Pharmacology Mnemonics - Flash Cards

Other Migraine Drugs

b Blockers: Propanolol, timolol, nadolol, metoprolol for continuous prophylaxis. S.E.s include fatigue, depression, orthostatic hypotension. C/I in asthmatics & congestive heart failure patients.

Ca²⁺ Channel Blockers: Verapamil & flunarazine ® moderatey efficacious prophylaxis.

Analgesics: Fiorinal: aspirin + caffeine + butalbital. Midrin: acetaminophen + isometheptene (sympathomimetic) + dichloralphenazone (sedative). NSAIDS, esp. naproxen sodium (but ¯ gastric motility during acute attack may interfere w/absorption). Butorphanol (opioid agonist antagonist) nasal spray. Methadone (IM).

Overuse may cause a headache (“analgesic rebound”).

Name: Methysergide (Sansert)

Class: Anti-Migraine (Serotonin Agonist)

Mechanism: Partial agony at 5-HT₂ vascular receptors & partial agonist at a-adrenergic receptors (can act as a blocker) ® vasoconstriction (cerebral vasc. most sensitive), uterine smooth muscle contraction, n/v, diarrhea.

Absorption:

Dist.:

Metabolism.:

Excretion, t½:

Toxicity/S.E.s: Weight gain, peripheral edema, fibrosis (retroperitoneal, pleuropericardial, subendocardial). Concurrent use of ergot alkaloids, b adrenergic blockers, erythromycin, or dopamine ® ­ risk of arterial spasm & occlusion. Occasional central stim. & hallucinations.

Utility: Migraine prevention. Reserved for recurrent, refractory, severe migraine, as fibrosis is assoc. w/prolonged use.

Special Features: Relatively ineffective in treatment of impending/active migraines. Useful as a prophylactic.

Name: Dihydroergotamine

Class: Anti-Migraine (Serotonin Agonist)

Mechanism: Partial agony at 5-HT₂ vascular receptors & partial agonist at a-adrenergic receptors (can act as a blocker) ® vasoconstriction (cerebral vasc. most sensitive), uterine smooth muscle contraction, n/v, diarrhea.

Absorption: IV. Investigational use intranasally & orally.

Dist.:

Metabolism.:

Excretion, t½:

Toxicity/S.E.s: Most common = GI (n/v, diarrhea). Most dangerous = vasospasm from overuse/overdose (intense & prolonged, but can be blocked w/a blockers). Drowsiness.

Utility: Treat migraines.

Special Features: Lower direct smooth muscle, vasospasm, and serotonin effects and more selective a receptor blockade than ergotamine.

Name: Ergotamine

Class: Anti-Migraine (Serotonin Agonist)

Mechanism: Partial agony at 5-HT₂ vascular receptors & partial agonist at a-adrenergic receptors (can act as a blocker) ® vasoconstriction (cerebral vasc. most sensitive), uterine smooth muscle contraction, n/v, diarrhea.

Absorption: IV, IM, oral, sublingual, rectal, & inhaler.

Dist.:

Metabolism.:

Excretion, t½:

Toxicity/S.E.s: Most common = GI (n/v, diarrhea). Most dangerous = vasospasm from overuse/overdose (intense & prolonged, but can be blocked w/a blockers). Drowsiness.

Utility: Treat migraines.

Special Features: Most effective when given during prodrome period. Often combined w/caffeine to facilitate absorption.

Name: Sumatriptan (Imitrex)

Class: Anti-Migraine (Serotonin Agonist)

Mechanism: Stim 5-HT_1D receptors ® cranial vasoconstriction ® ­ resistance in carotid arteriovenous anastomoses and shunts w/minor effects on systemic and coronary artery vasculature.

Absorption: Subcut. (96% bioavailability) ® peak plasma conc. in 5-20 min. Response in 10-30 min; 10-13 hour duration. Oral (14% bioavailability) ® clinical response in 30-60 min.

Dist.:

Metabolism.: 80% Metabolism.

Excretion, t½: 2 hr.

Toxicity/S.E.s: Pain, swelling, redness at injection site. Feeling of heaviness, tightness in chest (injection). Neuro symptoms (tingling, warm/burning sensation). Rare vasospasm in patients w/coronary artery disease (® angina, MI). 34-46% headaches recur in 24-48 hr.

Utility: Partial/complete relief of migraine headache in 80% w/in 2 hr (subcut). Relieves n/v, photophobia, phonophobia.

Special Features: Oral effective, w/few side effects at lowest doses. Expensive.

Name: Clonidine (Catapres)

Class: Centrally Acting Antiadrenergic Agent/Opioid Withdrawal Suppressant

Mechanism: Stim. inhib. a2 receptors in central cardiovasc pathways involving EPI or NE. a2 are G-protein coupled to inhibit adenylyl cyclase ®
¯ cAMP ® ¯ central symp. activity.

Absorption:

Dist.: Act at medullary and spinal sites.

Metabolism.:

Excretion, t½:

Toxicity/S.E.s: Prominent sedation, dry mouth.

Utility: Treat hypertension. DOC for treating opioid w/drawal (probably substitutes for opioid depression of adenylate cyclase in locus coeruleus & pregang. symp. neurons. No abstinence synd. when withdrawn.

Special Features: Direct a2 activation. Very potent (<0.5>

Name: Naltrexone (Trexan)

Class: Opioid Antagonist

Mechanism: Competitive inhib. at opioid receptors.

Absorption: Oral

Dist.:

Metabolism.:

Excretion, t½: Long duration of action.

Toxicity/S.E.s:

Utility: “Maintenance” drug for opioid addicts in rehab. programs. May also decrease alcohol craving in chronic alcoholics.

Name: Naloxone (Narcan)

Class: Opioid Antagonist

Mechanism: Competitive inhib. at opioid receptors.

Absorption: IV

Dist.:

Metabolism.:

Excretion, t½: Duration of action ~ 1 hr.

Toxicity/S.E.s:

Utility: Treat opioid poisoning.

Special Features: May require intermittent dosing, as half life is so short.

Name: Diphenoxylate-Atropine (Lomotil)

Class: Opioid (Antidiarrheal)

Mechanism: Increased gastric tone ® delayed gastric emptying. ­ tone and ¯ propulsive peristaltic waves in large intest. ® ¯ gut motility. Effects due to inhib. of ACh release by neurons in the intest. wall. Naloxone sensitive.

Absorption: Oral

Dist.:

Metabolism.:

Excretion, t½:

Toxicity/S.E.s: Recommended dose ® dizziness, drowsiness, mild euphoria. Excessive doses ® pronounced euphoria, potentially serious respiratory depression (may not be evident until 12-30 hr later). ¯ peristalsis ® ¯ evacuation of bacteria and toxins. Use w/great caution in kids. Potentiates effects of barbiturate, tranquilizers, alcohol, other narcotics. Hypertensive crisis w/MAOI.

Utility: Antidiarrheal.

Special Features:

Name: Loperamide (Imodium)

Class: Opioid (Antidiarrheal) (OTC)

Mechanism: Increased gastric tone ® delayed gastric emptying. Increase tone and decreasesd propulsive peristaltic waves in large intest. ® decreased gut motility. Effects due to inhib. of ACh release by neurons in the intest. wall. Naloxone sensitive. Anti-secretory effect (non-naloxone sensitive).

Absorption: Oral

Dist.: 90% ® GI tract and liver. Very little CNS.

Metabolism.:

Excretion, t½:

Toxicity/S.E.s: ¯ peristalsis ® ¯ evacuation of bacteria and toxins.

Utility: Antidiarrheal.

Special Features: No abuse liability. Preferred anti-diarrheal of the opioids. Less potential for analgesia, respiratory depression, and addiction than other opioids. Much safer than other opioids. Longer lasting effects than dephnoxylate.

Name: Tramadol (Ultram)

Class: Opioid (Synthetic-Analgesic)

Mech: Low affinity binding of tramadol to mu-opioid receptors and higher affinity binding of the M1 Metabolismolite. Opioid effects only partially antagonized by naloxone. Also inhibits reuptake of norepinephrine and serotonin.

Absorption:

Metabolism:

Excretion, t½:

Toxicity/S.E.s: Sim. to opioids—dizziness, somnolence, nausea, constipation, sweating, & pruritus. Unlike opioids, significantly less respiratory depression, no histamine release. At therapeutic doses, no effect on heart rate, left-ventricular function, or cardiac index. Some orthostatic hypotension. Seizures. Use w/caution w/CNS depressants, MAO inhibitors. May trigger opioid w/drawal symptoms.

Utility: Analgesia.

Special Features: Inhib. reuptake of NE and 5HT.

Name: Fentanyl (Innovar)

Class: Opioid (Synthetic-Analgesic)

Mechanism: Agonist of opioid receptors. Causes analgesia (­ threshold for pain, ¯ subjective rxn), antitussive effects, euphoria/dysphoria (atypical), sedation (rarely stimulation), resp. depression, miosis, n/v, ¯ body temp., ­ ACTH/PRO/GH, ¯ LH/TSH (hormone effects usu. non-consequential), occasionally hypotension, constipation, ­ biliary/ureteral/bladder muscle tone, ¯ uteral muscle tone, histamine release (hypotension, urticaria, itching).

Absorption: Parenteral, transdermal patch, lollipop.

Metabolism.: Hepatic conjug. ® polar Metabolismolites.

Excretion, t½: Urine. Duration of analgesia—1-1.5 hr.

Toxicity/S.E.s: Histamine release ® asthma in suscept. patients. Use w/caution w/compromised resp. patients. CO2 retention ® ­ intracranial pressure (may mask signs of head injury). Poisoning ® coma, severe resp. depression, pinpoint pupils. Rapid onset of tolerance (up to 100x) to analgesia, euphoria/dysphoria, sedation, n/v, resp. depression, cough suppression. Physical dependence—abrupt w/drawal ® rhinorrhea, lacrimation, chills, goose pimples, hyperventilation, mydriasis, myalgia, vomiting, diarrhea, anxiety, hostility (but it’s not fatal). Also psychological dependence. Drug interactions—sedative hypnotics ® severe CNS/resp. depression; phenothiazines/tricyclic antidepressants ® ­ sedation, freq. resp. depression.

Utility: Analgesia. Induction of general anesthesia.

Special Features: Very high maximum efficacy. High addiction/abuse liability. Psych. dependence.

Name: Pentazocine (Talwin)

Class: Opioid (Synthetic-Analgesic)

Mechanism: Mixed agonist-antagonist of opioid receptors. Causes analgesia (­ threshold for pain, ¯ subjective rxn), sedation, resp. depression.

Absorption: IM, subcut, oral (1st pass Metabolism ® med. oral:parenteral potency).

Metabolism.: Hepatic conjug.®polar Metabolismolites. Excretion, t½: Urine. Duration of analgesia—3-4 hr.

Toxicity/S.E.s: CO₂ retention ® ­ intracranial pressure (may mask signs of head injury). Tolerance (up to 100x) to analgesia, sedation, resp. depression. Physical dependence—abrupt w/drawal ® rhinorrhea, lacrimation, chills, goose pimples, hyperventilation, mydriasis, myalgia, vomiting, diarrhea, anxiety, hostility (but it’s not fatal). Also psychological dependence. Precipitates w/drawal synd. Large doses ® dysphoria & hallucinations. Drug interactions—sedative hypnotics ® severe CNS/resp. depression; phenothiazines/tricyclic antidepressants ® ­ sedation, freq. resp. depression.

Utility: Analgesia. Orig. thought to lack abuse liability.

Special Features: Mod. maximum efficacy. Low addiction/abuse liability. Psych. dependence.

Name: Propoxyphene (Darvon)

Class: Opioid (Synthetic-Analgesic)

Mechanism: Agonist of opioid receptors. Causes analgesia (­ threshold for pain, ¯ subjective rxn), antitussive effects, euphoria/dysphoria (atypical), sedation (rarely stimulation), resp. depression, miosis, n/v, ¯ body temp., ­ ACTH/PRO/GH, ¯ LH/TSH (hormone effects usu. non-consequential), occasionally hypotension, constipation, ­ biliary/ureteral/bladder muscle tone, ¯ uteral muscle tone, histamine release (hypotension, urticaria, itching).

Absorption: Oral

Metabolism.: Hepatic conjug. ® polar Metabolismolites.

Excretion, t½: Urine. Duration of analgesia—4-5 hr.

Toxicity/S.E.s: Histamine release ® asthma in suscept. patients. Use w/caution w/compromised resp. patients. CO2 retention ® ­ intracranial pressure (may mask signs of head injury). Poisoning ® coma, severe resp. depression, pinpoint pupils. Rapid onset of tolerance (up to 100x) to analgesia, euphoria/dysphoria, sedation, n/v, resp. depression, cough suppression. Physical dependence—abrupt w/drawal ® rhinorrhea, lacrimation, chills, goose pimples, hyperventilation, mydriasis, myalgia, vomiting, diarrhea, anxiety, hostility (but it’s not fatal). Also psychological dependence. Drug interactions—sedative hypnotics ® severe CNS/resp. depression; phenothiazines/tricyclic antidepressants ® ­ sedation, freq. resp. depression.

Utility: Limited analgesia (no more than aspirin in usu. therapeutic dose, but augments the effects of aspirin & acetaminophen.

Special Features: Very low maximum efficacy (limited analgesia). Low addiction/abuse liability.

Name: Meperidine (Demerol)

Class: Opioid (Synthetic-Analgesic)

Mechanism: Agonist of opioid receptors. Causes analgesia (­ threshold for pain, ¯ subjective rxn), antitussive effects, euphoria/dysphoria (atypical), sedation (rarely stimulation), resp. depression, miosis, n/v, ¯ body temp., ­ ACTH/PRO/GH, ¯ LH/TSH (hormone effects usu. non-consequential), occasionally hypotension, constipation, ­ biliary/ureteral/bladder muscle tone, ¯ uteral muscle tone, histamine release (hypotension, urticaria, itching).

Absorp.: IM, subcut., oral (1st pass Metabolism ® med. oral:parenteral potency).

Metabolism.: Hepatic conjug.®polar Metabolismolites. Excretion, t½: Urine. Duration of analgesia—2-4 hr.

Toxicity/S.E.s: Histamine release ® asthma in suscept. patients. Use w/caution w/compromised resp. patients. CO2 retention ® ­ intracranial pressure (may mask signs of head injury). Poisoning ® coma, severe resp. depression, pinpoint pupils. Rapid onset of tolerance (up to 100x) to analgesia, euphoria/dysphoria, sedation, n/v, resp. depression, cough suppression. Physical dependence—abrupt w/drawal ® rhinorrhea, lacrimation, chills, goose pimples, hyperventilation, mydriasis, myalgia, vomiting, diarrhea, anxiety, hostility (but it’s not fatal). Also psychological dependence. Drug interactions—sedative hypnotics ® severe CNS/resp. depression; phenothiazines/tricyclic antidepressants ® ­ sedation, freq. resp. depression; MAO inhib ® hyperpyrexia, coma, convulsions.

Utility: Analgesia.

Name: Methadone (Dolophine)

Class: Opioid (Synthetic-Analgesic) (Withdrawal Suppressant)

Mechanism: Agonist of opioid receptors. Causes analgesia (­ threshold for pain, ¯ subjective rxn), antitussive effects, euphoria/dysphoria (atypical), sedation (rarely stimulation), resp. depression, miosis, n/v, ¯ body temp., ­ ACTH/PRO/GH, ¯ LH/TSH (hormone effects usu. non-consequential), occasionally hypotension, constipation, ­ biliary/ureteral/bladder muscle tone, ¯ uteral muscle tone, histamine release (hypotension, urticaria, itching).

Absorption: IM, subcut., oral (high oral:parenteral potency).

Metabolism.: Hepatic conjug. ® polar Metabolismolites.

Excretion, t½: Urine. Duration of analgesia—4-6 hr.

Toxicity/S.E.s: Histamine release ® asthma in suscept. patients. Use w/caution w/compromised resp. patients. CO2 retention ® ­ intracranial pressure (may mask signs of head injury). Poisoning ® coma, severe resp. depression, pinpoint pupils. Rapid onset of tolerance (up to 100x) to analgesia, euphoria/dysphoria, sedation, n/v, resp. depression, cough suppression. Physical dependence—abrupt w/drawal ® rhinorrhea, lacrimation, chills, goose pimples, hyperventilation, mydriasis, myalgia, vomiting, diarrhea, anxiety, hostility (but it’s not fatal). Also psychological dependence. Drug interactions—sedative hypnotics ® severe CNS/resp. depression; phenothiazines/tricyclic antidepressants ® ­ sedation, freq. resp. depression.

Utility: Treatment of physical dependence to other opioids, esp. heroin (less severe w/drawal synd.). Analgesia. Migraine relief.

Special Features: High maximum efficacy. High addiction/abuse liability. Psych. dependence.

Name: Dextromethorphan

Class: Opioid (Semi-synthetic) (OTC)

Mechanism: Agonist of opioid receptors ® depression of CNS cough center.

Absorption: Oral.

Metabolism.: Hepatic conjug. ® polar Metabolismolites.

Excretion, t½: Urine.

Toxicity/S.E.s:High doses ® hallucinations. Potentially fatal interactions with MAOIs.

Utility: Antitussant.

Special Features: Minimal addiction/abuse liability.

Name: Heroin

Class: Opioid (Semi-synthetic)

Mechanism: Agonist of opioid receptors. Causes analgesia (­ threshold for pain, ¯ subjective rxn), antitussive effects, euphoria/dysphoria (atypical), sedation (rarely stimulation), resp. depression, miosis, n/v, ¯ body temp., ­ ACTH/PRO/GH, ¯ LH/TSH (hormone effects usu. non-consequential), occasionally hypotension, constipation, ­ biliary/ureteral/bladder muscle tone, ¯ uteral muscle tone, histamine release (hypotension, urticaria, itching). Init. ¯ of adenylate cyclase in locus coeruleus & symp. pregang. neurons. Tolerance develops.

Absorption: IM, subcut., mucous membranes, oral, smoking.

Metabolism.: Hepatic conjug. ® polar Metabolismolites. Excretion, t½: Urine.

Toxicity/S.E.s: Histamine release ® asthma in suscept. patients. Use w/caution w/compromised resp. patients. CO2 retention ® ­ intracranial pressure (may mask signs of head injury). Poisoning ® coma, severe resp. depression, pinpoint pupils. Rapid onset of tolerance (up to 100x) to analgesia, euphoria/dysphoria, sedation, n/v, resp. depression, cough suppression. Physical dependence—abrupt w/drawal (prob. med. by hyperactive adenylate cyclase) ® rhinorrhea, lacrimation, chills, goose pimples, hyperventilation, mydriasis, myalgia, vomiting, diarrhea, anxiety, hostility (but it’s not fatal). Also psychological dependence. Drug interactions—sedative hypnotics ® severe CNS/resp. depression; phenothiazines/tricyclic antidepressants ® ­ sedation, freq. resp. depression.

Special Features: High addiction/abuse liability. Psych. dependence.

Name: Codeine

Class: Opioid (Alkaloid)

Mechanism: Agonist of opioid receptors. Causes analgesia (­ threshold for pain, ¯ subjective rxn), antitussive effects, euphoria/dysphoria (atypical), sedation (rarely stimulation), resp. depression, miosis, n/v, ¯ body temp., ­ ACTH/PRO/GH, ¯ LH/TSH (hormone effects usu. non-consequential), occasionally hypotension, constipation, ­ biliary/ureteral/bladder muscle tone, ¯ uteral muscle tone, histamine release (hypotension, urticaria, itching).

Absorption: IM, subcut., mucous membranes, oral (high oral:parenteral potency).

Metabolism.: Hepatic conjug. ® polar Metabolismolites.

Excretion, t½: Urine. Duration of analgesia—3-4 hr.

Toxicity/S.E.s: Histamine release ® asthma in suscept. patients. Use w/caution w/compromised resp. patients. CO2 retention ® ­ intracranial pressure (may mask signs of head injury). Poisoning ® coma, severe resp. depression, pinpoint pupils. Rapid onset of tolerance (up to 100x) to analgesia, euphoria/dysphoria, sedation, n/v, resp. depression, cough suppression. Physical dependence—abrupt w/drawal ® rhinorrhea, lacrimation, chills, goose pimples, hyperventilation, mydriasis, myalgia, vomiting, diarrhea, anxiety, hostility (but it’s not fatal). Also psychological dependence. Drug interactions—sedative hypnotics ® severe CNS/resp. depression; phenothiazines/tricyclic antidepressants ® ­ sedation, freq. resp. depression.

Utility: Antitussant. Analgesia.

Name: Morphine

Class: Opioid (Alkaloid)

Mechanism: Agonist of opioid receptors. Causes analgesia (­ threshold for pain, ¯ subjective rxn), antitussive effects, euphoria/dysphoria (atypical), sedation (rarely stimulation), resp. depression, miosis, n/v, ¯ body temp., ­ ACTH/PRO/GH, ¯ LH/TSH (hormone effects usu. non-consequential), occasionally hypotension, constipation, ­ biliary/ureteral/bladder muscle tone, ¯ uteral muscle tone, histamine release (hypotension, urticaria, itching).

Absorption: IM, subcut., mucous membranes, intrathecal, oral (1st pass Metabolism ® low oral:parenteral potency)

Metabolism.: Hepatic conjug. ® polar Metabolismolites.

Excretion, t½: Urine. Duration of analgesia—4-5 hr.

Toxicity/S.E.s: Histamine release ® asthma in suscept. patients. Use w/caution w/compromised resp. patients. CO₂ retention ® ­ intracranial pressure (may mask signs of head injury). Poisoning ® coma, severe resp. depression, pinpoint pupils. Rapid onset of tolerance (up to 100x) to analgesia, euphoria/dysphoria, sedation, n/v, resp. depression, cough suppression. Physical dependence—abrupt w/drawal ® rhinorrhea, lacrimation, chills, goose pimples, hyperventilation, mydriasis, myalgia, vomiting, diarrhea, anxiety, hostility (but it’s not fatal). Also psychological dependence. Drug interactions—sedative hypnotics ® severe CNS/resp. depression; phenothiazines/tricyclic antidepressants ® ­ sedation, freq. resp. depression.

Utility: Analgesia. Intrathecal for post-surg. pain ® long duration of action, few side effects.

Special Features: High maximum efficacy. High addiction/abuse liability. Psych. dependence.

Name: Diphenhydramine (Benadryl)

Class: H₁-Histamine Antagonist (OTC)

Mechanism: Competitive inhib. of histamine and histamine receptor interaction.

Absorption:

Dist.: Enters CNS

Excretion, t½:

Toxicity/S.E.s: Sedation (not in everyone). Taken w/alcohol ® enhanced CNS depression. Local anesthetic activity. Acute poisoning in kids ® complex CNS excitatory and depressant effects (convulsions, hyperpyrexia). Topical use = highest risk of sensitization, \ shouldn’t be applied topically.

Utility: Treat allergic rxns (e.g., hay fever). Prevent motion sickness. Can be used for morning sickness. Treat PD symptoms (esp. geriatric patients).

Special Features: Most effective if taken prophylactically. Can’t reverse effects once histamine has bound to receptor. Therapeutically effective dose related to amount of antigen.

Name: Zolpidem (Ambien)

Class: Antianxiety-Sedative-Hypnotic Agent

Mechanism: Binds to BDZ receptors, although it’s not structurally related to BDZs.

Absorption:

Dist.:

Metabolism.:

Excretion, t½:

Toxicity/S.E.s: Tolerance and physical dependence rarely develop.

Utility: Short-term treatment of insomnia. As effective as BZDs in prolonging total sleep time and shortening sleep latency. Little effect on sleep stages.

Special Features:

Name: Chloral hydrate

Class: Antianxiety-Sedative-Hypnotic Agent

Mechanism: Sim. to barbiturates

Absorption:

Dist.:

Metabolism.:

Excretion, t½:

Toxicity/S.E.s:

Utility: Used in hospitals, nursing homes, pediatric dental settings. Mickey Finn.

Special Features: Rarely used.

Name: Pentobarbital

Class: Antianxiety-Sedative-Hypnotic Agent (Barbiturate)

Mechanism: Potentiates GABA transmission by interacting w/GABA receptor. High doses ® direct activation of Cl^- channel ® global CNS synaptic depression.

Absorption:

Dist.:

Metabolism.: Hepatic Metabolism ® inactive Metabolismolites. Signif. induction of hepatic microsomal enzymes ® ­ potential for drug interactions.

Excretion, t½:

Toxicity/S.E.s: Dose-dependent depression of CNS fxn (mild sedation ® sleep ® coma ® coma w/resp. depression ® death). Chronic use of doses 2x-4x hypnotic dosage ® tolerance & psych/phys. dependence. W/drawal symptoms include grand mal seizures and DTs and are potentially lethal.

Utility: Rarely used as backup to other sedative-hypnotic drugs. Suicide.

Special Features: Short-acting agent

Name: Phenobarbital

Class: Antianxiety-Sedative-Hypnotic Agent (Barbiturate) (Antiepileptic:Tonic-Clonic)

Mechanism: Potentiates GABA transmission by interacting w/GABA receptor ® ­ duration of channel opening. High doses ® direct activation of Cl^- channel ® global CNS synaptic depression & block of sustained high freq. repetitive firing..

Absorption:

Dist.: 40-60% protein binding.

Metabolism.: Hepatic Metabolism ® inactive Metabolismolites. Signif. induction of hepatic microsomal enzymes ® ­ potential for drug interactions.

Excretion, t½: 46-136 hr (adults), 37-173 hr (kids).

Toxicity/S.E.s: Dose-dependent depression of CNS fxn (mild sedation ® sleep ® coma ® coma w/resp. depression ® death), cognitive impairment, hyperactivity, ataxia, changes in sleep patterns. Non-dose-rel.—lethargy, ¯ attention span, osteopenia. Idiosync.—allergic dermatitis, Stevens Johnson synd., serum sickness rxn, granulocyte suppress. Chronic use of doses 2x-4x hypnotic dosage ® tolerance & psych/phys. dependence. W/drawal symptoms include grand mal seizures and DTs and are potentially lethal.

Utility: Alt. treatment for gen. tonic-clonic & partial seizures. Alt. treatment of status epilepticus. Rarely used as backup to other sedative-hypnotic drugs. Suicide.

Special Features: Long-acting agent

Name: Buspirone (Bu Spar)

Class: Antianxiety-Sedative-Hypnotic Agents (Selective Antianxiety Agent)

Mechanism: Agonist for 5-HT 1A and D₂ receptors.

Absorption: Oral ® rapid absorption.

Dist.:

Metabolism.: Extensive 1st-pass Metabolism. (hepatic hydroxylation & dealkylation) ® Metabolismolites that may have slight activity.

Excretion, t½: 2-4 hr.

Toxicity/S.E.s: Wide safety margin. Dizziness, insomnia, nervousness, nausea, headache, myoclonic jerks, chest pain, tinnitus, fatigue. Lower incidence of CNS S.E.s than w/BZDs, but higher incidence of GI S.E.s. Coadmin. w/haloperidol ® ­ serum haloperidol. W/MAO inhib. may cause ­ BP.

Utility: Short-term relief of anxiety w/o signif. sedation, drowsiness, or amnesia.

Special Features: No synergistic/additive effect w/other antianxiety or hypnotic agents. No CNS depression. No known potential for tolerance, dependence, abuse, or withdrawal. May take more than a week for anxiolytic effects to develop.

Name: Flumazenil (Romazicon)

Class: Benzodiazepine Antagonist

Mechanism: Competitive antagonist for BZD receptor ® antagonism of BZD CNS effects, including respiration depression.

Absorption: IV

Dist.: CNS

Metabolism.:

Excretion, t½: Duration of action 1-4 hr. \ repeated admin. often required.

Toxicity/S.E.s: Can precipitate severe abstinence synd. in BZD-dependent patients.

Utility: Treat CNS depressant effects of BZD overdose.

Special Features:

Name: Flurazepam (Dalmane)

Class: Antianxiety-Sedative-Hypnotic Agent (Benzodiazepine)

Mechanism: Acts on BZD receptors closely coupled to GABA_A receptors ® enhancement of GABA inhib. action via ­ freq. of Cl^- channel opening.

Absorption: Oral ® rapid absorption (large variability in indiv. responsiveness).

Dist.: Protein binding ³50%. CNS.

Metabolism.: Liver microsomal N-dealkylation/hydroxylation, then conjug ® inactive glucuronides. No induction of hepatic microsomal enzymes.

Excretion, t½: Urine—mostly Metabolismolized. Long—24-100 hr. Active Metabolismolites.

Toxicity/S.E.s: Acute—excessive depression of CNS fxns (drowsiness, sleep, confusion, disorientation, ataxia, slurred speech, nystagmus, mild amnesia, dementia). May also cause aggression, hyperactivity, delirium, insomnia. Large doses or mixture w/depressants (e.g., EtOH) may cause resp. depression, coma, hallucinations, nightmares, confusion. Chronic—impaired thinking/memory, weight gain/loss. Habituation & physical dependence ® w/drawal syndrome. Abrupt discontinuation ® risk for convulsion (less risk than w/newer BZDs). Metabolism. ¯ in elderly and by cimetidine. Overdose ® serious resp. depression (rarely fatal w/support). ALL BZDs—Use caution w/­ age, pregnancy, EtOH/subst. abuse, depression, driving/dangerous machinery, use of other CNS depressants, narcolepsy, hypersensitivity, chronic use > 1 wk- 1 month (except for epilepsy). Psych & phys dependence.

Utility: Anxiety, insomnia, alcohol w/drawal. Sedation—all BZDs are DOCs for sedation.

Special Features: Older BZD (longer t½, less potency).