PharmII_Exam2(p4-5) Flashcards
What is considered a 2nd line treatment
for depression
TCAs
Tricyclic anti-depressants
What is considered a 2nd line treatment
for depression
SSRIs
Selective serotonin reuptake inhibitors
What is the amine hypothesis?
Reserpine leads to depression suggests that depression
is caused by a decrease of amine mediated neurotransmission in the brain.
Which class have adrenergic, histaminic, and muscarinic side effects including sedation, dry mouth, urinary retention, constipation, orthostatic hypotension and cardiac arrhythmias.
TCAs
Which three categories of anti-depressants block the reuptake of serotonin and norephinephrine?
NRIs
TCAs
SSRIs
What does MAO inhibitors block?
THe major metabolic pathways for the monamine neurotransmitters
serotonin, norepinephrine, and dopamine.
Name the class of anti-depressants that has a contraindication of taking these drugs within 2 weeks of going through MAOI therapy?
TCAs
SSRIs(will result in serotonin syndrome)
Will result in death
Why is there The delay in onset of the antidepressant effect?
there is a down-regulation of post synaptic receptors (β1
adrenergic and/or serotonin receptors).
Which of the anti-dression classes is deadly if you overdose on it?
TCAs
MAOIs raise levels of what in the body?
Catecholamines.
This can lead to hypertensive crisis.
Amitriptyline
Mixed NE and SRIs. Nortiptyline is an active metabolite. Non-FDA approved use has been for
neuropathic pain, enuresis, ADHD, hiccups and headache.
Imipramine
Mixed NE and SRIs. Desipramine is major metabolite. Tx for anuresis, depression tourettes
and hyperactivity in children unresponsive to stimulants(very imp).
Nortriptyline
Metabolite of amytriptiline so similar characteristics but longer ½ life.
Clomipramine
More selective for SRI. FDA approved for Depression and OCD. Non approved uses
include autism and premature ejaculation. Most likely to cause orthostatic hypotension
Doxepin
More selective for serotonin transporters than NE. Highly sedating.. Approved for anxiety, topical for
eczema (Zonalon), insomnia. Non FDA approved uses include Migraine prophy and alcoholism.
Desipramine
More selective for NERI. Actions similar to imipramine. Non FDA use includes bulimia,
and as an adjunct to cocaine cessation.
Trimipramine
UNIQUE
Does not alter the reuptake of either serotonin or nerepi
Has efficacy for depression. MOA is unknown.
It is highly sedating.
Protriptyline
Less sedating than other agents and may actually act as a stimulant. Non FDA for COPD and
sleep apnea.
Why are there many unwanted GI and sexual side effects.
DUe to the widespread serotonin receptors in the GI and sex organs.
T/F?
I can use SSRIs for mania?
False!
What can you mix fluoxetine with to treat bipolar disorder?
Olazapine
Which is the only SSRI approved for pediatric patients with depression or OCD?
Fluoxetine
Which SSRI has the longest t1/2?
Fluoxetine
What are some contraindications for fluoxetine?
Don’t give within 2 weeks of MAOI therapy
-It increases thioridazine which can generate QT prolongation
Citalopram
Escaitalopram (Lexapro) is the active enantiomer of racemic mix. May be beneficial for hot
flashes in post menopausal women
QT prolongation warning when mixed with other drugs
Fluvoxamine
Shortest ½ life, more sedating, removed from market in 2002. FDA reissued approval in Dec.
2007
Paroxetine
most specificity for the serotonin transporter. Suicidal thoughts
Sertraline
less likely to have metabolic drug interactions
NRI speel
May be less likely to trigger
mania with bipolar disorder or seizures in the epileptic than agents action on the serotonergic system.
Strattera and Vextra
Strattera
Off label for depression. FDA warnings include liver problems and suicidal thoughts in
children and adolescents being treated for ADHD.
MOA of monamine oxadase inhibitors
Block the major metabolic pathways for the degradation of monoamine NTs
(Serotonin, Norepinephrine, Dopamine.) by monoamine oxidase (Found in mitochondrial membranes and is
responsible for the deamination and metabolism of monoamine NTs).
When are MAOIs used?
For patients refractive to SSRIs and TCAs.
Which group of antidepressants cause hypertensive crisis when mixed with sympathomimetics like amphetamine, cocaine, tyramine?
MAOIs
How do you treat hypertensive crisis?
5mgs of phentolamine intravenously
Describe Phenelzine?
Nonspecific and irreversible.
This is a MAOI of A and B
Phenel is FINAL, u cann’t reverse it.
Describe Tranylcypromine?
Nonspecific and Reversibly inhibits MAO-A and B
Moclomide
(MAO-A) and reversible. A newer class described as RIMAs (Reversible inhibitors of MAO-A).
Amoxapine
closely related to loxapine (antipsychotic)~beneficial for depression in psychotic
patients. May have anti dopaminergic (D2) receptor effects and therefore extrapyrimidal side effects
2nd generation Heterocyclic
Bupropion
Unique since it blocks dopamine re-uptake and only weakly inhibits norepinephrine
uptake. Little to no sedation or muscarinic effects. Indications for general depression and smoking cessation.
2nd gen heterocyclic
CI for bupropion?
Seizure disorders
AE for bupropion?
Dizziness, dry-mouth, tremor, aggravation of psychosis, seizures
Trazodone
Blocks serotonin reuptake and postsynaptic serotonin receptors. A 5-HT receptor
agonist in high doses.
2nd gen heterocyclic
Maprotiline
Similar to TCAs but selective for NE reuptake
2nd generation heterocyclic
Mirtazapine
Blocks Serotonin receptors and presynaptic a2 adrenergic receptors. Also has antihistaminic
actions and is very sedating.
3rd generation heterocyclic
Venlafaxine
Blocks Serotonin receptors and presynaptic a2 adrenergic receptors. Also has antihistaminic
actions and is very sedating.
3rd generation heterocyclic
Name two minor 3rd generation heterocyclics?
Duloxetine
Milnacipran (approved for fibromyalgia)
What drugs exacerbate mania?
Drugs that increase catecholamines like anti-depressants
Tell me about lithium?
Safe and efficacious for mania and recurrent attacks of manic depressive illness (terminates manic episodes and
decreases cyclic mood swings).
T/F?
THe therapeutic index for lithium is large?
False.
Patients need to be monitored really closely.
How long does it take for lithium to start working?
Delay in action onset about 7-10 days
• Use of haloperidol or olanzapine (atypical) and a potent sedative/benzodiazepine like lorazapam of
clonazepam can be used initially to control a severely manic patient
Clinical efficacy of lithiuM?
The clinical efficacy of Lithium is likely due to its ability to reduce catecholaminergic transmission through a
combination of mechanisms.
Tell me about the relationship between lithium and sodium?
Renal elimination of Lithium is markedly affected by sodium intake, low sodium levels lead to an
accumulation of lithium due to excessive reabsorption by in the tubules and because of the small therapeutic
window there is often an emergence of toxicities.
What should the plasma concentration be for lithium in acute mania?
0.75 to 1.2 mEq/L
What should the plasma concentration be for lithium in long term maintenance?
0.6 to 1.2 mEq/L
What is the plasma concentration for toxic levels for lithium in the body?
greater than 2.0 mEq/L
What can cause lithium toxicity?
Increased Lithium absorption • Anything that decreases Na plasma concentration like reduced renal function, diarrhea, sweating, diuretics (Thiazide). • NSAIDS • ACE inhibitors
What are some signs of lithium toxicity?
Confusion Vomiting Diarrhea Renal failure Tremor Ataxia Coma Convulsions Confusions Blurred vision Delirium Stupor
How do you treat an overdosage of lithium?
Gastric levage
• Fluid and electrolyte replacement
• Osmotic diuretics and aminophylline increase lithium exctretion
• Dialysis
AE for lithium at therapeutic levels?
Tremor
Polyuria
What trt do you use for refractive patients with Bipolar disorder?
ECT.
In addition: tamoxifen, allopurinol.
Valproate
Anticonvulsant.
becoming more common as a 1st line agent. Less toxic. Has good side effect profile
and therapeutic doses can be rapidly obtained. Rapid tx for acute mania. Add Lithium for longer term.
Carbamazepine
Anticonvulsant.
More adverse effects than lithium but 3rd alternative to Lithium
Do not combine with anti-psychotics
Lamotrigine
Anticonvulsant.
Shown to be effective for maintenance therapy.
Olanzapine
atypical antipsychotic. With Prozac it is called Symbyax but should be used carefully
so mania does not precipitate. Clozapine (Clozari)l can also be used.
What causes psychoses?
The “dopamine hypothesis” states that excessive dopaminergic activity causes schizophrenia
and thus is the basis for treatment rationale.
-Mesocortical
-Mesolimbic
Doesn’t fully explain what is taking place.
Drugs that block NMDA receptors (like PCP) produces psychosis (more so than Dopamine receptor agonists.)
Newer atypical antipsychotics are effective yet do not target the D2 receptor (clozapine, olanzapine, quetiapine)
Are antipsychotic agents fully effective?
No,
Antipsychotic agents are only partially effective
Chlorpromazine
prototype for an entire class of antipsychotics. A neuroleptic- strong tranquilizing effect
What does blockade of dopamine receptors in the mesolimbic-mesocortical pathway do?
Antipsychotic effectiveness
What does blockade of dopamine receptors in the nigro-striatal pathway do?
Unwanted extrapyramidal effects like Parkinsonism, tardive dyskinesia, akathisia, dystonias.
What does blockade of dopamine receptors in the tuberoinfundibular pathway do?
Increased prolactin secretion from pituitary which leads to hyperprolactinemia. Amenorrhea-galactorrhea
(female),
Gynecomastia (male). Also infertility and impotence
What does blockade of dopamine receptors in the chemoreceptor trigger zone do?
Anti-emetic
How do you treat parkinsonism in a patient with psychosis?
Tx by dose reduction or switch to atypical antipsychotic
What is acute dystonia?
AE of blockade of dop receptors in nigrostriatal pathway.
Spasms of muscle in head, face, tongue
Trt of acute dystonia?
Parenteral anticholinergic antiparkinsonian drugs like Benztropine
How to treat perioral tremor?
Tx with an anticholinergic and/or removal of drug
When is the onset for perioral termor?
Months or years after the start of treatment.
What is the Most important unwanted effect of
antipsychotics?
Tardive dyskinesia
Trt of tardive dysk?
Discontinue or reduce dose of antipsychotic
Switch to atypical
or Benzodiazepines or tricyclic antidepressants.
Early recognition is imp bcaz symptoms are irreversible.
What is neuroleptic malignant syndrome
Severe extrapyrimidal effects, muscle rigidity,
catatonia, hyperthermia, and autonomic instability. Rare but life threatening and due to XS
dopamine receptor blockade caused by potent agents like Haloperidol.
How do you treat neuroleptic malignant syndrome?
Stop antipsychotic TX
and give:
• Bromocryptine (Parlodel) Dopamine agonist
• Dantrolene (Dantrium) and Diazepam: Muscle relaxant
What AE can u get with clozapine usage?
BLood Dyscrasias
Which antipsychotic is approved as a monotherapy for mania?
Olanzapine
What is the current way to go about treating psychosis?
Start with an atypical like risperidoe, olanzapine, or aripiprazole.
Have low extrapyramidal toxicities and hoigh potencies.
What is the side effect profile of clozapine that makes it so bad?
Agranulocytosis
Seizures
Myocarditis
Chlorpromazine
Conventional antipsychotic(phenothiazine).
Inexpensive
Low potency and many adverse effects
Thioridazine
Conventional antipsychotic (phenothiazine). Few extrapyramidal effects Fatal cardiac arrhythmias. QT prolongation
Fluphenazine
Conventional antipsychotic(phenothiazine).
High potency
High extrapyramidal effects
Thiothixene
Conventional antipsychotic(thioxanthene). Horrible side effect profile
Haloperidol
Conventional antipsychotic(butyrophenones).
Potent
Severe extrapyramidal syndrome
Clozapine
Oldest atypical
Fatal agranulocytosis in 1% of patients.
Used only for severe schizo unresponsive to conventional antipsychotics.
Respiridone
1st line agent for many psychoses
@ high dose, we see extrapyramidal effects
Olanzapine
Effective against neg and positive symptoms
Weight gain
Quetiapine?
Similar to risperidone. Also used for anxiety disorder
Also considered 1st line agent with less weight gain than Zyprexa
Ziprasidone?
Less weight gain than other atypicals.
Disad: QTc prolongation
Asenapine
New drug
Sublingual.
Marketed as better for neg symptoms, but more likely to cause extrapyramidal side effects.
Aripiprazole?
New class of atypicals. Partial dopamine agonist thus allows dopamine system to stabilize. Has differential effects on serotonin.
Lurasidone
No clear advantages.
Name some drugs that are adjunct with antipsychotics?
Fluoxetine
Valproate
Benztropine
Propranolol effects on schizo?
Marked agitation
Hostility
Belligerence.
These symptoms are improved.
Benzodiazepines effects on schizo?
Useful for controlling disturbed behavior in high doses.
