antipsychotics Flashcards
tricyclic antidepressant pharm action
mood elevating agents do not act as stimulants of CNS.
Only after a period of 2-3 weeks of chronic dosing will a therapeutic benefit emerge.
the precise mechanism responsible for the antidepressant action of the TCA is unknown
TCA theory of action
inhibition of norepi neuronal uptake
time dependent changes in beta adrenergic function parallel the delayed onset of clinical efficacy
mild effect on 5-HT central serotonin receptor sensitivity
TCA pharmacokinetics
well absorbed by GI tract large volume of distribution half lives range from 8-89 hours most require once a day dosing inactivation through oxidative metabolism by hepatic microsomal enzymes
TCA adverse effects
antimuscarinic efects (tachy, burry vision, constipated, dry mouth) sedation toxic delirium seizures weight gain involuntary movements neuroleptic malignant syndrome
TCA
weak alpha adrenergic antagonists, most common CV effects are ortostatic hypotension and tachy, sedation is thought to be mediated through antagonist properties at the apha 1 adrenoreceptor and H1 histaminergic receptor sites in the brain
lowers seizure threshold
CNS toxicity presents as a delirium with affective, cognitive, motor, and psych symptoms
overdose is frequently fatal with unresolvable arrhythmia’s
Selective Serotonin Re-uptake Inhibitors
produce therapeutic action through an ability to modulat serotonin neurotransmission in the brain
long cascade of events causes poentiation of serotonin neurotransmission at central synaptic sites.
SSRI pharm and kinetics
onset is the same as TCA
anticholinergic and cV side effects were not present in SSRI
side effects tolerated better:
GI effects- nausea and diarrhea
CNS stimulation- insomnia and anxiety
sexual dysfunction- aorgasmia and delayed ejaculation
weightloss
SSRI warnings
caution in combo with other antidepressants, benzos, neuroleptics, carbamepazine, and blood levels increase
elimination half life of fluoxetine
2-3 days
SSRI absorption dependent on food?
NO
Monoamine Oxidase Inhibitors (MAOI)
developed from iproniazid, a drug used to combat TB, patients noted to be happier while on med.
Reserved for atypical depression unresponsive to TCAs or SSRIs and depression resistant to ECT
MAOI mechanism of action
monoamine oxidase exists on the body as A and B
transmiter amines, such as norepi, are preferrably metabolized by MAO-A in brain tissue
MAO-B is involved in the catabolism of dopamine
drugs inhibit both A and B, but A is where therapeutic effect occurs
MAOI changes and side effects
adaptive effects occur in 2-3 weeks
side effects:
occasion with long term therapy, particulary for those who are slow acetylators
non hydrazine derivatives have low hepatotoxicity risk
CV effects- occur with ingestion of certain foods, low tyrosine diet, cheese beer and wine
tremors
ejaculatory delay
orthostaic hypotension
hyperpyrexia with meperidine dextromethorphan and TCA
trazadone
desyrel
less toxic and faster acting
anxiolytic properties acts at both seratonin and norepi sites in brain
common side effects are sedation dizziness hypotension and nausea
bupropion
wellbutrin and zyban
MOA unknown
free of muscarinic side effects
CNS stimulation with insomnia and nervousness
contraindicated in seizures or head trauma
lithium
effective 60-80% of BOD patients
mood stabilizing agent
replaces sodium at certain active sites
selective to CNS non selective excitatory tissues (CV)
Manic Depressive on lithium
adverse reactions are associated directly with therapeutic levels
narrow window (0.5-1.5mEq/L) necessitates frequent monitoring
toxicity presents as nausea, diarrhea, vomiting, abd pain, polyuria, sedation and mild tremor
many become hypothyroid after long term use
antipsychotic MOA
block synaptic actions of dopamine in the brain
the antagonism of dopamine in the medolimbic-mesocortical system is thought to be the basis of the therapeutic actions of the antipsychotic drugs, while antagonism of the nigrostriatal system in the major factor in the extrapyramidal side effects seen with antipsychotics
antipsychotic side effects
sedation- common with all antipsychotics, activate histamine receptors, given at bedtime
extrapyramidal effects- acute dystonia, akathisia, parkinsonism
antipsychotics extrapyramidal effects
actute dystonia in 5% of cases- treated centrally acting muscarinic agent (cogentin)
akathisia- unresponsive to cogentin- treated with benzos or beta blockers
tardive dyskenesia is a late occuring and usually an irreversabe phenomenon
neuroleptic malignant syndrome- fever, diffuse muscle rigidity, severe EPS, autonomic dysfunction (elev BP &HR)
Neuroleptic Malignant Syndrome
more common in men than women
80% of cases occur under age 40
can be misdiagnosed as MH
treated with cooling, hydration, dantrium has been useful
bromocriptine (parlodel) can ease the rigidity as well
discontinue the antipsychotic drug ASAP
can occur with phenothiazine admin preop
more antipsychotic side effects
autonomic- alpha adrenergic antagonists cholinergic antagonism postural hypotension hyperprolactinemia- removing dopamine inhibition on prolactin secretion- amenorrhea, galactorrhea, infertility in women and impotence in men cholestatic jaundice cutaneous allergic reactions photosensitive opacities of the cornea agranulocytosis
antipsychotics contraindications
parkinsons, hepatic failure, bone marrow depression, use o other sedatives
overdose rarely fatal
hypotension responds better to norepi then to epi
antiparkinson drugs
most prominent pathological finding in parkinsons disease is the degeneration of neurons that originate in the sunstantia nigra of the midbrain and terminate in the basal ganglia (caudate nucleus, putamen, palladium)
levodopa/carbidopa
most reliable and effective
considered a form of replacement therapy
precursor to dopamine
levodopa, an amino acid, is transported across the BBB and converted to dopamine y the enzyme L-aromatic amoni acid decarboxylase
levodopa/ carbidopa activity
carbidopa is a decarboxylase inhibitor, which is active i the lover, kidney, and GI tract
these sites are where the levodopa is metabolized prior to getting across the BBB
carbidopa does not cross the barrier, so it has peripheral effects only
levodopa/carbidopa ….
pharmacologic effects are caused by newly formed dopamine in the brain
levodopa can improve the quality of life of most patients
improvements in rigidit and bradykinesia are generally more complete and appear sooner than do improvements in tremor
Levodopa/ carbidopa sie effects
intial treatment side effects are nausea, anorexia, and vomiting
most patients develop a tolerance
CTZ activation in the area postrema in the medulla oblongata by newly formed dopamine
orthostatic hypotension
cardiac dysrhythmias- beta adrenergic dopamine stimulation
levodopa/ carbidopa long term side effects
abnormal choreiform movements of limbs, hands, trunk, and tongue
movements improve with lower dose but parkinsons increase
serious mental disturbances
psychotic episodes
drug holiday x 1 week
levodopa/ carbidopa contraindications
MAOI narrow angle glaucoma cardiac arrythmias recent MI phenothiazines, butyrophenones and reserpine can produce EPS
Selegiline
MAO-B inhibitor
first line drug for parkinsons before levodopa
enhances action of endogenous dopamine
same precautions with MAOI
interacts with TCA causing fever, agitation, delirium, and coma
belladonna alkaloids
used only in mild cases
combat tremor
help in drug induced dystonias
antihistamines like diphenhydramine can be used to control monir tremors in elderly patients
dopamine agonists
only 20-30% of patients respond favorably
bromocriptine (parlodel) pergolide (permax)
loss of response typically occurs over time
anorexia and nausea due to stimulation of the CTZ
anesthetic implications of parkinsons
have patients take medications preop (lasts 6-12 hrs)
avoid phenothiazines, butyrphenones, and metoclopramide
muscle rigidity can impede mask ventilation
increased risk of aspiration
intravascularly volume depleted
normal responses to muscle relaxants
increased risk of laryngospasm
voilent tremors on emergence
no ephedrine if patient taking deprenyl
ketamine causes exagerated response
potential hyperkalemia for succs
more anesthetic implications of parkinsons
skeletal muscle tremor may mimic VFIB on ECG
may have diminished reserve due to chronically poor exercise tolerance
muscle relaxants will relax even the most rigid of patients
anticonvulsants
goal is to raise seizure threshold
therapuetic goal is to control seizures without excessive side effects
only 40% of epileptics become seizure free with medications
20% of epileptic patients get NO benefit from currently available meds
anticonvulsants MOA
appears to be inhibition of neuronal sodium channels in hyperexcitable cells
disinhibition may increase seizures
reduction in GABA increases seizures
anticonvulsants are classified as the 1-4 for MOA
type 1
block sustaines high frequency repetatice firing by enhancing sodium channel activation
phenytoin carbamazepine, oxycarbazepine, lamotagrine, and felbamate
type 2
multiple actions: enhance GABAergic inhibition, reduce T calcium currents, and possibly block SRF
valproic acid, benzo, phenobarbitolprimidone
type 3
block T calcium currents only
ethosuximide, trimethadione
type 4
only enhances GABAergic inhibition. Has no known effect on SRF, GABAergic inhibition, or T calcium currents
Vigabatrin and gabqpentin
anticonvulsants sodium channel blockers MOA
capacity to block the sustained high frequency repetitive firing of action potentials
anticonvulsants of this class bind preferenctially to the inactive or non inactive site
block in time dependent, because it takes a while to dissociate the drug from the site to make it active again
phenytion
generalized tonic clonic seizures partial seizures antiarrhythmic propertoes slow and complete GI absorption highly plasma potein bound (90%) zero order kinetics leads to hepatic induction of microsomal enzymes
phenytoin adverse effects
acute overdose- nystagmus, ataxia, vertigo, diplopia, cognitive changes
idiosyncratic- skin rashes, dermatitis, heptic necrosis
common- gingival hyperplasia, enlargement of lips and nose
fetal hydantoin syndrome
folate deficiency
phanytoin drug interatcions
cimetidine, chloramphenicol, disulfram, isoniazid
dilantin reduces the half life of quinidine by 50%
carbamazepine (tegretol)
for tonic clonic and absence seizures
most common side effect is drowsiness
allergic response usually rash, fever SLE
can exacerbate seizures in some patients
causes significant enzyme induction
will increase rate of metabolism of other anticonvulsants
barbituates
primary mechanism of action is facilitation of GABA inhibition- prolonged opening of chloride channels
main side effect is sedation- disturbance is cognitive functioning
will also cause hepatic microsomal enzyme induction
valproic acid
MOA is blockage of sodium channels that are voltage dependent
causes increased brain GABA
side effects- hepatotoxicity and failure, fetal neural tube defects, alopecia
benzodiazepines
interaction with GABA
cause sedation
not first line therapy
rapid development of tolerance
anesthetic implications of phenytoin
resistance to nondepolarizing muscle relaxants
shorter duration of action of muscle relaxants
administer at 25-50mg/min to avoid hypotension
Stevens-Johnson syndrome
anesthetic implications of anticonvulsants
induction with thiopental or propofol
N2O/ narc techniques
avoid enflurane, methohexital
show a tolerance to opiods secondary to enzyme activation caused by their anticonvulsant
