Week 15: Neuro Meds Flashcards
Prototype Neuro Drugs
- Vaproic Acid (Depakote, Depakene)
- Lamotrigine (Lamictal)
- Cabamazepine (Tegretol)
- Neostigmine (Prostigmin)
- Atropine
- Levodopa/Carbidopa (Sinemet) (Parkinsons)
- Donepezil (Aricept)
Seizure
disturbance in electrical activity of the brain caused by excessive discahrge of neurons
Epilepsy
disorder characterized by recurrent seizures
most say “seizure disorder” now
What do seizure medications do
they depress abnormal neuronal discharges
What are some considerations one needs to have when choosing an anti seizure medication
type of seizure (s)
age and developmental level
cost
personal habits (particularly alcohol intake)
What is the trend for seizure med therapy
monotherapy - want to treat seizures with one medicaiton if possible
Most anti seizure drugs do one or more of what 3 things
- Decrease rate sodium flows into cells
- Inhibits calcium flow into the cell
- Increases the effect of GABA (Neuroinhibitor)
Most anti seizure medications are also what
CNS depressants (no alcohol)
Anti Seizure medications do cause a risk of…
teratogenicity (structural abnormalities in a fetus)
Valproic Acid (Depakote, Depakene) Classification
Anticonvulsant
Action of valproic acid
increases concentration of GABA (inhibitory NT) in the brain
This suppresses neuron abnormal discharges
Route and Absorption of Valproic Acid
rapidly absorbed ORALLY - onset in 15-30 minutes
ADRs of Valproic Acid
- Most Common - GI RELATED - NVD (tends to ease after being on it for a bit)
Other: Drowsiness - mild and transient, HA, tremor, dizziness, weight gain
How should dosages of valproic acid work
start low and titrate slowly
When taking valproic acid avoid…
concomitant alcohol and other CNS depressants
Are the various formulations of valproic acid interchangeable (Oral, IV, SR)
NO
Valproic Acid is the drug of choice for what things
Primary Generalized Tonic Clonic Seizures
Migraine Prophylaxis
Mania of Bipolar Disorder
___ lowers serum levels of valproic acid and should not be taken with it
Aspiring
Black Box warning of Valproic Acid
Never use in children 2 years or younger - can cause fatal hepatotoxicity
Valproic acid should never be abruptly ___
stopped
Most anti-convulsants require a patient to have what
medic-alert (bracelet, etc)
Lamotrigine (Lamictal) Classification
anti convulsant
Action of Lamotrigine
exact mechanism unknown
Inhibits flow through Na ion channels and possibly Ca channels too
Absorption and Route of Lamotrigine
Readily Absorbed Orally
ADRs of Lamotrigine
Generally Well Tolerated !!!
- SERIOUS SKIN TOXICITY / SKIN RASHES
OtherL Drowsiness, dizziness, ataxia, somnolence, HA, diplopia, NV, insomnia
What drug is the preferred choice for epilepsy treatment in pregnant women and the elderly
lamotrigine (safe)
Lamotrigine must be discontinued when what occurs
any sign of a skin rash
this skin rash can cause fatal skin loss
Uses for Lamotrigine
many seizures - absent, partial, tonic clonic
bipolar disorder
pregnant epilepsy
elderly
What has fewer cognitive effects: Lamotrigine or Carbamazepine
Lamotrigine
What reduces serum levels of lamotrigine and should not be used alongside it
oral contraceptives
Avoid ___ while taking lamotrigine
alcohol
all anticonvulsants need what when stopping
gradual reduction not suddenly stopping
Carbamazepine (Tegretol) Classification
anti convulsant
Action of Carbamazepine
suppresses high frequency neuronal discharge in and around seizure foci
similar to phenytoin (Dilantin)
Carbamazepine acts similarly to
Phenytoin (Dilantin)
What kind of seizure can carbamazepine NOT be used for
absent seizures
Route and Absorption of Carbemazepine
oral - delayed and variable absorption
What is important to know about the distribution and half life of carbemazepine?
Half life is 25-65 hours but decreases over time to 12-17 hours as people continue to take it because of enzymes produced
it is distributed widely with 75-90% protein bound and peaks at 4-12 hours
ADRs of Carbemazepine
- HEMATOLOGIC: MILD LEUKOPENIA (more worrisome than thrombo), ANEMIA, THROMBOCYTOPENIA
Other: Neurologic (visual disturbances, dizziness, vertigo, confusion, nystagmus), NVD, Abdominal pain, hyponatremia, cardiovascular problems, rash, RARE APLASTIC ANEMIA
What lab value needs close watch when taking carbemazepine and why
CBC - we need to monitor and grow concerned if WBC falls below 3000
While carbemazepine has a little cognitive effect (but more than lamotrigine) what is the concern about the effect?
It is still not good for those wiht suppressed cognition and since many children develop seizure disorders early in development it can effect cognitive development over time
What does it mean that carbemazepine is an effective inducer of the microsomal system?
It will decrease the effectiveness of oral contraceptives and warfarin because it boosts metabolism in the liver
Therapeutic Range of Carbemazepine
4-12 mcg/mL
What inhibits carbemazepine metabolism and cannot be taken with it
Grapefruit juice
Neostigmine (Prostigmin) Classification
Anticholinesterase (Indirect Acting)
Action of neostigmine
reversibly inhibits acetylcholinesterase - blocking AcH destruction
AcH will accumulate in the synapse to increase muscle strength and duration of action
Indirectly boosts AcH levels
Neostigmine is used in the diagnosis and treatment of what
Myasthenia Gravis (Muscle Fatigue Disorders) - improves grip strength
Rare - Post Op Abdominal Distension (stim PNS to rest and digest)
Neostigmine is the opposite of ____
atropine
What is the neostigmine antidote
atropine
Route of Neostigmine
IV, SC, IM (Oral poorly absorbed)
ADR of Neostigmine
- CHOLINERGIC CRISIS
- PNS OVERACTIVITY - DROP BP, SWEATING, BRONCHOCONSTRICTION, DROOLING
Other: Bradycardia, Cramps
Atropine Classification
Anticholinergic (Muscarinic Antagonist)
Action of Atropine
BLOCK AcH at muscular receptors (PARASYMPATHOLYTIC)
Blocks effects of vagus nerve on the heart - enhances conduction thru the AV node
Various Blocking PNS effects
What aresome of the effects around the body atropine causes since it blocks the PNS
CNS - stimulate medulla/higher cerebral centers
Eye - Dilate pupil and paralyze accomodation
Resp - Inhibits secretions, dry mucous membranes, relax smooth bronchi muscles
CV - moderate to large dose accel HR
Circulation - large dose cause vasodilation of vessels in face and neck (atropine flush)
GI - inhibit salivation, gastric secretion mildly affected, decreases tone and peristalsis in stomach and intestines
Glands - inhibits sweat glands
Other Smooth Muscles: Urinary retention and hesitancy (decreases bladder tone but increase sphincter tone)
Atropine can be used to do what things?
- Dry Secretions
- In Acute Cardiac Conditions (Bradycardia)
- Treat eye disorders
- Diarrhea in things like Lotomil to prevent abuse
The main two things to know atropine does is..
1, DRYING SECRETIONS
- STOPS BRADYCARDIA (speeds HR)
(NON REST AND DIGEST)
When is an example of when atropine may be given in reference to surgery
prior to surgery to dry secretions
during surgery to prevent slowing of the heart by anesthetcs
ADRs of Atropine
WIDE MARGIN OF SAFETY (doesnt make the heart super fast just prevents it being Slow.
Other: Drymouth, great thirst, swallowing and talking trouble, constipation, blurred vision, photophobia, cutaneous flush (esp in children)
Contraindications of Atropine
- Glaucoma (can increase intraocular pressure in some types)
- BPH (increases voiding difficulties)
Potential big syndrome issue with too much atropine
ANTICHOLINERGIC OVERDOSE
What does “Mad as a hatter, dry as a bone, red as a beet, and blind as a bat” mean?
It is referring to Anticholinergic Overdose from something like Atropine
There is a psychotic effect, decreased salivation, peripheral vasodilation, and mydriasis (4 things)
Parkinsons Disease
a degenerative neurological disorder (movement disorder)
relative lack of dopamine and relative increase of AcH (only a drop in dopamine occurs which is the relaxing effect)
S/S of Parkinsons Disease
Resting Tremor
Rigidity
Postural Instability
Slow Movements (Bradykinesia) progressing to Akinesia
Major effects on ADLS
Cause of Parkinsons Disease
Loss of doapminergic neurons in the substantia nigra
Onset of Parkinsons
Middle age and older (rises with age)
How does drug therapy for parkinsons disease work
1 of 2 ways - but does not alter course of the disease:
- Directly or Indrectly activate dopamine receptors (dopamine agonist)
- Block AcH receptors (anticholinergic)
Drug of choice for Parkinsons disease? the issue with this drug?
Levodopa
Long term effectiveness is an issue as it usually only works for about 5 years
Levodopa (L-Dopa / Sinemet (LevodopaCarbidopa)
Anti Parkinson: Dopaminergic Drug
Is levodopa Dopamine itself
no it doesnt cross the BB and has a small half life
It must cross into the CNS and convert to dopamine
Action of Levodopa
promotes synthesis of dopamine in the striatum (a precursor of dopamine is what it is)
Crosses the BBB with help and converts to dopamine
Where is levodopa absorbed
the small intestine
What is important to know about levodopa distribution
less than 2% reaches the brain
How does the metabolism of levodopa work
the 2% that reaches the brain converts to dopamine by Dopa Decarboxylase
The other 98% metabolise elsewhere
ADRs of Levodopa
- NV
- DYSKINESIAS (Involuntary muscle movements: Facial grimace, tic, head nodding, tongue protrusion)
- LIGHTHEADEDNESS DUE TO ORTHOSTATIC HYPOTENSION (fall can be worse than it already is)
Other: Anorexia, Cardiac Dysrhythmia (Dopamine stim heart), Mental changes (hallucination, delusion, mood changes)
MAY DARKNE SWEAT OR URINE
MANY DRUG INTERACTIONS
What is important to know about levodopa dosage
levels increase slowly
it is given multiple times throughout the day
What is Parkinsonism
Not Parkinsons Disease
its an iatrogenic disease from long term anti psychotic meds - it looks like parkinsons and is tx the same but they are different
What must be avoided with Levodopa
Vitamin B6 therapy
MAOIs
High Protein Intake
Why can you not ahve high protein intake with levodopa
because the amino acids will compete with the drug for absorption
On-Off Phenomenon
People taking levodopa wiht parkinsons disease will freeze up when it wears off
Why can we not give levodopa with Vitamin B6 therapy
Vitamin B6 is a precursor to the enzyme Dopa Decarboxylase which turns L dopa into Dopamine
If we give Vitamin B6 then there will be more Dopa Decarboxylase out in the periphery converting it to dopamine before it can cross the BBB into the brain
This is why it should be avoided despite the fact it would seem to help otherwise
Why is Sinemet (Carbidopa/Levodopa) almost always the version of Levodopa given to patients
The carbidopa will inhibit dopa decarboxylase in the periphery allowing for more levodopa to enter the brain and convert to dopamine
basically MORE WILL REACH THE CNS
Donepezil (Aricept) Classification
Acetylcholinesterase Inhibitor
What drug is also in the same class as Donepezil
neostigmine - but the difference is their use and effect
Action of Donepezil
inhibits acetylcholinesterase int eh CNS - increases level of AcH
Improved transmission by the neurons can cause modest cognitive improvement in Alzheimers Disease
What is important to know about the absorption of Donepezil
FOOD DECREASES ABSORPTION AND CAUSE NV
You can take it at bedtime but this can cause insomnia and fatigue simultaneously
What leads to the NV from levodopa
dopamine stimulating the CTZ
ADRs of Donepezil
NVD
HA
Insomnia
Dream Disturbances
Fatigue
Is donepezil a cure for Alzheimer’s?
No - there is no cure
What are some reasons why anticholinesterase drugs like donepezil only give modest reuslts to Alzheimer’s?
- They are best used early in the condition but the disease begins long before symptoms appear so often its very late
- The tech and meds are not there yet to cure or reverse the disease
