Enzymes in Biological Processes

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Questions and Answers

What is the primary mechanism of action of COMT inhibitors in the management of Parkinson's disease?

Inhibition of voltage-activated Na+ channels

Enhancement of GABA-mediated synaptic inhibition

Antagonism of AMPA or NMDA receptors

Inhibition of Catechol-O-methyl transferase (COMT) (correct)

Which of the following acetylcholine receptor antagonists is known to have favorable effects on rigidity and bradykinesia?

Entacapone

Trihexyphenidyl

Tolcapone

Benztropine (correct)

What is a significant adverse effect of tolcapone that requires close monitoring?

Diarrhea

Brown-orange urine discoloration

Hepatotoxicity (correct)

Orthostatic hypotension

Which anti-epileptic drug has a mechanism of action involving the inhibition of voltage-activated Na+ channels?

Phenytoin Signup and view all the answers

What is the primary reason for adjusting total phenytoin levels?

Protein binding Signup and view all the answers

Which of the following is a significant interaction of SSRIs?

MAOIs Signup and view all the answers

What is a common adverse effect of acetylcholine receptor antagonists?

Urinary retention Signup and view all the answers

What is the target concentration of free phenytoin in the blood after 5 days of dosing?

1-2 mcg/mL Signup and view all the answers

Which COMT inhibitor is combined with levodopa/carbidopa in the medication Stalevo?

Entacapone Signup and view all the answers

What is the primary mechanism of action of SSRIs?

Inhibition of reuptake of serotonin Signup and view all the answers

What is the primary function of Acetylcholinesterase in the body?

To hydrolyze Acetylcholine Signup and view all the answers

What is the mechanism of action of Memantine?

It attenuates the excitotoxic effects of glutamate Signup and view all the answers

What is the primary advantage of using Rytary over Sinemet CR?

It can be opened and sprinkled Signup and view all the answers

What is the primary function of Carbidopa?

To inhibit the conversion of levodopa to dopamine in peripheral tissues Signup and view all the answers

What is the primary reason for combining Levodopa with Carbidopa?

To decrease the incidence of peripheral conversion of levodopa Signup and view all the answers

What is the primary advantage of using Acetylcholinesterase Inhibitors in the treatment of Alzheimer's disease?

They preserve memory, learning, and attention Signup and view all the answers

What is the primary reason for the wearing off phenomenon of Levodopa?

Loss of efficacy over time due to increased conversion in peripheral tissues Signup and view all the answers

What is the primary difference between Donepezil and Galantamine?

Donepezil is available in a transdermal patch, while Galantamine is not Signup and view all the answers

What is the primary mechanism of action of Rivastigmine?

It selectively inhibits cholinesterase in the CNS Signup and view all the answers

What is the primary adverse effect of Memantine?

Headache, confusion, dizziness, hallucinations Signup and view all the answers

What is the frequency of administration for IM available antipsychotics?

Every 4 or 6 weeks Signup and view all the answers

Which of the following antipsychotics is associated with a higher risk of agranulocytosis?

Clozapine Signup and view all the answers

What is the primary reason for monitoring A1C periodically in patients treated with atypical antipsychotics?

Risk of diabetes mellitus Signup and view all the answers

Which of the following antipsychotics is approved for the treatment of agitation associated with dementia due to Alzheimer's disease?

Brexpiprazole Signup and view all the answers

What is a common neurological side effect of antipsychotics?

Sedation Signup and view all the answers

Which of the following antipsychotics is known to cause the most weight gain?

Clozapine Signup and view all the answers

What is a characteristic of newer second-generation antipsychotics, such as Brexpiprazole and Cariprazine?

They have a more complex mechanism of action Signup and view all the answers

Which of the following antipsychotics can be used for the treatment of bipolar disorder?

All of the above Signup and view all the answers

What is a common cardiovascular side effect of antipsychotics?

Prolongation of QT interval Signup and view all the answers

What is the primary reason for continuing PO treatment during the first 3 weeks when transitioning to IM antipsychotics?

To overlap with the IM formulation Signup and view all the answers

What should be done when switching from a SSRI to a MAOI?

Wait 2 weeks after stopping SSRI before starting a MAOI Signup and view all the answers

What is the mechanism of action of bupropion?

Blocks the reuptake of dopamine and norepinephrine Signup and view all the answers

What is the most significant adverse effect of brexanolone?

Sedation/loss of consciousness Signup and view all the answers

What is the term for the symptoms of schizophrenia that are not present in normal individuals?

Positive symptoms Signup and view all the answers

What is the mechanism of action of typical antipsychotics?

Dopamine receptor blockers Signup and view all the answers

What is the term for the symptoms of schizophrenia that are present in normal individuals but are diminished in schizophrenia?

Negative symptoms Signup and view all the answers

What is the drug that is chemically identical to allopregnanolone and is used to treat post-partum depression?

Brexanolone Signup and view all the answers

What is the time frame for improvement in hallucinations and disturbances with antipsychotic treatment?

Late > 8 weeks Signup and view all the answers

What is the mechanism of action of aripiprazole?

Partial D-2 agonist, 5HT-1A agonist, 5HT-2A antagonist Signup and view all the answers

What is the SSRI that is least likely to cross into breast milk?

Sertraline Signup and view all the answers

Study Notes

Enzymes

Enzymes typically end in –ASE
Acetylcholinesterase (AChE) is responsible for hydrolyzing Acetylcholine (ACh) and decreases the amount of ACh

Acetylcholinesterase Inhibitors

Selectively inhibit cholinesterase in the CNS
Increase Ach concentrations in the cerebral cortex
May slow deterioration of cognitive function and preserve memory, learning, and attention
Examples of agents: Donepezil (Aricept), Rivastigmine (Exelon), Galantamine (Razadyne)
Adverse effects: Memantine (Namenda) - constipation, headache, confusion, dizziness, hallucinations, hypertension

Levodopa

Biosynthetic precursor of dopamine
Increases the concentration of dopamine in the brain
Metabolized in peripheral tissue by Decarboxylase and Catechol-O-methyl transferase (COMT)
Adverse effects: nausea, vomiting, orthostatic hypotension, sedation, depression, delirium, paranoia, delusions, hallucinations
Always given in combination with carbidopa (Sinemet, Sinemet CR, Parcopa)

Carbidopa

MOA: Decarboxylase Inhibitor
Inhibits conversion of levodopa to dopamine in peripheral tissues
Increases the amount of levodopa that enters the brain
Decreases GI and cardiovascular adverse effects due to less conversion in peripheral tissue

COMT Inhibitors

Inhibits peripheral metabolism of levodopa through inhibition of Catechol-O-methyl transferase (COMT)
Used in combination with levodopa/carbidopa to enhance its effectiveness and manage wearing off
Examples of agents: Tolcapone, Entacapone, Opicapone
Adverse effects: Hepatotoxicity (tolcapone), orthostatic hypotension, diarrhea, hallucinations, brown-orange urine discoloration (benign)

Acetylcholine Receptor Antagonists

Mechanism of action: Competes with Ach at muscarinic receptors (anticholinergic)
Helps reduce tremor
Adverse effects: sedation, depression, confusion, dry mouth, blurred vision, constipation, urinary retention

Antiepileptic Drugs

Four primary mechanisms: Inhibit voltage-activated Na+ channels, inhibit voltage-activated Ca2+ channels, enhance GABA-mediated synaptic inhibition, and attenuate Glutamate-mediated excitatory responses
Examples of agents: Phenytoin (Dilantin), Phenytoin Pharmacokinetics - half-life ~ 24 hours, highly protein bound, metabolized by the liver, dose-dependent (Michaelis-Mentin also known as non-linear kinetics)

SSRIs

Adverse effects: cardiovascular (QT prolongation with citalopram and escitalopram), withdrawal syndrome (GI complaints, flu-like symptoms, anxiety, insomnia)
Drug interactions: MAOIs, TCAs, SNRIs, 5HT over-the-counter supplements
Examples of agents: Bupropion (Wellbutrin), Venlafaxine (Effexor), Desvenlafaxine (Pristiq), Duloxetine (Cymbalta), Milnacipran (Savella)

SNRIs

Bind to serotonin (SERT) and norepinephrine (NET) transporters
Prevent reuptake of both 5HT and NE (selective for NE)
Adverse effects: hypertension, sexual dysfunction, insomnia, nausea

Depression in Pregnancy

Reported in 14 to 23% of pregnant patients
Mild to moderate depression: Discontinue pharmacotherapy unless severe history, Cognitive behavioral therapy/interpersonal psychotherapy
Severe depression: Initiate/continue pharmacotherapy, Sertraline (least likely to cross into breast milk)

Brexanolone (Zulresso)

Post-partum depression
MOA: Allosteric modulator of GABAa
Chemically identical to allopregnanolone
Restores dysregulated neural network activity associated with depression
One-time 60-hour infusion
Adverse effects: sedation/loss of consciousness (dose-related), start in AM to best assess degree of sedation

Schizophrenia

Positive (+) symptoms: delusions, hallucinations, disorganized speech, unusual behavior, hostility, excitement, grandiosity
Negative (-) symptoms: blunted affect, lack of motivation and pleasure, emotional withdrawal, uncooperativeness, social withdrawal, poverty of speech
Antipsychotic class: Dopamine (D2) receptor blockers, Serotonin (5-HT2) receptor agonist/antagonist
Typical antipsychotics: Phenothiazines (Chlorpromazine, Fluphenazine, Thioridazine, Perphenazine, Trifluoperazine), Thioxanthenes (Thiothixene), Butyrophenones (Haloperidol)
Atypical antipsychotics: Clozapine (Clozaril), Loxapine (Loxitane), Olanzapine (Zyprexa), Quetiapine (Seroquel), Ziprasidone (Geodon), Aripiprazole (Abilify), Aristada (IM), Asenapine (Saphris), Iloperidone (Fanapt), Lurasidone (Latuda), Risperidone (Risperdal), Paliperidone (Invega)
Adverse effects: weight gain, impaired glucose tolerance, clear risk of diabetes mellitus, sexual dysfunction, hematologic (clozapine may cause agranulocytosis)

Newer Second Generation Antipsychotics

Brexpiprazole (Rexulti)
Cariprazine (Vraylar)
Both have complex (theoretically better targeted) mechanisms of action (sub-receptors)
Similar side effect profile to Aripiprazole
Brexpiprazole: slightly more weight gain seen in MDD studies but less EPS symptoms

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Description

Learn about enzymes, specifically Acetylcholinesterase, and their role in biological processes such as neurotransmission and cognitive function. Understand how Acetylcholinesterase Inhibitors work to increase Ach concentrations and preserve memory, learning, and attention.