Chapter 4. Pharmacology Flashcards

Question

165. Which of the following two opioids are inherently, pharmacologically, and relatively longacting? (A) Morphine and oxycodone (B) Morphine and oxymorphone (C) Oxycodone and fentanyl (D) Methadone and levorphanol (E) Methadone and oxymorphone

Answer 1

181. (C) The NSAIDs are weak organic acids, consisting in one or two aromatic rings connected to an acidic functional group. They do not cross the blood–brain barrier, are 95% to 99% bound to albumin, are extensively metabolized by the liver and have low renal clearance (

Answer 2

182. (B) Coxibs do not have any advantages in terms of renal effects. COX-2 inhibitors are associated with less GI toxicity than standard NSAIDs but they are more expensive. There is a possible increased risk of myocardial infarction (MI) and thrombotic stroke events associated with the continuosly long-term use of coxibs. Those concerns led to rofecoxib and valdecoxib being withdrawn from the market in the year 2004 and 2005, respectively. Regular NSAIDs inhibit the synthesis of TXA2 by inhibiting COX-1, which is spared with the use of COX-2 inhibitors.

Answer 3

183. (E) NSAIDs inhibits the prostaglandin G/H synthase enzymes, colloquially known as the COX, therefore inhibiting the synthesis of prostaglandin E, prostacyclin, and thromboxane. NSAIDs inhibit the production of not only COX-2 but also COX-1. Steroids inhibit phospholipase A2.

Answer 4

184. (C) Prostaglandins are not important primary pain mediators, they do cause hyperalgesia by sensitizing peripheral nociceptors (to mechanical an chemical stimulation) to the effects of pain mediators, such as bradykinin, somatostatin, and histamine, producing hyperalgesia. They do so by lowering the threshold of the polymodal nociceptors of C fibers. NSAIDs act mainly in the periphery, but they may have a central effect. COX-2 induction within the spinal cord may play an important role in central sensitization. The acute antihyperalgesic action of NSAIDs has been shown to be mediated by the inhibition of constitutive spinal COX-2, which has been found to be upregulated in response to inflammation and other stressors.

Answer 5

185. (C) In the kidney, prostaglandins help to maintain GFR and blood flow. They also contribute to the modulation of renin release, excretion of water, and tubular ion transport. In patients with normal renal function NSAID-induced renal dysfunction is extremely rare. Risk factors for NSAID-induced renal dysfunction are: • Prolonged and excessive NSAID use • Older patients • Chronic renal dysfunction • Congestive heart failure • Ascites • Hypovolemia • Treatment with nephrotoxic drugs (aminoglycosides and vancomycin) In these scenarios NSAIDs may decrease rapidly the GFR, release of renin, which can progress to renal failure. Sodium, water retention, hyperkalemia, hypertension, acute papillary necrosis, chronic interstitial nephritis, and nephrotic syndrome can also occur. Coxibs (COX-2 inhibitors) have similar renal effects and it should be closely monitored, as is required for conventional NSAIDs.

Answer 6

186. (E) Platelets are very susceptible to COX inhibition, which also inhibits the endogenous procoagulant thromboxane. Long-term use of standard NSAIDs produces a consistently prolonged bleeding time, but the prolongation is mild and values tend to remain below the upper limits of normal.

Answer 7

187. (C) Aspirin covalently acetylates COX-1 and COX-2, irreversibly inhibiting COX activity. This makes the duration of aspirin’s effects related to the turnover rate of COX in different target tissues. NSAIDs competitively inhibit the active site of COX enzymes which relates its duration more directly to the time course of drug disposition.

Answer 8

188. (B) The unique sensitivity of platelets to inhibition by low doses of aspirin, as low as 30 mg/d is related to their presystemic inhibition in the portal circulation before aspirin is deacetylated to salicylate on first pass through the liver. Aspirin irreversibly inhibits COX activity, making the aspirin’s effect related to the turnover rate of COX in different target tissues. Enzyme turnover is most notable in platelets because they are anucleated with a marked limited capacity for protein synthesis. Therefore the inhibition of platelet COX-1 (COX-2 is expressed only in megakaryocytes) last for the lifetime of the platelet, 8 to 12 days (10 days average) after therapy has been stopped. In general NSAIDs are well absorbed orally, but that is not the reason for high platelet sensitivity to ASA.

Answer 9

189. (B) The antiplatelet effect of NSAIDs is rapidly reversible, 24 hours cessation is probably sufficient, although 2 to 3 days cessation is advised. Aspirin because of its irreversible antiplatelet effect should be stopped 10 days before elective surgery.

Answer 10

190. (D) Ketorolac is one of the few NSAIDs that the FDA approved for parenteral use. It is highly efficacious, with efficacy close to that of morphine and other opioids for simple outpatient procedures to major operations. Ketorolac’s side effects, like other NSAIDs include GI bleeding, other bleeding problems, and reversible renal dysfunction (Possibly related with use of high doses or failure to recognize its contraindications). Nonunion, deleterious effects in bone osteogenesis during bone repair are some other side effects, more likely to occur if ketorolac was administered after surgery, compared with no use of NSAIDs. Decreased posterior spine fusion rates have been demonstrated in rat models, with the long-term use of indomethacin, but even the short-term administration of NSAIDs may possibly significantly affect spinal fusion. These findings have not been confirmed in humans, but many surgeons prefer to avoid the use of NSAIDs in the postoperative period of bone fusion, especially in the spine. COX-2 inhibitors can have similar effects, which is unlikely with short-term perioperative use in humans. No human studies to date document that coxibs have these negative effects in bone healing.

Answer 11

191. (C) All are well-known and not uncommon side effects of NSAIDs. Borderline increases of one or more liver tests, may occur in up to 15% of patients taking NSAIDs, approximately 1% of patients taking NSAIDs have shown notable increases in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (X3 or more the upper limit of normal). These findings may progress, remain unchanged, or be transient with continuing therapy. Rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis, and hepatic failure (some with fatal outcome), have been reported with NSAIDs.

Answer 12

192. (B) Oxcarbazepine [10, 11-dihydro-10-oxo-5Hdebenz (b, f) azepine-5-carboxanide] is an analogue of carbamazepine with a keto group at the 10 carbon position. It is roughly 50% protein bound in the plasma. The dose should be at least cut by half if the patient has significant renal insufficiency. The most frequent adverse effects experienced include dizziness and vertigo, weight gain and edema, GI symptoms, fatigue, and allergic-type reactions. Cross-allergy to carbamazepine occurs in about 25% of patients and may be severe.

Answer 13

194. (C) A structural analogue of GABA is considered by many practitioners to be a first-line drug for treatment of PHN and PDN because of its tolerability and efficacy. Dose should be reduced in renal dysfunction. Dose increases are usually made every 3 to 4 days.

Answer 14

197. (B) Anticholinergic side effects are generally | very significant for TCAs.

Answer 15

198. (C) Antidepressants which selectively inhibit serotonin with minimal effects on norepinephrine reuptake are referred to as SSRIs (eg, paroxetine). Protriptyline, desipramine, and amoxapine are secondary amine TCAs. Duloxetine inhibits both norepinephrine and serotonin (SNRIs).

Answer 16

199. (A) Side effects of antidepressants include anticholinergic effects, antihistaminergic effects, α1- aderenergic receptor bloackade, and cardiac effects. Individual may possess significant side effects in one specific area (eg, doxepin is a strong antihistaminergic agent). As a generalization,the most common adverse effects associated with TCAs are anticholinergic in nature.

Answer 17

202. (D) Tramadol hydrochloride is a centrally acting analgesic which is thought to provide analgesia via at least two mechanisms: some analgesia may be derived from the relatively weak interaction of tramadol with the μ-opioid receptor. The second and major mechanism, which is thought to account for at least 70% of tramadol’ s analgesic activity, is via inhibiting the reuptake of norepinephrine and serotonin

Answer 18

203. (C) Clonazepam is a benzodiazepine—which binds to the GABAB receptor (other benzodiazepines bind to the GABAA receptor) and has been utilized to treat various neuropathic pain syndrome and lower extremity muscle conditions.

Answer 19

204. (B) Carisoprodol may be useful for the short-term treatment of acute musculoskeletal disorders, especially in combination with acetaminophen, aspirin, or NSAIDs. Carisoprodol is primarily metabolized in the liver to several metabolites, including meprobamate. This metabolic conversion, although relatively small, has been postulated to be the reason that carisoprodol may have abuse potential. The formation of meprobamate from carisoprodol is by N-dealkylation via CYP2C19. Poor metabolizers of mephenytoin have a diminished ability to metabolize carisoprodol and therefore may be at increased risk of developing concentration-dependent side effects (eg, drowsiness, hypotension, CNS depression) at “usual” adult doses. Although the precise mechanisms of action of carisoprodol (as well as meprobamate) are uncertain, one theory is that they act as indirect agonists at the GABAA receptor, yielding CNS chloride ion channel conduction effects similar to benzodiazepines. Therefore, flumazenil may be a potentially useful antidote to carisoprodol toxicity.

Answer 20

205. (E) Tizanidine is an imidazoline derivative that is structurally related to clonidine. Its action is primarily derived from agonism at the α2- adrenoreceptor. Metabolism of tizanidine occurs primarily in the liver through oxidative processes, and metabolites of the parent compound have no known pharmacologic activity. Excretion of tizanidine and its metabolites occurs primarily via the kidneys (53%-66%).

Answer 21

210. (C) The previously proposed classification of μ- receptors into μ1 and μ2 subtypes, with the rationale that selective μ1-agonist could produce analgesia without the undesirable effects of respiratory depression has not been proven. Gene experiments have demonstrated that μ- receptors mediate all morphine activities including analgesia, tolerance, dependence, and respiratory depression. Opioid receptors are coupled to G proteins and they act mostly through phosphorylations via a second messenger. Opioids act pre- and postsynaptically. Presynaptically, inhibit the release of neurotransmitters including substance P and glutamate. Postsynaptically inhibit neurons by hyperpolarization, through the opening of potassium channels

Answer 22

211. (C) When choosing between partial agonists (ie, buprenorphine) and mixed agonist-antagonists (ie, pentazocine, nalorphine) versus pure agonists, pure opioid agonists are preferred, especially in chronic pain patients, because of their superior efficacy and easier titratable nature

Answer 23

212. (E) Analgesic effects of systemic administration of opioids result from receptor opioid activity at different sites, including: 1. The sensory neuron in the peripheral nervous system. 2. The dorsal horn of the spinal cord (inhibition of transmission of nociceptive information). 3. The brainstem medulla (potentiates descending inhibitory pathways that modulate ascending pain signals). 4. The cortex of the brain (decreases the perception and emotional response to pain).

Answer 24

213. (C) The liver metabolizes opioids by dealkylation, glucuronidation, hydrolysis, and oxidation, any hepatic disease can increase the accumulation of toxic metabolites, that is, morphine-6-glucuronide, normeperidine (CNS toxicity), norpropoxyphene (cardiac toxicity). Kidneys account for 90% of opioid excretion. Therefore any hepatic or renal disease increases the likelihood of opioid-related toxicity.

Answer 25

214. (C) The use of hydrophilic opioids like morphine in the epidural space produces a biphasic respiratory depression pattern. One portion of the initial bolus is absorbed systemically, accounting for the initial phase, which usually occurs within 2 hours of the bolus dose. The second phase occurs 6 to 12 hours later owing to the slow rostral spread of the remaining drug as it reaches the brainstem.

Answer 26

215. (E) Opioids should be used with caution in any situation with decrease respiratory reserve, that is, emphysema, obesity, scoliosis. Opioids that release histamine (ie, morphine) may precipitate bronchospasm, especially in asthma.

Answer 27

216. (C) The opioid receptors, μ-, δ-, κ-, ORL receptors are highly similar, their genes have been cloned in many species, including humans. The molecular structure of these G protein–coupled receptors (GPCRs) comprises 7 hydrophobic transmembrane domains interconnected by short loops, an intracellular C-terminal tail and an extracellular N-terminal domain. The transmembrane domains and intracellular loops have amino acid sequences that are 65% identical or similar, whereas the amino (N), carboxy (HOOC) terminal and the extracellular loops are very different

Answer 28

217. (B) When noxious stimuli are produced, they are transmitted to higher centers through spinal routes arriving at the parabrachial area, central gray, and the amygdala. The pathways which project to these supraspinal sites and the sites themselves contribute mostly to the emotional aspects of pain, whereas those which project to the thalamus and somatosensory cortex produce the sensory aspects of pain. Opioids suppress both pathways but the dissociation of the emotional and sensory aspects of pain is most likely produced by brain mechanisms. Opioids can also prevent the supraspinal activation by noxious stimuli through increased activity in inhibitory descending controls terminating in the dorsal horn of the spinal cord. The action of opioids on peripheral structures does not abolish the emotional aspects of pain. There is a hypothesis describing two major populations of RVM output neurons, ON cells and OFF cells. ON cells activity coincides with spinal reflexes and OFF cell activity is associated with the suppression of those reflexes. Morphine produces a pronounced reduction in the activity of ON cells.

Answer 29

218. (A) Opioids exert their analgesic effects through central and peripheral mechanisms. Although it was believed that opioids act exclusively within the CNS, there are opioid receptors outside the CNS able to produce analgesic effects in the periphery. The opioid receptors are synthesized in the dorsal root ganglia (DRG) and transported toward the peripheral sensory nerve endings. These peripheral actions are enhanced under inflammatory conditions. Immune cells may release endogenous opioid-like substances, which act on opioid receptors located on the primary sensory neuron. Centrally, the opioids inhibit directly the ascending transmission of painful stimuli arising from the spinal cord (dorsal horn) and activate circuits that descend from the midbrain via the RVM to the dorsal horn.

Answer 30

219. (C) Opioids are a primary pain medication that has no ceiling effect , and there is no “mild” opioids, because they can be titrated to produce equianalgesic effects. Although some opioids have been considered “mild” because of dose-related side effects or because commercial preparations are combined with adjuvant drugs (ie, aspirin or acetaminophen) limiting its dosing. There is evidence indicating that morphine has greater potency but slower speed of onset and offset in women. Opioids acting in μ- and κ-receptors constrict the pupil by exciting the Edinger Westphal nucleus (parasympathetic). Long-term opioid use can produce tolerance to miotic effects of opioids.

Answer 31

220. (C) Tramadol has a different profile from that of conventional opioids. It is very effective in the treatment of severe pain, with fewer side effects than morphine. The risk of respiratory depression is lower at equianalgesic doses; the risk of fatal respiratory depression is minimal at appropriate oral dosing, and limited essentially to patients with severe renal failure. Tramadol has a low abuse potential, however, nausea and vomiting occur at the same rate as with other opioids.

Answer 32

221. (D) Morphine is metabolized by the liver to morphine-6-glucuronide which is more potent than morphine itself and has a longer half-life, resulting in additional analgesia. Morphine is also metabolized to morphine-3-glucuronide which causes adverse effects and is inactive according to others. Renal dysfunction can produce accumulation of morphine-6-glucuronide, with subsequent opioid effects, including respiratory depression, so morphine should be used with care in renal dysfunction. Patients with liver failure can tolerate morphine (even in hepatic precoma), because glucuronidation is rarely impaired. Short bowel syndrome and vomiting and diarrhea limit the efficacy of controlled-release morphine, which relies in slow absorption from the GI tract

Answer 33

222. (A) Fentanyl is 80 times as potent as morphine. Transdermal fentanyl is extremely useful as a treatment in chronic pain especially in cancer patients. It causes less constipation than sustained-release morphine. Ninety-two percent of fentanyl delivered transdermally reaches systemic circulation as unchanged fentanyl. Peak plasma concentration after application is 12 to 24 hours and a residual depot remains in subcutaneous tissues for about 24 hours after removal of the patch, therefore care needs to be taken with the use of transdermal system.

Answer 34

223. (A) Normeperidine is a neurotoxic metabolite of meperidine; its accumulation is more likely in patients with poor renal function, especially in the elderly. The use of meperidine should be limited to 1 to 2 days for acute pain and should be avoided in chronic pain management.

Answer 35

224. (A) Opioid distribution is a function of lipophilicity and plasma protein binding. Fentanyl is both lipophilic and highly protein bound. Fentanyl also distributes to fat tissue and redistributes slowly from there into the systemic circulation. The opioids are mainly metabolized in the liver and to a minor extent in CNS, kidneys, lung, and placenta.

Answer 36

225. (B) Investigations have showed that endogenous and exogenous opioids can bind to opioid receptors primarily in the hypothalamus but also in the pituitary gland and testes, decreasing the release of gonadotropin-releasing hormone (GnRH), luteinizing hormone–follicle-stimulating hormone (LH–FSH), and testosterone-testicular interstitial fluid, respectively. Clinically this will manifest as hypogonadism, including: loss of libido, impotence, infertility (males and females), depression, anxiety, loss of muscle strength, fatigue, amenorrhea, irregular menses, galactorrhea, osteoporosis, and fractures. Opioids have also been found to decrease cortisol levels and cortisol responses, but they do not modify thyroid function. Opioids also have been shown to increase pituitary release of prolactin in preclinical studies and one study also documented decreased growth hormone (GH), without clear clinical significance.

Answer 37

226. (E) NSAIDs may diminish the antihyperptensive effects of ACE inhibitors (ACEIs) and the natriuretic effect of furosemide and thiazides in some patients. Anticoagulant therapy with warfarin should be monitored, especially in the first few days of changing therapy, because all the currently available COX-2 inhibitors may increase serum warfarin levels. Lithium levels may also increase with celecoxib, valdecoxib, and rofecoxib.

Answer 38

227. (C) All sulfonamides can be regarded to one of the two main biochemical categories, arylamines or nonarylamines. The sulfonamide allergicity is thought to be related to the formation of hydroxylamine a metabolite of the nonarylamine group. Celecoxib and valdecoxib belong to the former group and are contraindicated in patients allergic to sulfonamides.

Answer 39

228. (C) Nabumetone (nonacidic prodrug metabolized to a structural analogue of naproxen) is minimally toxic to the GI tract, and it is the choice when GI side effects are a special concern. Coxibs are also a good choice if there is any history of GI symptoms. Coxibs are associated with less GI toxicity than standard NSAIDs, since they do not inhibit the constitutive COX-1 and therefore the production of the cytoprotective PGI2 in the stomach mucosa.

Answer 40

229. (A) Coxibs show less GI side effects, and have similar renal effects to those of standard NSAIDs. COX-2 is not present in platetelets, and up-to-date under most conditions, coxibs are not associated with platelet dysfunction. There is no documentation in humans that the coxibs impairs bone remodeling and delay fracture healing.

Answer 41

230. (E) The potency of NSAIDs in general is similar or equipotent to ASA, except for diflunisal, indomethacin, ketorolac, and diclofenac. Diflunisal is a difluorophenyl derivative of salicylic acid, more potent than aspirin in anti-inflammatory tests in animals. It is used primarily as analgesic in osteoarthritis and musculoskeletal sprains, where is 3 to 4 times more potent than ASA. It also produces fewer and less intense GI and antiplatelet effects than ASA. Indomethacin is 10 to 40 times more potent inhibitor of COX than ASA, but intolerance limits its dosing to short-term. It also may have a direct, COX-independent vasoconstrictor effect. Some studies have suggested the possibility of increased risk of MI and stroke, but controlled trials have not been performed. Ketorolac is a potent analgesic, poor antiinflammatory. Has been used as a short term alternative (less than 5 days) to opioids, for moderate to severe pain. Diclofenac is more potent than ASA; its potency against COX-2 is substantially greater than that of indomethacin, naproxen, or several other NSAIDs. Naproxen is more potent in vitro.

Answer 42

231. (B) Amultimodal approach (the combination of different, appropriate pain treatments) seems to be the best approach in terms of synergy and reducing the side effects of each. The opioid sparing effects of NSAIDs use in postoperative pain, has been confirmed in multiple controlled trials. This can be of particular benefit when the opioids side effects are especially undesirable, including preexisting ventilatory compromise, strong history of opioid induced side effects and the very young

Answer 43

232. (C) Coxibs are a good choice in patients with a history of GI symptoms or sensitivity to NSAIDs, because they are associated with less GI side effects than standard NSAIDs. Although they are more expensive and they carry the concern of increase cardiovascular risk (increased thrombotic events: MI, stroke), with continuous and prolonged used. Standard NSAIDs combined with GI prophylaxis seems to be equally effective in terms of efficacy and freedom from GI toxicity. The GI prophylaxis can consist of: parietal cell inhibitors (acid inhibitors, ie, omeprazole), prostaglandin analogues (misoprostol), and H blockers (ie, ranitidine, cimetidine). Diclofenac is available in combination with misoprostol, retaining the efficacy of diclofenac while reducing the frequency of GI toxicity; it is cost effective relative to coxibs despite the cost of added misoprostol. Diclofenac with enteric coat does not offer a marked less GI toxicity.

Answer 44

233. (E) The combination of opioid/nonopioid (ie, NSAIDs) for mild to moderate cancer pain is synergistic and has the ability to reduce the side effects of each drug. NSAIDs in advanced cancer, are particularly useful for bone pain (distension of the periosteum by metastases, for soft tissue pain (distension or compression of tissues), and for visceral pain (irritation of the pleura or peritoneum). ASA and other salicylates are contraindicated in children and young adults (younger than 20 years) with fever associated with viral illness, owing to the association with Reye syndrome. Acetaminophen: nonacidic, crosses the blood–brain barrier, acts mainly in the CNS, peripheral, and anti inflammatory effects are weak

Answer 45

234. (D) Unlike ibuprofen, naproxen, and ketorolac, celecoxib does not interfere with the inhibition of platelet COX-1 activity and function by aspirin.

Answer 46

236. (A) The drug was approved by the European Union in 2004. Pregabalin received US FDA approval for use in treating epilepsy, diabetic neuropathy pain, and pain in June 2005, and appeared on the US market in 2005. In June 2007 the FDA approved it as a treatment for fibromyalgia. It was the first drug to be approved for this indication and remained the only one, until duloxetine gained FDA approval for the treatment of fibromyalgia in 2008.

Answer 47

237. (B) GBP has a chemical structure similar to GABA. It seems not to act directly at the GABAbinding site in the CNS, however. The mechanism of action is still unclear. It may enhance the release or activity of GABA and seems to inhibit voltage-dependent sodium channels

Answer 48

238. (A) Case report evidence suggests that clonazepam may have a useful effect in treatment of the shooting pain associated with phantom limb pain. Somnolence is a predominant side effect, and with this drug’s long half-life, daytime sedation may complicate use. As it belongs to the benzodiazepine group of drugs, anxiolysis and muscle relaxation may also be produced by its use, and this combination of properties may, in some patients, be useful.

Answer 49

239. (B) Case report evidence suggests that lamotrigine may reduce the symptoms of complex regional pain syndrome (type 1), with the sudomotor changes seen in this condition being alleviated along with pain and allodynia. Perhaps the major side effect limiting rapid titration to a therapeutic dose is skin rash. Higher doses may be used, but, if no effect is observed at 300 mg/d, further increases are unlikely to produce analgesia. In view of the relatively long half-life of lamotrigine, oncedaily dosing may be appropriate.

Answer 50

``` 240. (B) The TCAs can be divided into tertiary amines and their demethylated secondary amine derivatives. Tertiary amine TCAs ("ACID T ") Amitriptyline Imipramine Tripramine Clomipramine Doxapin Secondary amine TCAs ("PAND") Nortriptyline Desipramine Protriptyline Amoxapine ```

Answer 51

246. (B) The liver receives the major insult from acetaminophen toxicity, with the predominant lesion being acute centrilobular hepatic necrosis. It is suggested the use of the glutathione precursor of N-acetylcysteine for the treatment of acetaminophen intoxication in efforts to maintain hepatic reduced glutathione concentrations and adrenergic agonists may lower hepatic glutathione significantly.

Answer 52

247. (A) Baclofen is the ρ-chlorophenyl derivative of GABA. Baclofen is a GABAB agonist that has been used for muscle spasms and spasticity, neuropathic pain, and so on. Baclofen may enhance the effectiveness of antiepileptic drugs in certain neuropathic pain states. Side effects include sedation, weakness, and confusion. Abrupt cessation may cause a withdrawal syndrome, such as hallucinations, anxiety, tachycardia, or seizures.

Answer 53

248. (D) The two clinically available botulinum toxins in the United States are botulinum toxin type A and botulinum toxin type B. A different formulation of botulinum toxin Ais used in Europe as well as a version used in China but are currently not available in the United States. Effects seem to last for roughly 3 to 6 months after injection, at which point a repeat injection generally reproduces the effect. Although it is generally accepted that botulinum toxins may lead to diminished pain in patients with painful muscle spasms or cervical dystonia by diminishing muscle tone, it is also felt that botulinum toxin may itself possess analgesic properties. The mechanism of botulinum toxin–induced analgesia are unknown. The most evident mechanism of botulinum toxin-induced analgesia is via reduction of muscle spasm by cholinergic chemodenervation at motor end plates and by inhibition of gamma motor endings in muscle spindles. Future uses of botulinum toxins for analgesia may lead to redesign toxins for intrathecal use.

Answer 54

249. (A) Cyclobenzaprine is structurally similar to TCAs and, as such, demonstrates significant anticholinergic side effects. It exhibits a sideeffect profile similar to that of the TCAs, including lethargy and agitation, although it usually does not appear to produce significant dysrhythmias beyond sinus tachycardia. Elderly patients seem to tolerate cyclobenzaprine less well and may develop hallucinations as well as significant anticholinergic side effects, such as sedation. The use of significant lower dosing schedules in elderly patients may be prudent.

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Chapter 4. Pharmacology Flashcards

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