Flashcards in Principles in Neurology_3 Deck (317):
clinical features of CJD?
rapidly progressive dementia with myoclonus
what are the histologic/gross findings in CJD?
spongiform cortex • prions (PrPc→PrPsc sheet [β-pleated sheet resistant to proteases])
what is MS?
autoimmune inflammation and demyelination of CNS
Patients with MS can present how?
optic neuritis • MLF syndrome • hemiparesis • hemisensory symptoms • bladder/bowel incontinence
what is the course in MS?
relapsing and remitting
MS most often affects who?
women in their 20's and 30's; more common in whites
what is Charcot's classic triad of MS?
a SIN: • Scanning speech • Intention tremor/Incontinence/INO • Nystagmus
what are the findings in MS?
↑ protein (IgG) in CSF • Oligoclonal bands are diagnostic • MRI is gold standard • Periventricular plaques with destruction of axons
what is the treatment for MS?
β-interferon, immunosuppression, natalizumab • symptomatic tx for neurogenic bladder, spasticity, and pain
what is the most common variant of Guillain-Barre syndrome?
Acute Inflammatory demyelinating polyradiculopathy
what is acute inflammatory demyelinating polyradiculopathy?
autoimmune condition that destroys Schwann cells → inflammation and demyelination of peripheral nerves and motor fibers
acute inflammatory demyelinating poly radiculopathy results in what?
symmetric ascending muscle weakness/paralysis beginning in lower extremities • facial paralysis in 50% of cases • autonomic dysfunction
prognosis of acute inflammatory demyelinating polyradiculopathy?
almost all patients survive; majority recover completely after weeks to months
what are the findings in acute inflammatory demyelinating polyradiculopathy?
↑CSF protein with normal cell count (albuminocytologic dissociation). • ↑protein →papilledema
acute inflammatory demyelinating polyradiculopathy is associated with which infections?
Campylobacter jejuni and CMV
how does infection cause acute inflammatory demyelinating polyradiculopathy?
autoimmune attack of peripheral myelin due to molecular mimicry, inoculations, and stress, but no definitive link to pathogens
Tx for acute inflammatory demyelinating polyradiculopathy?
respiratory support is critical until recovery. • additional: plasmapharesis, IV immune globulins
what is progressive multifocal leukoencephalopathy?
demyelination of CNS due to destruction of oligodendrocytes
PML is associated with what?
PML is seen in which patients?
2-4% of AIDS patients
prognosis of PML?
rapidly progressive, usually fatal
what is acute disseminated (postinfectious) encaphalomyelitis?
multifocal perivenular inflammation and demyelination after infection (measles or VZV) or vaccination (rabies, small pox)
what is metachromatic leukodystrophy?
autosomal recessive lysosomal storage disease, most commonly due to aryl sulfatase A deficiency.
what causes demyelination in metachromatic leukodystrophy?
build up of sulfatides leads to impaired production of myelin sheath
Charcot-Marie-Tooth disease is AKA what?
hereditary motor and sensory neuropathy
what is HMSN?
group of progressive heeditary nerve disorders related to the defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath
What is Krabbe's disease?
AR lysosomal storage disease due to deficiency of galactocerebrosidase
how does Krabbe's disease cause demyelination?
build up of galactocerebroside destroys myelin sheath
seizures are characterized by what?
synchronized high frequency neuronal firing
partial seizures affect what?
1 area of the brain
partial seizures most commonly originate where?
medial temporal lobe
partial seizure is often preceded by what?
secondary consequence of some partial seizures?
can secondarily generalize
what are the types of partial seizure?
simple partial • complex partial
what is a simple partial seizure?
consciousness intact: • motor, sensory, autonomic, psychic
what is a complex partial seizure?
partial seizure with impaired consciousness
what is epilepsy?
a disorder of recurrent seizures- excluding febrile seizures
what is status epilepticus?
continuous seizure for >30 min or recurrent seizures without regaining consciousness between seizures for >30min
what are the causes of seizures in children?
genetic • infection (febrile) • trauma • congenital • metabolic
what are the causes of seizures in adults?
tumors • trauma • stroke • infection
what are the causes of seizures in the elderly?
stroke • tumor • trauma • metabolic • infection
what are the types of generalized seizures?
Absence (petit mal) • myoclonic • tonic-clonic (grand mal) • tonic • atonic
features of absence seizure?
3Hz • no postictal confusion • blank stare
features of myoclonic seizure?
quick repetitive jerks
features of tonic-clonic seizure?
alternating stiffening and movement
features of tonic seizure?
features of atonic seizure?
drop' • commonly mistaken for fainting
head aches are all characterized by what?
pain due to structures such as the dura, cranial nerves, or extracranial structures
localization of cluster HA?
duration of cluster HA?
clinical presentation of cluster HA?
repetitive brief HA. excruciating periorbital pain with lacrimation and rhinorrhea
cluster HA may induce what?
cluster HA is more common in whom?
what is the treatment for cluster HA?
inhaled O2 • sumatriptan
localization of tension headache?
duration of tension HA?
>30 min (~4-6hr); constant
clinical presentation of tension HA?
steady pain. no photophobia or phonophobia. no aura
localization of migraine HA?
duration of migraine HA?
clinical features of migraine?
pulsating pain with nausea, photophobia, phonophobia, aura
what causes migraine?
irritation of CN V, meninges, or blood vessels (release of substance P, GCRP, vasoactive peptides)
what are the abortive therapies for migraine?
what are the prophylactic therapies for migraine?
propanolol • topiramate
what is vertigo?
sensation of spinning while stationary
what is the more common type of vertigo?
what causes peripheral vertigo?
inner ear etiology: • semicircular canal debris • vestibular nerve infection • Menieres disease
what is the finding of positional testing in peripheral vertigo?
delayed horizontal nystagmus
what causes central vertigo?
brainstem or cerebellar lesion: • stroke affecting vestibular nuclei • posterior fossa tumor
what are the findings in central vertigo?
directional change of nystagmus • skew deviation • diplopia • dysmetria
results of positional testing in central vertigo?
immediate nystagmus in any direction; may change directions
what are the neurocutaneous disorders?
1. Sturge-Weber syndrome • 2. Tuberous sclerosis • 3. NF1 • 4. Von Hippel-Lindau disease
what is Sturge-Weber syndrome?
congenital disorder with port-wine stains (nevus flammeus) typically in V1 ophthalmic distribution
what tumors are seen with Sturge-Weber syndrome?
leptomeningeal angiomas • pheochromocytomas
Sturge Weber syndrome can cause what?
glaucoma • seizures • hemiparesis • MR
inheritance of Sturge-Weber syndrome?
clinical features of Tuberous Sclerosis?
HAMARTOMAS: • Hamartomas in CNS and skin • Adenoma sebaceum (cutaneous angiofibroma) • Mitral regurgitation • Ash-leaf spots • cardiac Rhabdomyoma • Tuberous sclerosis • autosomal dOminant • Mental retardation • Angiomyolipoma • Seizures
what are the clinical features of NF1?
Cafe-au-lait spots • Lisch nodules • neurofibromas in skin • optic gliomas • pheochromocytomas
genetic features of NF1?
AD • 100% penetration • variable expressivity • mutated NF1 gene on chromosome 17
what are the clinical features of VonHippel-Lindau disease?
Cavernous hemangiomas in skin, mucose, organs; • bilateral RCC • hemangioblastoma in retina, brainstem, cerebellum; • pheochromocytomas
genetic features of VonHippel-Lindau disease?
AD • mutated tumor suppressor VHL gene on chromosome 3
what is the most common 1° brain tumor in adults?
GBM/ Grade IV astrocytoma
prognosis for GBM?
malignant with <1yr life expectancy
where is GBM found?
cerebral hemispheres • can cross corpus callosum (butterfly glioma)
how do you stain GBM?
stain astrocytes for GFAP
histologic findings in GBM?
pseudopalisading pleomorphic tumor cells- border central areas of necrosis and hemorrhage
what is the 2nd most common 1° brain tumor in adults?
meningioma most commonly occurs where?
in convexities of hemispheres (near surfaces of brain) and parasagital region
morphologic features of meningiomas?
1. arise from arachnoid cells • 2. are extra-axial (external to brain parenchyma) • 3. may have a dural attachment (tail)
prognosis of meningioma?
typically benign and resectable
clinical presentation of meningioma?
often asymptomatic; may present with seizures or focal signs
what is the 3rd most common 1° brain tumor in adults?
morphologic features of Schwannoma?
Schwann cell origin; often localized to CNIII →acoustic neuroma
treatment for Schwannoma?
resectable or treated with stereotactic radiosurgery
Schwannoma is usually found where?
how does a Schwannoma stain?
bilateral acoustic neuromas found in what?
frequency of oligodendroglioma?
relatively rare, slow growing
oligodendroglioma is most often located where?
morphologic features of oligodendroglioma?
chicken wire capillary pattern • oligodendrocytes= fried egg cells- round nuclei with clear cytoplasm • often calcified in oligodendroglioma
pituitary adenoma is most commonly what?
symptoms of prolactinoma?
bitemporal hemianopia and hypo/hyperpituitarism
what are the childhood primary brain tumors?
1. pilocytic (low-grade) astrocytoma • 2. medulloblastoma • 3. ependymoma • 4. hemangioblastoma • 5. craniopharyngioma
morphologic features of pilocytic astrocytoma?
well circumscribed • cystic and solid
where is pilocytic astrocytoma most often found in children?
posterior fossa/cerebellum • may be supratentorial
how does pilocytic astrocytoma stain?
prognosis of pilocytic astrocytoma?
benign • good prognosis
histologic findings in pilocytic astrocytoma?
Rosenthal fibers- eosinophilic corkscrew fibers
what is a medulloblastoma?
highly malignant cerebellar tumor • form of primitive neuroectodermal tumor
medulloblastoma can compress what?
4th ventricle → hydrocephalus
how does medulloblastoma metastasize?
can send drop mets to spinal cord
morphologic findings in medulloblastoma?
Horner-Wright rosettes • Solid • small blue cels
treatment of medulloblastoma?
ependymal cell tumors are most commonly found where?
in 4th ventricle
ependymal cell tumors can cause what?
prognosis of ependymal tumors?
morphologic findings in ependymoma?
characteristic perivascular pseudorosettes. rod-shaped blepharoplasts (basal ciliary bodies) found near nucleus
hemangioblastomas in the brain are most often where?
hemangioblastomas are associated with what condition when seen with retinal angiomas?
VonHippel Lindau disease
hemangioblastomas can produce what?
what findings are characteristic of hemangioblastoma?
foamy cells and high vascularity
what is a craniopharyngioma?
benign childhood tumor, confused with pituitary adenoma (can also cause bitemporal hemianopia)
what is the most common childhood supratentorial tumor?
craniopharyngioma is derived from what?
morphological features of craniopharyngioma?
calcification is common (tooth enamel like)
what are the herniation syndromes?
1. cingulate (subfalcine) herniation under falx • 2. downward transtentorial (central) herniation • 3. uncal herniation • 4. cerebellar tonsillar herniation into the foramen magnum
cingulate herniation under falx can do what?
where is the uncus?
medial temporal lobe
complications of cerebellar tonsilar herniation into the foramen magnum?
coma and death result when these herniations compress the brain stem
what do glaucoma drugs do?
↓ IOP via ↓ amount of aqueous humor (inhibit synthesis/secretion or increase drainage)
what are the classes of glaucoma drugs?
α1-agonists • β-blockers • diuretics • cholinomimetics • prostaglandin
what are the α agonists used to treat glaucoma?
Epinephrine • Brimonidine (α2)
what is the MOA of epinephrine for glaucoma?
↓ aqueous humor via vasoconstriction
what is the MOA of brimonidine for glaucoma?
↓ aqueous humor synthesis
what are the side-effects of epinephrine for glaucoma?
mydriasis; do not use in closed angle glaucoma
what are the side effects of brimonidine for glaucoma?
Blurry vision, ocular hyperemia, foreign body sensation, ocular allergic reactions, ocular pruritus
what are the β-blockers used for glaucoma?
timolol • betaxolol • carteolol
what is the MOA of timolol, betaxolol, and carteolol for glaucoma?
↓ aqueous humor synthesis
what are the side effects of timolol, betaxolol, and carteolol for glaucoma?
no pupillary or vision changes
what are the diuretics used for glaucoma?
what is the MOA of acetazolamide for glaucoma?
↓aqueous humor synthesis via inhibition of carbonic anhydrase
what are the side effects of acetazolamide for glaucoma?
no pupillary or vision changes
what are the direct cholinomimetics used for glaucoma?
what are the indirect cholinomimetics used for glaucoma?
physostigmine • echothiophate
what is the mechanism of action of cholinomimetics for glaucoma?
↑ outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork
what are the side effects of cholinomimetics for glaucoma?
miosis and cyclospasm
which drug should be used for glaucoma emergency?
pilocarpine- very effective at opening meshwork into canal of Schlemm
what is the prostaglandin used for glaucoma?
what is the MOA of latanoprost?
↑ outflow of aqueous humor
what are the side effects of latanoprost for glaucoma?
darkens color of iris
which drugs are opioid analgesics?
1. morphine • 2. fentanyl • 3. codeine • 4. heroin • 5. methadone • 6. meperidine • 7. dextromethorphan • 8. diphenoxylate
what is the MOA of opioid analgesics?
agonists at opioid receptors to modulate synaptic transmission- open K+ channels, close Ca2+ channels→ ↓ synaptic transmission • - inhibit release of ACh, NE, 5-HT, glutamate, substance P
what is the clinical use of opioid analgesics?
pain, cough suppression (dextromethorphan), diarrhea (loperamide and diphenoxylate), acute pulmonary edema, maintenance programs for addicts (methadone)
what happens in opioid analgesic toxicity?
addiction • respiratory depression • constipation • miosis (pinpoint pupils) • additive CNS depression with other drugs
there is no tolerance to which side effects of opioids?
miosis • constipation
opioid toxicity is treated with what?
naloxone or naltrexone (opioid receptor antagonist)
what stimulates opioid mu receptor?
what stimulates opioid delta receptor?
what stimulate opioid kappa receptor?
what is the MOA of Butorphanol?
mu-opioid receptor partial agonist and kappa-opioid receptor agonist; produces analgesia
what is the clinical use of Butorphanol?
severe pain (migraine, labor, etc.) causes less respiratory depression than full opioid agonists
what happens in butorphanol toxicity?
can cause opioid withdrawal symptoms if patient is also taking full opioid agonist (competition for opioid receptors). overdose not easily reversed with naloxone
what is the MOA of tramadol?
very weak opioid agonist; also inhibits 5HT and NE reuptake (works on multiple neurotransmitters)
what is the clinical use of tramadol?
what happens in tramadol toxicity?
similar to opioids. decreases seizure threshold
What kind of seizures do you treat with phenytoin?
- 1st LINE: Tonic-Clonic + Prophylaxis of status epilepticus • - Simple and complex partial
what type of seizures do you treat with carbamazepine?
1st LINE: Simple and complex partial + Tonic-Clonic
which types of seizures do you treat with lamotrigine?
- Simple and complex partial • - Generalized tonic-clonic
which types of seizures do you treat with gabapentin?
- Simple and complex partial • - generalized tonic-clonic
which types of seizures do you treat with topiramate?
- Simple and Complex Partial • - Generalized Tonic-clonic
which types of seizures do you treat with phenobarbital?
- Simple and complex partial • - generalized tonic-clonic
which types of seizures do you treat with Valproate?
1st LINE: Tonic-Clonic • - Simple and Complex partial • - absence
which types of seizures do you treat with ethosuxamide?
1st LINE: absence
which types of seizures do you treat with Benzodiazepines?
1st LINE: acute status epilepticus
which types of seizures do you treat with tiagabine?
simple and complex partial seizures
which types of seizures do you treat with vigabatrin?
simple and complex partial
which types of seizures do you treat with levetiracetam?
- simple and complex partial • - generalized tonic clonic
what is the first line treatment for prohpylaxis of Status epilepticus?
what is the 1st line treatment for acute status epilepticus?
what is the first line treatment for absence seizures?
what are the first line treatments for tonic-clonic seizures?
phenytoin • carbamazepine • valproic acid
what are the first line treatments for simple and complex partial seizures?
MOA of phenytoin?
use dependent blockade of Na channels; inhibition of glutamate release from excitatory presynaptic neuron
how do you give parenteral phenytoin?
MOA of carbamazepine?
↑ Na+ channel inactivation
which drug is the 1st line treatment for trigeminal neuralgia?
MOA of lamotrigine?
blocks voltage gated Na+ channels
what is the MOA of gabapentin?
designed as GABA analog, but primarily inhibits high-voltage-activated Ca++ channels
gabapentin is used for what other than seizures?
peripheral neuropathy • postherpetic neuralgia • migraine prophylaxis • bipolar disorder
MOA of topiramate?
blocks Na+ channels • ↑GABA action
topiramate is used for what other than seizures?
MOA of phenobarbital?
when is phenobarbital 1st line?
MOA of valproic acid?
↑Na+ channel inactivation, • ↑ GABA concentration
valproic acid can be used for which unusual type of seizure?
MOA of ethosuxamide?
blocks thalamic T-type Ca++ channels
MOA of diazepam/lorazepam?
benzodiazepines are used for what in pregnancy?
seizures in eclampsia, but 1st line is MgSO4
MOA of tiagabine?
inhibits GABA reuptake
MOA of vigabatrin?
irreversibly inhibits GABA transaminase →↑GABA
MOA of levetiracetam?
may modulate GABA and glutamate release
Sedation • Tolerance • Dependence
Diplopia • ataxia • blood dyskrasias (agranulocytosis, aplastic anemia) • liver toxicity • teratogenesis • P450 induction • SIADH • SJS
GI distress • fatigue • headache • urticaria • SJS
Sedation • tolerance • dependence • induction of P450
nystagmus • diplopia • ataxia • sedation • gingival hyperplasia • hirsutism • megaloblastic anemia (↓folate absorption) • teratogenesis (fetal hydantoin syndrome) • SLE like syndrome • induction of P450 • lymphadenopathy • SJS • osteopenia
Valproic acid toxicity?
GI distress • rare but fatal hepatotoxicity • NTD • tremor • weight gain • CI in pregnancy
toxicity of lamotrigine?
sedation • ataxia
sedation • mental dulling • kidney stones • weight loss
clinical presentation of SJS?
prodrome of malaise and fever followed by rapid onset of erythematous/purpuric macules • skin lesions progress to epidermal necrosis and sloughing
Clinical use of phenytoin?
tonic-clonic seizures • class 1B antiarrhythmic
which drugs are the barbiturates?
phenobarbital • pentobarbital • thiopental • secobarbital
mechanism of action of Barbiturates?
facilitate GABAa action by *↑ duration* of Cl channel opening→↓ neuron firing
what is the clinical use of barbiturates?
sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental)
Respiratory and cardiovascular depression (can be fatal) • CNS depression (↑ by EtOH) • dependence • induces P450
when are barbiturates contraindicated?
what is the treatment for barbiturate overdose?
supportive (assist respiration and maintain BP)
which drugs are benzodiazepines?
diazepam • lorazepam • triazolam • temazepam • oxazepam • midazolam • chlordiazepoxide • alprazolam
what is the mechanism of action of benzodiazepines?
facilitates GABAa action by ↑ frequency of Cl channel opening
effect of benzodiazepines on REM sleep?
t1/2 of benzodiazepines?
most have long half lives and active metabolites except for triazolam, oxazepam, and midazolam which are short acting →higher addictive potential
what do benzos barbs and EtOH all have in common?
all bind GABAa receptor= ligand gated Cl channel
clinical use of benzodiazepines?
anxiety • spasticity • status epilepticus • detoxification • night terrors • sleepwalking • general anesthesia (amnesia, muscle relaxation) • hypnotic
which benzos can be used for status epilepticus?
lorazepam and diazepam
toxicity of benzodiazepines?
dependence • additive CNS depression FX with EtOH • less risk of respiratory depression and coma than with barbiturates
treat overdose of benzodiazepines with what?
flumazenil (competitive inhibitor at benzodiazepine GABA receptor)
which drugs are the nonbenzodiazepine hypnotics?
Zolpidem (Ambien) • zalephon • eszopiclone
mechanism of nonbenzodiazepine hypnotics?
act via the BZI subtype of the GABA receptor
how are effects of Zolpidem, zalephon, and eszopiclone reversed?
what is the clinical use of zolpidem and other non benzodiazepine hypnotics?
toxicity of zolpidem, zalephon, eszopiclone?
ataxia • HA • confusion
duration of non BZD hypnotics?
short because of rapid liver metabolism
difference between zolpidem and older sedative hypnotics?
cause only modest day after psychomotor depression and few amnestic effects • lower dependence risk than benzos
what is necessary for a drug to work on the CNS?
lipid soluble (cross BBB) • or • be actively transported
features of anesthetics with ↓ solubility in blood?
rapid induction and recovery times
features of anesthetics with ↑ solubility in lipids?
↑ potency= 1/MAC
what is MAC?
minimal alveolar concentration at which 50% of the population is anesthetized
MAC varies with what?
solubility properties of N2O?
↓ blood and lipid solubility, and thus fast induction and low potency
solubility properties of halothane?
↑lipid and blood solubility, and thus high potency and slow induction
which drugs are inhaled anesthetics?
halothane • enflurane • isoflurane • sevoflurane • methoxyflurane • nitrous oxide
what is the mechanism of inhaled anesthetics?
what are the effects of inhaled anesthetics?
myocardial depression • respiratory depression • nausea/emesis • ↑ cerebral blood flow (↓cerebral metabolic demand)
toxicity of halothane?
toxicity of methoxyflurane?
toxicity of enflurane?
which inhaled anesthetics carry risk of malignant hyperthermia?
all but N2O; rare life threatening inherited susceptibility
toxicity unique to N2O?
expansion of trapped gas in a body cavity
what are the intravenous anesthetics?
Barbiturates • Benzodiazepines • Arylcyclohexylamines (Ketamine) • Opioids • Propofol
MC barbiturate IV anesthetic?
PK of thiopental as IV anesthetic?
high potency, high lipid solubility, rapid entry into brain
thiopental is used as an IV anesthetic for what?
induction of anesthesia and short surgical procedures
effect of thiopental as IV anesthetic is terminated by what?
rapid redistribution into tissues (MSK + Fat)
effect of IV thiopental on cerebral blood flow?
↓cerebral blood flow
which IV benzodiazepine is most common anesthetic used for endoscopy?
how is midazolam used as IV anesthetic?
adjunctively with gaseous anesthetics and narcotics
risk of IV midazolam for anesthesia?
may cause severe post/op respiratory depression, ↓BP and amnesia
what are arylcyclohexylamines like ketamine?
PCP analogs that act as dissociative anesthetics
PD of IV ketamine in anesthesia?
blocks NMDA receptors
effect of IV ketamine on Cardiovascular system?
congitive effects of arylcyclohexylamines?
cause disorientation, hallucination, and bad dreams
effect of arylcyclohexylamines on cerebral blood flow?
↑ cerebral blood flow
use of IV opioids in anesthesia?
morphine, fentanyl used with other CNS depressants during general anesthesia
propofol is used for what?
sedation in ICU • rapid anesthesia induction • short procedures
PD effects of IV propofol?
difference in side effects between propofol and thiopental?
propofol has less postoperative nausea than thiopental
what are the local anesthetic esters?
procaine • cocaine • tetracaine
what are the aminde local anesthetics?
lidocaine • mepivacaine • bupivacaine
MOA of local anesthetics?
block Na+ channels by binding to specific receptors on inner portion of channel
local anesthetics preferentially bind to what?
activated Na+ channels, so most effective in rapidly firing neurons
PK of 3° amine local anesthetics?
penetrate membrane in uncharged form, hen bind to ion channels as charged form
Local anesthetics can be given as what combination?
can be given with vasoconstrictors (epi) to enhance local action= • ↓bleeding, ↑anesthesia by ↓systemic concentration
what happens when you use an alkaline anesthetic in infected tissue?
in acidic tissue, alkaline anesthetics are charged and cannot penetrate membrane effectively →need more anesthetic
what is the order of nerve blockade by local anesthetics?
small diameter myelinated > small unmyelinated> large myelinated fibers > large unmyelinated
what is the order of loss of sensation in local anesthesia?
1 pain • 2 temperature • 3 touch • 4 pressure
what is the clinical use of local anesthetics?
minor surgical procedures, spinal anesthesia. If allergic to esters, give amides
toxicity of local anesthetics?
CNS excitation, severe cardiovascular toxicity (bupivacaine), HTN, arrhythmia (cocaine)
neuromuscular blocking drugs are used for what?
muscle paralysis in surgery or mechanical ventilation. selective for motor vs autonomic nicotinic receptor
prototypical depolarizing neuromuscular blocker?
MOA of succinylcholine?
strong ACh receptor agonist; produces sustained depolarization and prevents muscle contraction
steps in reversal of succinylcholine blockade?
Phase I (prolonged depolarization) no antidote. block potentiated by cholinesterase inhibitors • Phase II (repolarized but blocked) antidote consists of cholinesterase inhibitors
complications of succinylcholine use?
hypercalcemia • hyperkalemia • malignant hyperthermia
what are the nondepolarizing neuromuscular blockers?
tubocurarine • atracurium • mivacurium • pancuronium • vecuronium • rocuronium
MOA of nondepolarizing neuromuscular blockers?
competitive antagonists- compete with ACh for receptors
how do you reverse blockade by nondepolarizing neuromuscular blockers?
neostigmine • edrophonium • and other cholinesterase inhibitors
what is the MOA of dantrolene?
prevents the release of Ca++ from the sarcoplasmic reticulum of skeletal muscle
what is the clinical use of dantrolene?
used in the treatment of malignant hyperthermia and neuroleptic malignant syndrome
what are the strategies for the treatment of Parkinson's disease?
1. Dopamine agonists • 2. ↑dopamine • 3. prevent dopamine breakdown • 4. Curb excess cholinergic activity
what is the mnemonic for the treatment of Parkinson's?
BALSA • Bromocriptine • Amantadine • Levodopa • Selegiline • Antimuscarinics
what are the dopamine agonists used for Parkinson's?
Bromocriptine (ergot) • pramipexole • ropinirole (non-ergot) • Non ergot are preferred
what are the agents used to ↑dopamine in Parkinson's?
Amantadine (may ↑dopamine release) • L-dopa/carbidopa
Amantadine is also used for what?
antiviral against influenza A and rubella
toxicity of Amantadine?
MOA of Ldopa?
converted to DA in CNS
what agents prevent dopamine breakdown in Parkinson's?
Selegiline • entacapone • tolcapone
MOA of selegiline?
selective MAO type B inhibitor which preferentially metabolized dopamine over NE and 5HT
MOA of entacapone, tolcapone?
COMT inhibitors- prevent Ldopa degradation
which agents curb excess cholinergic activity in Parkinson's?
MOA of benztropine?
Antimuscarinic; • improves tremor and rigidity but has little effect on bradykinesia
difference between Ldopa and DA?
L dopa can cross BBB and is converted by dopa decarboxylase in the brain to DA
MOA of carbidopa?
a peripheral decarboxylase inhibitor, is given with Ldopa to ↑bioavailability of Ldopa in the brain and to limit peripheral side effects
toxicity of Ldopa/carbidopa?
arrhythmia from increased peripheral formation of catecholamines • long term use can lead to dyskinesia following administration, akinesia between doses
clinical use of selegiline?
adjunctive agent to L dopa in Tx of Parkinsons
toxicity of selegiline?
may enhance adverse effects of Ldopa
what are the Alzheimer's drugs?
Memantine • Donepezil, galantamine, rivastigmine
MOA of memantine?
NMDA receptor antagonist; helps prevent excitotoxicity
toxicity of memantine?
dizziness • confusion • hallucinations
MOA of donepezil, galantamine, rivastigmine?
toxicity of AChE inhibitors in AD?
nausea • dizziness • insomnia
what are the neurotransmitter changes in Huntington's disease?
↓GABA • ↓ACh • ↑DA
what are the treatments for Huntingtons?
Terbenazine and reserpine • Haloperidol
MOA of terbenazine and reserpine in huntingtons?
inhibit VMAT; limit DA vesicle packaging and release
MOA of haloperidol for huntingtons?
DA receptor antagonist
MOA of sumatriptan?
5HT1B/1D agonist- • inhibits trigeminal nerve activation • prevents vasoactive peptide release • induces vasoconstriction
t1/2 of sumatriptan?
clinical use of sumatriptan?
acute migraine • cluster HA attacks