1.Acute decompensated heart disease.pptx

Pharmacotherapy for pharmacy students

1. Attention Deficit/Hyperactivity Disorder Desalegn Feyissa( B.Pharm ., MSc, RPh . Assistant Professor of Clinical Pharmacy) 4/4/2024 1 Attention Deficit/Hyperactivity Disorder Attention Deficit/Hyperactivity Disorder

2. Introduction The common childhood psychiatric disorders where the onset of symptoms explicitly occurs during childhood are: Attention deficit/hyperactivity disorder (ADHD) Tourette's disorder Enuresis Treating children with psychotropic drugs requires a very different approach than treating adults. Age-related pharmacodynamic and pharmacokinetic differences can alter drug disposition and response 2 4/4/2024 Attention Deficit/Hyperactivity Disorder

3. Cont… Children may not be able to articulate symptom response or adverse effects of a medication. Psychotropic drug treatment of children is intended to control symptoms or behaviors that impair learning and development. The psychiatric assessment of a child requires obtaining information from: the child, parents, caregivers and teachers. 4/4/2024 3 Attention Deficit/Hyperactivity Disorder

4. Definition A diagnosis of ADHD should be considered whenever a child presents with developmentally inappropriate inattention, impulsivity, and/or hyperactivity. Symptom presence and severity vary with the situation. It is unusual for a child to display signs of the disorder in all settings or even in the same setting at all times. 4/4/2024 4 Attention Deficit/Hyperactivity Disorder

5. Clinical Presentation and Epidemiology Several inattentive or hyperactive-impulsive symptoms have to present prior to age 12 years to meet the diagnostic criteria of DSM-V ADHD occurs in 6% to 9% of children and is estimated to be present in 4% of adults. In the United States, four boys are diagnosed with ADHD for every girl. Symptoms can persist lifelong for both sexes, but hyperactivity is much less prominent in adolescence and adulthood 4/4/2024 5 Attention Deficit/Hyperactivity Disorder

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7. Cont… Inattention and distractibility can be symptoms of an anxiety, mood, or psychotic disorder. In some cases, other disorders coexist with ADHD; learning deficiencies and conduct or oppositional disorders are common comorbid conditions. The presence of multiple comorbid conditions, particularly conduct or mood disorder, can increase the likelihood of ADHD chronicity into adulthood 4/4/2024 7 Attention Deficit/Hyperactivity Disorder

8. Etiology and Pathophysiology Both genetic and non-genetic factors are implicated in the pathogenesis. First-degree relatives of an individual with ADHD have a four- to eightfold increased chance of developing ADHD compared with the general population monozygotic twins have up to a 90% concordance rate for ADHD. Children with fetal alcohol syndrome, lead poisoning and meningitis have a higher incidence of ADHD symptomatology. 4/4/2024 8 Attention Deficit/Hyperactivity Disorder

9. Cont… ADHD is associated with a variety of environmental risks, including: obstetric adversity, maternal smoking, and adverse parent–child relationships. Although there are no definitive pathophysiologic markers for ADHD, imaging studies show subjects with ADHD have decreased total brain volume 4/4/2024 9 Attention Deficit/Hyperactivity Disorder

10. Cont… Brain changes are thought to impair executive functioning necessary for prioritization of tasks, decision making, motor control, and an awareness of space and time. Genetically mediated changes in serotonergic , cholinergic , and most notably dopaminergic function have been documented in children and adults with ADHD. Deficits in the dopaminergic reward pathway in the ADHD brain impair the ability to delay gratification, resist distractions, regulate arousal, and attend to information or tasks that are dull or repetitive 4/4/2024 10 Attention Deficit/Hyperactivity Disorder

11. Cont… This dysfunction involves multiple dopaminergic receptors (D 2 , D 3 , D 4 and D 5 ) and dopamine active transporter protein (DAT), which is pre-synaptic. Norepinephrine and epinephrine are agonists at dopaminergic receptors and are modulated by DAT as well. Treatment with stimulants has been shown to improve the rate of cortical thickening , and pharmacotherapy can improve or normalize dopaminergic receptor function. 4/4/2024 11 Attention Deficit/Hyperactivity Disorder

12. Cont… Those with demonstrated abnormalities in DAT seem to respond better to methylphenidate and atomoxetine Effective treatments modulate dopamine and norepinephrine to improve executive functioning, regulate arousal, and sustain attention for improved performance. The clinical response associated with stimulants is not diagnostic for ADHD because stimulants can increase attention, decrease motor activity, and improve learning tasks in those with subclinical ADHD or in individuals with such problems from other sources (e.g., fatigue). 4/4/2024 12 Attention Deficit/Hyperactivity Disorder

13. Treatment Stimulants Stimulants are considered first-line therapy in most cases of ADHD; however, comorbid conditions impact the drug selection process. Pharmacotherapy should be considered whenever a thorough diagnostic assessment results in a diagnosis of ADHD. Several studies demonstrate the superiority of stimulants over behavioral interventions in alleviating core symptoms of ADHD. 4/4/2024 13 Attention Deficit/Hyperactivity Disorder

14. Cont… Emerging literature shows improvement in academic performance in medicated children with ADHD versus those un-medicated Multimodal treatment, individualized to the specific needs of the child and family, is crucial for an overall positive therapeutic outcome which includes: parent training family therapy classroom interventions and contingency management (e.g., rewards for good behavior). 4/4/2024 14 Attention Deficit/Hyperactivity Disorder

15. Behavioral Interventions for ADHD Technique Description Example Positive reinforcement Providing rewards or privileges contingent on the child’s performance Child completes an assignment and is permitted to play on the computer Time-out Removing access to positive reinforcement contingent on the child’s performance of unwanted or problem behavior Child hits sibling impulsively and is required to sit 5 minutes in the corner of the room Response cost Withdrawing rewards or privileges contingent on the child’s performance of unwanted or problem behavior Child loses free-time privileges for not completing homework Token economy Combining positive reinforcement and response cost. The child earns rewards and privileges contingent on performing desired behaviors and loses the rewards and privileges based on undesirable behaviors Child earns stars for completing assignments and loses stars for getting out of seat. The child cashes in the sum of stars at the end of the week for a prize 4/4/2024 Attention Deficit/Hyperactivity Disorder 15

16. Cont… Stimulants are the most effective drug treatment options, with efficacy ranging from 70% to 96%. e.g., methylphenidate, dexmethylphenidate, mixed amphetamine salts, and dextroamphetamine Methylphenidate and amphetamines block dopamine and norepinephrine reuptake amphetamines also increase catecholamine release. Both drugs inhibit monoamine oxidase (MAO), or amphetamines, more potently than methylphenidate 4/4/2024 16 Attention Deficit/Hyperactivity Disorder

17. Cont… Because different stimulants work through slightly different mechanisms, the lack of response to one chemical class of stimulant does not preclude response to another class Stimulant dosing should be titrated for maximum individual efficacy and minimum side effects With immediate-release stimulants, most patients require a two or three times daily dosing schedule because of the short half-lives of these drugs 4/4/2024 17 Attention Deficit/Hyperactivity Disorder

18. Cont… Immediate-release formulations have the advantage of lower cost, less insomnia, and potentially fewer growth effects versus extended-release products. Drug response is maximal during the absorption phase, is evident in 15 to 30 minutes, and lasts 2 to 6 hours Methylphenidate transdermal system provides 12 hours of symptom control when worn for 9 hours. 4/4/2024 18 Attention Deficit/Hyperactivity Disorder

19. Cont… Drug delivery systems of once-daily products provide 8 to 12 hours of symptom control Once-daily stimulant formulations are the preferred treatment for ADHD in most individuals due to convenience and better medication adherence. Adolescents and adults with ADHD are also responsive to stimulants. 4/4/2024 19 Attention Deficit/Hyperactivity Disorder

20. Adverse Effects: Stimulants Psychiatric The Food and Drug Administration (FDA) has added warnings to the labeling of all stimulants & atomoxetine. Hundreds of post-marketing reports of three broad categories of psychiatric adverse events have been associated with stimulants: psychosis or mania aggression or violent behavior and severe anxiety or panic attacks. All of these reactions require dose reduction or cessation of stimulant therapy and supportive treatment 4/4/2024 20 Attention Deficit/Hyperactivity Disorder

21. Cardiac A boxed warning for cardiovascular risks including sudden unexplained death has been added to ADHD stimulant drug labeling Stimulant products generally should not be used in pediatrics or adults with known structural cardiac abnormalities. AHA recommends careful screening of all children and adolescents prior to initiating pharmacologic therapy for ADHD, including a detailed patient and family history and physical examination 4/4/2024 21 Attention Deficit/Hyperactivity Disorder

22. Cont… Ideally, a baseline electrocardiogram (ECG) should also be obtained, along with routine monitoring of pulse and blood pressure. The FDA did not find the risk of sudden unexplained death to be greater in those taking stimulants than in the general population; therefore, no restriction in stimulant use has been recommended 4/4/2024 22 Attention Deficit/Hyperactivity Disorder

23. Growth Stimulant treatment of ADHD can affect growth, but the effects are minimal or insignificant for most children. Amphetamine products may be associated with more prominent growth effects than methylphenidate Proposed mechanisms of stimulant effects on growth include: alterations in growth hormone or growth factor decreased thyroxine secretion and suppression of appetite leading to reduced caloric intake. 4/4/2024 23 Attention Deficit/Hyperactivity Disorder

24. Cont… In most cases, children should be given a drug-free trial every year. Time off stimulant appears to lessen stimulant growth suppressant effects, but evidence is lacking to firmly determine the impact of drug holidays on growth. 4/4/2024 24 Attention Deficit/Hyperactivity Disorder

25. Cont… Consideration must be given to the risks of negative effects on learning, socialization, and self-image while off stimulant therapy when determining the frequency and duration of the drug-free trial Drug holidays are important because they provide time to reassess the need for continued treatment. Drug dosage often varies from year to year, largely because of age-related pharmacokinetic changes. 4/4/2024 25 Attention Deficit/Hyperactivity Disorder

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29. Treatment Non-stimulants Extended-release atomoxetine and guanfacine are second-line alternatives to the stimulants for treatment of ADHD in children and adolescents. Their potential benefits relative to stimulants include: no abuse potential less potential for growth effects and less sleep disturbance 4/4/2024 29 Attention Deficit/Hyperactivity Disorder

30. Cont… Atomoxetine is a selective NERI Twice-daily dosing is optimal in children and adolescents to improve tolerability. also approved in adults. Adults can take it once daily , usually in the morning. has a significantly slower onset of therapeutic effect than stimulants (2–4 weeks vs 1 hour ) sometimes combined with a stimulant in partially responsive patients describing fewer late-day rebound effects and better sleep when it is given in the evening; however, adverse effects are additive

31. Cont… Guanfacine and clonidine are central alpha 2 -adrenergic agonists, acting post- synaptically to increase blood flow in the prefrontal cortex. Increased blood flow in the prefrontal cortex has been shown to enhance working memory and executive functioning. Both interact with a multitude of neurotransmitter systems, including: catecholamine, indolamine , alpha 2 -receptors on parasympathetic neurons, opioids , imidazole , and amino acid systems. 4/4/2024 31 Attention Deficit/Hyperactivity Disorder

32. Cont… Guanfacine has a longer elimination half-life (12–18 hours) compared with clonidine (2.5–4 hours), and its greater selectivity for the alpha 2a -receptor, compared with clonidine, imparts less sedation. Clonidine and immediate-release guanfacine are not as effective as stimulants for monotherapy treatment. They are prescribed frequently as adjuncts to reduce disruptive behavior, control aggression, or improve sleep 4/4/2024 32 Attention Deficit/Hyperactivity Disorder

33. Cont… Extended-release guanfacine is approved for children and it appears at least as effective as other non-stimulants and is an acceptable second-line agent for children and adolescents unresponsive to or unable to tolerate stomach upset or insomnia with stimulant medications. is more sedating than stimulants or atomoxetine therefore, sleepiness during the school day requires careful monitoring. 4/4/2024 33 Attention Deficit/Hyperactivity Disorder

34. Cont… Bupropion , a monocyclic antidepressant, is a weak dopamine and norepinephrine reuptake inhibitor with no significant direct effect on serotonin or MAO. has less appetite suppression compared with stimulants but has a greater risk of seizures. metabolized faster in prepubertal children , making twice daily dosing optimal for efficacy (even for bupropion SR) It also may be effective in adults at antidepressant doses. Once-daily dosing is possible for most adults. 4/4/2024 34 Attention Deficit/Hyperactivity Disorder

35. Cont… Tricyclic antidepressants (TCAs) last-line agents because they are the most dangerous in overdose and pose the greatest risk for cardiovascular side effects. Imipramine and desipramine are the most systematically studied TCAs in the treatment of ADHD, although nortriptyline is also effective. The onset of TCA clinical response occurs within the first 2 to 4 weeks 4/4/2024 35 Attention Deficit/Hyperactivity Disorder

36. Cont… Lithium and anticonvulsants are used increasingly to control aggression and explosive behavior in patients with a diagnosis of ADHD. Lithium , valproate , and carbamazepine are effective for explosive behavior, aggression, and impulsivity, but they are not beneficial treatments for a child with the inattentive subtype of ADHD. Dosing starts in low divided doses with titration over 1 to 2 weeks to therapeutic response 4/4/2024 36 Attention Deficit/Hyperactivity Disorder

37. Cont… Antipsychotics Conventional antipsychotics improve symptoms of hyperactivity and impulsivity but can have negative effects on learning and cognitive functioning and can cause extrapyramidal side effects (e.g., dystonia and tardive dyskinesia) that limit their usefulness. atypical antipsychotics have been used to control severe aggression in refractory cases of ADHD, particularly if conduct disorder or bipolar disorder coexists. E.g. risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole 4/4/2024 37 Attention Deficit/Hyperactivity Disorder

38. Cont… If multiple drugs are started simultaneously, it is impossible to determine the impact of each drug. The predominance and urgency of symptoms guide the drug-selection process For example, if a child presents as severely anxious or depressed with associated attentional problems, then an antidepressant should be initiated first with monitoring to determine if attentional symptoms improve 4/4/2024 38 Attention Deficit/Hyperactivity Disorder

39. Cont… When a child presents with severe ADHD and associated anxiety or depression, a stimulant should be initiated to treat the more severe ADHD. If ADHD symptoms improve significantly, but anxiety or depression persists, then an antidepressant can be added . Careful monitoring is needed to detect drug interactions that lead to higher drug plasma levels and increased adverse effects. 4/4/2024 39 Attention Deficit/Hyperactivity Disorder

40. Adverse Effects Non Stimulants Atomoxetine Possible adverse effects of atomoxetine, and their management, are similar to those of stimulants, including psychiatric and cardiac adverse effects It has been associated with less growth suppression compared with stimulants, 0.44 cm over 2 years of treatment. 4/4/2024 40 Attention Deficit/Hyperactivity Disorder

41. Cont… It has a greater risk of fatigue , sedation , and dizziness compared with stimulants and bupropion Unlike stimulants, atomoxetine labeling includes a bolded warning of potential for severe liver injury It is the only FDA-approved ADHD medication with a labeled warning for new onset suicidality , 0.4% in atomoxetine treated patients versus 0% in patients receiving placebo 4/4/2024 41 Attention Deficit/Hyperactivity Disorder

42. Cont… Clonidine and guanfacine The most common side effects of clonidine and guanfacine are dose-dependent sedation , hypotension , and constipation . Sedation usually subsides after 2 to 3 weeks of therapy. Of concern are reports of bradycardia, syncope, rebound hypertension, heart block, and sudden death with clonidine. Extended-release guanfacine appears to pose a lower risk of cardiac adverse effects 4/4/2024 42 Attention Deficit/Hyperactivity Disorder

43. Cont… Bupropion Nausea can resolve over time or with slower dosage titration rash , which can require discontinuation of therapy if severe Bupropion should not be used in children with a seizure because of unacceptable risk of seizures in these patients. Bupropion can cause or exacerbate tics 4/4/2024 43 Attention Deficit/Hyperactivity Disorder

44. Cont… TCA Possible CNS adverse effects of TCAs include dizziness, aggressiveness, excitement, nightmares, insomnia, forgetfulness and irritability. Similar to other antidepressants, TCAs carry a warning of the risk of new-onset suicidality in pediatric patients. TCA-withdrawal effects are severe in children and include nausea , vomiting and diarrhea . 4/4/2024 44 Attention Deficit/Hyperactivity Disorder

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47. Cont… 47 DEX, dextroamphetamine; DMPH, dexmethylphenidate; MPH, methylphenidate; MXA, mixed amphetamine salts;

48. Evaluation of Therapeutic Outcomes Careful documentation of baseline symptoms and complaints over a 1-month pre-drug period is essential to the evaluation of therapeutic and adverse outcomes. Investigation regarding family history of psychiatric disorders and cardiac disease is essential to determine risk for related adverse drug reactions and to implement appropriate monitoring The benefits of drug therapy must outweigh the potential for adverse effects. 4/4/2024 48 Attention Deficit/Hyperactivity Disorder

49. Cont… After the initiation and titration of any drug treatment, it is necessary that parents, teachers, and clinicians assess the overall functioning of the child using standardized rating scales to determine if significant therapeutic benefit justifies continuing medication. Therapeutic effects of the stimulants include decreased motor activity and impulsivity and increased attention span. 4/4/2024 49 Attention Deficit/Hyperactivity Disorder

50. Reading Assignment (1%) Tourette's Disorder Enuresis Conduct disorder 4/4/2024 50 Attention Deficit/Hyperactivity Disorder

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