CNS DISEASE STUDY GUIDE

Central nervous system neurotransmitters 1. Amino acid neurotransmitters a. Excitatory- glutamate b. Inhibitory- GABA (target in CNS for anticonvulsants/benzo) 2. Amine neurotransmitters a. Catecholamines i. Dopamine controls mvmt and emotions ii. Norepi affects HR, BP, bladder iii. epinephrine BP, HR, attention b. Serotonin c. Histamine d. Acetylcholine in ANS movment e. Nicotine in PNS f. Muscarinic in PNS 3. Neuropeptide transmitters a. Vasopressin, Oxytocin, Insulin, Somatostatin, Endorphins 4. Structures a. Cerebrum- LOC, mentation b. Cerebellum- coordination, balance c. Hypothalamus- coordinating center for PNS, endocrine d. Thalamus- sensation, reflexes e. Brainstem- HR, RR, BP, swallowing f. Reticular activating system- wakefulness, attention DEMENTING ILLNESS 1. Diffuse lewy body disease- progressive disease, tremors and early on hallucinations a. Treated with alz drugs, Seroquel or Abilify 2. Frontal lobe disease- dementia with loss of inhibition 3. Mild cognitive impairment- change in mentation with no impairment to ability to function 4. Vascular dementia- have had a stroke, stable, abnormalities on neuro exam, control BP, BS, hyperlipidemia 5. Mixed dementia- have both alz dementia + PMH of cerebral vascular disease 6. ALZHEIMERS a. Neurodegenerative disease with cognitive and functional decline b. Loss of cholinergic activity and acetyl synthesis results in brain atrophy c. Drug goal increase cerebral blood flow, prevent neuron degeneration, no reversal of dx Acetylcholinase inhibitors 1. DONEPIZIL (Aricept) RIVASTIGMINE (Exelon) GALANTAMINE (Razadyne) a. Blocks enzymes that degrade acetyl (most important neurotransmitter for memory) b. SE- N/V, diarrhea, syncope, bradycardia, hypokalemia c. OD is cholinergic crisis, antidote is atropine, Avoid anticholinergics (Benadryl, Ditropan, oxybutynin) d. Cross taper, no washout period e. Try for 6 months before change, Aricept at bedtime, Exelon has patch, Razadyne from daffodil bulbs f. Need baseline mental test, drug interaction with Aricept/Paxil, monitor LFT, CBC, ortho HTN, HR NMDA Receptor Antagonists 1. MEMANTINE (Namenda) a. Blocks excitotoxic effects with transmission of glutamate b. Treats alzheimers dementia, long ½ life c. Decreases sz threshold d. SE- dizziness, ANTI-SEIZURE 1. Generalized- whole brain involved, simple partial most common a. Absence- LOC, most common in children b. Myoclonic- LOC, rapid muscle contraction c. Clonic- febrile pedi seizure, muscle contraction and then relaxation d. Atonic- LOC and muscle tone e. Tonic- LOC and increased muscle tone f. Tonic-clonic- most common, LOC, tonic stiffening of upper limbs, then jerking, loss of continence, post-ictal state 2. Adverse- nausea, drowsiness, ataxia, no swimming alone, take meds HS, bone loss 3. Drug interaction- P450 inducers, preg cat C, liver, GI, heme side effects, lamotrigine causes skin rash, sleep deprivation, ETOH lowers seizure threshold 4. Pearls a. Monitor trough yearly, random level if they have a sz b. CBC, electrolyte level yearly c. Baseline DEXA, annual check- weight bearing exercise, vit D 5. Generalized tonic clonic- Phenytoin , VPA, Carmazepine, Lamotrigine 6. Absence- VPA, Ethosuximide, Lamotrigine 7. Partial- Phenytoin, VPA, Carmazepine, Felbamate ANTI-EPILEPTICS 1. ZONISAMIDE (Zonegan) a. Long ½ life, can use with Dilantin, tegretol, VPA, adverse-dizziness, ataxia, anorexia, SJS rash, aplastic anemia 2. PREGABALIN (Lyrica) 3. PHENOBARBITAL (Lamictal) increases sz threshold, adverse sedation, confusion, CNS depressant, may need folate 4. PRIMADONE (Mysoline) converted to phenobarb, less sedation 5. Status epilepticus a. Benzo- Ativan, Valium, Klonipin IV ativan 1st then IV fosphenytoin b. MOA inhibit nerve impluses, inc GABA 6. Herbals- Ginger, SJW, Gingko, milk thistle, Vit C,E,beta carotene, Coq10 Hydantoins GABA Analogs Succinimides Misc Prolong refractory period, selective inhibitor of Na Increases and potentiates GABA Blocks Ca /NA influx, inc GABA Block seizure transmission, inc GABA PHENYTOIN- Dilantin LAMOTRIGINE (Lamictal) ETHOSUXIMID CARMAZIPINE GABAPENTIN (Neurontin) TOPIMARATE (Topamax) VALPROIC ACID (Depakote) salt form E (Zarontin) (Tegretol) LEVETIRACETAM (Keppra) Liver metabolism, use for all sz except absence, titrate slowly by 50mg at a time If unsure of type of seizure, use Valproic acid for any kind of seizure Avoid ETOH, CNS depressant, check CBC, LFT Carma used for all except gen absence, ok for pedi 6 Adverse- Gingival hyperplasia, DC if rash, folic acid and vit K deficiency Liver fx, check LFT & ammonia, Lamo SJS rash tremors, alopecia, hirsutism, GI, sedation Adverse- dizziness, drowsiness, GI, ataxia, headache Adverse- aplastic anemia, low Na, rash SJS Interact with warfarin, NSAID, azoles, SSRI, statins, tagament, no IV form, no antidote, ETOH dec effect Avoid TCA, anticoags, preg cat D neural tube defects, Serum levels inc if on VPA Avoid for liver disease, Asians with allele at higher risk for SJS, monitor levels 6-12 Small increases in dosages cause large increases in blood levels Topi for migraine, can be combined with phent for weight loss, adverse fatigue, speech probs, somnolence, inc risk of kidney stones, caution with VPA Used for absence Trileptal same as tegretol but no risk for aplastic anemia Gabapent for periph neuropathy/neurogenic pain/RLS, adverse sedation, dizziness, ataxia, wt gain, inexpensive Carma for trigeminal neuralgia, bipolar, RLS, Schizo Lamotrigine blocks Na channels, blocks release of glutamate & aspartate, adverse is rash, Carma monitor CBC, LFT, renal q2-3 months, photosensitivity MOVEMENT DISORDERS 1. Essential tremor of head or upper ext, worse with purposeful movement, abates with ETOH, tx with beta blockers, mysoline 2. Parkisonism chronic debilitating, excess cholinergic , deficiency of dopamine with unopposed acetyl a. Tremors at rest, muscled rigidity, bradykinesia, postural instability, shuffling gait, fall backwards, mask like face, excessive sweating, constipation, slow speech b. Drug induced- phenothiazines, Haldol, reglan, methyldopa, lithium, Demerol, amph B, fluoxetine, amiodarone 3. CARBIDOPA/LEVODOPA (Sinemet) DOC a. Combo decreases effects in periphery, monitor liver blood, heart, kidney function b. L-dopa  enzyme dopadecarboxylase (w/ vit b6/protein)  dopamine c. No B6 supplements with L dopa, protein at end of the day d. Absorbed in SBO, liver metabolism e. Carbidopa is decarboxylase inhibitor, does not cross BBB, helps prevent conversion of L-dopa to dopamine to allow more of the drug to go directly to the brain f. Short term adverse- N/V, anorexia, take on empty stomach, psych anxiety, insomnia so reduce L-dopa g. Long term adverse- end of dose phenomenon so hold of if pt 60, taper off slowly, on-off pheno unpredictable shifts in between steady states so if no dyskinesia can change to ER, add dopamine agonist, COMT inhibitor or apomorphine h. Contraindications- malignant melanoma, asthma, MI, COPD, glaucoma i. Interactions- cardiac drugs, antagonized by psych drugs, vit B6, high prot meals, OD is psychosis, dyskinesia, arrhythmias, hypotension j. CARBI/LEVO/ENTECAPONE (Stevela) k. RIVASTIGMINE (Exelon) patch for demetial from Parkinsons 4. Parkinsons treatments a. 1st line- Rasagiline, dopamine agonist or low dose carbi/levo esp for older pt’s b. 2nd line- add on dopa agonist or carbi/levo whichever not already used, add on COMT inhibitor c. 3rd line- multiple agent in combination Monoamine Oxidase Inhib B Dopamine agonist Non-ergot dopa recept agonist COMT Inhibitors Block metabolism of dopamine by MAO-B Support inhibition D1 D2 dopamine agonist Block metabolism of levo in periphery SELEGILINE (Eldepryl) RASAGILINE (Azilect) PRAMIPEXOLE (Mirapex) ROPINIROLE (Requip) ROTIGOTINE (Neupro) patch APOMORPHINE (Apokyn) TOLCAPONE (Talmar) ENTACAPONE (Comtan) No Demerol, hold TCA, Prozac for 14 days Can be used with Sinemet Used for end stage Parkinsons, ø sulfa Ø MAOI inhib, monitor LFT for rhabdo Adverse CHF, edema, ortho BP, hallucinations N/V, dizziness, hallucination Yawning, drowsiness, edema, hallucinations, inc erection Rhabdomylosis Glutamate agonist Promotes release of dopamine AMANTADINE (Symmetrel) Used for rigidity and akinesia, added to levodopa Adverse insomnia, dizziness, reticularis mottled skin