indirect-acting sympathomimetics Flashcards
-phenylpropanolamine derivative with tricyclic-like structure
-nonstimulant drug used to treat ADHD; no abuse potential
MOA: selective inhibition of presynaptic NE transporter
Does not have significant cardiovascular effects because of clonidine-like effect in the CNS to decrease sympathetic outflow while potentiating effects of NE at the periphery
Does not induce DA release in the nucleus accumbens - low potential for abuse, unlike methylphenidate and amphetamine
Side effects: abdominal discomfort, vomiting, nausea, diarrhea, decreased appetite with weight loss, sexual dysfunction, dizziness, vertigo, irritability, mood swings, somnolence, minor increases in BP and HR (orthostatic tachycardia), rare severe liver injury causing jaundice (discontinue)
mean height and weight percentiles declined in children, but this is reversed with discontinuation of the drug
Interactions: Do NOT take within two weeks of taking a MAOI (fatal hypertensive crisis) or with narrow-angle glaucoma, CYP2D6 inhibitors paroxetine and fluoxetine can increase its half-life
Dosing can be a single daily dose or broken into several evenly divided doses
Atomoxetine
Strattera
indirectly-acting sympathomimetic used as first line to treat ADHD MOA: transport reversal cause release of dopamine & NE from presynaptic neurons; weak inhibition of NT reuptake and MAOIs Metab: peak 2-3 hours, half-life 6 hours; must dose once or twice daily Side effects (all stimulants!): twice as potent as methylphenidate, worsens tic disorders, stomach pain, anxiety, irritability, insomnia, tachycardia, cardiac arrhythmias, dysphoria, decreased appetite, increase in HR and BP, palpitations, induction of movement disorders (tics, Tourette's disorder-like symptoms, dyskinesias), can exacerbate glaucoma (alpha receptor activation), HTN, cardiovascular disorders, hyperthyroidism, anxiety disorders, psychotic disorders, seizure disorders, High doses can cause: dry mouth, pupillary dilation, bruxism, formication,excessive ebullience, restlessness, emotional lability, long-term use can cause paranoid schizophrenia Most limiting aspect of sympathomimetic use: dependence, but this is not typical at dosing for ADHD Do not use in pregnancy. Interactions: coadministration with tricyclic or tetracyclic antidepressants, warfarin (Coumadin), primidone (Mysoline), phenobarbital (Luminal), phenytoin (Dilantin) or phenylbutazone (Butazolidin) decreases metabolism of these drugs therefore increasing plasma levels; Sympathomimetics also decrease therapeutic efficacy of antihypertensive drugs (Esimil, Ismelin); Use with caution with MAOIs **Note: all sympathomimetics should be tried before switching to drugs in a different class **Lab Interference: Can elevate plasma corticosteroid levels & interfere with some assay methods for urinary corticosteroids
Dextroamphetamine
Dexedrine
Class: Indirectly-acting sympathomimetic (psychostimulant)
MOA: causes release of catecholamines from presynaptic neurons, increasing release of dopamine and NE; weak inhibitor of catecholamine reuptake & MAO
Schedule II controlled substance, because of its propensity for diversion & abuse
In ADHD: improve hyperactivity, impulsivity, inattentiveness, improve social interactions with teachers, family & other adults & peers; most commonly used first
Dose: 5-10 mg q 3-4 hrs to max 20 mg qid
Metab: peak 1-2 hrs with Half-life 2-3 hrs
Interactions: coadministration with tricyclic or tetracyclic antidepressants, warfarin (Coumadin), primidone (Mysoline), phenobarbital (Luminal), phenytoin (Dilantin) or phenylbutazone (Butazolidin) decreases metabolism of these drugs therefore increasing plasma levels; Sympathomimetics also decrease therapeutic efficacy of antihypertensive drugs (Esimil, Ismelin); Use with caution with MAOIs
derivative of amphetamine
Concerta is extended release.
methylphenidate
Ritalin
racemic mixure of phenylisopropylamine used as a CNS stimulant
stimulates mood & alertness, while acting as an appetite suppressant
MOA: release of NE and dopamine by reversing the DA and NE transporters, resulting in DA & NA release into the synapse
Neurons in ventral tegmental area contain dopamine
Neurons in locus coeruleus contain NE
amphetamine
Adderall
Class: psychostimulant
MOA: increases release of DA, NE and 5-HT via transporter reversal
like amphetamine but with higher ratio of central to peripheral actions
methamphetamine
Class: psychostimulant (amphetamine substitute)
MOA: inhibits both NE and dopamine transporters and increases synaptic concentrations of NE, dopamine, serotonin and glutamate, while decreasing GABA
Use: narcolepsy
Side Effects: mild increased bp and HR, appetite suppression
modafinil
Provigil
normal byproduct of tyrosine metabolism in the body
-Can be produced in high concentrations in protein-rich foods by decarboxylation of tyrosine during fermentation
-Metabolized by MAO in the liver and inactive if taken orally due to high first-pass effect
-If given parenterally (infusion, injection or implantation), causes INDIRECT SYMPATHOMIMETIC action by release of stored catecholamines with spectrum of action similar to NE
MAOIs greatly increase its effects - increased bp
Tyramine
d-enantiomer of methylphenidate
pharmacologically more active than the racemic mixture and can be given at half the dose
dexmethylphenidate
Focalin
MOA: transport reversal, increasing NE and DA
pro-drug formulation of amphetamine which is d-amphetamine bonded covalently to L-lysine. Once ingested it is converted to d-amphetamine and L-lysine by enzymatic hydrolysis.
Designed to have less abuse potential but is still a Schedule II controlled substance
lisdexamfetamine
Vyvanse
over-the-counter appetite suppressant component that was removed from the market because of hemorrhagic strokes in women
Can increase bp in patients with impaired autonomic reflexes
phenylpropanolamine
Class: psychostimulant
MOA: NET blocker so blocks reuptake of DA, NE and 5-HT
results in increase in NE in the synapse and therefore activation of alpha and beta adrenoreceptors
cocaine
Mixed-acting sympathomimetic that is the precursor for methamphetamine
Use: decongestant
pseudoephedrine
