Other Nervous System Pharmacology Flashcards
Nondepolarizing neuromuscluar blocking drugs
Used for muscle paralysis during mechanical ventilation or surgery.
Used for long term motor paralysis which may occur within 5 minutes and most agents are later excreted or metabolized by the liver
How do nondepolarizing neuromuscular blocking drugs work
Competitive antagonists with acetylcholine at the post junctional membrane nicotonic receptors of the neuromuscular junction leaving fewer bindin gsitres for ach
Are nondepolarizing neuromuscular blocking drugs reversible
Yup
How do you reverse nondepolarizing neuromuscular blocking drugs
Cholinesterase inhibitors
What can cholinesterase inhibitors be used to diagnose
Myasthenia gravis
Suffix of nondepolarizing neuromuscular blocking drugs
Rium besides tubocurarine
Examples of nondepolarizing neuromuscular blocking drugs
Tubocurarine, atracurium, mivacurium, pancuronim, vecuronium, rocuronium
Nondepolarizing neuromuscular blocking drugs are competitive antagonists
With acetylcholine at the post junctional membrane nicotonic receptors of the neuromuscular junction. Leave few binding sites
Nondepolarizing neuromuscular blocking drugs reversal
Cholinesterase inhibitors
Nondepolarizing neuromuscular blocking drugs. What cholinesterase inhibitors may be used to reverse
Neostigmine and edrophonium
Diagnosis and treatment of myasthenia gravis
Diagnose with neostigmine and edrophonium
Treat with neostigmine
Succinylcholine
Paralytic agent used for surgeries or short procedures such as intubation
How does succinylcholine work
Binding at motor nicotonic acetylcholine receptors and keeping myocytes in a depolarizes state
Prevents ach from binding to receptors and muscle contraction
What is the first phase of succinylcholine mechanism of action
Phase 1-administered agent is non-reversible. Myocytes still have succinylcholine actively bound to motor nicotonic receptors and there is constantt depolarizes state.
Patients often show fasciculations and held contractions
What is phase 2 of succinylcholine mechanism of action
Receptors become sensitized and repolarize. They can only be aroused for action potential with larger amounts of acetylcholine, which is why neostigmine can be used to help reverse paralysis in phase 2
How can we reverse phase II of succinylcholine
Neostigmine (an acetylcholinesterase inhibitor )
Major side effect of succinylcholine
Malignant hyperthermia
Who should we not give succinylcholine to
Patients in a hyperkalamic state
Indications for succinylcholine
In surgery or short procedures can be used for patients in trauma care to help withintubation or those undergoing electroconvulsive therapy
How does succinylcholine cause neuromuscular block
Binds to the nicotonic acetylcholine receptor and keeps the muscular action potential stuck in a depolarizes state
What receptor does succinylcholine bind to
Motor nicotinic receptor , which normally binds ach
Succinylcholine is an ach receptor ___
Agonist
Opens sodium channels and causes membrane depolarization
Why does succinylcholine prevent muscular contraction
Cells cant repolarize and contract again
Can be observed immediately after IV. Patients fasciculate and are unable to contract again even after electrical stimulation
Phase 1 succinylcholine
Maintaining the muscle cels membrane potential above threshold.
Cells kept in a depolarizes state as succinylcholine is bound to the receptor and succinylcholine isn’t broken down quickly .
This period of paralysis cant be overcome bc no where for ach to bind
Phase 2 succinylcholine
Cells being repolarized but blocked . The myocytes become sensitive to ach; they are desensitized
This phase is reversible but needs a larger ach stimulus to cause contraction
How can we reverse phase 2 of succinylcholine
Neostigmine which prevents breakdown of ach in the plasma which leads to an increase ach concentration.
Why would we want to reverse phase 2 of succinylcholine
To overcome desensitization experience by paralyzed patients in phase 2
What do parkinsons drugs do
Counter neurotransmitter pathologies experienced by patients
How do parkinsons drugs work
Increase dopamine bioavailability or antagonizing acetylcholine
Describe parkinsons
Cell death in midbrain, with degeneration of the substantia nigra, which serves to generate dopamine. This leads to a neurotransmitter imbalance with decreased dopamine and relatively increased ach(a balance of these neurotransmitters is necessary for coordinated motor movement)
What are the antiparkinson drugs
BALSA
Bromocriptine, amantadine, levodopa, selegiline, antimuscarinics
Bromocriptine
Potent dopaminergic agonist
Amantadine
Unknown mechanism
But can also be antiviral
Levodopa (L-Dopa)
Dopamine isomer which readily crosses the BBB
Selegiline
Inhibits MAO-B , an enzyme which acts to break down dopamine.
Anti muscarinic drugs, like benztropine
Block cholinergic neuronal activity and are more successful at treating tremor and rigidity than bradykinesia
Parkinson
Neurodegeneratice disorder caused by death of dopamine generating cells in the substantia nigra. It is due to this cellular death and decreased dopamine the motor symptoms arise
Why do parkinsons get increase in ach
Bc dopamine decreases and there is an imbalance of neurotransmitters required for motor control (not a gross excess of ach, just an imbalance leading to higher ach in comparison to dopamine)
Bromocriptine
Ergot alkaloid
Dopamine agonist and increases its bioavailability
Also effects serotonergic, alpha adrenergic and glutamate receptors
Amantadine
Antiparkinsons and antiviral
Increases dopamine release by a poorly understood mechanism
Also has anticholinergic action
Levodopa
Dopamine isomer commonly administered with carbidopa
Protected from breakdown by carbidopa in the gut and periphery and readily passes through the blood brain barrier to increase central dopamine bioavailability
Selegiline
MAO-B -enzyme which metabolizes dopamine int he body
Selegiline is an MAO-B inhibitor and prevents breakdown of dopamine, increasing its bioavailability
Antimuscarinic drugs, like benztropine
Block muscarinic receptors to curb cholinergic neuron activity.
Works to alleviate tremor and rigidity associated with parkinsons but does not work well for treating bradykinesia
Levodopa/carbidopa
Levocarb
Treat parkinsons
Increases dopamine delivery in the brain.
Does levodopa cross the BBB
Yup
What happens to levodopa once cross BBB
Converted to dopamine centrally
Why is levodopa given with carbidopa
Inhibits DOPA decarboxylase, and protects L dopa from being broken into dopamine peripherally and in the gut before it crosses the BBB
Side effect of levocarb
Arrhythmia/tachyarrhythmia
Dyskinesia
Why does levocarb cause arrhythmia
Peripheral conversion of the drug into catecholamine
But usually mitigated by carbidopa
Why does levocarb cause dyskinesia
Distortion or difficulty with voluntary movement may occur with long term use
Carbamazepine (tegretol)
Anticonvulsant medication that decreases seizure activity caused by high frequency neuronal discharge
Indication for carbamazepine (tegretol)
Seizures
Trigeminal neuralgia
Symptoms associated with bipolar disorder
Side effects of carbamazepine (tegretol)
Blurred vision, vertigo, and headache are common Steven-johnson syndrome (SJS) Toxic epidermal necrolysis (TEN) Hepatotoxicity Blood dyscrasias (aplastic anemia)
Why not give carbamazepine (tegretol) to pregnant women
Teratogen
What do when give patient carbamazepine
Monitor for signs of water retention
Why not give someone on carbamazepine (tegretol) grapefruit juice
Increases serum carbamazepine
How does carbamazepine work
Binds to sodium channels and prevents the normal action potential activity resulting in prolonged sodium channel inactivity and decreased neuronal excitability that leads to seizure activity
Indications for carbamazepine
Seizures
Bipolar
Trigeminal neuralgia
How does carbamazepine treat seizures
Prolongs inactivation of sodium channels and suppresses high frequency neuronal discharge that contribute to the development of partial seizures and tonic clones seizures.
This drug does not help treat absence, myoclonic, or atomic seizures
How does carbamazepine treat bipolar
It is an antiepilectic drug used to suppress mania and stabilize mood.
Continued use may prevent mania and depression
How does carbamazepine treat trigeminal neuralgia
Decreases neuropathic pain along the trigeminal nerve but is not indicated as an analgesic for other types of pain
Why might carbamazepine cause nystagmus, blurred vision, and diplopia
Idk but tolerance with continued use
Why does carbamazepine cause ataxia , vertigo, headache
In first weeks.
Minimize by starting on low dose with largest dose at bedtime
Whay does carbamazepine cause hepatotoxicity
Increases the number of drug metabolizing enzymes in the liver
A dysfunctional liver may lead to liver damage and result in hepatotoxicity and hepatitis
How manage liver concern in patient on carbamazepine
Do liver tests
Inform patient to contact doctor if get symptoms of liver damage
What are symptoms of liver damage
Dark urine, clay colored stools, jaundice , rash
Why does carbamazepine cause blood dyscrasias (agranulocytosis and fatal aplastic anemia)
May cause bone marrow suppression
How manage blood dyscrasias in patient on carbamazepine
Obtain blood count before treatment
Do not give to patients with pre existing hematologist abnormalities
Notify physician if patient has symptoms of blood dyscrasias
What are symptoms of blood dyscrasias
Fever, pallor, weakness, easy bruising, petechiae
Why does carbamazepine cause water retention
Increases secretion of ADH and inhibits renal excretion of water. Leading to water retention and decreased blood osmolarity
Who may water retention be determinetal to
Patients with heart failure
How manage a patient on carbamazepine if concerned about water retention
Monitor sodium level in serum
How does carbamazepine cause SJS, rash, toxic epidermal necrolysis
Genetic variation primarily found in patients of Asian descent have an increased susceptibility of developing SJS or TEN on carbamazepine
What do if patient has rash? SJS or TEN?
Antihistamine
Stop the drug
Why avoid grapefruit juice on carbamazepine
Grapefruit juice prevents normal drug metabolism and increases serum levels
Increases the amount of toxic carbamazepine to toxic plasma levels
Memantine
NMDA receptor antagonist which helps prevent excitotoxicity in patients with Alzheimer’s disease
It is a glutamergic antagonist at NMDA receptors
How does memantine work
Halting an influx of Ca preventing excitotoxicity to neurons, (neuronal excitotoxicity is mediated by Ca which activated intracellular enzymes leading to cell destruction ) this shows symptomatic improvement in patients
Side effects of memantine
Confusion and hallucinations
General purpose of memantine
NMDA receptor antagonist which helps prevent excitotoxicity in patients with Alzheimer’s disease
Memantine is a glutamatergic __ at NMDA receptors
Antagonist (impede an influx of Ca , halting excitotoxicity to neurons) this drug is low affinity and short acting with a modest effect
How does memantine prevent excitotoxicity
Antagonizing NMDA receptors
Preventing excitotoxicity
How does excitotoxicity happen
Ca which activates intracellular enzymes leading to cell destruction
Donepezil
Acetylcholinesterase inhibitor used to treat Alzheimer’s disease
What other drug can be used for Alzheimer’s
Rivastigmine
How does donepezil work
Inhibiting the actions of acetylcholinesterase which acts to break down the neurotransmitter acetylcholine
Leading to an increase in circulating ach
Side effects of donepexzil
Related to excess cholinergic activity
Include dizziness, nausea, and vomiting, vivid dreams, and GI upset
Sumatriptan
Triptan family
For acute migraines and cluster headaches
Half life of sumatriptan
Short 2 hours
How does sumatriptan work
Agonist at 5HT 1B/1D autoreceptors and acts to inhibit the firing of serotonin neurons
Causing a reduction in the synthesis and release of serotonin
What happens when sumatriptan binds to 5HT 1B/1D receptors
Adenylate cyclase is inhibited via regulatory G proteins, increasing intracellular Ca and affecting other intracellular events
Eventually this results in inhibition of trigeminal nerve firing and vasoconstriction
Side effects of sumatriptan
Coronary vasospasm which may lead to MI
Who should we not give sumatriptan to
Prinzmetals angina or severe coronary artery disease
How do Tristan’s inhibit trigeminal nerve activation
Inhibit firing of trigeminal nerve
Why do Tristan’s cause vasoconstriction
Inhibit AC and intracellular Ca increases causing vasoconstriction and reduces vascular dilation
Why does sumatripatan cause coronary vasoaspam
Can cause MI
Why not give sumatriptan to people with prinzmetals angina or people with CAD
Due to vasospastic side effects
Butorphanol
For migraine headaches and severe pain (labor pains)
How does butorphanol work
Mixed actions at the receptor level and is an agonist for micro and kappa receptors while being a competitive antagonist at micro receptors
What is the significance of butorphanol being an agonist/antagonist at micro receptors
It causes less respiratory depression than full opioid agonist drugs
Side effects butorphanol
Withdrawal
Usually happen when patient also treated with full opioid agonist
-competing with the opioid at micro receptors competing with the adjunct opioid drug being taken leading to withdrawal
Indications for butorphanol
Migraine , severe pain, labor
How is butorphanol administered for migraine
Nasal spray
Is butorphanol more effective in women or men
Women labor
Micro receptors
Mu receptor
Withdrawal symptoms from butorphanol . How can we treat
Naloxone-but cant reverse overdose really
Gabapentin
To treat different seizure presentations, peripheral neuropathic pain and migraine prophylaxis
Bipolar and post herpetic neuralgia-off label though
What was the original purpose of gabapentin
GABA analog but does not act on the same neuronal receptors
How does gabapentin works
A lot of gaps in knowledge
Inhibitshigh coltage gated Ca channels leading to decreased levels of mono amine neurotransmitters
Side effects of gabapentin
Sedation/sluggish
Ataxia
Indication for cabapentin (primary)
Seizure bc has anticonvulsant actions against smile and complex partial seizures as well as tonic clonic generalized seizures (grand mal)
Indication for gabapentin (secondary)
Peripheral Neuropathy (chronic neuropathic pain or fibromyalgia), postherpetic neuralgia (along dermatomic regions in response to varicella infections-but pregabalin is more commonly used), bipolar (combined with another mood stabilizer), migraine prophylaxis
Mechanism of action gabapentin
Inhibits voltage gated Ca channels inhibiting their action and decreasing monoamine neurotransmitters.
Pregabalin (Lyrica)
GABA analog that binds to the nerve terminals of the calcium channels and prevent calcium influx , which inhibits release of certain neurotransmitters
Indication for pregabalin
Seizures, neuropathic pain and fibromyalgia
Side effects of pregabalin
Dizziness, somnolence, weight gain, headache, angioedema
Patients on pregabalin have an increased risk of developing ___ or __ __
Rhabdomyolysis
Drug dependence
How does pregabalin work
Bind and inhibit Ca channels at nerve terminal and inhibits calcium influx.
Decreases release of glutamate, norepinephrine, and substance P
How does decrease in neurotransmitters from pregabalin help control seizures
Control them and give relief to neuropathic pain
Pregabalin is a GABA analog, does it enhance GABA inhibitory actions?
Nope
How does pregabalin decrease seizure
Decreasing abnormal electrical activity int he brain
How does pregabalin help with neuropathic pain
Alters chemicals int he brain responsible for transmitting pain signals across the nervous system and decrease neuropathic pain
How can pregabalin help diabetics
Neuropathic pain associated with nerve damage
How can pregabalin help patients with spinal cord injury caused by herpes zoster
Receive pain
How can pregabalin help patients with fibromyalgia
They may have neuropathic pain relief
How does pregabalin help fibromyaligai
Decrease pain
But decrease pain relief after a few months
Side effects pregabalin
Headache, dizziness, somnolence, weight gain, angioedema (allergic type reaction), rhabdomyolysis
What is a problem with pregabalin
Dependence
Pregabalin is listed as what
Under schedule V of the drug enforcement agency’s controlled substances act
