Chapter 3 CNS - anticonvulsants + general anesthetics Flashcards
principles of anticonvulsant
- follow serum drug levels
- 2nd drug can be added if maximal dose of 1st is reached (the inital drug should be then tapered and discontinued)
- abrupt d/c of anticonvulsant can induce status epilepticus (always tape doses)
- inform female pt of association w/ birth defects
general anesthetics
- theories suggest anesthetics work by altering lpids in cell membrane stem
measure of potency is minimum alveolar concentration (MAC)
* or concentration of anesthetic that causes immobility in 50% of subjects exposed to agent at one atmosphere
1) halothane - 0.75
2) enflurane - 1.68
3) isoflurane 1.15
4) nitrious oxide - 105.0
Diazepam (valium)
lorazepam (ativan)
indication
* status epilepticus
* rapid onset for stopping active sz
* NOT FOR chronic sz control
effects
drowsiness
clouded mind
ataxia
CNS depression
IV/PO/PR
MANY drugs inhibit metabolism of diazepam
clonazepam (klonopin)
clorazepate (tranxene)
- absence sz; alternative to ethosuximide or valproic acid
effects
drowsiness
clouded mind
ataxia
CNS depression
PO
additive w/ CNS
tiagabine (gabitril)
- blocks presynaptic GABA-uptake
indication
* partial seizure
effects
1) dizziness
2) nervousness
3) tremor
4) fatigue/weakness
5) confusion
PO titrate dose over 6-20 weeks until effective
clear faster in pts taking other anticonvulsants
phenytoin (dilatin)
fosphenytoin (cerebyx)
- reduces Na+, Ca++, K+ currents across neuronal membranes
indication
* all sz except absence
effects
* nystagmus (vision condition in which the eyes make repetitive, uncontrolled movements)
* ataxia
* CNS disturb
* bone marrow suppression
* gingival hyperplasia (excessive gum growth){
* hepatotoxic
* GI disturbances
IV — CNS depression, severe hypotension, arrhythmias, hyperkinesis
PO/IV/IM
serum level 10-20 mcg/ml
metabolized in liver; long half life
carbamazepine (tegretol)
oxcarbazepine (tripleptal)
eslicarbazepine (apitom)
- similar to phenytoin (na+, ca++, k+ stopped those currents)
- antidiuretic effect
- SIMILAR structure to TCA
indication
* all sz except absence
* trigeminal neuralgia (type of chronic pain disorder that involves sudden, severe facial pain)
* manic depression
* schizo when fail to respond to antipsychotics
effects
* agranulocytosis (absolute neutrophil count (ANC) is less than 100 neutrophils per microlitre of blood)
* aplastic anemia (bone marrow cannot make enough new blood cells for your body to work normally)
* vertigo
* n/v
PO induces metaoblism by stimulating p450 enzymes in liver
DO NOT ADMINISTER TO PTS taking monoamine oxidase inhibitors
valprioc acid (depakote)
- enhance gaba neurotransmission postulated?
indication
* all sz types; particularly d/o of combined sz types
* manic ep in bipolar d/o
effects
* severe/fatal hepatotoxicity – small children especially
* less in adults
* thrombocytopenia (platelet count in your blood is too low)
* hyperammoemia (metabolic condition characterized by raised levels of ammonia, a nitrogen-containing compound. Ammonia is a potent neurotoxin)
* When you eat proteins, the body breaks them down into amino acids. Ammonia is produced from leftover amino acids, and it must be removed from the body. The liver produces several chemicals (enzymes) that change ammonia into a form called urea, which the body can remove in the urine.
PO/IV metabolized in liver, highly protein bound
interactions
* additive with other anticonvulsants
* levels decreased by aspirin and cimetidine (reduce gastric acid)
ethosuximide (zarontin)
indication
* absence sz
effects
1) n/v
2) decreased appetite
3) wt loss
PO – 40-100 mcg/ml
interaction
* inc’s phenytoin
* dec primidone
gabapentin (neurontin)
- related to GABA, likely reacts to distinct receptor
indication
* adjunctive tx of partial sz
indication
* somnolence (state of drowsiness or strong desire to fall asleep)
* ataxia
* dizziness
* CNS effects
PO
Gabapentin absorption dec by antacids
lamotrigine (lamictal)
- may stabilize neurons and affect glutamate (memory, cognition, and mood regulation) / aspartate (nutritional potential, regulation on reproduction and hormone biology, and neuron protection) release
- both at low levels can stimulate neurons
indication
* adult patients w/ partial seizures
* lennox-gastaut syndrome
* Lennox-Gastaut syndrome is a severe condition characterized by repeated seizures (epilepsy) that begin early in life. Affected individuals have multiple types of seizures, developmental delays, and particular patterns of brain activity measured by a test called an electroencephalogram (EEG). An EEG shows a slow spike-and-wave pattern during wakefulness and generalized paroxysmal fast activity during sleep.
effects
* dizziness
* headache
* nausea
* ataxia
* somnolence
* diplopia
* blurred vision
* life threatening rash in children (1:50) and adult (1:1000)
PO, induce own metabolism
interaction
* reduce dose if on valproate
topiratemate (topamax)
- r/t to GABA? or kainate/AMPA receptors (AMPA receptors were capable of driving a sustained train of action potentials while kainate receptors tended to activate action potential firing more transiently.)
indication
* partial onset sz
effect
* psychomotor slowing
* somnolence
* ataxia
* dizziness
* speech impairment
PO, reduce dose with kidney impairment
interaction
* reduce level of oral contraceptives
* Enhance CNS depressants
rufinamide (banzel)
- inhibit Na+ channel
indication
* lennox-gastaut syndrome sz (severe condition characterized by repeated seizures (epilepsy) that begin early in life. Affected individuals have multiple types of seizures, developmental delays, and particular patterns of brain activity measured by a test called an electroencephalogram (EEG). An EEG shows a slow spike-and-wave pattern during wakefulness and generalized paroxysmal fast activity during sleep.)
effect:
* CNS adverse effects
PO
drugs that reduce liver enzymes ==> inc this drug’s metabolism
zonisamide (zonegran)
- may block na+ channel
- or facilitate dopamine or serotonin
indication:
* partial onset seizure
effects
1) elevated body temp in some children
2) agitation
PO
drugs that reduce liver enzymes ==> inc this drug’s metabolism
levetirceptam (keppra)
levetiracetam (spritam)
- unknown mechanism
indication
* myoclonic ( brief, jerking spasms of a muscle or muscle group.), partial onset, primary generalized
effects
1) somonolence
2) dizziness
3) BH change
PO
- may cause toxicity with carbamazepine
pregabalin (lyrica)
- GABA receptor gaonist
indication:
* neuropathic pain
* sz
* fibromyalgia (pain and tenderness throughout the body, as well as fatigue and trouble sleeping.)
effect
* dizziness
* somnolence
* headache
* blurred vision
* weight gain
PO minimal metabolism
interact w/ ACE inhibitors, CNS depressants
lacosamide (vimpat)
- enhances slow inactivation of volage-gated sodium channels
indication
* w/ other drugs for partial seizures
effects
* dizziness
* n/v
perampanel (fycompa)
indication:
w/ other drugs for partial sz
effects
1) dizziness
2) drowsiness
3) nausea
PO
brivaracetam (briviact)
- synpatic vesicle protein 2a (SV2A) ligand
indication
sz d/o
effect
* suicide risk
* psychiatric effects
Thiopental
general anesthetic
CNS – sedation, hyponosis, CNS depression, decreased cerebral blood flow and metabolism (reduce intracranial pressure)
CV – dec BP (10-20%)
Resp – Apnea, bronchoconstriction
Toxic – hypotension, tachycardia, resp depression, bronchospasm, anaphylaxis
IV, onset 40 sec (drug released rom fat stores may prolong anesthesia){
Propofol (diprivan)
- more potent than thiopental
- CV (brady, hypotensive, decreaed heart perfusion) + resp (apnea)
- use lidocaine first d/t pain on injection
Toxicology – CNS stimulation, severe cardiovascular depression in elderly and hypovolemic pts
constant infusion to maintain anesthesia
Etomidate (amidate)
- similar to thiopental, less CV and resp depression
toxicity – vomiting, adnrenal insuff, myoclonus
ketamine (ketalar)
CNS – dissociative (disconnected from surrounding) anesthesia, analgesia, increased intracranial pressure
CV - inc or dec in BP, HR
resp – apnea, broncho dilation
Toxicitiy — hallucinations (moreso adults), nightmares, increased secretions
IV or IM
Halothane (H) or fluothane
Enflurane (E) or ethrane
Isoflurane (I) or forane
CNS — anesthesia, skeletal muscle relaxation (E)
CV – myo depression, decreased resistance, sensitize heart to catecholamines (H)
Resp – resp depression, bronchodilation (H)
toxicity — malignant hyperthermia possible w/ all (dangerously high body temperature, rigid muscles or spasms, a rapid heart rate, and other symptoms); H — hepatotoxicity and infrequent liver failure // E – nephrotoxicity
Isoflurane is the least of all those effects (least metabolized too) ==> hepatic and renal safety
Desflurane and sevoflurane newer agents
Nitrious oxide
CNS – anesthesia (100% NO fails to induce it in >50% people — usually used w/ other agents)
CV — when used w/ halotahne or enflurane, less hypotension
Resp – little effect
Toxicology – transient hypoxia following use
least soluble in blood; thus excreted rapidly by expiration of unmetabolized gas
Migraine headache therapy
- sumatriptan (imitrex)
- naratriptan (amerge)
- rizatriptan (maxalt)
- zolmitriptan (zomig)
all are vascular 5ht1 (serotonin) receptor agonist that cause vasoconstriction of basilar artery and dura mater vessels
pain relief in 15-80% of patients (onset 10-120 minutes)
toxicity – dizziness, tingling, flushing, chest discomfort, neck pain, and marked HTN
- fremanezumab-vfrm (ajovy)
- erenumab-aooe (aimovig)
- galcanezumab-gnlm (emgality)
injectable drugs that block calcitonin gene related peptide (CGRP) —- During a migraine attack the cerebral nerves and blood vessels release substances including CGRP. CGRP is known to be involved in the brain processes which cause pain during the attack.
- propranolol
- timolol
(used to prevent onset of migraine headaches)