Drug-induced psychosis Afrillia Nuryanti Garmana Definitions • “gross impairment in reality testing” or “loss of ego boundaries” that interferes with the capacity to meet the ordinary demands of life (APADSM IV) • the presence of hallucinations, delusions, or both (APA-DSM V, WHOICD10) • “formal thought disorder” (ie, disorganized thinking, including illogicality, tangentiality, perseveration, neologism, thought blocking, derailment, or some combination of these disturbances of thought) is one of several commonly co-occurring features of psychotic disorder (APA, WHO) • Related physical symptoms can include agitation, anxiety, aggressions, pacing, unusual behavior • Psychosis is not a specific diagnosis but rather a feature of many disease states Causative agents NK: Not known Causative agents NK: Not known Causative agents NK: Not known Mechanisms • Psychosis is not a single disorder but rather a symptom induced by multiple mechanisms: • Increased dopamine and NE concentrations • NMDA antagonism • Down regulation of serotonin 1 receptor density • Up regulation of serotonin 2 receptor density • Decrease cholinergic function Clinical presentation and diagnosis • Many symptoms in in patients with drug-induced psychosis are similar to those patients with idiopathic psychoses observed in conditions such as schizophrenia. • There is no individual test that is diagnostic for drug-induced psychosis • Diagnosis depends on identification of a temporal relationship between the ingestion of the suspect substance and the onset of psychotic symptoms, clinical presentation, and a through medical and medication history. • Consultation with family , friends and other healthcare providers is useful in understanding any preexisting mental health issue and recent changes in behavior or medical treatment. Risk factor Approaches to help prevent drug-induced psychosis • Use lowest dosage possible • Minimize total number of medications • Limit medication with anticholinergic properties • Adjust dosage for elderly • Avoid use of multiple psychotomimetic medications • Complete a through medication history, including non-prescription drugs, herbal formulations, alcohol, and illicit drugs Management • Typically, drug-induced psychosis is self-limiting and remits within several hours or several days after drug discontinuation. • The choice of medication should be based on efficacy, patient acceptability, and the adverse effect profile of the drug. • Treatment should include discontinuation of the agent. • If it can’t be done, decrease the dose to below psychotomimetic levels, treatment with antipsychotic medication or both. • During acute illness, keeping the patient in a save environment is important. • The goal of short-term treatment is to contain and calm the patient • Hydration to decrease the risk of delirium • Treatment of acute agitation and anxiety: benzodiazepine • Antidots Drug-induced Gastrointestinal Diseases Afrillia Nuryanti Garmana Upper gastrointestinal ulceration Pancreatitis Hepatic disease Diarrhea Constipation Upper Gastrointestinal Ulceration Causative agents Mechanisms Mechanisms • Aspirin and NSAIDs : inhibition of COX → reduce prostaglandins → cytoprotective effect on the GI mucosa ↓ • Corticosteroids: impair mucosa healing • Direct irritant: • Formulation: Tablets may be difficult to swallow or contain a caustic coating; slow-release, wax-matrix formulation • pH and concentration of medication Clinical presentations Risk factors Management • • • • Correct administration of drug Use the lowest possible dose Replacement of prostaglandin deficiency and inhibition of acid secretion Acid suppression with traditional ulcer healing doses of H2-blockers is effective in healing gastric and duodenal ulcers upon discontinuation of the offending drug • Acid suppression with proton pump inhibitors (omeprazole 20–40 mg, lansoprazole 30 mg daily) also appears to be very effective in healing gastric and duodenal ulcers in patients continuing the offending drug as well • In long-term prevention studies, omeprazole (20 mg daily) and pantoprazole (40 mg daily) have also been shown to reduce the risk of gastric and duodenal ulcers and non-steroidal anti-inflammatory drug-related dyspepsia Diarrhea Causative agents Causative agents Causative agents Causative agents Causative agents Causative agents Mechanisms of drug-induced diarrhea Mechanisms of drug-induced diarrhea Clinical presentations Management • Withdrawal • Use solid dosage form • CTID (cancer treatment-induced diarrhea): • Uncomplicated, grade 1 or 2: loperamid reassessed after 12 or 24 hours. If diarrhea persist, increase loperamid dose • Unresolved diarrhea after additional 12 or 24 hours: ocreotide • Grade 3 or 4: admitted to the hospital and given i.v. fluids and antibiotics • Cytotoxic chemotherapy should be discontinued Constipation Causative agents Causative agents Causative agents Mechanisms • 2 categories: anatomic and functional • Anatomic constipation is not drug-related • Functional constipation results from abnormalities in colonic neural regulation or motor function. • Elimination from colon normally occurs within 4 days • Colonic dysfunction increase colonic transit time: 10 days or longer Mechanisms Clinical presentations Risk factor Management Management Pancreatitis Causative agents Mechanisms • Potential mechanisms for drug-induced acute pancreatitis include: • pancreatic duct constriction, • cytotoxic and metabolic effects, • accumulation of a toxic metabolite or intermediary, and • hypersensitivity reactions. • Negative effects of drugs, such as hypertriglyceridemia and chronic hypercalcemia, are also mechanisms for drug-induced acute pancreatitis, as these effects are risk factors for acute pancreatitis. • Other possible mechanisms of action are localized angioedema effect in the pancreas and arteriolar thrombosis Angiotensin-Converting Enzyme Inhibitors • bradykinins are released during acute pancreatitis • vascular permeability increased in the pancreas during acute pancreatitis • It results in pancreatic edema, causing enzymes and other toxic substances to be trapped within the pancreas and leading to tissue damage in the pancreas and acute pancreatitis • angiotensin II receptors may be important in regulating secretion and microcirculation within the pancreas Statins • Direct toxic effect to the pancreas and the accumulation of a toxic metabolite • speculated to be associated with rhabdomyolysis, myalgia, and/or metabolism or drug interactions through cytochrome P-450 3A4 (CYP3A4) • Pravastatin does not metabolize CYP3A4, it may have fewer case reports of drug-induced acute pancreatitis than other statins Oral Contraceptives/Hormone Replacement Therapy • patients develop hypertriglyceridemia as a new diagnosis, existing hypertriglyceridemia is exacerbated, patients are diagnosed with previously unknown familial hyperlipoproteinemia. • rapid accumulation of triglyceride-containing lipoproteins, mostly chylomicrons, are believed to lead to ischemic events in the microcirculation of the pancreas • Pancreatic necrosis is induced by a hypercoagulable state Diuretics • direct toxic effect to the pancreas, diuretic-induced stimulation of pancreatic secretion, and ischemia • a decreased volume of extracellular fluid lessens pancreatic blood flow, thereby leading to ischemia • the negative effects of hydrochlorothiazides are hypercalcemia and hyperlipidemia → risk factor Highly Active Antiretroviral Therapy • HIV directly causes inflammation of the pancreas • the antiretroviral therapy could potentially cause a toxic effect directly to the pancreas or induce negative effects associated with acute pancreatitis • Protease inhibitors (PIs) can cause metabolic disturbances, including development of insulin resistance, hyperglycemia, hypercholesterolemia, and hypertriglyceridemia. Hypoglycemic Agents • The pathogenesis of GLP-1 analog-induced pancreatitis is unclear, but current evidence suggests an additive or synergistic exacerbation of pancreatitis when GLP-1 analogs are used in the presence of a high fat diet • injury appears to begin with acinar cell hypertrophy, progress to proinflammatory cytokine induction, and culminate in pancreatic vascular injury. Clinical presentations • The symptoms depend on the severity of the pancreatitis. • Abdominal pain, nausea, and vomiting • Patient with mild acute pancreatitis may experience only minimal tenderness to palpation • The pain is constant, usually located in the epigastrium, and generally described as knifelike and radiating to the midcentral back • Restless • Jaundice • Patients with severe acute pancreatitis can also develop fever, tachypnea, hypoxemia, and hypotension • Alterations in mental status • Local complications include fluid accumulation, pancreatic pseudocyst, necrotic collection, and walled-off necrosis. The fluids and necrotic tissue can become secondarily infected, leading to systemic inflammatory response syndrome and sepsis Diagnosis • Serum lipase and amylase, serum trypsinogen, pancreatic proteases, C-reactive protein, interleukin-6, and interleukin-8 • Medical history and the patient’s medications record • Medical history and the patient’s medications must be recorded. Focus on: previous symptoms and any record of gallstones, ethanol abuse, hypercalcemia, hypertriglyceridemia, and trauma • Abdominal and endoscopic ultrasounds should be performed to evaluate for gallstones and other obstructive possibilities such as tumors of the pancreas head Prevention Management • Discontinuation of the suspect agent • Administering nothing by mouth • Providing adequate analgesia
