Module VII - Motion Disorders
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| Antiepileptic drugs and pregnancy | carbamazepine, lamotrigine and phenytoin have lower rates of major malformations than do valproate and phenobarbital
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| Tx for Tonic-Clonic (Grand Mal) Partial (focal) seizures | #Carbamazepine, phenytoin or valproic acid
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| Tx for Absence (Petit Mal) | Ethosuximide, DOC
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| Tx for Atypical Absence, Myoclonic, Atonic | Valproic acid or clonazepam
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| Tx for Status Epilepticus | Lorazepam IV
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| Hydantoins is in what group of drugs? | anticonvulstant; antiepileptic drugs
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| Indication for Phenytoin (Dilantin) | tx of tonic-clonic & digoxin toxicity
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| pharmacological effect of Phenytoin (Dilantin)? | localized, may cause dowsiness @ start of med; may cause excitatory, dizzy, blurred vision, N/V
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| MOA of phenytoin (Dilantin) | stabilizer; decr resting fluxes of Na+ during action potential (acts like local anesthetic)
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| Kinetics of phenytoin (Dilantin) | very alkaline; GI absorption
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| SE of phenytoin (Dilantin) w/ toxicity? | toxic doses: excitatory signs; lethal doses: decerebate rigidity
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| You are awesome! | You know you're doing wonderfully!
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| phenytoin (Dilantin) usually requires loading dose | phenytoin (Dilantin) usually requires a loading dose
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| What percentage of binding does phenytoin hv w/ albumin? | 90%; which causes prob w/ toxicity, esp for babies
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| a greater fraction of phenytoin remains unbound in whom? | neonate, crit ill, pts w/ hypoalbuminemia
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| What is the best indicator of the concentration of phenytoin? | unbound drug
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| Phenytoin may be displaced from serum albumin by? | valproic acid
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| What are 2 ways to manage possible phenytoin oversaturation? | reduce drug dose or extend time btw doses
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| Primary eliminatin of phenytoin is what? | kidneys
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| SE of pheytoin Na+ | b/c of alkalinity, irritating on GI; give w/ food; IV irritation, cardiac arrythmias, phlebitis, give slowly
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| What is fosphenytoin (Cerebyx)? | it's a prodrug of phenytoin Na+ that's freely soluble in aqueous solutions and can be given at rate of 150 phenytoin equivalents/min; less irritating to veins and can be diluted with D5W w/o precipitation
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| How and why is fosphenytoinc (Cerebyx) used? | MAY GIVE IV w/ less vein irritation; freely soluble in aqueous solution & can give @ rate of 150 phenytoin equivilents (PE)/min; may dilute with D5W
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| fosphenytoin injection (Cerebyx) is absorbed well in what form? | IM
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| SE of phenytoin (Dilantin) on body? | GI upset: give w/ meals; Gingival hyperplasia: teach good oral hygiene; Hirsuitism & coarse face features; folic acid deficiency anemia; fetal hydantoin syndrome; toxicty (hyperglycemia)
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| Explain Hirsutuism & phenytoin relation | SE of phenytoin, causes male type hair growth, and coarse facial features; this is a major reason why It's not a DOC for women and kids
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| Explain Folic acid deficiency & phenytoin relation | phenytoin causes folic acid deficiency anemia (megaloblastic anemia); tx is to give folic acid (which would then offset the phenytoin again--best to monitor phenytoin levels
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| Explain phenytoin's pregnancy category and why? | Cat D because causes fetal hydantoin syndrome anomalies (cleft lip/palate); but must weight risk and danger bc risk is only 4-5% w/ drug vs 1% w/o drug, but definitely convulsions could affect fetus
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| Explain phenytoin toxicity effects; what should be done? | phenytoin toxicity causes hyperglycemia AND nystagmus (CNS), drowsiness, ataxia, diplopia, cardiac arrythmias; be sure to do FREE PHENYTOIN LEVEL
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| Education on various drug preparations? | Don't change drug brand preparations
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| Explain drug interactions of phenytoin as OBJECT DRUG? | *metabolized in liver; affected by carbamazipine & phenobarb (enzyme inducers)-will LOWER phenytoin level; Valproic acid displaces phenytoin & --> phenytoin toxicity
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| Explain drug interactions of phenytoin as PRECIPITANT DRUG? | phenytoin is enzyme INDUCER (3A4), so decr bld level of other drugs
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| Phenytoin may be displaced by what drug? | Valproic acid
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| Why is plasma albumin binding a big deal w/ phenytoin? | phenytoin is 90% bound to plasma albumin, so in situations hwere there isn't sufficient albumin, that leaves XS serum phenytoin wich could lead to toxicity.
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| What are situations of decr albumin | neonate, crit ill, pts w/ hypoalbuminemia, DM, CHF, & uremic pts w/ hepatic dz
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| Which type of lab do you draw to check phenytoin levels? | trough levels
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| Fosphenytoin sodium [Cerebyx] | prodrug approved for the control of generalized convulsive status epilepticus and the prevention and treatment of seizures during neurosurgery or as a substitute for oral phenytoin
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| What are the common drug inducers? |
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| What are the common drug inhibitors? |
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| Phenobarbital (primidone [Mysoline] | an anticonvulsant barbituate; DOC for seizure ONLY in INFANTS
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| MOA of phenobarb | block sodium channels, enhance the action of GABA, and diminish the activity of glutamate
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| Why is phenobarb use decr in older children & adults? | bc of adverse effects on cognitive function and school performances
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| How is phenobarb given in neonates? | Phenobarbital is an anticonvulsant given 20 mg/kg IV slowly as a loading dose & 3-5 mg/kg/day IV, IM or PO as maintenance dose.
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| Main adverse effect of phenobarb? | drowsiness
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| Carbamazepine [Tegretol] | anticonvulsant barbiturate and DOC for partial seizures and tonic-clonic seizures
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| Carbamazepine was initially developed for tx of what? | trigeminal neuralgia; but it caused agranulocytosis (bone marrow suppression), but later determined this prob wasn’t very common, so used more
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| MOA of carbamazepine? | stabilizes Na+ cells
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| Use of carbamazepine? | tonic-clonic, generalized, and partial seizures
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| Kinetics of carbamazepine? | enzyme INDUCER
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| SE/ADR of carbamazepine? | fever, no hirsuitism, easier kinetics than phenytoin
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| Carbamazepine also used as mood stabilizer (in manic-depressant) | Carbamazepine also used as a mood stabilizer (in manic-depressant)
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| Carbamazepine and ________ are used in manic phase of depression? | valproic acid
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| SE of carbamazepine? | GI upset, so give WITH FOOD
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| Toxic doses of carbamazepine cause what ADRs? | coma, convulsions, and resp depression
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| Most common SE of carbamazepine? | GI upset, HA
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| ADR high toxic doses causes this? | (symptoms like phenytoin) nystagmus, diploplia, vertigo, ataxia
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| Carbamazepine interactions | limited enzyme inducer
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| What is the DOC of absence seizures? | Ethosuximide (Zarontin)
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| MOA of Ethosuximide (Zarontin)? | CCB that’s diff from cardiac muscle
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| Kinetics of Ethosuximide (Zarontin)? | good GI absorption ; long t1/2 life (QD dosing makes compliance better)
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| SE of Ethosuximide (Zarotin)? | GI upset & drowsiness
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| What is the DOC for the manic phase of manic depression? | Valproic acid (Divalproex)
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| What is the first wide-spectrum anticonvulsant? | Valproic Acid (Divalproex)
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| General psych uses of valproic acid (divalproex) | tonic-clonic & absence seizures
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| What are alternative uses of valproic acid? | prophylaxis of migraine HA (along w/ propranolol); make CA meds more effective
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| Kinetics of Valproic acid (Divalproex) | long t1/2; rapidly absorbed; highly aluminum bound 90% given QD @night to assist drowsiness from other drugs
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| What is the relation btw Valproic acid and ASA w/ albumin? | valproic acid is 90% bound to albumin & ASA is 90+% bound and can displace valproic acid and lead to valproic toxicity
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| SE of Valproic Acid | GI upset, ataxia, wt incr, hepatic damage (fatal), teratogenic (<- - that’s why carbomezopine or phenytoin)
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| What’s the Blk Box Warning of Valproic Acid (Divalproex) | PANCREATITIS, esp in kids
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| Which drug is DOC for myoclonic seizures in children? | clonazepam (Klonopin)
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| Clonazepam (Klonopin) is in what class of drugs? | benzodiazepines
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| SE of clonazepam (Klonopin)? | drowsy, pretty safe
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| Probs w/ clonazepam (Klonopin)? | not vry effective; tolerance builds
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| MOA of clonazepam (Klonopin)? | enhances GABA action as inhibitory transmitter
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| What group of drugs is Lorazepam (Ativan) and why sometimes preferred? | benzodiazepine; it has long t1/2
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| How does GABA work in body? | GABA stimulates inhibitory neurons, & stops transmission of impulses
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| Gabapentin (Neurontin) is in what group of drugs? | Benzodiazepines
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| IND of gabapentin (Neurontin)? | neuronal pain; tonic-clonic seizures
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| MOA of gabapentin? | unknown
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| Pregabalin (Lyrica) is in what group of drugs? | Benzodiazepines
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| IND of pregabalin (Lyrica)? | fibromyalgia; diabetic neuropathies; partial onset seizures
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| Kinetics of Pregabalin (Lyrica)? | short t1/2; not metabolized so 0 drug interactions (WELL ABSORBED); kidney elimination
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| SE of pregabalin (Lyrica) | drowsy, ataxia, fatigue; DIZZINESS & falling (ataxia)
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| IND for Lamotrigine (Lamictal)? | Wide-spread anti epileptic for tonic clonic, absence, & bipolar disorder
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| MOA of Lamotrigine (Lamictal)? | Blocks Na+ channels
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| Blk Box of Lamotrigine (Lamictal)? | Skin rash that cn --> Steven -Johnson Syndrome & can become fatal
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| IND for Topiramate (Topamax)? | Tonic-clonic seizures, migraine
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| SE of Topiramate (Topamax)? | Cognitive dysfunction
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| Hx btw Topiramate and wt? | Wt loss @ 1st few wks (made it popular)
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| What type of drug is Levetiracetam [Keppra]? | Unique agent chemically and pharm diff from all other Anti-epileptic drugs
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| IND of Levetiracetam [Keppra]? | Tx of myoclonic seizures in adults, partial-onset seizures in adults & kids, and primary generalized tonic-clonic in adults & kids; unlabeled use of migraines bipolar disorder (NICU use often)
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| Kinetics of Levetiracetam (Keppra)? | Fast & complete absorb, 0 affected by food, no P450 enzyme effect, excreted mostly unchanged in urine
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| SE of Levetiracetam (Keppra)? | Mild to mod. drowsiness, asthenia
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| What makes Levetiracetam (Keppra) diff from other AEDs? | 0 impair speech or other cognitive fnctns; 0 drug interactions
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| Parkinson's disease caused by what? | Loss of D2 & XS ACh --> uncontrollable mvmts
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| Action of levadopa in body? | Levadopa uses ACTIVE transport from GI and crosses BBB ad enters substantia nigra where it’s metabolized into D2 and restores balance of dopamine
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| Kinetics of Levadopa/Carbidopa | Absorb w/ active transport, and can be interfered w/ by protein in foods
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| What metabolizes Levadopa/Carbidopa? | MAO & COMT in GI (70%), bld stream(28%), and liver
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| What % of levadopa gets to brain? | About 2% gets to BBB
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| SE of levodopa/carbidopa? | Anorexia (activates trigger zone), GI upset, dyskinesia, depression & suicide, sinus tachy from dopamine
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| To try and prevent negative side effects of levodopa what was added to it? | Carbidopa
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| How does carbidopa work? | Carbidopa is a typical depocarboxylate inhibitor that blocks change (metabolism) of levodopa to dopamine in GI and bld, so that more levadopa will be available for brain
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| DOC for parkinson’s dz | Sinemet (a combo of levodopa/carbidopa)
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| What group of drugs is Amantadine and what’s the MOA? | Amantadine is a D2 agonist that facilitates release of D2 in substantia nigra
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| Kinetics of Amantadine? | Good PO absorb, 0 chgnd in kidney excretion
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| SE/ADR of Amantadine? | Mild, infrequent N/V, large doses in combo /c anticholinergics --> psychotic rxns (drug 0 used often)
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| What group of drugs is Bromocriptine (Parlodel) & MOA? | Bromocriptine (Parlodel) is D2 agonist in substantia nigra
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| Kinetics of Bromocriptine (Parlodel)? | Ergot alkaloid derivative so, many ADVERSE EFFECTS
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| SE of Bromocriptine (Parlodel)? | N/V, postural hypotnsn, anxiety, confusion, hallucinations, anorexia, N/V (bttr w/ food)
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| What group of drugs is Ropinirole (Requip)? | SELECTIVE D2 agonist, non-ergot derivative, so selective /c D2 receptors ONLY
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| DOC for Parkinson’s Dz (and RLS) in CHILDREN/younger pts? | Ropinirole (Requip)
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| SE of Ropinirole (Requip)? | Nausea, dizziness; TEACH OF SLEEP ATTACKS**
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| Warning of Ropinirole (Requip)? | SLEEP ATTACKS- teach pt
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| What is D2 normally metabolized by? | MAO and COMT
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| What is the negative side of MAOIs? | hypotension and drowsiness, hyperpyrexia, CVAs and heart attacks
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| What drug group is Selegiline (Eldepryl) in? | it's an MAO – B inhibitor
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| MOA of selegiline (Eldepryl)? | in low doses, selegiline inhibits MAO-B in brain and prolongs availability of D2 in substantia nigra, thereby maintaining normal skeletal movement
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| What is Emsam? | Emsam is the transdermal patch form of selegiline that helps the drug to last longer decreasing the yo-yo effect
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| SE of selegiline Eldepryl? | Nausea, dizzy, dyskinesia
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| What group of drugs does Rasagiline (Azilect) belong to? | MAO-B inhibitor
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| MOA of Rasagiline (Azilect)? | highly selective MAO-B inhibitor
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| Kinetics of the Rasageline (Azilect)? | Metabolized in liver by CYP1A2; ciprofloxacin and fluvoxamine incr concentration
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| What group of drugs are entacapone (Comtan) & tolcapone (Tasmar)? | Selective reversible COMT inhibitors
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| MOA of entacapone & tolcapone? | Prevent catabolism of levodopa, increasing brain concentration of dopamine & prolonging duration of levodopa; reduces "wearing off" effect
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| IND of entacapone (Comtan) & tolcapone (Tasmar)? | Used as adjunct drugs to be taken with levodopa/carbidopa (Sinemet)
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| Which COMT inhibitor has warning of severe liver damage? | Tolcapone (Tasmar)
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| Relation between D2 and ACh in Parkinsonâs Dz: low D2 & XS Ach--> various uncontrolled mvmts | In Park. Dz, thereâs low D2 and XS Ach--> various uncontrolled mvmts
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| Benztropine (Cogentin) is what group of drugs? what is the MOA? | centrally-acting anti-cholinergic (anti-muscarinic) & blocks receptor site of ACh in substantia nigra
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| SE of Benztropine (Cogentin)? | Dry mouth, fuzzy vision, urinary retention
CNS: confusion, agitation, memory loss, drowsiness
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| Benztropine (Cogentin) has a risk of what from use? | Risk of CENTRAL ANTICHOLINERGIC SYNDROME; frm pts on XS anticholinergics that cross BBB
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| What is propranolol and what is its indication? | Propranolol is a beta blocker and it blocks beta-2 receptors that cause tremors
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| Describe Huntington's disease and the drug of choice for treatment | Huntington's disease causes progressive CHOREA (jerky, unpredictable, involuntary movement) and dementia; DOC: haloperidol (Haldol)
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| how does haloperidol (Haldol) work and what is it a DOC for? | Haloperidol is a D2-blocker; DOC Huntington's dz
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| Describe spasticity | It's a problem in the spinal cord, hypersensitivity, spinal cord not receiving messages in brain to control them, denervation hypersensitivity
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| What is GABA? | An inhibitory neuron
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| What types of drugs are baclofen (Lioresal) and diazepam (Valium) & what is the MOA? | they are CNS drugs that enhance effect of GABA, stabilizing neurons and decreasing spasticity
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| Side effect of baclofen (Lioresal) and diazepam (Valium)? | Sedation, drowsy, muscle incoordination
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| What group of drug is dantrolene (Dantrium)? MOA? | Dantrolene is a (Muscle Relaxer) CNS drug, skeletal muscle calcium blocker
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| SE of dantrolene (Dantrium)? | Muscle weakness
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| Blackbox warning of dantrolene (Dantrium)? | Hepatotoxicity for use over time
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| what group of drugs is tizanidine (Zanaflex)? | Central alpha 2 agonist; works in the spinal cord but not on GABA; (inhibitory effect) & decr spasticity
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| SE of tizanidine (Zanaflex)? | Sedation, ataxia, weakness, WARN: FALLS
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| Treatment for acute muscle spasms? | bed and rest, physical therapy; Cyclobenzaprine (Flexeril)
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| MOA of cyclobenzaprine (Flexeril)? | Primarily CNS depressant, sedative; causes sleepiness and makes them go to bed and rest, plan for physical therapy
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| SE cyclobenzaprine (Flexeril)? | Drowsiness
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