Neurology - Pharmacology Flashcards

Question

Barbiturates * Examples * Mechanism * Clinical use * Toxicity

Answer 1

* Examples * Phenobarbital, pentobarbital, thiopental, secobarbital. * Mechanism * Facilitate GABA_A action by **increasing duration** of Cl- channel opening, thus decreasing neuron firing * **Barbi**_durat_**es increase **_durat_**ion** * Contraindicated in porphyria. * Clinical use * Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental). * Toxicity * Respiratory and cardiovascular depression (can be fatal) * CNS depression (can be exacerbated by EtOH use) * Dependence * Drug interactions (induces cytochrome P-450). * Overdose treatment is supportive (assist respiration and maintain BP).

Answer 2

* Examples * Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam. * Mechanism * Facilitate GABA_A action by **increasing frequency** of Cl- channel opening. * **“**_Fre_**nzodiazepines” increase **_fre_**quency** * Decrease REM sleep. * Most have long half-lives and active metabolites * Exceptions: triazolam, oxazepam, and midazolam are short acting --\> higher addictive potential * Benzos, barbs, and EtOH all bind the GABA_A receptor, which is a ligand-gated Cl- channel. * Clinical use * Anxiety, spasticity, status epilepticus (lorazepam and diazepam), detoxification (especially alcohol withdrawal–DTs), night terrors, sleepwalking, general anesthetic (amnesia, muscle relaxation), hypnotic (insomnia). * Toxicity * Dependence, additive CNS depression effects with alcohol. * Less risk of respiratory depression and coma than with barbiturates. * Treat overdose with flumazenil (competitive antagonist at GABA benzodiazepine receptor).

Answer 3

* Examples * **_Z_**olpidem (Ambien), **_Z_**aleplon, es**_Z_**opiclone. * **“All **_ZZZ_**s put you to sleep.”** * Mechanism * Act via the BZ1 subtype of the GABA receptor. * Effects reversed by flumazenil. * Clinical use * Insomnia. * Toxicity * Ataxia, headaches, confusion. * Short duration because of rapid metabolism by liver enzymes. * Unlike older sedative-hypnotics, cause only modest day-after psychomotor depression and few amnestic effects. * Decrease dependence risk than benzodiazepines.

Answer 4

* CNS drug solubility * CNS drugs must be lipid soluble (cross the blood-brain barrier) or be actively transported. * Drugs with decreased solubility in blood = rapid induction and recovery times. * Drugs with increased solubility in lipids = increased potency = 1 / MAC * MAC * **_MAC_** = **_M_**inimal **_A_**lveolar **_C_**oncentration (of inhaled anesthetic) required to prevent 50% of subjects from moving in response to noxious stimulus (e.g., skin incision). * Examples * N2O has decreased blood and lipid solubility, and thus fast induction and low potency. * Halothane, in contrast, has increased lipid and blood solubility, and thus high potency and slow induction.

Answer 5

* Examples * Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide. * Mechanism * Mechanism unknown. * Clinical use * Myocardial depression, respiratory depression, nausea/emesis, increased cerebral blood flow (decreased cerebral metabolic demand). * Toxicity * Hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane), expansion of trapped gas in a body cavity (nitrous oxide). * Can cause **malignant hyperthermia**—rare, life-threatening hereditary condition in which inhaled anesthetics (except nitrous oxide) and succinylcholine induce fever and severe muscle contractions. * Treatment: dantrolene.

Answer 6

* **_B_. _B_. **_K_**ing on _OPIOIDS_ **_PROPO_**ses **_FOOL_**ishly.** * **_B_**arbiturates * **_B_**enzodiazepines * Arylcyclohexylamines (**_K_**etamine) * **_Opioids_** * **_Propofol_**

Answer 7

* Intravenous 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. * Decreased cerebral blood flow.

Answer 8

* Intravenous anesthetics * Midazolam most common drug used for endoscopy * Used adjunctively with gaseous anesthetics and narcotics. * May cause severe postoperative respiratory depression, decreased BP (treat overdose with flumazenil), and anterograde amnesia.

Answer 9

* Intravenous anesthetics * PCP analogs that act as dissociative anesthetics. * Block NMDA receptors. * Cardiovascular stimulants. * Cause disorientation, hallucination, and bad dreams. * Increased cerebral blood flow.

Answer 10

* Intravenous anesthetics * Morphine, fentanyl used with other CNS depressants during general anesthesia.

Answer 11

* Intravenous anesthetic * Used for sedation in ICU, rapid anesthesia induction, and short procedures. * Less postoperative nausea than thiopental. * Potentiates GABA_A.

Answer 12

* Examples * Esters—procaine, cocaine, tetracaine. * Amides—l**_I_**doca**_I_**ne, mep**_I_**vaca**_I_**ne, bup**_I_**vaca**_I_**ne * **Am**_I_**des 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+ channels, so most effective in rapidly firing neurons. * 3° amine local anesthetics penetrate membrane in uncharged form, then bind to ion channels as charged form. * Principle * 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 --\> need more anesthetic. * Order of nerve blockade: small-diameter fibers \> large diameter. * Myelinated fibers \> unmyelinated fibers. * Overall, size factor predominates over myelination such that small myelinated fibers \> small unmyelinated fibers \> large myelinated fibers \> large unmyelinated fibers. * Order of loss: (1) pain, (2) temperature, (3) touch, (4) pressure. * Clinical use * Minor surgical procedures, spinal anesthesia. * If allergic to esters, give amides. * Toxicity * CNS excitation, severe cardiovascular toxicity (bupivacaine), hypertension, hypotension, and arrhythmias (cocaine).

Answer 13

* Clinical use * Used for muscle paralysis in surgery or mechanical ventilation. * Selective for motor (vs. autonomic) nicotinic receptor. * Depolarizing * Succinylcholine * Strong ACh receptor agonist * Produces sustained depolarization and prevents muscle contraction. * Reversal of blockade * Phase I * Prolonged depolarization * No antidote. * Block potentiated by cholinesterase inhibitors. * Phase II * Repolarized but blocked * ACh receptors are available, but desensitized * Antidote consists of cholinesterase inhibitors. * Complications include hypercalcemia, hyperkalemia, and malignant hyperthermia. * Nondepolarizing * Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rocuronium * Competitive antagonists * Compete with ACh for receptors. * Reversal of blockade * Neostigmine (must be given with atropine to prevent muscarinic effects such as bradycardia), edrophonium, and other cholinesterase inhibitors.

Answer 14

* Mechanism * Prevents the release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle. * Clinical use * Used to treat malignant hyperthermia and neuroleptic malignant syndrome (a toxicity of antipsychotic drugs).

Answer 15

* Parkinsonism is due to... * Loss of dopaminergic neurons and excess cholinergic activity. * Strategies * Dopamine agonists * **_B_**romocriptine (ergot), pramipexole, ropinirole (non-ergot) * Non-ergots are preferred * Increase dopamine * **_A_**mantadine * May increase dopamine release * Also used as an antiviral against influenza A and rubella * Toxicity = ataxia * **_L_**-dopa/carbidopa * Converted to dopamine in CNS * Prevent dopamine breakdown * **_S_**elegiline * Selective MAO type B inhibitor * Entacapone, tolcapone * COMT inhibitors * Prevent l-dopa degradation --\> increased dopamine availability * Curb excess cholinergic activity * **_Benz_**tropine * **_A_**ntimuscarinic * Improves tremor and rigidity but has little effect on bradykinesia * Mnemonics * **_BALSA_:** * **_B_**romocriptine * **_A_**mantadine * **_L_**evodopa (with carbidopa) * **_S_**elegiline (and COMT inhibitors) * **_A_**ntimuscarinics * For essential or familial tremors, use a β-blocker (e.g., propranolol). * **_Park_ your Mercedes-_Benz_.**

Answer 16

* Mechanism * Increased level of dopamine in brain. * Unlike dopamine, L-dopa can cross blood-brain barrier and is converted by dopa decarboxylase in the CNS to dopamine. * Carbidopa, a peripheral decarboxylase inhibitor, is given with L-dopa to increase the bioavailability of L-dopa in the brain and to limit peripheral side effects. * Clinical use * Parkinson disease. * Toxicity * Arrhythmias from increased peripheral formation of catecholamines. * Long-term use can lead to dyskinesia following administration (“on-off” phenomenon), akinesia between doses.

Answer 17

* Mechanism * Selectively inhibits MAO-B, which preferentially metabolizes dopamine over norepinephrine and 5-HT, thereby increasing the availability of dopamine. * Clinical use * Adjunctive agent to l-dopa in treatment of Parkinson disease. * Toxicity * May enhance adverse effects of L-dopa.

Answer 18

* Mechanism * NMDA receptor antagonist * Helps prevent excitotoxicity (mediated by Ca2+). * Clinical use * Alzheimer's * Toxicity * Dizziness, confusion, hallucinations.

Answer 19

* Mechanism * AChE inhibitors. * Clinical use * Alzheimer's * Toxicity * Nausea, dizziness, insomnia.

Answer 20

* Neurotransmitter changes in Huntington disease * Decreased GABA * Decreased ACh * Increased dopamine. * Treatments * Tetrabenazine and reserpine * Inhibit vesicular monoamine transporter (VMAT) * Limit dopamine vesicle packaging and release. * Haloperidol * Dopamine receptor antagonist.

Answer 21

* Mechanism * 5-HT_1B/1D agonist. * Inhibits trigeminal nerve activation * Prevents vasoactive peptide release * Induces vasoconstriction. * Half-life \< 2 hours. * Clinical use * Acute migraine, cluster **_head_**ache attacks. * **A **_SUM_**o wrestler **_TRIP_**s **_AN_**d falls on your _head_.** * Toxicity * Coronary vasospasm (contraindicated in patients with CAD or Prinzmetal angina), mild tingling.

Neurology - Pharmacology Flashcards

(45 cards)