Comprehensive Pharmacology of ADHD and Narcolepsy: Stimulants, Non-Stimulants, Wakefulness-Promoting Agents, Mechanisms, Formulations, Clinical Uses, Adverse Effects, and Evidence-Based Management Strategies Verified Questions Provided with A+ Graded Rati

Comprehensive Pharmacology of ADHD and Narcolepsy: Stimulants, Non-Stimulants, Wakefulness-Promoting Agents, Mechanisms, Formulations, Clinical Uses, Adverse Effects, and Evidence-Based Management Strategies Verified Questions Provided with A+ Graded Rationales Latest Updated 2026 Stimulants • Amphetamine- Dextroamphetamine Mixed salts • Dexmethylphenidate • Dextroamphetamine • Lisdexamfetamine • Methylphenidate Non-Stimulants • Atomoxetine • Guanfacine XR • Clonidine XR Stimulants -increase available nuerotransmitters in the synaptic cleft to increase neurotransmission in under-responsive neuronal pathways -decreases impulsivity and decreases motor activity -2 Classes: Amphetamines and Methylphenidates Stimulants Indications: • ADHD, narcolepsy • High efficacy: 1st-line therapy for ADHD • Specific agents: binge-eating disorder Stimulants • Generally recommended to avoid in pregnancy if able • ↑ risk of gastroschisis, omphalocele, transverse limb deficiency when used early in pregnancy Amphetamines Mechanism: -enters synapse using NET transporter and displaces stored catecholamines from vesicles -causes reverse tranport into synapse via NET -also competitively inhibits dopamine transport -inhibits VMAT and the filling of synaptic vesicles Methylphenidates Mechanisms: -Interferes with norepinephrine reuptake by blocking NET -also interferes with dopamine reuptake by blocking DAT Amphetamines -Dextroamphetamine -MXA -Methamphetamine -Lisdexamfetamine Amphetamines -Cause release of dopamine (DA) and norepinephrine (NE) from vesicular storage sites into synapse Efficacy: amphetamine methylphenidate • ↑ tolerability -considered 1st line in adults Methylphenidates -Blocks reuptake of DA and NE into presynaptic terminals • Overall better tolerability in children and adolescents -1st line in younger age groups • Mild CNS stimulant with more prominent effects on mental than on motor activities Lesdexamfetamine a prodrug converted to dextroamphetamine via hydrolysis in the gut Acidification ___________________ of the urine increases excretion of stimulants IR Which type of Stimulant formulation? -typically dosed 2-3 times daily • Short t1/2 • Higher risk of diversion and abuse • Lower cost, less insomnia, fewer growth effects ER or Patch Which type of Stimulant formulation? -dosed once-daily • Convenience and better medication adherence; often preferred -Cardiovascular risk, including sudden death • Avoid in structural cardiac abnormalities, cardiomyopathy, serious arrhythmia, CAD, Marfan syndrome, or serious cardiac issue • Abuse/misuse/diversion: high potential for abuse and dependence BW for Stimulants Stimulants CIs: -hypersensitivity -use w/in 14 days of MAOIs -Additional CIs on specific products: advanced arteriosclerosis; symptomatic cardiovascular disease, severe hypertension, hyperthyroidism; glaucoma, agitated states; history of drug abuse Stimulants AEs: -↑ BP; reflex bradycardia, arrythmia -Insomnia, headache, confusion, emotional liability and rebound symptoms, dizziness, ↑ irritability, ↑ nervousness, agitation -↓ appetite (anorexic, wt. loss), xerostomia, abdominal pain, nausea, vomiting, diarrhea -RARE: skin discolorat