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Pharm Exam 4

Module VII - Motion Disorders

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