-HT 1B, 1D, and other 1 subtypes (agonist)
- also have agonist activity on D2 receptors (pre-treat with DA blockers to prevent side effects)
SNRI
- selective inhibition of both serotonin and NE
- duloxetine, venlafaxine, desvenlafaxine
Bupropion
- weak reuptake inhibitor of both DA and NE
Mirtazapine
- antagonist of presynaptic α2‐adrenergic autoreceptors and a2-heteroreceptors
- antagonist at post-snaptic 5-HT2, 5-HT3, and H1 receptors
Buspirone
- selective partial agonist activity at the 5-HT1A receptor (pre-synaptic)
- inhibitory effect on DA D2 Receptors
Dimethyl fumurate (Tecfidera)
- activating the nuclear erythroid 2-related factor 2 (Nrf2)
- side effects: flushing and GI distress
Most likely secondary antipsychotic to increase likelihhood of seizures
clozapine
Tertiary TCA
- amitriptyline, clomipramine, doxepin, imipramine
- block serotonin transporters and inhibit serotonin reuptake –> increased serotonin synaptic levels
Secondary TCA
- nortriptyline, protriptyline, desipramine
- block NE transporters and inhibit uptake of NE
TCA Side effects
- anticholinergic: dry mouth, constipation, urinary retention
- headache, weight gain, sweating
- cardiac arrhythmias
MAOI
- increase in synaptic serotonin, dopamine, and NE
- lots of SE: orthostatic hypotension, edema, weight gain, dizziness
- interactions with tyramine containing food
- need to wait for 3-4 week washout period before initiating SSRI, SNRI, TCA, dextromethorphan, ephedrine, and stimulants
SSRI
- fluoxetine, paroxetine, sertraline, citalopram, and escitalopram
- block serotonin reuptake; decrease in 5-HT1a receptors
- SE: diarrhea, anorgasmia, suicidality, serotonin syndrome
Disulfiram
- used in tx of alcohol dependence
- binds irreversibly to aldehyde dehydrogenase –> accumulation of aldehyde when alcohol is consumed –> flushing, nausea, vomiting, headache, & confusion
Naloxone
- short acting mu opioid receptor antagonist (high affinity) and kappa and delta opioid receptor antagonist (low affinity)
- used to treat opioid overdose –> withdrawal
Naltrexone
- long acting competitive opioid antagonist that blocks the subjective effects of opiates; does not block cravings
Methadone
long acting opioid agonist used as maintenance treatment of opioid dependence
Buprenorphine
mu-opioid receptor partial agonist (high affinity) and kappa-opioid receptor antagonist (lower affinity) used to treat opioid dependence. Allow for accelerated withdrawal without significant distress
Clonidine
- centrally acting alpha-adrenergic agonist
- used off label to treat opioid withdrawal
- most effective for autonomic signs and symptoms
