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SEARCH RESULTS FOR: Lithium

Serotonin Syndrome Pathogenesis and Clinical Findings

Serotonin Syndrome: Pathogenesis and Clinical Findings 
Serotonergic Agents SSR1s, SNRIs, MOAIs, TCAs, atypical antidepressants, antibiotics, mood stabilizers (valporate, lithium), opioids, antiemetic agents, triptans, weight loss agents, drugs of abuse (e.g. cocaine, amphetamines) 
Therapeutic drug use 
• Drug interactions (esp. combo of serotonergic agents) Serotonin Syndrome  Variable combination of mental status changes, autonomic instability, and neuromuscular hyperactivity ranging from mild to life-threatening with an abrupt onset (within minutes to hours) after medication ingestion and most cases resolving within 24 hours of cessation of offending medication 
Intentional self-poisoning 
Excessive serotonergic activity at 5-HT receptors centrally (brainstem) and peripherally 
serotonin synthesis and release 
serotonin reuptake and metabolism 
IN receptor agonism and sensitivity 
4, 
Drug-induced changes in the relative ratio of non-serotonergic neurotransmitters (e.g. increase in noradrenaline)  
Altered Mental Status 
Anxiety, confusion, agitation, hypervigilance, pressured speech, delirium, coma 
Autonomic Instability 
Shivering, diaphoresis, fever, diarrhea, tachycardia, mydriasis, hypertension 
Authors: Preeti Kar Reviewers: Erika Russell Usama Malik Aaron Mackie* * MD at time of publication 
Notes: The Hunter Serotonin Toxicity Criteria is used to make a clinical diagnosis • History of serotonergic agent taken within past 5 weeks + any of the following clinical features: • Spontaneous clonus • Inducible clonus and either agitation or diaphoresis • Ocular clonus and either agitation or diaphoresis • Tremor and hyperreflexia • Hypertonia, temperature > 38 °C, and either ocular clonus or inducible clonus 
Neuromuscular Hyperactivity 
Hyperreflexia, muscle rigidity (esp. lower extremities), myoclonus, tremor, incoordination, trismus*, opisthotonus*, ocular clonus*, seizures 
*Notes: • Trismus or lockjaw, is the reduced opening of the jaw • Opisthotonus is an abnormal body position where the person is usually rigid and arches their back, with their head thrown backwards • Ocular Clonus is rhythmic or equal movements of both eyes; should be distinguished from nystagmus which has a fast and slow component 
Legend: Pathophysiology Mechanism 
Sign/Symptom/Lab Finding 
Abbreviations: • 5-HT = serotonin • SSRI = selective serotonin reuptake inhibitors • SNRI = selective noradrenaline reuptake inhibitors • MOAI = monoamine oxidase inhibitors • TCA = tricyclic antidepressants

diabetes-insipidus-pathogenesis-and-clinical-findings

Diabetes Insipidus: Pathogenesis and clinical findings
Hereditary
Autoimmune/ Idiopathic
Auto-antibodies destroy neurons that release antidiuretic hormone (ADH)
Mass Effect/ Tumor Invasion
Mass pressing on hypothalamus or pituitary
       Electrolyte Imbalance
(mechanism unclear)
Hereditary
Lithium (Li)
(mechanism unclear)
Li enters principal cells of collecting ducts via ENaCs
Li inhibits GSK3β, reducing adenylyl cyclase activity
↓ cAMP- dependent phosphorylation of aquaporin-2
           ↑ Serum [Ca2+]
Activation of
CaSR in thick ascending limb of Loop of Henle
↓ NaCl reabsorption in thick ascending limb
↓ Generation of medullary osmotic gradient
↓ Serum [K+]
↑ Degradation of aquaporin-2 channels in collecting duct
↓ Aquaporin- 2 channels transporting water across apical membrane of collecting duct
Mutation of AVPR2 gene on X chromosome
Antidiuretic hormone (ADH) receptor cannot reach basolateral surface of principal cells of collecting duct
Mutation of aquaporin-2 gene on chromosome 12
↓ Fusion of aquaporins with apical membrane of collecting duct
Mutation of WFS1 gene on chromosome 4 (Wolfram syndrome)
↓ Processing of antidiuretic hormone (ADH) precursors and ↓ADH-releasing neurons
Surgery/ Trauma
Injury to hypothalamus or pituitary stalk
Mutation of PCSK1 gene on chromosome 5
Deficiency in PC1/3 (encoded by PCSK1)
↓ Processing of ADH by PC1/3
                        Aquaporin dysfunction
     ↓ Kidney response to ADH, which mediates reabsorption of water down its osmotic gradient through aquaporins
↓ Production of ADH by hypothalamus or ↓ secretion from ADH-releasing neurons in posterior pituitary (depending on location of lesion)
Central Diabetes Insipidus
 Nephrogenic Diabetes Insipidus
   Abbreviations:
AVPR2: arginine vasopressin receptor 2 CaSR: calcium-sensing receptor
ENaC: epithelial sodium channel
GSK3β: glycogen synthase kinase type 3 beta PC1/3: proprotein convertase
Diabetes Insipidus
Decreased ability of kidneys to concentrate urine
↓ Reabsorption of water from collecting duct into vasculature
    Author:
Oswald Chen
Reviewers:
Huneza Nadeem,
Ran (Marissa) Zhang,
Yan Yu*
Sam Fineblit*
* MD at time of publication
Urine becomes more dilute
↓ Urine osmolality
↑ Urine output
↓ Blood volume
Blood becomes more concentrated
           Occurs during late sleep period
Nocturia
Polyuria
(>3 L/day)
↑ Serum osmolality
Activation of hypothalamic osmoreceptors
Hypernatremia
(Serum [Na+] >145 mEq/L)
Polydipsia
     Legend:
 Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
 Complications
Published September 25, 2022 on www.thecalgaryguide.com

Lithium

Lithium: Mechanism of action and side effects
Bipolar (I & II)
Treatment-resistant
depression
Accumulated Li
inhibits adenylyl
cyclase
Suicidality
Schizoaffective Disorder
Li passively enters
cells in kidney,
thyroid, & area
postrema via
sodium channels
Li’s small
size
prevents
active
transport
out of cells
↓ cAMP
↓ PKA phosphorylation
Lithium (Li)
Magnesium (Mg²⁺) analog which inhibits
Mg²⁺-dependent enzymes such as
glycogen synthase kinase-3β (GSK-3β)
& inositol monophosphatase (IMPase).
This activity modulates neuroplasticity,
inflammation, & mood regulation.
↓ T3/T4 synthesis &
release from thyroid
Authors:
Rida Mahmood,
Hadi Hassan
Reviewers:
Taryn Stokowski,
Emily J. Doucette,
Rohit Ghate*
* MD at time of publication
↓ T3/T4
↑ TSH
↓ Aquaporin insertion in
principal cells of collecting
ducts of kidneys
↓ Water
reabsorption
Nephrogenic
diabetes insipidus**
Li carbonate (an
inorganic salt) irritates
gastric mucosa
Li stimulates chemoreceptor trigger zone
Subclinical
or overt
hypothyroidism
Li competes with Mg2+ at cofactor
site of IMPase & GSK-3β
Enterochromaffin cells
↑ serotonin release
↑ Gut motility & vagal
afferent nerve activation
Activation of vomiting center
in area postrema
Nausea &
vomiting**
↓ GSK-3β activity throughout brain
IMPase & inositol
polyphosphate phosphatase
(IPP) inhibition prevents
hydrolysis of inositol
monophosphate to free
inositol within neurons
Inhibited IRS &
↓ Phosphorylation of transcription factors,
PI3K/Akt signaling
signaling proteins, & metabolic enzymes
↓ GLUT4 translocation
& ↓ glucose uptake in
muscle & adipose tissue
↓ Systemic
insulin
sensitivity
Weight
gain
↓ Downstream dopamine release in mesolimbic,
mesocortical, & nigrostriatal pathways
↓ Conversion of inositol
into phosphatidylinositol
4,5-bisphosphate (PIP2)
↓ Pro-apoptotic
signaling
(Bax, p53, &
caspases) ↓
neural apoptosis
↑ Neurotrophic
signaling (Akt &
MAPK/ERK)
↓ D2 receptor stimulation in nucleus
accumbens, prefrontal cortex, & striatum
Sustained cAMP
Response Element-
Binding Protein
activity promotes
gene transcription
↑ Circadian clock
proteins &
transcription
factor (CLOCK,
BMAL1, CRY1, &
PER2) stabilization
in suprachiasmatic
nucleus
↓ PIP2 available for cleavage
into second messengers
inositol triphosphate (IP3) &
diacylglycerol (DAG) during G
Protein activation
↓ Dopaminergic
inhibition of
GABAergic
interneurons
↓ Availability of IP3 & DAG
↓ Reward
drive in
nucleus
accumbens ↓ Drive &
arousal in
prefrontal
cortex
Dopamine & acetylcholine
imbalance in striatum
↑ Circadian rhythm
stabilization
Thalamocortical
motor circuit
instability
↑ Brain-Derived
Neurotrophic Factor
expression in hippocampus
& prefrontal cortex
Improved sleep
timing & stability
↓ Impulsivity
Glutamatergic signalling
stabilizes (↓ release,
↑ reuptake, ↓ NMDA activity)
↓ Aggression
↑ Involuntary
rhythmic
muscle activity
↑ Neuronal survival,
synaptogenesis, &
dendritic growth
↓ Tau hyper-
phosphorylation
↑ GABAergic
inhibition
Excitatory–inhibitory
balance in cortical &
limbic regions normalizes
↓ Psychomotor
agitation
Upper
extremity
postural
tremor
↑ Gray matter volume &
prefrontal cortex–
hippocampus connectivity
Neuroprotection
& ↓ dementia risk
Prefrontal cortex exerts
better top-down control
↓ Amygdala hyper-responsivity ↑ Hippocampal regulation
of thought loops
Improved
↓ Irritability
↓ Mood lability
decision-making ↑ Working memory
↓ Distractibility
↓ Racing thoughts
Mood stabilization (↓ frequency & severity of manic & depressive episodes)
** See Corresponding Calgary Guide slides
Legend: Pathophysiology Mechanism
Pharmacologic Effect Side Effects
Published Nov 2, 2025 on www.thecalgaryguide.com

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