NUR2060 - Neuro Lecture 2

What are the two major categories of drugs for Parkinson’s Disease?

1. Dopaminergic agents

   1. Promote activation of dopamine receptors

2. Anticholinergic agents

   1. Prevent activation of cholinergic receptors

What are the Dopaminergic Agents used in Parkinson’s Disease to Replace Dopamine?

1. Levodopa PO

2. Carbidopa/Levodopa PO

What are the Dopaminergic Agents used in Parkinson’s Disease to Activate Dopamine Receptors?

1. Ropinerole

2. Apomorphine

What is Levodopa?

[Dopaminergic Agents used in Parkinson’s Disease to Replace Dopamine]

1. Initially effective in 75% of patients with a 50% reduction in symptoms - full effect may take several months

2. Amino acids compete in intestine for absorption

   1. Encourage a low-protein diet

What are the Side Effects/Adverse Effects of Levodopa?

1. N/V - Chemoreceptor zone in medulla is triggered by drug.

   1. Give with low dose or with food

2. Extrapyramidal Symptoms: Involuntary movements. 80% of patients develop this

   1. Includes acute dystonias (muscle spasms)

   2. Akathisia (restless movement)

   3. Tardive dyskinesia (Involuntary face & jaw movements)

3. Darkens sweat and urine - tell patient its harmless

4. Risk for Hypertension when administered with Monoamine Oxidase (MAO) - Inhibitors:

What is Levodopa/Carbidopa?

[Dopaminergic Agents used in Parkinson’s Disease to Replace Dopamine]

The carbidopa portion of the drug decreases destruction of peripheral levodopa by decarboxylase, allowing more levodopa to cross BBB & get to the brain

1. Results in greater degree of clinical improvement

2. Increases stability of symptom control

3. Decreases stimulation of medullary emetic center (less nausea)

What are the Advantages of Drugs used for Parkinson’s Disease to Activate Dopamine Receptors?

• Does not compete with dietary protein

• Less nausea

• No need for enzymatic conversion

• Lower incidence of dyskinesias

• Fewer response failures

What is Apomorphine?

Dopaminergic Agents used in Parkinson’s Disease to Activate Dopamine Receptor

1. Administer with Trimethobenzamide premedication for treatment of nausea side effect.

2. Do not chew, cut, or swallow strip; Allow it to dissolve under tongue.

What is Entacapone?

Drug for Parkinson’s Disease - COMT Inhibitor

1. Blocks degradation of levodopa in periphery, prolongs levodopa availability to cross the BBB and get to the brain.

2. Essentially increases ½ life of levodopa

What is Selegiline?

Selective MAO-B Inhibitor for Parkinson’s Disease Treatment - Enzyme specific for dopamine breakdown

1. Inhibits monoamine oxidase (MAO)

   1. More dopamine from levodopa is available

   2. May decrease progression of disease, if used early.

   3. Effect may be brief (1-2 years)

What is Benztropine?

Anticholinergic Drug used for Parkinson’s Disease

1. Reduces tremors & rigidity, not bradykinesia

2. Used in the early stages of Parkinson’s Disease (esp. in younger patients).

What is Donepezil?

Reversible Cholinesterase Inhibitor used for the treatment of Alzheimer’s disease

1. Prevents breakdown of Acetylcholine

2. Slows progression of disease (by a few months only)

3. Side/Adverse Effects:

   1. Cholinergic effects

   2. Dizziness

   3. Headache

   4. Bronchoconstriction

   5. Bradycardia

What is Rivastigmine?

Reversible Cholinesterase Inhibitor used for the treatment of Alzheimer’s disease

1. Prevents breakdown of Acetylcholine

2. Slows progression of disease (by a few months only)

3. Side/Adverse Effects:

   1. Cholinergic effects

   2. Dizziness

   3. Headache

   4. Bronchoconstriction

   5. Bradycardia

What is Memantine?

NMDA-receptor antagonist drug used for the treatment of Alzheimer’s Disease

1. Binds N-methyl-D-aspartate receptors, may slow calcium influx & nerve damage

2. Moderate or severe cases, may slow decline & cause symptom improvement, but does not change underlying disease process.

What is Multiple Scelorsis?

1. MS: myelin sheath on neurons in CNS destroyed by immune system: relapsing and non relapsing forms.

2. Cells of the immune system mistakenly identify components of myelin as being foreign and mount an attack against them.

What is Interferon beta-1b?

Disease-Modifying Drug/Immunomodulator-1 for treatment of Multiple Sclerosis

1. Binds to Type 1 Interferon receptors; thought to inhibit the migration of leukocytes across the blood-brain barrier, preventing these cells from reaching neurons of the CNS and suppress t-cell activity

2. Decrease symptom severity and frequency, help prevent damage to axons, suppress destruction of myelin sheath

3. Many ADRs: flu symptoms, liver toxicity, blood cell suppression

What is Glatiramer acetate?

Disease-Modifying Drug/Immunomodulator-1 for treatment of Multiple Sclerosis

1. •decrease symptom severity and frequency, help prevent damage to axons, suppress destruction of myelin sheath

2. Boxed Warning - Life threatening anaphylaxis risk even after years of use

What is Ocrelizumab?

Disease-Modifying Drug/Immunomodulator-1 for treatment of Multiple Sclerosis

Monoclonal antibody that specifically binds to a protein which is found on the surface of immature & mature B lymphocytes; it triggers the body’s immune system to destroy the B Cells

1. All patients with relapsing-remitting RRMS should receive an immunomodulator beginning as soon as possible after diagnosis and continuing indefinitely

2. Risks: Infections, dangerous opportunistic infections, hypersensitivity reaction, anaphylaxis

What is Mitoxantrone?

Immunosuppressant drug used for the treatment of Multiple Sclerosis

Delays relapse and disability time, decreases autoimmune destruction of sheath, work against cells that grow & divide rapidly

1. Severe ADR’s to rapidly producing cells and BOTH are teratogens.

What are the two types of Seizures?

1. Partial seizures

   1. Focal (Limited to one part of brain)

2. Generalized Seizures

   1. Throughout brain

   2. Convulsive (tonic-clonic)

   3. Nonconvulsive (Absence)

What is Phenytoin/Fosphenytoin?

Antiepileptic drugs that inhibit sodium entry into hyperactive neurons.

Used for all seizure types except absence

1. Side Effects/Adverse Effects: 

   1. Gingival hyperplasia - Prevent/decrease with flossing and gum massage

   2. Monitor for toxicity - Narrow therapeutic range

   3. Boxed Warning - Risk for severe hypotension if given IV too rapidly

   4. High interaction potential with other drugs - Stimulates metabolism of other drugs, especially warfarin, oral contraceptives, and glucocorticoids

   5. Avoid in Pregnancy

What is Carbamazepine?

Hallmark Antiepileptic drug used for the treatment of Epilepsy

1. Action is similar to Phenytoin

   1. Suppresses neuronal discharge, decreases spread of seizure

   2. Active against partial seizures and tonic-clonic types, but not absence

2. Side + Adverse Effects:

   1. BBW - Rare but serious anemias; teach patient to report flu-like symptoms

   2. Birth defects: Optimally avoid in pregnancy

What is Oxcarbazepine?

Antiepileptic drug that is similar to carbamazepine; blocks neuronal Na channels

1. Used for partial seizures and trigeminal neuralgia

2. Teratogenic: Teach use of birth control

3. Interactions: Decreases oral contraceptives effect

What is Valproic Acid/Divalproex sodium?

Antiepileptic drug that blocks Na and Ca channels and increases GABA Influence

Used for: Seizure disorders ALL TYPES

1. Preferred drug for absence and myoclonic seizures and is used in combination with other drugs for partial seizures

2. Side Effects/Adverse Effects:

   1. GI Effects - Take with food, try coated formulas

   2. Hepatotoxic

   3. Teratogenic effects (Avoid in pregnancy)

What is Phenobarbital?

“Classic” Antiepileptic drug used for generalized & partial seizures

1. Promotes sleep & sedation (can be great)

2. IV for status epilepticus

3. Side Effects/Adverse Effects: Neurotoxicity; drowsiness; depression; very narrow therapeutic index

4. Use is now limited as other drugs have fewer & less severe ADRs

What is Gabapentin?

Antiepileptic drug used for the treatment of absence and other seizures; also post-herpetic neuralgia and neuropathy

1. Wide therapeutic index

2. Side-Effects/ADRs: Confusion, depression, and drowsiness

What is Pregabalin?

Antiepileptic drug that is similar to gabapentin in action (Chemical analog)

Used for: Neuropathic pain, postherpetic neuropathy, partial seizure adjunct, fibromyalgia

What is Diazepam/Clonazepam?

Benzodiazepine antiepileptic drugs; used for treating general, simple partial, absence, and status epilepticus seizures

1. Action: Increase the seizure threshold by intensifying the effect of GABA in the brain.

What is Lacosamide?

Newer antiepileptic drug.

Action: Exact action is unknown; thought to stabilize neuronal membranes & inhibit repetitive firing.

Used for: Tonic-clonic & partial seizures

Side Effects/Adverse Effects: Monitor for skin rashes & hypersensitivity reacitons

What is Levetiracetam?

Newer antiepileptic drug.

Action: Action unknown, thought to prevent synchronization of seizure burst firing

Used with tonic-clonic and partial seizures or adjunct.

What is Ethosuximide?

Drug of choice for absence seizures

More effective (up to 80-90% of patients) than other meds

1. Action: Suppresses neurons in the thalamus by depressing the motor cortex; inhibits calcium influx, doesn’t do anything to sodium or GABA.

2. Increases seizure threshold

3. Side effects: Few; drowsiness at first, sometimes N/V

What is Cyclobenzaprine?

Drug used for treatment of muscle spasm

What is Dantrolene?

Direct-acting Muscle Relaxant

1. For spasticity, prevention of malignant hyperthermia, and treatment of Neuroleptic Malignant Syndrome

What is Haloperidol?

Conventional antipsychotic drug used for the treatment of Psychosis, Tourette’s syndrome, and agitation

Side Effects/Adverse Effects: Increased incidence of EPS, but fewer “other” ADRs, thus preferred for initial therapy

Monitor CBC, can decrease neutrophil count & may need to discontinue.

What is Chlorpromazine?

Conventional antipsychotic drug used for the treatment of Psychosis.

Side Effects/Adverse Effects: Sedation, orthostatic hypotension, anticholinergic effects

Low risk of EPS but equal risk of TD

What is Clozapine?

Atypical Antipsychotic Drug used for the treatment of Schizophrenia

1. Action: Blocks dopamine and serotonin receptors

2. Side Effects/Adverse Effects: 

   1. Agranulocytosis; key point - makes this drug less desirable

   2. Teach patient to report signs of infection

   3. Risk for seizures, diabetes onset, weight gain, myocarditis.

What is Risperidone?

Aytpical Antipsychotic drug used for the treatment of Schizophrenia and Bipolar 1 Disorder

1. Side Effects: EPS, NMS, aggressive behavior, insomnia, sedation

What is Aripiprazole

Atypical Antipsychotic drug used for the treatment of Schizophrenia, Bipolar 1 Disorder, and adjunct for Major Depressive disorder

1. Side Effects: EPS, NMS, aggressive behavior, insomnia, sedation, weight gain

What is Ziprasidone?

Atypical Antipsychotic drug used for the treatment of Schizophrenia, Bipolar 1 mania.

1. Not used for dementia-related psychosis due to associated mortality

2. ADRs: NMS, dizziness, drowsiness, restlessness, prolonged QT interval

What are the Depression Treatment Modalities?

1. Selective Serotonin reuptake Inhibitors (SSRIs)

2. Selective serotonin/norepinephrine reuptake inhibitors (SSNRIs)

3. Tricyclic antidepressants (TCAs)

4. Monoamine oxidase inhibitors (MAOIs)

5. Atypical Antidepressants

What is fluoxetine?

Selective Serotonin Reuptake Inhibitor (SSRI) drug used for the treatment of Depression.

1. Action: Selectively blocks reuptake of serotonin

2. Side Effects/Adverse Effects: Suicide risk exists, caution

What is citalopram?

Selective Serotonin Reuptake Inhibitor (SSRI) drug used for the treatment of Depression.

1. Action: Selectively blocks reuptake of serotonin

2. Side Effects/Adverse Effects: Suicide risk exists, caution

What is sertaline?

Selective Serotonin Reuptake Inhibitor (SSRI) drug used for the treatment of Depression.

1. Action: Selectively blocks reuptake of serotonin

2. Side Effects/Adverse Effects: Suicide risk exists, caution

What is duloxetine?

SNRI used for the treatment of depression, diabetic peripheral neuropathy, and fibromyalgia

What is amitriptyline and Imipramine?

Tricyclic Antidepressants used for the treatment of depression.

Action: Potential effects of norepinephrine and serotonin by blocking reuptake

Side Effects/Adverse Effects: Orthostatic hypotension, anticholinergic effects, sedation, cardiac toxicity

1. Not as considered as safe as newer SSRI type but still helpful in many patients

What is isocarboxazid?

MAO-I used for the treatment of depression.

1. Action: Inhibits the enzyme that converts norepinephrine, serotonin, and dopamine into inactive products

2. Use: Rare, as other produces safer and more effective

3. Side Effects/Adverse Effects:

   1. Avoid tyramine-containing foods

   2. Meperidine - risk malignant hyperthermia

   3. HTN crisis also with levodopa and MAO-I

What is Lithium?

Treatment drug for Bipolar Disorder (Euphoric mania stage)

1. Sodium levels - Lithium excretion reduced when sodium levels are low

2. Monitor serum lithium levels twice weekly during initiation and q1-3 months during chronic therapy

3. Plasma levels - 0.4 to 1.0 mEq/L

What is buspirone?

Treatment drug for Generalized Anxiety Disorder

Binds to serotonin and dopamine receptors

1. Side effects: Usually mild, usually drowsy, dizzy, or tired