Neuropharmacology and Pain Anesthetics (Ch. 23, 24, 25, 27, 29-31, 33, 37, 43)

Blood Brain Barrier

-protects brain

-impedes drug entry

-obstacle for therapeutic agents

-not fully developed at birth***

WILL PASS = SMALL, uncharged particles

WON'T = LARGE, polar/ionized or protein-bound particles

Outcomes of Prolonged Drug Exposure

1. increased therapeutic effects

-some drugs take time for full effect, such as antipsychotics and antidepressants

2. decreased side effects

-some drugs have SE will subside with long term use, such as phenobarbital

3. tolerance and physical dependence

BEERS Criteria

identifies drugs that carry high risks for older adults and criteria for potentially inappropriate medication use in older adults

FDA Pregnancy Risk Categories

A, B, C, D, X

FDA Pregnancy Risk A

in human studies, pregnant women used the medicine, and their babies did not have any issues related to using the medication

FDA Pregnancy Risk B

1. in humans, there are no good studies; in animal studies, pregnant animals received the medicine and the babies did not show any problems

OR

2. in animal studies, pregnant animals received medicine, and some babies had issues; in human studies, no babies had issues

FDA Pregnancy Risk C

1. in humans, there are no good studies; in animal studies, pregnant animals received the medicine and the some babies did have issues; however, the benefits may outweigh the risk for human mothers and babies

OR

2. no animal studies and no good studies in pregnant women

FDA Pregnancy Risk D

risky, studies shows drugs may harm fetus, may use if another safer therapy is unavailable

FDA Pregnancy Risk X

these medications should NEVER be used by pregnant women

Cardinal Symptoms of Parkinson's

1. tremor at rest

2. rigidity

3. postural instability

4. slowed movement

other: shuffling gait, poor handwriting, clumsiness, dementia, psychosis, sleep disturbances, and depression

Treatment Goal of PD

symptom relief; no cure/way to slow the progression

-restore balance between dopamine & acetylcholine

Purpose of Dopaminergic Agents

activate dopamine receptors

Purpose of Anticholinergic Agents

block acetylcholine receptors

Levodopa

dopamine replacement

Levodopa MOA

converted into dopamine by the brain, which then activates dopamine receptors to decrease movement s/sx of PD

-most effective drug for parkinson's

Levodopa Indications

1st line drug given to reduce movement disorders

-ALWAYS combined with carbidopa

-may also be used as a supplement to dopamine agonist

Levodopa Dose & Route

PO

-only given with carbidopa OR carbidopa & entacapone

-larger dose of levodopa compared to carbidopa

-max dose is 8 tablets/day regardless of strength

Levodopa AE

AE dependent on dose

-dyskinesias

-dark urine and sweat

-insomnia, nightmares

-dysrhythmias

-psychotic thoughts, hallucinations

early = N/V, postural hypotension

Levodopa Drug Interactions

1. INCREASED EFFECTS

-carbidopa

-entacapone

2. DECREASED EFFECTS

-first generation antipsychotics

3. INCREASED TOXICITY

-MAOIs; RF hypertensive crisis

Levodopa Contraindications

-giving without carbidopa

-caution in renal failure

-narrow-angle glaucoma

Levodopa Patient Education

-eat a consistent amount of protein; AVOID HIGH PROTEIN

-effects may "wear off" between doses

-a noticeable difference may take weeks

-give with food for early GI sx

-report any psychosis sx to MD

Levodopa Monitoring

-sx of drug-induced dyskinesias (tremors, twitching, dystonia)

-lessened efficacy; NOT due to a tolerance but related to disease progression

Carbidopa

dopamine agonist

Carbidopa MOA

inhibits decarboxylation of levodopa in intestines and peripheral tissues

Carbidopa Indications

used in combination with levodopa to increase therapeutic effects so that lower doses of levodopa can be used

Carbidopa AE

none, any AE are due to the better absorption of levodopa

Carbidopa Drug Interactions

increases beneficial effects of levodopa

Entacapone

COMT inhibitor

Entacapone MOA

selectively inhibits COMT, resulting in decreases metabolism of levodopa in intestines and peripheral tissues

Entacapone Indications

prolongs half-life of levodopa & prevents "wearing off"

Entacapone Dose & Route

PO, 200mg with each dose of levodopa/carbidopa

max: 1600mg

Entacapone AE

-vomiting, diarrhea, constipation

-yellow-orange discolored urine

-increased levels of levodopa may lead to AE

***DO NOT STOP TAKING ABRUPTLY!

Entacapone Drug Interactions

increases drug levels of other drugs metabolized by COMT

-methyldopa

-dobutamine

-isoproterenol

Long-term use of Levodopa is associated with...?

1. off times (loss of relief/wearing off)

-treat with DA agonists, COMT inhibitors, and MAOB inhibitors

2. drug-induced dyskinesias

-treat by decreasing dose or using amantadine

Pramipexole

non ergot dopamine receptor agonist

Pramipexole MOA

-selectively binds to & activates dopamine D2 and D3 receptors

-mildly blocks serotonergic and alpha-adrenergic receptors

-decreases motor control fluctuations

Pramipexole Indications

1. monotherapy

-produces significant motor performance improvement

-restless leg syndrome (moderate to severe)

-early stages of PD

2. combined with levodopa

-reduces motor control fluctuations

-may reduce levodopa doses

-later stages of PD

Pramipexole AE

-nausea and constipation*

-daytime somnolence (sleepiness)

-insomnia and sleep attacks

-dizziness, weakness

-hallucinations

-impulse control disorders (drinking, gambling, drugs, sex addiction)

Pramipexole + Levodopa AE

-hallucinations

-daytime somnolence (sleepiness)

-postural hypotension

Pramipexole Drug Interactions

cimetidine alters elimination (increases drug levels)

Pramipexole Nursing Considerations

-contraindicated in compulsive behaviors; screen prior to prescription

-reduce dosage with renal impairment

-may take several weeks to see full benefits

-monitor kidney function

Pramipexole Patient Education

-may take several weeks to see full benefits

-report sleep attack SE to MD

Selegiline

MAO-B inhibitor

remember:

-selegiline is getting her MAsters in OB in her OFF TIME (treatment for off times of levodopa)

-she never gets enough sleep (insomnia AE) and is always stressed (RF hypertensive crisis)

-she is always up for BRUNCH (take with breakfast and lunch)

-she NEVER ORDERS MIMOSAS OR CHEESE because they contain tyramine

Selegiline MOA

selectively and irreversibly inhibits MAO-B, which is the enzyme that inactivates dopamine

Selegiline Indications

-improves motor function

-delays neurodegeneration (maybe? not confirmed)

-can prolong effects of levodopa

***current guidelines recommend using in new diagnosis

Selegiline AE

-insomnia*

-orthostatic hypotension & dizziness

-GI symptoms

-hypertensive crisis

-ODT (oral disintegrating tabs) route may cause buccal mucosa irritation

Selegiline Drug Interactions

-tyramine

-sympathomimetics

-intensifies effects of levodopa

-contraindicated with meperidine and SSRIs due to RF serotonin syndrome

Selegiline Nursing Considerations

-contraindicated with meperidine and SSRIs

-benefits may decline after 1-2 years

-administer last dose before noon to avoid insomnia

-pt avoids sympathomimetics and foods containing tyramine

-ODT route = no liquids

-monitor BP and drug effectiveness

Foods Containing Tyramine

fermented/aged/cured foods

-beer

-cheese

-wine

-smoked meats

Alzheimer's - Pharmacological Treatment Goals

-slow progression

-prolong independence

-individualized for each patient

-improvements statistically significant but clinically marginal

Donepezil

cholinesterase inhibitor

Donepezil MOA

inhibits the breakdown of acetylcholine, thus increasing the amount available at cholinergic synapses

Donepezil Indications

all stages of alzheimer's

Donepezil AE

common: HA, insomnia, dizziness/vertigo,

serious: bronchoconstriction, bradycardia, sick sinus syndrome

Donepezil Drug Interactions

-first generation antihistamines

-tricyclic antidepressants

-first generation antipsychotics

Donepezil Nursing Considerations

-caution with asthma, COPD, liver, and heart disease

-avoid administering with other agents that block cholinergic receptors

-risk of AE increase with high doses

-monitor for effectiveness, airway, & HR

-titrate carefully, go slow and low

-WILL NOT CURE THE PT

-give ODT at hour of sleep QHS

-pt is fall risk

Donepezil Patient Education

-this drug will NOT cure AD but may briefly slow the progression

-risk for AE increases with high doses

Memantine

NMDA receptor antagonist

Memantine MOA

regulates calcium uptake into cells, preventing toxic levels of calcium from blocking memory formation

Memantine Indications

moderate to severe alzheimer's

Memantine AE

-dizziness, headache, confusion

-constipation or diarrhea

-hypertension or hypotension

Memantine Drug Interactions

-other NMDA antagonists (amantadine & ketamine)

-sodium bicarbonate

Memantine Nursing Considerations

-contraindicated with drugs that alkalinize urine

-caution in renal or hepatic impairment

-monitor kidney function (BUN & creatinine)

Memantine Patient Education

-may see improvement in symptoms but is not a cure

-takes about 1-3 months for effect

Anti-Epileptic Drugs (AEDs)

-suppress discharge of neurons within seizure focus & spread of activity from focus

-trial and error is used to individualize tx plan

-most drugs are selective for seizure type

-valproic acid is effective for all types of seizures

***treatment goal = reduce or eliminate seizures as much as possible

Considerations to take when using AEDs

-avoid driving and hazardous activities before pts know how the drug affects them

-plasma drug levels may determine effectiveness

-consider increasing dose before switching

-patient education is crucial for adherence

-withdrawing drugs should be done SLOWLY

-there is uncertainty regarding potential suicidal ideation w/ these drugs

Phenytoin

traditional anti-epileptic drug/anticonvulsant

Phenytoin MOA

blocks entry of sodium into neurons to decrease activity of seizure-producing neurons

Phenytoin Indications

-partial seizures

-generalized tonic-clonic

-can be used for dysrhythmias

-IV admin for convulsive SE

Phenytoin Dose & Route

1. PO: 100-125mg TID

-may switch to ER once maintenance dose is established

2. IV: 50mg/min, give slowly in saline only, do not piggyback onto other drugs

Phenytoin AE

-gingival hyperplasia

-dysrhythmias and hypotension with IV admin

-measles-like rash

-bleeding tendencies in newborn babies (give vitK)

TOXICITY = CNS: diplopia, nystagmus, cognitive impairment, ataxia (FALL RISK!), sedation

Phenytoin Drug Interactions

-inactivates PO contraceptives & warfarin

-glucocorticoids

-isoniazid

-cimetidine

-alcohol, diazepam, barbiturates, & other CNS depressants

-valproic acid & carbamazepine

Phenytoin Nursing Considerations

-contraindicated in asian pts with HLA genetic mutation

-FDA pregnancy risk category D (last resort med)

-pt maintain good oral hygiene, take folic acid daily, birth control, and avoid alcohol & other CNS depressants

-monitor for suicide risk, LFTs, adverse effects that indicate toxicity, drug levels (narrow therapeutic range)

*** drug levels should = 10-20 mcg/mL

Phenytoin Patient Education

-notify MD sx of CNS toxicity and/or rashes (SJS risk)

-take with food for GI sx

-backup sex protection if taking PO contraceptive

-do NOT stop abruptly

-need good oral hygiene

-daily folic acid

-avoid alcohol and other CNS depressants

Phenytoin Therapeutic Range

10-20 mcg/mL

Carbamazepine

traditional anti-epileptic/anticonvulsant, mood stabilizer

remember: our CAR got lost in a MAZE of PINES, but my GF (grapefruit) has the best FOCAL (DOC) VISION (AE) and saw an arrow (bone marrow) to the nearest TAXI (ataxia)

Carbamazepine MOA

suppresses high-frequency neuronal discharge in and around seizure focus

Carbamazepine Indications

-DOC for partial/focal seizures****

-tonic-clonic seizures

-symptomatic control for bipolar

-glossopharyngeal and trigeminal neuralgias

-can be used in pedi pts

***NOT USED FOR ABSENT SEIZURES

Carbamazepine AE

-diplopia, nystagmus, blurry vision

-ataxia, vertigo, unsteadiness, headache

-hyposmolarity

-bone marrow suppression

-leukopenia, anemia, thrombocytopenia

-measles like rash

-suicide risk

-SJS

Carbamazepine Drug Interactions

-PO contraceptives

-warfarin

-phenytoin

-phenobarbital

-grapefruit juice

Carbamazepine Nursing Considerations

-contraindicated in preexisting hematologic abnormalities

-FDA pregnancy risk cat. D

-screen patients of asian descent for HLA genetic mutation

-screen for suicide risk

-monitor LFTs, CBC, BMP

-no grapefruit juice

Carbamazepine Patient Education

-tolerance will decrease adverse effects after a few weeks

-take largest dose at bedtime QHS

-avoid grapefruit juice

-take with meals

-talk to HCP if experiencing CNS/dycrasias

-backup sex protection if taking POBC

Valproic Acid

traditional anti-epileptic/anticonvulsant that treats almost all seizure types, migraine prophylaxis, and bipolar

remember: VAL is a PRO at all things (most seizure types), including drinking (hepatotoxicity), pan frying (pancreatitis), and being hyper on Mondays (hyperammonemia), but he can't get pregnant (X), which makes him sad, so he gained weight (SE) and lost his hair (SE)

Valproic Acid MOA

-suppresses high frequency neurons targeting Na channels

-prevents calcium from entering calcium channels

-may enhance inhibitory influence of GABA

Valproic Acid Indications

seizures, migraines, bipolar

Valproic Acid AE

-NV, indigestion

-hepatotoxicity, hyperammonemia

-pancreatitis

-rash, weight gain, and hair loss (reversible)

-tremor

-blood dyscrasia

*** generally well tolerated

Valproic Acid Drug Interactions

-phenobarbital

-phenytoin

-topiramate

-carbapenem abx (avoid admin with meropenem and imipenem/cilastatin)

-inactivates PO contraceptives and warfarin

Valproic Acid Nursing Considerations

-FDA pregnancy risk cat D (most teratogenic; give only if other AED don't work)

-avoid using in combination with other drugs in children <2 y/o

-contraindicated preexisting liver dysfunction

-women of childbearing age should take folic acid

-screen for suicide risk

-contraindicated using with carbapenem antibiotics

-monitor LFTs, pancreatic enzymes, therapeutic effects, and for blood dyscrasias

-switch from IV to PO ASAP

Valproic Acid Patient Education

-report sx of liver injury, pancreatitis, blood dyscrasias

-backup sex protection if taking POBC

Phenobarbital

anticonvulsant barbiturate

Phenobarbital MOA

binds to GABA receptors, leading to greater response

Phenobarbital Indications

-partial seizures

-general tonic-clonic seizures

-IV form can tx generalized convulsive status epilepticus

-sedation

-sleep aid

Phenobarbital Routes

IV, IM, PO

Phenobarbital AE

-depression, lethargy

-may cause learning impairment

-dependence risk

-acute intermittent porphyria

-bleeding tendencies in newborn babies; paradoxical response in children; causes agitation & confusion in elderly

-nystagmus

-rickets and osteomalacia

-respiratory depression

Phenobarbital Drug Interactions

-inactivates PO contraceptives and warfarin

-other CNS depressants such as alcohol

-valproic acid

Phenobarbital Contraindications

-hx of intermittent porphyria

-suicidal tendencies

-FDA pregnancy risk cat D

Phenobarbital Patient Education

-dose for seizures usually not high enough for dependence

-as tolerance builds, drowsiness will decrease

-limit/avoid alcohol

-do not stop abruptly

-may take weeks to reach therapeutic levels

Phenobarbital Monitoring

-screen for suicide risk

-monitor for nystagmus, ataxia, CNS depression

-monitor liver and kidney function and drug levels

*** plasma drug levels = 15-40 mcg/mL

Phenobarbital Therapeutic Range

15-40 mcg/mL

Gabapentin (Neurontin)

new anti-epileptic drug with broad spectrum of antiseizure activity that may enhance GABA release