CNS part 2 Flashcards
Drugs to Manage Schizophrenia
a. First generation antipsychotics (FGA) – the class are the ________
phenothiazines
How First generation antipsychotics (AKA conventional antipsychotics) (class = phenothiazines) work-
what’s their MOA^ and what do they cause?
– Block receptors for dopamine in CNS: In particular, they block dopamine2 (D2) receptors in the mesolimbic area in the brain
–
* Cause serious movement disorders - extrapyramidal symptoms [EPS]
Do First-generation antipsychotics (phenothiazines) work better than other classes, such as 2nd gens?
Both groups/gens have equal efficacy; Drugs in all groups equivalent with respect to antipsychotic actions
(1st and 2nd gen antipsychotics are equally effective)
a. First generation antipsychotics (FGA) – the class are the phenothiazines.
Side effects- 1st just list the 4 types of extrapyramidal symptoms (EPS) and what some of them mean
Acute dystonia- muscle spasm of face (eyes), neck or back (opisthotonus)
Parkinsonism
Akathisia- pacing and squirming
Tardive dyskinesia-facial grimacing, slow involuntary tongue rolling, lip smacking, and pill-rolling
List the onset of the 4 types of extrapyramidal symptoms- after being treated with phenothiazines, when would you see each of them appear?
– Acute dystonia - first few hours/days of treatment
– Parkinsonism – within 1st month
– Akathisia – within first 2 months
-– Tardive dyskinesia- late onset
(– 1st three have an earlier onset (spasms, twitches and tremors)
Is Tardive dyskinesia reversible?
NO- it can be irreversible
How would acute dystonia be treated?
tx with diphenhydramine (Benadryl) & benztropine (anti-ChE eft/drugs)
How would parkinsonism be treated?
(tx w/ no levodopa or DA agonists)
How would Akathisia be treated?
tx with anti-ChE drugs
How would Tardive dyskinesia be treated?
by switching to SGA
no actual treatment?
What are some other adverse effects of 1st gen antipsychotics/phenothiazines
(focus on bold)
- Anticholinergic effects from cholinergic blockade
- Orthostatic hypotension
- Sedation – at beginning of tx
- Neuroendocrine effects – gynecomastia, galactorrhea
- Seizures from conventional reducing seizure threshold
- Sexual dysfunction – 25-60%
- Dermatologic effects – UV sensitivity & pigment deposits (phenothiazines)
- Agranulocytosis – chlorpromazine…reg check WBCs
- Severe dysrhythmias – prolonged QT interval..risk for ventricular arrythmias (chlorpromazine, haloperidol, thioridazine, pimozide)
1st gen/conventional antipsychotics will end with what?
also what’s a high potency agent drug?
-azine
Haloperidol
Drugs to manage schizophrenia b. Must know neuroleptic malignant syndrome including how to recognize and manage
- Neuroleptic malignant syndrome (NMS)
– Rare but serious reaction
– Risk of death without treatment
– Sweating, rigidity, sudden high fever*, autonomic instability (HR/BP could be up/down), seizures - tx w/ dantrolene to reduce muscle rigidity which helps reduce fever and bromocriptine (Dompaine agonist)
Cardinal signs of NMS (neuroleptic malignant syndrome)
Cardinal features are as follows:
- Severe muscular rigidity
- Hyperthermia (temperature >38°C)
- Autonomic instability
- Changes in the level of consciousness
c. Second generation antipsychotics (SGA) also known as the
atypical antipsychotics
Why has the use of Second generation antipsychotics (SGA) /atypical antipsychotics superseded the use of the FGAs (1st gens)
- Less risk of EPS (the 4types) than conventionals
Side effects of Second generation antipsychotics (SGA) /atypical antipsychotics
Metabolic effects:
weight gain, new-onset DM, and dyslipidemia
Drugs to manage schizophrenia:
d. Be familiar with the drug Clozapine which is unique
MOA plus one thing to note
- First atypical – now 2nd line for schizophrenia
- MOA
– Blocks dopamine (low affinity – lower EPS)
– Blocks serotonin
Clozapine therapeutic use
– Schizophrenia
– Levodopa-induced psychosis
Clozapine AEs (important)
– Fatal agranulocytosis – monitor WBCs before & post
– Seizures in ~3%
– Metabolic efx
– EPS
– Myocarditis
– Older adult patients with dementia
* About double the mortality rate – not used for dementia
II. Antidepressants
a. Know the different classes of antidepressants including the following:
i. ______ inhibitors
ii. _______ antidepressants
iii. __________
iv. _____________
v. Atypical antidepressant – _______
II. Antidepressants
a. Know the different classes of antidepressants including the following:
i. MAOI inhibitors
ii. Tricyclic antidepressants
iii. Selective Serotonin Reuptake Inhibitors (SSRIs)
iv. Selective Serotonin Norepinephrine Reuptake Inhibitors (SSNRI)
v. Atypical antidepressant – Bupropion
MAO inhibitors (MAOI) are the DOC for
atypical depression
MAO inhibitors:
* As effective as TCAs or SSRIs, but more _______
What’s the risk?
more dangerous
Risk of triggering hypertensive crisis if the patient eats foods rich in tyramine
Mech of action of MAO inhibitors
– Inactivate monoamine neurotransmitters (NE, serotonin, and dopamine)
All current MAOIs cause ______________ inhibition- – when changing/starting other antideps, keep at least __ ______ b/t MAOIs and other deps (5 wks w/ fluoxetine [VERY long ½ life….2-4d, metabolite 7-15d]. MAOIs are also _____
All current MAOIs cause irreversible inhibition- – when changing/starting other antideps, keep at least 2 weeks b/t MAOIs and other deps (5 wks w/ fluoxetine [VERY long ½ life….2-4d, metabolite 7-15d]. MAOIs are also nonselective
Adverse effects of MAOIs
- direct CNS stimulation – anxiety, insomnia, agitation, hypomania & mania
- Orthostatic hypotension – from NE binding to what receptors in vasomotor center? Alpha 2 receptors
- Hypertensive crisis from dietary tyramine
– tyramine stims release of accumulated NE (& epi) – NE activates which adrenergic receptors?
MOA of MAOIs
– MAOI prevents breakdown (-ase) of NE in neurons
FYI-
– NE regulates cardiac fx and vascular tone …what receptors & eft?
– Inhibiting hepatic & intestinal MAO allows dietary tyramine to enter systemic circ intact
Pt teaching for MAOIs
Avoid tyramine-containing foods like
yeast extracts, most cheeses, fermented sausages, and aged fish or meat – to name some…. salami, pepperoni, bologna.
Why does tyramine need to be avoided with MAOI’s?
causes hypertensive crisis
Drug interactions for MAOI inhibitors and what it will cause (there’s two)
Taking it with antidepressants: TCAs and SSRIs
* TCAs: hypertensive episode; SSRIs: serotonin syndrome/crisis
Tricyclic Antidepressants MOA
Mechanism of Action
* Block neuronal reuptake of:
– Norepinephrine (NE)
– Serotonin (5HT)
Tricyclic antidepressants are best used for
patients with major depression and neuropathic pain
Most common adverse effects of Tricyclic antidepressants
- sedation
- orthostatic hypotension - for hosp pts, need to monitor regularly
- anticholinergic effects
Most dangerous adverse effects of Tricyclic antidepressants
cardiac toxicity
- lethal w/ OD
Tricyclic antidepressants may increase risk of what? and when
- May increase risk of suicide early in treatment
A/E of Tricyclic Antidepressants- know all
- Orthostatic hypotension
- Anticholinergic effects (TCAs block Cho receptors)
- Diaphoresis
- Sedation
- Cardiac toxicity –
- increase risk of dysrhythmias – **must have EKG b/f tx and then monitor periodically after
- Seizures – lowers seizure threshold**
- Hypomania
- “Yawngasm”
TCA Toxicity:
* Clinical manifestations – (antiCHo efx:
hyperthermia, flushing, dry mouth & dilation of pupils)
Treatment for TCA Toxicity
Physostigmine
TCA drugs end with
-tyline
TCA- when should it be given
initial doses should be low; give at bedtime
SSRIS are most commonly prescribed antidepressants- why?
As effective as TCAS but causes fewer SEs (hypotension, sedation, or anticholinergic efx)
Death by overdose is extremely rare- OD doesn’t cause cardiac toxicity