Precursor to DA Crosses BBB (and is converted to DA; improves nigrostriatal functioning) 1st line tx for Parkinson's unless pt young (want to delay as long as possible)

Pharmacology - CNS Drugs - Dopaminergic Agents Flashcards by B -

Hyperfunctioning (dopamine) in the mesolimbic pathway causes:

Addiction, hallucination

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Hyperfunctioning (dopamine) in the mesocortical pathway causes:

Hypervigilance

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Hyperfunctioning (dopamine) in the tuberoinfundibular pathway causes:

Hypoprolactinemia

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Parkinsonism is hypodopamine in what brain area?

Nigrastriatal system

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What is the main theory behind high or low dopamine functioning?

If you inherit an abnormal gene (val substitution), then you have aggressive COMT (catechol-O-methyltransferase) and break down too much dopamine and develop symptoms

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What is Levodopa?

Precursor to DA
Crosses BBB (and is converted to DA; improves nigrostriatal functioning)
1st line tx for Parkinson’s unless pt young (want to delay as long as possible)

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What drug is often used in combination with Levodopa, and why?

Carbidopa
b/c it prevents peripheral dopamine activity and lowers fatigue, dizziness, and nausea SEs

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Give the side effects: Levodopa

If too much dopamine –> psychosis, mania, dyskinesias (abnormal, involuntary movements)
Hypotension, syncope, nausea, anxiety/agitation, fatigue

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People with the T-allele for folate metabolism have less of what chemical that may contribute to depression?

less dopamine
T allele = faulty methylhydrofolate reductase enzyme (MTHFR) –> less DA
“you don’t want to have T (allele for MTHFR) with Val (substitution –> abn, aggressive COMT)”

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What is the mechanism of action of Norepinephrine Dopamine Reuptake Inhibitors (NDRIs)?

NDRIs block the dopamine transporter (aka dopamine reuptake inhibition)
Leaves more DA in the synapse to increase to increase DA in the mesocortical pathway
Can lower depression symptoms
Buproprion is an example

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Give the side effects of NDRIs.

Insomnia, jitteriness, hypervigilance, seizures, anxiety, dry mouth, palpitations, mild increases in BP, sweating think sympathetic stimulation (NE)

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Give the class: dextroamphetamine lisdexamfetamine mixed amphetamine salts

Stimulants

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Give the indication: dextroamphetamine lisdexamfetamine mixed amphetamine salts

ADHD

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What is the mechanism of action of the stimulant class?

Stimulants block the DAT like buproprion, and may even reverse it, and increase vesicular monoamine transport (VMAT2) , ejecting more DA from nerve terminals

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What is the mechanism of action of methylphenidate?

block DA transporter less effective than the stimulants

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Give the class: Modafinil; Armodafinil

Stimulants Different MOA than amphetamine

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Give the indications: Modafinil; Armodafinil

Narcolepsy, Apnea, Shiftwork disorder NOT ADHD approved Less severe side effects

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What are unique side effects of Modafinil; Armodafinil?

May lower birth control effectiveness bc may increase p450-3A4 enzymes

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Give the mechanism of action: Modafinil, Armodafinil

Increases histamine activity in the tuberomammilary nucleus; may block DAT May increase orexin activity

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What are side effects of stimulants?

Psychosis at high doses Addiction Weight loss DA and NE side effects at any dose

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Monoamine Oxidase Enzymes A and B are responsible for breaking down:

Dopamine and other monoamines like NE and serotonin

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Give the mechanism of action: MAOi

Block the breakdown of DA

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Give the indication for Selegiline.

Parkinson’s Depression MAO-B inhibitor at low dose, full MAO-A and B at higher dose (patch)

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Give the indication for Rasagiline.

Parkinson’s MAO-B inhibitor

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Give the mechanism of action: Tranylcypromine (Parnate); Isocarboxazid (Marplan); Phenelzine (Nardil)

Irreversibly inhibit both MAO-A and MAO-B

Give the side effects: MAOi

Hypotension, dizziness, insomnia, weight gain Hypertensive crisis (with tyramine-rich foods); serotonin syndrome (MAOI + SSRI)

What things in combination with MAOi use can precipitate a hypertensive crisis?

Tyramine-rich foods such as cheeses, fava beans or fermented things; Nasal decongestants NE-based antidepressants

Give two examples of COMT inhibitors.

Entacapone (nausea and fatigue) Tolcapone (not used anymore bc of liver failure) Catechol-O-methyltransferanse inhibitors COMT is an enzyme that degrades monoamines. Inhibit this enzyme to increase DA or NE Used to help treat Parkinson's

D2 receptor agonism increases DA activity mainly in the nigrastriatal pathway. In this way, it is therapeutically indicated for what diagnosed?

Parkinson's Restless Leg Syndrome

Give the class: Bromocriptine

Ergot D2 receptor agonist

Give the class: Pramipexole (Mirapex); Ropinerole

Selective D2 receptor agonist

Give the class: Apomorphine

D2 receptor agonist

Give the class: Aripiprazole (Abilify)

D2 & D3 receptor (partial) agonist

Give the class: Amantadine

Antiviral

Bromocriptine, Pramipexole, Ropinerole and Apomorphine are all used to treat mild Parkinson's and RLS. What other diagnosis is indicated specifically for Bromocriptine?

Hyperprolactinemia

Give the indication: Aripiprazole

Schizophrenia and depression Antipsychotic

Give the indication: Amantadine

Mild Parkinson's (2nd-line); influenza

Give the side effects: Amantadine

Nausea, dizziness, psychosis, insomnia, seizures

Give the side effects: Bromocriptine, Pramipexole, Ropinerole and Apomorphine

Mania, nausea, dizziness, fatigue

The goal in therapy for narcolepsy, RLS and ADHD is to ____ DA activity

increase same with Parkinson's and Depression

Give the class: Reserpine Tetrabenazine

Synapse depleters

Give the indication: Reserpine

HTN can be used for schizophrenia

Give the indication: Tetrabenazine

Huntington's Chorea

Give the mechanism of action: Reserpine Tetrabenazine

Blocks VMAT (no release of monoamines into synapses) Synapse depleters

Give the notable side effect: Reserpine Tetrabenazine

Depression

What is the mechanism of action of the first generation antipsychotic (FGA)?

D2 receptor antagonism Non-selective, occurs in all DA pathways can lead to induced Parkinsonism

Give the side effects of FGAs such as: Chlorpromazine (Thorazine); Thioridazine

EPS - extrapyramidal syndromes - when DA is too low akathisia (restlessness) from D2 blockade, dystonia (muscle spasm), Parkinsonism, NMS (neuroleptic malignant syndrome)

What is Neuroleptic Malignant Syndrome (NMS)?

Hyperthermia Muscle rigidity Vital sign instability Rhabdomyolisis (kidney failure) SE of FGAs such as Chlopromazine, Thioridazine, Fluphenazine, Thioxixine, Haloperidol

Give the side effects: Fluphenazine, Thioxixine, Haloperidol

EPS; NMS

Why were anticholinergics such as Benztropine, Trihexyphenadyl and diphenhydramine used for Parkinson's disease?

Inhibiting cholinergic tone in the basal ganglia improves dopaminergic flow/tone in the nigrostriatal pathway, thus lowering Parkinson's symptoms

Give the side effects: Benztropine, Trihexyphenadyl and diphenhydramine (anticholinergics)

Dry mouth Blurred vision Tachycardia Constipation Confusion Delirium Hallicinations

Chronic D2 receptor antagonism may cause what permanent disorder?

Tardive Dyskinesia (longer effects than EPS side effect)

Name the high affinity FGAs.

Haloperidol Fluphenazine Thiothixine

Name the low potency FGAs.

Chlorpromazine Thioridazine

Serotonin 2a (5HT2a) antagonism has more or less risks for EPS than FGAs?

Less ie risperidone

How are SGAs different from FGAs?

SGAs have Greater blocking of DA in the mesolimbic system, while allowing better transmission in all other DA pathways

SGAs that agonize 5HT1a help to treat:

anxiety

SGAs that antagonize 5HT2c, 3, 7 help to treat:

depression

T/F: Some SGAs have SRI and NRI properties that treat depression.

True

D2 blockage lowers aggression in what diagnosis?

Autism

D2 blockade lowers mania in what diagnosis?

Bipolar disorder

Give the class: Risperidone

SGA

Give the class: Paliperidone

SGA

Give the class: Ziprasidone

SGA

Give the class: Iloperidone

SGA

Give the class: Lurasidone

SGA

Give the mechanism of action: Risperidone; Ziprazidone; Paliperidone; Iloperidone; Lurasidone

SGA D2 receptor antagonist; but various other receptor agonism/antagonism

Give the indication: Risperidone; Ziprazidone; Paliperidone; Iloperidone; Lurasidone

Psychosis, mania, aggression

Give the side effects: Risperidone; Ziprazidone; Paliperidone; Iloperidone; Lurasidone

Suicide risk in ages

Give the class: Olanzapine (Zyprexa); Quetiapine (Seroquel); Asenapine (Saphris)

SGA

Give the mechanism of action: Olanzapine (Zyprexa); Quetiapine (Seroquel); Asenapine (Saphris)

D2 receptor antagonist, 5HT2a receptor antagonist

Give the indication: Olanzapine (Zyprexa); Quetiapine (Seroquel); Asenapine (Saphris)

Psychosis, mania, aggression

Give the class: Clozapine

SGA

Give the mechanism of action: Clozapine

D2 (& D1, D4) receptor antagonist; 5HT2a receptor antagonist

Give the indication: Clozapine

Refractory schizophrenia

Give the side effects: Clozapine

Side effects similar to other "pines", but also agranulocytosis (inhibits bone marrow) (NMDA receptor antagonism?) Suicide risk in ages

Give the side effects: Olanzapine (Zyprexa); Quetiapine (Seroquel); Asenapine (Saphris)

Suicide risk in ages

What receptor antagonism in SGAs is responsible for weight gain?

5HT2c

Of the SGAs, which has the highest risk of developing metabolic syndrome?

Clozapine Developing diabetes is guaranteed

Expected side effects of a patient on high potency first generation antipsychotics:

EPS symptoms because DA is too low: akathisia (state of agitation, distress, and restlessness) dystonia (muscle spasm) parkansonianism

What are parkinsonian symptoms?

Decrease in facial expressions. Difficulty starting and controlling movement. Loss or weakness of movement (paralysis) Soft voice. Stiffness of the trunk, arms, or legs. Tremor.

Expected side effects of a patient on low potency first generation antipsychotics:

Less EPS symptoms (still more than SGAs) but also many other symptoms because interferes with other pathways Dry mouth blurred vision constipation Fatigue and increased appetite/weight Orthostasis (faint/dizzy)

If question asks what antipsychotics cause agranular anemia and Clozapine is not listed as answer choice which antipsychotic should you choose?

Chose the 2nd generation antipsychotic - always more likely to inhibit bone marrow than 1st gens

What are the D2 agonists?

Bromocriptine Pramipexole Ropinerole Apomorphine injections

What is a D3 receptor agonist?

Aripiprazole

What are the MAOi drugs used for depression?

Isocarboxazid, phenelzine, tranylcypromine, selegiline

What is Rasagiline? What is it used for?

MAO-B inhibitor for Parkinson’s

Which drugs inhibit COMT?

Entacapone- may cause nausea, fatigue side effects Tolcapone- liver failure too

COMT inhibiting drugs should be used to treat parkinson's disease or schizophrenia?

Parkinson's

Which class of drugs can cause Hyperthermia Muscle rigidity Vital sign instability Rhabdomyolysis

high potency first generation antipsychotics (D2 antagonists): Haloperidol Fluphenazine Thiothixine

In addition to blocking D2 receptors, 2nd generation antipsychotics also block Serotonin 2a (5HT2a) receptors. The benefit is:

lessens risk of EPS symptoms (dystonia, irritability, restlessness, agitation, parkinsonianism)

Which 2nd generation antipsychotic is actually a partial agonist at D2 and D3 receptors?

Aripiprazole

Major side effect relating to 5HT2c antagonism?

Weight gain!

Which drugs are synapse depleting drugs? What are they used for?

Reserpine - treats hypertension, it blocks VMAT so that vesicles with monoamines cannot be released into synapses Tetrabenazine - treats Huntington’s Chorea by inhibtiting VMAT

What drug would be used to control drooling in a Parkinson disease patient?

Benztropine - anticholinergic

Pharmacology - CNS Drugs - Dopaminergic Agents Flashcards

(95 cards)