Parkinson Disease, Chemotherapy and CAMs, Illicit Substances Lectures

Flashcards for Parkinson's Disease, Chemotherapy, CAMs, Illicit Substances lectures.

Parkinson's Disease

Progressive neurologic disorder of muscle movement due to dysfunction in the basal ganglia, typically starting around 50-60s and worsening over 10-20 years.

Neurons lost in Parkinson's Disease

Dopaminergic neurons in the nigrostriatal tract.

Secondary issue in PD: Overactive neurons

Excessive excitatory actions of cholinergic neurons.

Gold standard medication treatment for Parkinson Disease

Carbidopa/levodopa (Sinemet).

Symptoms dramatically improved by carbidopa/levodopa

Bradykinesia and rigidity.

Why can't someone with PD just take a dopamine pill?

DA cannot cross the BBB when taken orally.

Activity of levodopa with carbidopa

Levodopa is a dopamine precursor that can cross the BBB and be converted to dopamine by the CNS. Carbidopa prevents the peripheral conversion of levodopa, allowing more levodopa to reach the brain.

MOA of Carbidopa

DOPA decarboxylase inhibitor (DDI) which prevents the premature peripheral degradation of levodopa.

Long-term use issue in carbidopa/levodopa treatment

Eventually becomes less effective, with less predictable fluctuations in function, shorter duration of benefits, and periods of dyskinesia.

"On time" in Parkinson's disease

Period of relatively good motor control when medication seems to be working well.

"Off time" in Parkinson's disease

Period of relatively poor motor symptom control.

Dyskinesia

Broad clinical spectrum of different types of involuntary movements.

Why do “on/off” periods happen in levodopa/carbidopa treatment?

After taking levodopa for a prolonged period, the drug becomes less effective; additionally, there is gradual worsening of the underlying disease.

What symptoms of PD does not respond well to medications?

• Postural instability

• Freezing

• Mental changes

• Autonomic dysfunction

Timing of eating with levodopa/carbidopa

Take on an empty stomach, one hour before or two hours after eating, and avoid protein.

Adverse effects of carbidopa/levodopa (Sinemet)

Severe nausea and vomiting, arrhythmias, orthostatic hypotension, dyskinesias, choreoathetoid movements, ballismus, dystonia, myoclonus, and various ticks and tremors.

On-off phenomenon

Effectiveness suddenly and spontaneously decreases, resulting in abrupt worsening of symptoms (“off” period) and remission of symptoms with the next dose or spontaneously (“on” period).

End of dose akinesia

Effectiveness of L-dopa seems to wear off prior to the next dose.

Levodopa/Carbidopa MOA

DA precursor that can cross the BBB to be converted to DA. DOPA decarboxylase inhibitor (DDI) which prevents premature peripheral degradation of levodopa.

Levodopa/Carbidopa PT implications

better absorption on an empty stomach - 1 hour before a meal - or 2+ hours after a meal. NO PROTEIN.

Bromocriptine (Parlodel) MOA

dopamine agonist. Hallucinations

Bromocriptine (Parlodel) Indication/Stage

used alone in early stages before starting sinemet

Ropinirole (Requip) MOA/ Indication

dopamine agonist.Delays the need to use leva-dopa based therapy

Apomorphine (Apokyn) MOA

dopamine agonist. Severe and advanced stages of PD used for acute management of hypomobility off episodes subcutaneous injection

Benztropine (Cogentin) MOA

anti-cholinergic drug decrease cholinergic adjective treatment anticholinergic effects mood changes

Amantadine (Symmetrel) MOA

blocks NMDA receptor – inhibits excitatory glutamate enhances DA NT (mechanism is unclear)

Selegiline (Eldepryl) MOA/Indication

monoamine oxidase B inhibitor (MAO-B is responsible for metabolism of dopamine) inhibition of metabolism of DA leads to an increased concentration of dopamine

Entacapone (Comtan) MOA/Indications

inhibition of COMT: enzyme involved in alternative dopamine metabolism pathway - 3-O methyldopa is a minor must be used with L-dopa therapy

Levodopa phobia

Patients can have a large fear of L-dopa induced dyskinesias.

General PT implications for all PD medications

• Timing

  • Consider their staging and the effect of the med on their fxn/fall risk

• Fall risk

  • HUGE

  • How long are their on-off periods?

• Education

  • Levodopa phobia

  • Timing of food intake

Useful spasticity

Strength compensation in the setting of weakness, acts as a warning system when general health is impaired

Non-useful spasticity

Stiffness of a joint, painful, impairs ADLs, independence, increased burden of care

Diazepam (Valium) MOA

Benzodiazepine, facilitates binding of GABA.

Tizanidine (Zanaflex) MOA

Alpha 2 adrenergic agonist (presynaptic terminals)

Dantrolene sodium (Revonto) MOA

Works at the level of the muscle (SR) to inhibit Ca2+ release

Baclofen (Lioresel) MOA

GABA potentiation and GABA agonist inhibits LMN

Botulinum toxin A (Botox) MOA

Inhibits release of ACh from pre-synaptic terminals. Injection at muscle site

Intrathecal baclofen (ITB) pump

Surgically implanted under fascia of lower abdomen, catheter into the CSF, smaller doses compared to oral baclofen → less sedation.

Epilepsy

Chronic neurological disorder characterized by recurrent seizures

What causes a seizure?

Seizure results from uncontrolled excitation of brain neurons.

Two major types of seizure

• Generalized: Whole brain is involved,

• Focal: partial part of the brain is affected (1 hemisphere)

  • Can spread to whole brain

Difference between simple and complex partial seizures?

• Simple: no loss of consciousness

• Complex: consciousness is altered

Status epilepticus

2 or more subsequent seizures without regaining of consciousness or 30 minutes or more of continuous seizure activity.

Breakthrough seizure

When someone that is taking anti-seizure meds has a seizure. Not taking the meds is most common cause.

What is the primary cause of breath through seizures?

Non-adherence with anticonvulsants is a leading cause of the emergence of breakthrough seizures

Pentobarbital (Nembutal), Phenobarbital (Solfoton), Primidone (Myosiline) MOA

Enhance inhibitory effects of GABA

Clonazepam (Klonopin), Diazepam (Valium), Lorazepam (Ativan) MOA

enhance inhibitory effects of GABA potentiates GABA to LMN withdrawal and tolerance issues

Phenytoin (Dilantin) MOA

Decreases neuronal excitability by inhibition of Na2+ channels higher concentrations: inhibition of Ca2+ channels possible enhancement of GABA

Carbamazepine (Tegretol) MOA

Stabilized neuron via inhibition of sodium channels *similar to phenytoin *inhibits general action potentials may worsen absence seizures

Oxcarbazepine (Trileptal) MOA

Similar to carbamazepine less adverse effects

Ethosuximide (Zarontin) MOA

Inhibition of Ca2+ channels in thalamus - thalamus may be responsible for absence seizures

Valproic acid (Depakene) Divalproex sodium (Depakote) MOA

Limit sodium entry into rapidly firing neurons to stabilize neuronal activity also increase K+ influx to hyperpolarize neurons

Felbamate (Felbatol) MOA

NMDA antagonist, preventing glutamate

Gabapentin (Neurontin) MOA

GABA agonist, limits Ca2+ influx into neurons

Lacosamide (Vimpat) MOA

Slows the activation of Na2+ channels to inhibit neuronal activation

Lamotrigine (Lamictal) MOA

Blocks Na2+ channels similar to carbamazepine and phenytoin

Levetiracetam (Keppra) MOA

blocks Na2+ channels and/or increasing GABA effects

Pregabalin (Lyrica) MOA

Inhibits Ca2+ channels to decrease neuronal activity

Topiramate (Topamax) MOA

Inhibits Na2+ gates opening, stimulates GABA receptors, and decreased effectiveness of glutamate *all to stabilize neuron

Vigabatrin (Sabril) MOA

Increases levels of GABA by inhibiting its enzymatic degradation

Patients are MOST likely to come off their seizure meds?

Have been free of seizures for at least 2 years on medications, have good control of seizures within 1 year of after seizures started, have a normal neurologic exam prior to withdrawal, initial onset of seizures was in childhood

When do you call 911 for seizure meds?

If the person has never had a seizure before, the person has difficulty with breathing or waking after the seizure, the seizure lasts longer than 5 minutes, the person has another seizure soon after the first one, the person is hurt during the seizure, the seizure happens in water, the person has a health condition like diabetes, heart disease, or is pregnant

Cancer Definition

Cancer: a group of over 100 disease that involve uncontrolled division of the body cells

How does cancer spread?

Mutations to cellular replication regions of a cell’s DNA and Tumors at new sites are called metastases

Growth fraction

Percent of proliferating cells relative to entire population of cancerous cells.

Cell kill hypothesis

Each round of chemotherapy will kill a percentage of cancerous cells

Chemotherapy

Antineoplastic drugs that stop or slow growth of cancerous cells cytotoxic by nature → no receptors, just cell death

Chemotherapy and the Cell kill hypothesis

Chemo reduces the burden of the work

Therapeutic index of chemotherapy

Low/narrow → the pt can die from the chemotherapy before they die of CA

alternative medicine from complementary medicine

complementary medication a supplement taken at the same time as prescribed medication and alternative medicine a substance that is taken in place of traditional medicine

Regulation on supplements.

No pre market approval or testing

Who regulates health claims on supplements?

Federal Trade Commission

Complementary medication

A supplement taken at the same time as prescribed medication

Alternative medicine

A substance that is taken in place of traditional medicine

Alcohol overdose presentations:

Alcohol overdose vital signs lack of gag reflex. mental confusion, stupor. difficult remaining conscious or inability wake up. vomiting. seizures. slow breathing <8. slow HR. clammy skin. dulled responses (no gag). extremely low body temp, blue skin, or paleness

Meth overdose presentations:

Super fast HR 2-3x irregular breathing. pale clammy skin. high body temp (sweaty or hot, dry skin). painful HA. chest pain and tightness. can't walk or move. blue or purple fingernails. won't wake up. pinpoint pupil. unresponsiveness. cant feel arms or legs. seizure or shaking you cannot control

Signs of hallucinogen (LSD), K2 use

Dilated pupils. increased body temp. loss of appetite. sleeplessness. extreme sweating and flushing. drowsiness. tremors. increase HR and BP. nausea and vomiting

Binge drinking for men and women?

For men? 5+ drinks in 2 hours. For women? 4+ drinks in 2 hours

Definition of addiction/ Most common substance use disorder:

Addiction: neuropsychiatric disorder characterized by recurring desire to continue taking the drug despite harmful consequences most common: alcohol 1 in 12 adults has an alcohol use disorder

Neurophysiology/neuroanatomy of addiction:

Long term potential: strengthens neural connections long term depression: decreased responsiveness of a neural signal to a stimulation LTP and LTD are involved in habit formation and learning

Treatment of withdrawal:

Treatment of withdrawal is vital Medication management of the depression, anxiety, and physical attributes here is important

What percentage of people with a substance use disorder achieve recovery and survive?

75%!!

Difference between ionotophoresis and phonophoresis?

• Ionotophoresis: application of electric current

• Phonophoresis: application of ultrasound