CNS mood stabilizers/Antipsychotics Flashcards Preview

Neuro-Psych > CNS mood stabilizers/Antipsychotics > Flashcards

Flashcards in CNS mood stabilizers/Antipsychotics Deck (13):
1

Mood stabilizers

Lithium, anti-seizure drugs, atypical antipsychotics

2

Lithium MOA

-unknown, speculated...
1. inhibition of G protein coupled receptors --> receptor-mediated signal transduction:
↓adenylyl cyclase stimulated by NE→ (-) ADH & TSH
2. inhibition of inositol monophosphate, ↓inositol phosphatase → ↓receptor-activated PIP2 hydrolysis, ↓formation of IP3, DAG: proportional to activity of cell (selective for hyperactive neurons of mania)
3. inhibition of growth factor pathways

3

Lithium absorption and elimination

-Absorption: almost completely from GI (Oral); available in extended release form
- volume of distribution approaches total body water
- slowly passes through blood brain barrier → @steady-state CSF concentration = ~40% of plasma
→ optimal serum conc: 0.6-1.3 meq/L (2meq~toxic)
- considerable pharmacokinetic variation betw pts → optimal dosing varies; relatively stable w/in pts
- low therapeutic index: titrate up to level & must regularly monitor blood drug levels, esp. @early phase of treatment
Elimination (→ urine): biphasic
1. rapid: @10 hr, 60% remains
2. slower: after 10 hr
- t½ = 20-24 hr
- ↑t½ @repeated admin. → 2.4 d after 1 yr use
- ↑t½ @geriatric, @impaired renal fxn
Li competes w/ renal reabsorption of Na → Na depletion (ex. w/diuretic use) → ↑Li reabsorption

4

Lithium use

- [therapeutic] → no psychotropic effects in normal healthy humans (unique)
- delayed onset of action: sometimes used w/ antipsychotic, antidepressant for more immediate effects

Primary indications
- acute mania
- prevention of recurrent bipolar disorder

Other indications
- alternative to heterocyclic antidepressants @severe recurrent depression
- supplement to antidepressants @acute, major depression
- alcoholism, aggression, premenstrual syndrome
- management of some disorders of childhood: episodic changes of mood, aggression

5

Lithium AE

Polydipsia & polyuria
- common
- nephrogenic diabetes insipidus: ↓adenylyl cyclase → ↓cAMP → ↓ADH; resistant to vasopressin, give amiloride (b/c amil will ↓ ECM → helps Sx not problem)
- polyuria usu. resolves
- late-onset polyuria → evaluate kidney fxn → ↓dose, give amiloride
- inflammatory changes in renal tissue due to chronic Li Tx → monitor plasma creatinine & urine volume
- Amiloride: ↓Li uptake @collecting duct → ↓[Li]
- Thiazide: ↓Li clearance → ↑[Li], ↑toxicity
-avoid dehydration b/c ↑[Li] in serum
CNS
- tremor: frequent @[peak] after dosing
- nausea/V/D
- muscle hypertonicity
- transient choreoathetosis, ataxia, aphasia
- mental confusion
Weight gain & Edema, dermatitis, exacerbation of psoriasis, hairloss, acne
Thyroid → decrease fxn (monitor! this is reversible)
- some pts develop benign, diffuse, nontender thyroid enlargement: pts remain euthyroid
- rare: goiter → discontinue LI and/or thyroid hormone treatment

Other: - benign, reversible depression of T wave @prolonged use; depresses SA node (contra: sick sinus syndrome)
- ↑PMNs (reversible) @chronic treatment: exploited to treat low leukocyte states
- dermatitis, exacerbation of psoriasis, acne
- can use in pregnancy, but ↑ clearance
- do not use @nursing

6

Lithium OD and treatment of OD

Overdose
- convulsions, coma, confusion, coarse hand tremor, muscle rigidity, fasciculations, ataxia
- therapeutic overdose: Li accumulation from ↓Na+ (diuretics, changes in renal fxn)
-previously thought to be teratogenic in pregnancy but preg. have ↑clearance, dose needs adjustment after delivery
Tx of overdose
- osmotic diuresis & IV bicarb
- if kidney fxn OK → dialysis

7

Lithium drug interactions

-w/haloperidol→ extrapryamidal Sx (use atypicals)
- often used w/ anti-psychotics, sedatives, anti-depressants; monitor [drugs]
- diuretics, NSAIDS, ACE-I → ↓Li clearance

8

Anti-convulsants

Sodium Valproate (Valproic Acid)
Divalproex Sodium
Carbamazepine
Lamotrigine

9

Sodium Valproate (Valproic Acid)
Divalproex Sodium

Anti-convulsant

Divalproex Sodium
- enteric coated preparation → [peak] @4-6 hr
- delayed absorption @small intestine → ↓nausea, stomach cramps, tremor due to gastric abs.

Both: Mechanism:
-may ↑ GABA by inhibiting degradation or ↑ synthesis
-blocks sustained high freq. firing
-Well absorbed orally; serum protein binding ~80%

Complex metabolism → active metabolites
1. P450
2. mitochondrial β-oxidation

USE: 2nd choice after Li
- acute mania
- anti-mania prophylaxis
-Other uses:
-Absence seizures, when pt has concomitant tonic-clonic attacks
-migraine prophylaxis
-AE: Dose-related
- nausea, vomiting,
- dizziness, somnolence, tremor, increased accidents
- hair loss
- benign thrombocytopenia
- increased liver function test (not predictive of hepatitis): monitor
-not intended for pregnant pts or wanna be pregnants
-Idiosyncratic: pancreatitis; fulminant hepatits (esp. @initial stages of treatment, @children <2 yo): monitor → hepatic failure
Drug Interactions: see below

10

Carbamazepine

MOA: inhibits kindling, a process where repeated biochem/ psych stressors are thought to result in abnormally neuron excitability
- phenytoin-like
- blocks Na channels
- inhibits high-frequency repetitive firing of neurons
- acts presynaptically to ↓synaptic transmission
- binds to adenosine receptors
-PHARM: PO once/day
- rate of absorption varies widely among pts
- [peak] @4-6 hr
- slow distribution
- serum protein binding ~70%
-Induces microsomal enzymes so chronic use…
- ↑drug clearance rate (↓t½: 36 hr → 20 hr)
- ↑metabolism of other drugs: primidone, phenytoin, ethosuximide, valproate, clonazepine
- monitor LFTs & cardiac fxn
-USE: 2nd line drug
- @contraindication or no response to Li
- acute mania
- anti-mania prophylaxis
- mixed-state bipolar pt
- impacts manic > depressive phase
- prophylactic efficacy may ↓ w/ time
-neuropathic pain

- drug of choice for partial seizures
- generalized tonic-clonic seizures
- trigeminal neuralgia

-AE: skin rash which doesn’t require drug discontinuation
-impaired coordination, drowsiness, dizziness, slurred speech, ataxia
- inappropriate secretion of ADH → hyponatremia
- aplastic anemia, agranulocytosis, esp. @elderly pt w/ trigeminal neuralgia
- leukopenia
-Overdose/toxicity:
- drowsiness, ataxia, coma, cardiac toxicity
- treat w/ gastric lavage, charcoal
-Drug Interactions
- can reduce t½ of other drugs via P450 induction
- can displace other drugs from serum binding sites
- pharmacodynamic interaction w/ Li in brain (@same neurons)

11

Lamotrigine

MOA: voltage & use-dependent inactivation of Na channels
→inhibits release of pre-synaptic glutamate & aspartate
-Pharmacokinetics: completely absorbed orally, protein binding 55%
- t½-24 hrs, but ↓in pts taking enzyme inducers

-USE: maintenance/prophylaxis of both mania and depression
-better efficacy for prevention of relapse into depression >mania

-AE: Rash-greater risk in peds pts, can lead to toxic epidermal necrolysis or Stevens-Johnson syndrome
-Dizziness, headache, diplopia, somnolence

-Drug Interactions:
-w/valproate –lamotrigine ↑t½
-w/ CBM ↓t½

12

Atypical Antipsychotics

Risperidone
Olanzapine
Quetiapine
Ziprasidone
Aripiprazole

13

Risperidone
Olanzapine
Quetiapine
Ziprasidone
Aripiprazole

Atypical Antipsychotics
-generally well tolerated & easy to use
Mechanism: Antagonist of DA receptors
May enhance serotonergic transmission→ antidepressant effects

-Pharmacokinetics:
Completely absorbed after oral dosing Uses:
-alone for acute mania
-w/lithium for acute mania to achieve therapeutic goal more rapidly
-olanzapine & ariparzole approved for maintenance
-may be used w/ others for maintenance

-AE: olanzapine: significant weight gain risk → metabolic disorders
-monitor weight, glucose, & lipid profiles of patients
Drug interactions:
-CBM increase metabolism of these
-antipsychotics will enhance the effect of sedatives, alcohol, & anti-HTN drugs