antipsychotics

Question 1

tricyclic antidepressant pharm action

Answer 1

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

Question 2

TCA theory of action

Answer 2

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

Question 3

TCA pharmacokinetics

Answer 3

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

Question 4

TCA adverse effects

Answer 4

antimuscarinic efects (tachy, burry vision, constipated, dry mouth)
sedation
toxic delirium
seizures
weight gain
involuntary movements
neuroleptic malignant syndrome

Question 5

TCA

Answer 5

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

Question 6

Selective Serotonin Re-uptake Inhibitors

Answer 6

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.

Question 7

SSRI pharm and kinetics

Answer 7

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

Question 8

SSRI warnings

Answer 8

caution in combo with other antidepressants, benzos, neuroleptics, carbamepazine, and blood levels increase

Question 9

elimination half life of fluoxetine

Answer 9

2-3 days

Question 10

SSRI absorption dependent on food?

Answer 10

NO

Question 11

Monoamine Oxidase Inhibitors (MAOI)

Answer 11

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

Question 12

MAOI mechanism of action

Answer 12

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

Question 13

MAOI changes and side effects

Answer 13

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

Question 14

trazadone

Answer 14

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

Question 15

bupropion

Answer 15

wellbutrin and zyban
MOA unknown
free of muscarinic side effects
CNS stimulation with insomnia and nervousness
contraindicated in seizures or head trauma

Question 16

lithium

Answer 16

effective 60-80% of BOD patients
mood stabilizing agent
replaces sodium at certain active sites
selective to CNS non selective excitatory tissues (CV)

Question 17

Manic Depressive on lithium

Answer 17

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

Question 18

antipsychotic MOA

Answer 18

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

Question 19

antipsychotic side effects

Answer 19

sedation- common with all antipsychotics, activate histamine receptors, given at bedtime
extrapyramidal effects- acute dystonia, akathisia, parkinsonism

Question 20

antipsychotics extrapyramidal effects

Answer 20

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)

Question 21

Neuroleptic Malignant Syndrome

Answer 21

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

Question 22

more antipsychotic side effects

Answer 22

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

Question 23

antipsychotics contraindications

Answer 23

parkinsons, hepatic failure, bone marrow depression, use o other sedatives
overdose rarely fatal
hypotension responds better to norepi then to epi

Question 24

antiparkinson drugs

Answer 24

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)

Question 25

levodopa/carbidopa

Answer 25

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

Question 26

levodopa/ carbidopa activity

Answer 26

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

Question 27

levodopa/carbidopa ....

Answer 27

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

Question 28

Levodopa/ carbidopa sie effects

Answer 28

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

Question 29

levodopa/ carbidopa long term side effects

Answer 29

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

Question 30

levodopa/ carbidopa contraindications

Answer 30

``` MAOI narrow angle glaucoma cardiac arrythmias recent MI phenothiazines, butyrophenones and reserpine can produce EPS ```

Question 31

Selegiline

Answer 31

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

Question 32

belladonna alkaloids

Answer 32

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

Question 33

dopamine agonists

Answer 33

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

Question 34

anesthetic implications of parkinsons

Answer 34

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

Question 35

more anesthetic implications of parkinsons

Answer 35

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

Question 36

anticonvulsants

Answer 36

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

Question 37

anticonvulsants MOA

Answer 37

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

Question 38

type 1

Answer 38

block sustaines high frequency repetatice firing by enhancing sodium channel activation phenytoin carbamazepine, oxycarbazepine, lamotagrine, and felbamate

Question 39

type 2

Answer 39

multiple actions: enhance GABAergic inhibition, reduce T calcium currents, and possibly block SRF valproic acid, benzo, phenobarbitolprimidone

Question 40

type 3

Answer 40

block T calcium currents only | ethosuximide, trimethadione

Question 41

type 4

Answer 41

only enhances GABAergic inhibition. Has no known effect on SRF, GABAergic inhibition, or T calcium currents Vigabatrin and gabqpentin

Question 42

anticonvulsants sodium channel blockers MOA

Answer 42

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

Question 43

phenytion

Answer 43

``` 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 ```

Question 44

phenytoin adverse effects

Answer 44

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

Question 45

phanytoin drug interatcions

Answer 45

cimetidine, chloramphenicol, disulfram, isoniazid | dilantin reduces the half life of quinidine by 50%

Question 46

carbamazepine (tegretol)

Answer 46

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

Question 47

barbituates

Answer 47

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

Question 48

valproic acid

Answer 48

MOA is blockage of sodium channels that are voltage dependent causes increased brain GABA side effects- hepatotoxicity and failure, fetal neural tube defects, alopecia

Question 49

benzodiazepines

Answer 49

interaction with GABA cause sedation not first line therapy rapid development of tolerance

Question 50

anesthetic implications of phenytoin

Answer 50

resistance to nondepolarizing muscle relaxants shorter duration of action of muscle relaxants administer at 25-50mg/min to avoid hypotension Stevens-Johnson syndrome

Question 51

anesthetic implications of anticonvulsants

Answer 51

induction with thiopental or propofol N2O/ narc techniques avoid enflurane, methohexital show a tolerance to opiods secondary to enzyme activation caused by their anticonvulsant