Pharmacology Flashcards

Question

Nonbenzodiazepine hypnotics (names, MOA, clinical use, toxicity)

Answer 1

Zolpidem (Ambien), Zaleplon, esZopiclone. “All ZZZs put you to sleep.” MOA: 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. Decr dependence risk than benzodiazepines.

Answer 2

CNS drugs must be lipid soluble (cross the blood-brain barrier) or be actively transported. Drugs with low solubility in blood = rapid induction and recovery times. Drugs with high solubility in lipids = high potency = 1 MAC MAC = Minimal Alveolar Concentration (of inhaled anesthetic) required to prevent 50% of subjects from moving in response to noxious stimulus (e.g., skin incision). Examples: N2O has low blood and lipid solubility, and thus fast induction and low potency. Halothane, in contrast, has high lipid and blood solubility, and thus high potency and slow induction

Answer 3

Halothane, enflurane, isoflurane, sevoflurane, methoxyflurane, nitrous oxide. MOA: unknown Effects: Myocardial depression, respiratory depression, nausea/emesis, incr cerebral blood flow (decr 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 4

"B. B. King on OPIOIDS PROPOses FOOLishly" Barbiturates: 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. Decr cerebral blood flow. Benzodiazepines: Midazolam most common drug used for endoscopy; used adjunctively with gaseous anesthetics and narcotics. May cause severe postoperative respiratory depression, decr BP (treat overdose with flumazenil), and anterograde amnesia. Ketamine (arylcyclohexylamine): PCP analogs that act as dissociative anesthetics. Block NMDA receptors. Cardiovascular stimulants. Cause disorientation, hallucination, and bad dreams. Incr cerebral blood flow. Opioids: Morphine, fentanyl used with other CNS depressants during general anesthesia. Propofol: Used for sedation in ICU, rapid anesthesia induction, and short procedures. Less postoperative nausea than thiopental. Potentiates GABAA.

Answer 5

Esters—procaine, cocaine, tetracaine. Amides—lidocaine, mepivacaine, bupivacaine (amIdes have 2 I’s in name). MOA: 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 - decr bleeding, incr anesthesia by decr 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 6

Used for muscle paralysis in surgery or mechanical ventilation. Selective for motor (vs. autonomic) nicotinic receptor. 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.

Answer 7

Used for muscle paralysis in surgery or mechanical ventilation. Selective for motor (vs. autonomic) nicotinic receptor. 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 8

MOA: 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 9

Parkinson disease drugs. non-ergots are preferred. | Dopamine agonists.

Answer 10

Increase dopamine. Amantadine (may incr dopamine release); also used as an antiviral against influenza A and rubella Toxicity = ataxia L-dopa/carbidopa (converted to dopamine in CNS)

Answer 11

MOA: Selectively inhibits MAO-B, which preferentially metabolizes dopamine over norepinephrine and 5-HT, thereby incr 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 12

Curb excess cholinergic activity | Antimuscarinic; improves tremor and rigidity but has little effect on bradykinesia

Answer 13

MOA: Incr 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 incr the bioavailability of L-dopa in the brain and to limit peripheral side effects. Clinical use: Parkinson disease ``` Toxicity: Arrhythmias from incr peripheral formation of catecholamines. Long-term use can lead to dyskinesia following administration (“on-off” phenomenon), akinesia between doses. ```

Answer 14

COMT inhibitors— prevent L-dopa degradation--> incr dopamine availability

Answer 15

MOA: NMDA receptor antagonist; helps prevent excitotoxicity (mediated by Ca2+). Toxicity: Dizziness, confusion, hallucinations.

Answer 16

MOA: AChE inhibitors Toxicity: nausea, dizziness, insomnia

Answer 17

Neurotransmitter changes in Huntington disease: decr GABA, decr ACh, incr dopamine. -Tetrabenazine and reserpine—inhibit vesicular monoamine transporter (VMAT); limit dopamine vesicle packaging and release.

Answer 18

Neurotransmitter changes in Huntington disease: decr GABA, decr ACh, incr dopamine. -Haloperidol—dopamine receptor antagonist.

Answer 19

MOA: 5-HT1B/1D agonist. Inhibits trigeminal nerve activation; prevents vasoactive peptide release; induces vasoconstriction. Half-life < 2 hours Clinical use: Acute migraine, cluster headache attacks. Toxicity: Coronary vasospasm (contraindicated in patients with CAD or Prinzmetal angina), mild tingling

Pharmacology Flashcards

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