Neuro-03-Pharm Flashcards
(52 cards)
1
Q
Glaucoma drugs
A
- decrease intraocular pressure via decreasing aqueous humor (inhibit synthesis or increase drainage)
- Classes
- alpha agonists
- beta blockers
- diuretics
- Cholinomimetics
- Prostaglandins
2
Q
Alpha agonists used for glaucoma:
- Epinephrine, Brimonidine (selective alpha-2)
A
- Mechanism: decrease aqueous humor synthesis via vasoconstriction
- side effects:
- Blurry vision
- Ocular hyperemia
- Foreign body sensation
- Ocular allergic reactions
- Ocular pruritus
- Epinephrine causes mydriasis (acts on pupillary dilator muscle); do not use in closed-angle glaucoma
3
Q
Beta blockers used for glaucoma:
- Timolol, betaxolol, carteolol
A
- Mechanism: decrease aquesous humor synthesis (antagonize ciliary epithelium)
- Side effects: No pupillary or vision changes
4
Q
Diuretics used for glaucoma:
- Acetazolamide
A
- Mechanism: Decrease aqueous humor synthesis via inhibition of carbonic anhydrase
- side effects: no pupillary or vision changes
5
Q
Cholinomimetics used for glaucoma:
- pilocarpine, carbachol
- physostigmine
A
- Direct cholinomimetics: pilocarpine, carbachol
- Indirect cholinomimetics: physostigmine
- Mechanism: increased outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork
- Side effects:
- Miosis
- Cyclospasm (contraction of ciliary muscle)
- Use pilocarpine in emergencies: very effective at opening meshwork into canal of schlemm
6
Q
Prostaglandins used for glaucoma:
- Latanoprost (PGF-2alpha)
A
- Mechanism: incresed outflow of aqueous humor
* side effects: darkens color of iris (browning)
7
Q
Opioid analgesics:
- Morphine, fentanyl, codeine, heroinn, methadone, meperidine, dextromethorphan, diphenoxylate
A
- Mechanism:
- act as agonists at opioid receptors (mu, kappa, delta) and lead to:
- inhibit adenylyl cyclase activity
- Open + channels
- Close Ca++ channels)
- Decrease synaptic transmission and Inhibit release of neurotransmitters (ACh, NE, 5-HT, glutamate, substance P.)
- Toxicity:
- Addiction
- Respiratory depression
- constipation; no tolerance develops to constipation
- miosis (pinpoint pupils); no tolerance develops to miosis
- additive CNS depression with other drugs
- biliary colitis: mu opioids can constrict sphincter of oddi smooth muscle, leading to increased common bile duct pressures
- vasodilation, itchiness: mu opioid lead to histamine release
- Toxicity treated with naloxone or naltrexone (opioid receptor antagonist)
- Clinical use:
- Pain
- cough suppression (dextromethorphan)
- Diarrhea (loperamide and diphenoxylate)
- acute pulmonary edema
- maintenance program for addicts (methadone)
8
Q
Butorphanol
A
- Mechanism: Mu-opioid receptor partial agonist and kappa-opioid receptor agonist
- Produces analgesia
- Toxicity: can cause opioid withdrawal symptoms if patient is also taking full opioid agonist (competition for opioid receptors)
- Overdose not easily reversed with naloxone
- Clinical use: severe pain (migraine, labor, etc.) - causes less respiratory depression than full opioid agonists
9
Q
Tramadol
A
- Mechanism:
- very weak opioid agonist
- Also inhibits serotonin and NE reuptake (works on multiple neurotransmitters) {“tram it all” in with tramadol}
- Toxicity:
- Similar to opioids
- Decreases seizure threshold
- Clinical use: chronic pain
10
Q
Phenytoin
A
- Antiseizure medication
- Mechanism:
- increase Na+ channel inactivation
- Inhibition of glutamate release from excitatory presynaptic neuron
- first-line for:
- tonic-clonic seizures
- status epilepticus prophylaxis
- Can be used for:
- simple partial seizures
- complex partial seizures
- Use fosphenytoin for parenteral use
- Side effects:
- Nystagmus
- diplopia
- ataxia
- sedation
- gingival hyperplasia in children with chronic use
- hirsutism
- megaloblastic anemia (decrease folate absorption)
- teratogenesis (fetal hyantoin syndrome - intrauterine growth restriction, microcephaly, dysmorphic cranofacial and limb features)
- SLE-like syndrome
- Induction of cytochrome P-450
- Lymphadenopathy
- Also a class IB antiarrhythmic
- Stevens-Johnson syndrome
- Osteopenia
11
Q
Carbamazepine
A
- Antiseizure medication
- Mechanism: increase Na+ channel inactivation
- first-line for:
- Simple partial seizures
- Complex partial seizures
- Tonic-clonic seizures
- Also first line for trigeminal neuralgia
- Side effects:
- Diplopia
- ataxia
- blood dyscrasias (agranulocytosis, aplastic anemia)
- liver toxicity
- teratogenesis
- induction of cytochrome P-450
- SIADH
- Steven-Johnson syndrome
12
Q
Lamotrigine
A
- Antiseizure medication
- Mechanism: Blocks voltage-gated Na+ channels
- Can be used for:
- Simple partial seizures
- Complex partial seizures
- tonic-clonic seizures
- Side effects: Stevens-Johnson syndrome
13
Q
Gabapentin
A
- Antiseizure medication
- Mechanism: Designed as GABA analog, but primarily inhibits high-voltage-activated Ca++ channels
- Can be used for:
- Simple partial seizures
- Complex partial seizures
- Tonic-clinic seizures
- Also used in:
- Peripheral neuropathy
- Postherpetic neuralgia
- Migraine prophylaxis
- Bipolar disorder
- side effects:
- Sedation
- ataxia
14
Q
Topiramate
A
- Antiseizure medication
- Mechanism:
- Blocks Na+ channels
- increase GABA action
- Can be used for:
- Simple partial seizures
- Complex partial seizures
- Tonic-clinic seizures
- Also used for migraine prevention
- Side effects:
- Sedation
- Mental dulling
- Kidney stones
- Weight loss
15
Q
Phenobarbital
A
- Antiseizure medication
- Mechanism: Increase GABA-A action
- Can be used for:
- Simple partial seizures
- Complex partial seizures
- Tonic-clinic seizures
- First line in children
- Side effects:
- Sedation
- Tolerance, dependence
- Cytochrome P-450
16
Q
Valproic acid
A
- Antiseizure medication
- Mechanism:
- Increase Na+ channel inactivation
- Increase GABA concentration
- first-line for:
- Tonic-clonic seizures
- Can be used for:
- Simple partial seizures
- Complex partial seizures
- Absence seizures
- Also used in myoclonic seizures
- side effects:
- GI distress
- rare but fatal hepatotoxicity (measure LFTs)
- neural tube defects in fetus (spina bifida); contradicted in pregnancy
- tremor
- weight gain
17
Q
Ethosuximide
A
- Antiseizure medication
- Mechanism: Blocks thalamic T-type Ca++ channels
- first-line for:
- Absence seizures
- side effects:
- GI distress
- fatigue
- headache
- urticaria
- Stevens-Johnson syndrome
18
Q
Benzodiazepines (diazepam or lorazepam)
A
- Antiseizure medication
- Mechanism: increase GABA-A action
- first-line for:
- acute status epilepticus
- Also used for seizures of eclampsia (first line is MgSO4)
- side effects:
- Sedation
- Tolerance, dependence
19
Q
Tiagabine
A
- Antiseizure medication
- Mechanism: Inhibits GABA reuptake
- Can be used for:
- Simple partial seizures
- Complex partial seizures
20
Q
Vigabatrin
A
- Antiseizure medication
- Mechanism: Irreversibly inhibits GABA transaminase, leading to higher GABA levels
- Can be used for:
- Simple partial seizures
- Complex partial seizures
21
Q
Levetiracetam
A
- Antiseizure medication
- Mechanism: unknown; may modulate GABA and glutamate release
- Can be used for:
- Simple partial seizures
- Complex partial seizures
- Tonic-clonic seizures
22
Q
MgSO4
A
first-line anti-seizure medication for seizures of eclampsia
23
Q
Steven-Johnson syndrome
A
- Prodrome of malaise and fever followed by rapid onset of erythematous/purpuric macules (oral, ocular, genital)
- Skin lesions progress to epidermal necrosis and sloughing
24
Q
Barbiturates:
- Phenobarbital, pentobarbital, thiopental, secobarbital
A
- Mechanism: Facilitate GABA-A action by increasing duration of Cl- channel opening, thus decreasing neuron firing {barbidurates increase duration}
- Toxicity:
- Respiratory and cardiovascular depression (can be fatal)
- CNS depression (can be exacerbated by EtOH use)
- Dependence
- Drug interactions (induces P-450)
- Overdose treatment is supportive (assist respiration and maintain BP)
- Contraindicated in porphyria
- Clinical use:
- Sedative for anxiety
- seizures
- insomnia
- induction of anesthesia (thiopental)
25
Benzodiazepines:
| - Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam
* Mechanism:
* Facilitate GABA-A action by increasing the frequency of Cl- channel opening {Frenzodiazepines increase frequency}
* decrease REM sleep
* Most have long half-lives and active metabolits (exceptions: triazolam, oxazepam, and midazolam are short acting, which makes them have a higher addictive potential)
* Toxicity:
* Dependence
* Additive CNS depression effects with alcohol
* Less risk of respiratory depression and comma than with barbiturates
* Treat overdose with flumazenil (competitive antagonist at GABA benzodiazepine receptor)
* Clinical Use:
* Anxiety
* Spasticity
* Status epilepticus (lorazepam and diazepam)
* Detoxificaiton (especially alcohol withdrawal and DTs)
* Night terrors
* Sleepwalking
* general anesthetic (amnesia, muscle relaxation)
* Hypnotic (insomnia)
26
Molecules that bind to GABA-A receptors
* GABA-A receptor is a ligand-gated chloride channel
| * Benzos, barbs, and EtOH all bind to the GABA-A receptor
27
Nonbenzodiazepine hypnotics:
| - Zolpidem (ambien), zaleplon, ezopiclone
* Mechanism: act via the BZq subtype of the GABA receptor
* Effects reversed by flumazenil
* Toxicity:
* Ataxia
* Headaches
* Confusion
* Cause only modest day-after psychomotor depression and few amnestic effects (unlike older sedative-hypnotics)
* Short duration because of rapid metabolism by liver enzymes
* Lower dependence risk than benzodiazepines
* Used for insomnia
28
General principles of anesthetics
* CNS drugs must be lipid soluble to be able to cross the blood-brain barrier or be actively transported
* Drugs with lower solubility in blood have rapid induction and recovery times
* Drugs with higher solubility in lipds have higher potency
* Potency = 1/MAC
* MAC = minimal alveolar concentration and which 50% of the population is anesthetized; varies with age
* e.g., N2O has low blood solubility, thus fast induction and low potency; halothane has high blood solubility and thus high potency and slow induction
29
Inhaled anesthetics:
| - Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide
* Mechanism unknown
* Toxicity:
* Hepatotoxicity (halothane)
* Nephrotoxicity (methoxyflurane)
* Proconvulsant (enflurane)
* Malignant hyperthermia (all but nitrous oxide): rare, life-threatening, inherited susceptibility
* Expansion of trapped gas ina body cavity (nitrous oxide)
* Effects:
* Myocardial dpression
* respiratory depression
* nausea/emesis
* Increased cerebral blood flow due to decreased cerebral metabolic demand
30
Types of IV anesthetics
* B. B. King on OPIOIDS PROPOses FOOLishly:
* Barbiturates
* Benzodiazepines
* Arylcyclohexylamines (Ketamine)
* Opioids
* Propofol
31
Barbiturates as IV anesthetics:
| - Thiopental
* High potency, high lipid solubility, rapid entry into brain
* Used for induction of anesthesia and short surgical procedures
* Effect terminated by rapid redistribution into tissue (i.e. skeletal muscle) and fat
* Decreases cerebral blood flow
32
Benzodiazepines as IV anesthetics:
| - Midazolam
* Midazolam most common drug used for endoscopy
* Used adjunctively with gaseous anesthetics and narcotics
* May cause severe postoperative respiratory depression, decreased blood pressure, and amnesia
* Treat overdose with flumazenil
33
Arylcyclohexylamines (Ketamine)
* PCP analogs that act as dissociative anesthetics
* Block NMDA receptors
* Cardiovascular stimulants
* Cause disorientation, hallucination, bad dreams
* Increase cerebral blood flow
34
Opioids
• Morphine, fentanyl used with other CNS depressants during general anesthesia
35
Propofol
* Used for sedation in ICU, rapid anesthesia induction, and short procedures
* Less postoperative nausea than thiopental
* Potentiates GABA-A
* Michael Jackson
36
Local anesthetics:
- procaine, cocaine, tetracaine
- Lidocaine, mepivacaine, bupivacaine
* Esters: procaine, cocaine, tetracaine
* Amides: Lidocaine, mepivacaine, bupivacaine
* Amides have 2 I's in name
* Mechanism:
* Block Na+ channels by binding to specific receptors on inner portion of channel
* Preferentially bind to activated Na+ channel, so are most effective in rapidly firing neurons
* Tertiary amine local anesthetics penetrate membrane in uncharged form, then bind to ion channels as charged form
* Principle of use:
* Can be given with vasoconstrictors (usually epinephrine) to enhance local action: decrease bleeding, increase anesthesia by decreasing systemic concentration
* In infected (acidic tissue), alkaline anesthetics are charged and cannot penetrate membrane effectively, requiring more anesthetic
* Toxicity:
* CNS excitation
* severe cardiovascular toxicity (bupivacaine)
* Hypertension
* Hypotension
* Arrhythmias (cocaine)
* Clinical use: Minor surgical procedures, spinal anesthesia
* If allergic to esters, give amides
37
Order of nerve blockade in local anesthetics
* Smal-diameter fibers > large diameter
* Myelinated fibers > unmyelinated fibers
* Size factor predominates over myelination, so order is: small myelinated fibers > small unmyelinated fibers > large myelinated fibers > large unmyelinated fibers
* Order of loss: pain, then temperature, then touch, then pressure
38
Neuromuscular blocking drugs and types
* Used for muscle paralysis in surgery or mechanical ventilation
* Selective for motor (vs. autonomic) nicotinic receptors
* Two types:
* Depolarizing
* Nondepolarizing
39
Depolarizing neuromuscular blocking agents:
| - Succinylcholine
* Mechanism: Strong ACh receptor agonist; produces sustained depolarization and prevents muscle contraction
* Two phases of blockade
* Phase I: prolonged depolarization; no antidote; block potentiated by cholinesterasse inhibitors
* Phase II: repolarized ut blocked ; ACh receptors are available, but desensitized; antidoe consists of cholinesterase inhibitors (e.g., neostigmine)
* Complications:
* Hypercalcemia
* Hyperkalemia: nicotinic AChR opens, but it is nonselective, so K+ can leak out; In crush, burn injuries, or denervating disease, there is upregulation of NAChR, so these patients are more succeptible to the hyperkalemia
* Malignant hyperthermia
40
Nondepolarizing neuromuscular blocking agents:
| - Tubocurarine, atracurium, mivacurium pancuronium, vecuronium, rocuronium
* Mechanism: competitive antagonists of ACh receptors
| * Reversal of blockade: neostigmine, edrophonium, and other cholinesterae inhibitors
41
Dantrolene
* Mechanism: prevents the release of Ca++ from the sarcoplasmic reticulum of skeletal muscle
* Clinical use:
* treatment of malignant hyperthermia
* Also used to treat neuroleptic malignatn syndrome (a toxicity of antipsychotic drugs)
42
Parkinson's disease drugs
* Parkinsonism is due to loss of dopaminergic neurons and excess cholinergic activity
* drugs used:
* Dopamine agonists
* Drugs that increase dopamine
* Drugs that prevent dopamine breakdown
* Drugs that curb excessive cholinergic activity
* For essential or familial tremors, use a beta-blocker (e.g., propranolol)
* {BALSA: Bromocriptine, Amantadine, Levodopa (with carbidopa), Selegeline (and COMT inhibitors), Antimuscarinics}
43
Dopamine agonists for Parkinson's:
- bromocriptine
- pramipexole, ropinrole
* Ergot: bromocriptine
* Non-ergot: pramipexole, ropinrole
* Non-ergots are preferred
44
Parkinson's drugs to increase dopamine levels:
- Amantadine
- L-dopa/carbidopa
* Amantadine
* may increase dopamine release
* also used as an antiviral against influenza A and rubella
* Toxicity: ataxia
* L-dopa/carbidopa: converted to dopamine in CNS
45
Parkinson's drugs to prevent dopamine breakdown:
- Selegiline
- Entacapone, Tolcapone
* Selegiline: selective MAO type B inhibitor
| * Entacapone, Tolcapone: COMT inhibitors - prevent L-dopa degradation, thereby increasing dopamine availability
46
Parkinson's drugs to curb excess cholinergic activity:
| - Benztropine
Antimuscarinic; improves tremor and rigidity but has little effect on bradykinesia {Park your Mercedes-Benz}
47
L-dopa (levodopa)/carbidopa
* Parkinson's disease drug
* Mechanism:
* Increase level of dopamine in the brain
* Unlike dopamine, L-dopa can cross the blodd-brain barrier and is converted by dopa decarboxylase in the CNS to dopamine
* Carbidopa, a peripheral decarboxylase inhibitor, increases bioavailability of L-dopa in the brain and to limit peripheral side effecs
* Toxicity:
* Arrhythmias from increased peripheral formation of catecholamines
* Long-term use can lead to dyskinesia following administration, and akinesia between doses
48
Selegiline
* Adjunctive agent to L-dopa in the treatment of Parkinson's
* Mechanism: selectively inhibits MAO-B, which preferentially metabolizes dopamine over NE and 5-HT, thereby increasing the availability of dopamine
* Toxicity: may enhance adverse effects of L-dopa
49
Memantine
* treatment for Alzheimer's
* Mechanism:
* NMDA receptor antagonist
* Helps prevent excitoxicity (mediated by Ca++)
* Toxicity:
* dizziness
* confusion
* hallucinations
50
Donepezil, galantamine, rivastigmine
* treatment for Alzheimer's
* Mechanism: acetylcholinesterase inhibitors
* Toxicity:
* Nausea
* dizziness
* insomnia
51
Drugs for Huntington's:
- Tetrabenazine, reseprine
- Haloperidol
* neurotransmitter changes in Huntington's: lower GABA, lower ACh, higher dopamine
* Tetrabenazine and reseprine: inhibit VMAT, leading to decreased dopamine vesicle packaging and release
* Haloperidol: dopamine receptor antagonist
52
Sumatriptan
* Drug used for acute migraine and cluster headache attacks
* Mechanism:
* 5-HT-1B/1D agonist
* Inhibits trigeminal nerve activation and prevents vasoactive peptide release, inducing vasoconstriction
* Half life < 2 hours
* Toxicity:
* Coronary vasopasm (contraindicated in patients with CAD or Prinzmetal's angina)
* Mild tingling
* {A SUMo wrestler TRIPs ANd falls on your head}
