Tx Of Parkinson's And Sz D/os

Front 1

For Parkinson's, what does tx of patient depend on?

Back 1

Primary sx and severity of sx. Tx not initiated until some impairment is noted.

Front 2

Describe initial tx and progression of tx in Parkinson's.

Back 2

Initial:
If man sx is tremor - antimuscarinic agent
If main sx is mild akinesia/bradykinesia - amantadine (promote release of DA from intact terminals in striatum).

AS disease progresses, L-Dopa + carbidopa become mainstay of thx.
Bromocriptine and other DA agonists are used alone or with L-Dopa (where it lowers tx issues with L-Dopa -->bromocriptine has a long duration of action and can decrease on/off phenomenon)

Front 3

What are some issues associated with L-Dopa therapy?

Back 3

Problems with L-Dopa Thx:
Early:
GI - N/V (major dose limiting SE)
CNS - psychotic beh. (Tx is low potency phenothiazine [don't want to give high-potency PTZ b/c it more selectively blocks D2 receptors], thioridazine [though it blocks D2 in striatum, it also blocks Ach so maintains the DA/Ach balance], clozapine or other atypical [these are limbic specific, they do not work in the nigrostriatal pathway])
CV- orthostatic HOTN, dysrhythmias.

Later Tx:
Peak Dose Dyskinesias - Tx: reduce dose and/or increase dosing frequency w/smaller doses.

On/Off Fluctuations: tx is to adjust medication combination.

End of Dose Deterioration ("Wearing off") - tx: use a controlled release prep, give smaller doses more frequently, adjust med combo, limit dietary protein (competes with L-DOPA at NATs)

Front 4

Discuss Amantadine

Back 4

Amantadine is the least toxic agent. It enhances DA release from intact DAergic neurons in striatum.

Amantadine is useful in early stages with prominent symptoms of bradykinesia and/or rigidity.

Major SE is insomnia: take in A.M. or early afternoon.

May be used as monotherapy in early PD and with L-DOPA in late PD.

**Causes Livedo Reticularis - purple discolorations on legs d/t vasoconstrictin s/t local catecholamine release. Purely cosmetic. Do not D/C tx.

Front 5

Discuss Selegilene

Back 5

Selegilene is an MAO-B inhibitor...inhibition of MAO-B results in more DA.

**Selegilene can cause serotonin syndrome (rigidity, hyperthermia, MYOCLONUS, autonomic instability) if used with TCAs, SSRIs or meperidine**

Selegilene is neuroprotective. It prevents MPTP from being converting to MPP+ (which just kills DA neurons in striatum). Useful in younger patients to slow disease progression

Selegilene allows lower doses of L-DOPA, results in fewer SE, and minimizes "wearing off" effect of L-DOPA.

Selegilene is NOT effective on sx of Parkinson's disease when used alone.

Metabolized to amphetamine and methamphetamine - take in A.M. or early afternoon to avoid insomnia.

Front 6

Discuss carbidopa.

Back 6

Carbidopa inhibits peripheral AAAD, will NOT cross the BBB---> so increases amount of DA available in CNS.

Carbidopa increases apparent potency of L-DOPA.

Must give carbidopa with L-DOPA.

Carbidopa evens out fluctuations and decreases end of dose deterioration.

Carbidopa, by decreasing L-DOPA conversion to DA in the periphery, will decrease N/V (D2 receptors in CTZ), will decrease vasodilation (stim of B2 and Alpha receptors) and orthostatic HOTN which are peripheral SE of DA.

Front 7

Discuss Tocapone.

Back 7

Tocapone allows for a lower dose of L-DOPA and INCREASES L-DOPA's duration of action.

Tolcapone decreases end of dose deterioration seen with long-term L-DOPA tx.

Tolcapone inhibits COMT degredation of DA, reduces 3-OMT (which competes with L-DOPA at the NATs and DA receptors in striatum).

Tolcapone causes ACUTE HEPATIC NECROSIS... patients have to be on LFTs q2 wks for the first year then less freq'ly.

To be on tolcapone a pt. must have shown alternate therapies unsuccessful.

Tolcapone must be taken with L-DOPA (and generally carbidopa)

Front 8

Discuss bromocriptine.

Back 8

Bromocriptine is a DA agonist - it stimulates D2 receptors on the striatal neurons.

Bromocriptine decreases motor fluctuations and improves motor fx.

Bromocriptine allows for a decreased dose of L-DOPA.

Bromocriptine minimizes end of dose deterioration in early PD.

SE are similar to L-DOPA but bromocriptine has ↑psychosis and ↓dyskinesias.

Front 9

Discuss peroglide

Back 9

Peroglide is a DA agonist with the same profile as bromocriptine.

Front 10

Discuss benztropine mesylate.

Back 10

Benztropine mesylate is an antimuscarinic.

Benztropine mesylate blocks post-synaptic ACh receptors in the striatum and restores the ACh/DA ratio.

Benztropine decreases rigidity and tremors.

Use if tremor is an early sx.

Benztropine is CI in narrow angle glaucoma (dilates pupils), if patient is on other antimuscarinic drugs (can ↓GI motility and decrease L-DOPA effects b/c the longer L-DOPA stays in the gut the more it gets turned into D-DOPA)

Front 11

What are some thoughts on early and late PD tx options?

Back 11

Selegilene is best for early tx of PD.

DA agonist is better for late tx of PD. Bromocriptine (or another DA agonist) on post-synaptic terminal is all that is left for tx of late PD.

Front 12

Discuss diphenhydramine.

Back 12

Diphenhydramine is an H1 and M1 receptor antagonist.
It is used in early tx of PD due to its antimuscarinic effects.

It is also used to treat EPS related to too much DA in the nigrostriatal pathway.

It has a similar profile to benztropine mesylate.

Front 13

What is therapy for SZ d/o based on?

Back 13

Therapy for seizure d/o is based on accurate dx of seizure type, patient hx, EEG and CT/MRI scans...

Front 14

Describe monotherapy for sz d/o.

Back 14

Monotherapy for sz d/o involves increasing the total daily dose until sz is either controlled or SE appear.

TONIC-CLONIC or PARTIAL Sz: Phenytoin, Primidone, Phenobarbital, Carbamazepine, Valproic Acid, Lamotrigene

ABSENCE SZ: Ethosuxamate, Clonazepam, Valproate, Lamotrigine.

Front 15

Describe polytherapy for sz d/o.

Back 15

When sz is not controlled at maximally tolerated doses of one drug - can add a second drug.

TONIC-CLONIC & COMPLEX PARTIAL Sz:
Phenytoin + phenobarb
Phenytoin + primidone
Phenytoin + carbamazepine

ABSENCE
Ethosuxamide + Valproate

TONIC-CLONIC or COMPLEX PARTIAL & ABSENCE:
Valproate
Lamotrigine
Ethosuxamide or Valproate + Phenytoin or Phenobarb or Primidone or Carbamazepine or Lamotrigine.

Front 16

What AEDS are most likely to cause GI disturbances?

Back 16

N/V/D most likely with:
Ethosuxamide, Valproate (less with Divalproex Na+), Carbamazepine, Phenytoin

Front 17

What AEDS are most likely to cause sedation and drowsiness?

Back 17

Pretty much all of the AEDs that don't treat all sz types except for pheytoin.

Primidone
Phenobarbital
Ethosuxamide
Carbamazepine
Clonazepam (tolerance develops)
**Phenytoin DOES NOT!!**

Front 18

What AEDS are more likely to cause folate deficiency?

Back 18

All do...but,

Phenytoin>>Phenobarb>Primidone/Carbamazepine/Valproate

Tx: Folate

Front 19

What AEDs are most likely to cause Osteomalacia.

Back 19

The PPPC AEDs

They interfere with Vit D metabolism and absoprtion.

Tx. Vit D.

Front 20

What AEDS are most likely to cause livery or pancreatic dysfx?

Back 20

Carbamazepine - get baseline LFTs and monitor; can cause cholestatic jaundice.

Valproate - can cause hepatitis and pancreatitis

Front 21

What AED is most likely to cause blood dyscrasia?

Back 21

Carbamazepine can cause aplastic anemia, agranulocytosis and thrombocytopenia; get a baseline CBC/PLT and monitor.

**Clozaril can cause life-threatening agranulocytosis**

Front 22

What AEDS are most likely to cause a rash that can lead to SJS?

Back 22

Phenytoin and Lamotrigine can cause exfoliative dermatitis and a rash that can lead to SJS. D/C med if rash appears.

Front 23

What drug is noted for causing gingival hyperplasia?

Back 23

Phenytoin - s/t stimulation of oral mast cells.

Front 24

What AED is must likely to cause hirsutism?

Back 24

Phenytoin.

Front 25

What AEDs work by blocking Na channels and preventing spread of sz?

Back 25

These AEDs block Na+ channels:

Phenytoin
Carbamazepine

Valproic acid (also increases GABA inhibitory transmission)

Lamotrigine (also decreases release of glutamate)

Felbamate (also blocks Ca+ channels and NMDA receptors)

Front 26

What AEDs work by increasing GABA inhibitory transmission (increasing Cl- channel opening)?

Back 26

These AEDS ↑GABA inhibitory transmission.

Phenobarbital
Primidone (prodrug for phenobarbital)

Clonazepam

Valproic Acid (also blocks Na+ channels)

Gabapentin (also reduces release of glutamate)

Tiagabine (inhibits GABA uptake making more available in the synapse)

Front 27

What AEDs work by blocking Ca+ channels?

Back 27

Ethosuxamide: blocks slow Ca+ channels to prevent spike&wave of absence sz. DoC for absence sz.

Felbamate (also blocks Na+ and NMDA receptors)

Front 28

What AEDs work by decreasing release of glutamate or blocking NMDA receptors?

Back 28

Lamotrigine (decreases release of glutamate and blocks Na+ channels)

Felbamate (blocks NMDA receptors and blocks Ca+ and Na+ channels)

Front 29

What are the narrow spectrum AEDs???
(hint: know for test)

Back 29

Hint: both of these are used for partial sz that are refractory to STD AED therapy.

Gabapentin: enhances GABA and reduces glutamate levels. Used for complex partial sz and secondarily generalized tonic-clonic (starts out as comlex partial) sz. GABA analog that will x BBB. Also, commonly used for neuropathic pain

Tiagabine: Inhibits GABA uptake - makes more available in the cleft. This is an "add-on" agent for refractory partial or secondarily-generalized T-C sz.

Front 30

What are the broad spectrum AEDs?

Back 30

Felbamate (note: has BlackBox Warning d/t hepatic failure and aplastic anemia). Good for refractory sz (SEVERE complex-partial sz and Lennos-Gestaut syndrome). Blocks NMDA, Ca+ and Na+ channels to prevent sz spread.

Topiramate: "Add-on" tx for refractory partial sz. Also used for migraine prophylaxis. SE include angle-closure glaucoma and renal stones (ouch - of course, if you seize you will knock them loose so no biggy!)

Front 31

What is Lennox-Gestaut syndrome?

Back 31

Childhood epileptic encephalopathy, or Lennox-Gastaut syndrome (LGS), is a devastating pediatric epilepsy syndrome constituting 1-4% of childhood epilepsies.[1] The syndrome is characterized by multiple types of seizures; mental retardation or regression; and abnormal findings on electroencephalogram (EEG), with generalized slow spike-and-wave discharges (1.5-2 Hz).

The most common seizure types are tonic-axial, atonic, and absence seizures, but myoclonic, generalized tonic-clonic, and partial seizures can be observed