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Drug-induced psychosis & GI-D (ANG) (1)

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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
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