Insomnia is defined as the inability to fall asleep or to go back to sleep once one has awoken. Elderly pts may fall asleep very easily but wake up at 2 or 3 am and not be able to go back to sleep. In dentistry, you’ll encounter pts who may have trouble sleeping due to their anxiety about upcoming treatment. This requires an anti-anxiety agent, although there is a fuzzy line between anti-anxiety and anti-insomnia drugs- in any case, the dentist will most likely not be the one writing prescriptions for anti-insomniac drugs.
We deal with circadian rhythms, often times there are shifts in this cycle as in night workers and those with jet-lag.
Another rare, but real, syndrome is narcolepsy. This is when a person will enter a sudden deep sleep, and is hard to arouse. There are specific drugs that we will later allude to. Drugs that promote sleep are hypnotics, although most pharmacologists refer to sedatives/hypnotics together. Conscious sedation is not from hypnotic drugs, this is different from using a hypnotic to produce sleep in an insomniac.
“Therapeutic Overview”
The drugs used to treat insomnia can include drugs that suppress the CNS. The Benzodiazepines are the premier agents, and were developed in the 1970s. The barbiturates used to have a premier role as sedatives (Secobarbital, Pentobarbital) and were prescribed by an MD for insomniacs. But because they are very addictive, even short term use is now obsolete because the benzodiazepines have a much better therapeutic index, without the side effects of the barbiturates. However, there is still a use for barbiturates in dentistry, particularly for intravenous anesthesia. The antihistamines, particularly diphenhydramine, are contained in many of the otc sleep-aids. If a pt takes this they will have anticholinergic effects (severe xerostomia, etc.) along with sleepiness. Agents like chloral hydrate and paraldehyde are obsolete. Deaths have occurred in the dental office from injudicious use of chloral hydrate, it is a powerful CNS depressant with a very narrow therapeutic index. All of these drugs except diphenhydramine are CNS depressants, so the risk of overdose and coma/ respiratory suppression are very real.
The anti-hypersomnia drugs combat excess sleep and narcolepsy. These include CNS stimulants, dextroamphetamine, pemoline, and methylphenidate (Ritalin, to be used for Attention Deficit Disorder- ADD).
The phrase “benzodiazepine” is important, because all of the chemicals belonging to this class have the same basic structure, but vary in their potency, onset of action, and duration of action; this is the only way that we can distinguish between them because they have the same mechanism. Triazolam was the number 1 prescribed drug in the 1970s for insomnia, the brand name was Halcion. This drug is now obsolete because it can cause excitation, suicidal and homicidal tendencies, paradoxically. You will still find some pts taking Halcion though, it’s still available.
Pentobarbital is a different structure, there is a narrow therapeutic index (t.i.) and a high risk of dependence developing for the barbiturates. Pentobarbital is the sleeping pill most effective for committing suicide, because it can cause respiratory depression and cardiovascular collapse when overdosed… it is almost impossible to commit suicide taking a benzodiazepine.
All of these drugs have a quick onset of action. Obviously if you’re trying to fall asleep you don’t want to lie there for a long time. The CNS stimulants have significant abuse potentials, depending on which one we’re talking about. The amphetamines are schedule II drugs.
“I’m only going to point out the drugs that are important to you.” They’re all effective via the oral route. Triazolam (Halcion) was number 1 for many years, has a short ½ life. Most people wake up the next morning without any drug hangover. Flurazepam has a long ½ life, causes daytime drowsiness with prolonged sedation and “drug hangover.” Barbiturates have a long ½ life, same problems- daytime drowsiness, etc. With Diphenhydramine (Benadryl derivatives), pts will get xerostomia along with drowsiness. If you prescribe this to achieve xerostomia, don’t be surprised when the pt falls asleep in the chair.
Zolpedem (Ambien) is now the number 1 prescribed sedative in the world. Zaleplon (Sonata) is identical to Ambien, trying to get into the market. Diphenhydramine (Benedryl) is found in otc sleep aids.
Pts given a prescription for short-term management of insomnia (ideally 10-14 days) does nothing to cure the cause, only manages the problem. With the CNS stimulants, (amphetamine class) pts are irritable and get tachycardia, etc. Ritalin (methylphenidate) is a sympathomimetic, so parents must be careful- this is why treatment with Ritalin is controversial because of the number of kids being diagnosed with ADD.
The drug names that we should pay the most attention to include: Dalmane (flurazepam), Halcion (triazolam), Seconal (secobarbital), Ambien (zolpidem)
Rapid Eye Movement (associated with sleep cycle) is important because a hypnotic drug should not alter the normal REM cycle.
Transient insomnia can result from stress. The FDA doesn’t approve any drug for the management of stress, but there are obviously drugs for insomnia and anti-anxiety. People with acute medical illnesses, including pain, as a cause of their insomnia are not managed by hypnotics alone. One of the major problems with travelers is jet-lag, in which one’s circadian rhythm is disturbed. Ambien is a popularly prescribed drug for business travelers who travel a lot and must stay alert on arrival in a new time zone. The pt will fall asleep once they get on the plane, and when they arrive they are bright and alert. Pts who are heavy caffeine drinkers also have an inability to fall asleep, but you wouldn’t want to prescribe a drug to counter caffeine’s stimulatory effects, just reduce caffeine. “Some people are exquisitely sensitive to caffeine. If I were to drink 3 cups of coffee at 8pm I would have no trouble falling asleep… I’m very tolerant to caffeine. In fact in the morning I have to have about 4 cups before I can get going. In fact, I have a drug seeking behavior! Wherever I am, the first thing I look for is coffee.”
Barbiturates were the most commonly prescribed hypnotic agents until the introduction of the sedating-hypnotic benzodiazepines in the 1960s. Common agents were Phenobarbital, Pehtobarbital (Nembutal), and Secobarbital (Seconal). The barbiturates are controlled substances because of the disadvantages associated with their use, including high abuse potential, addiction and physical dependance, tolerance, and daytime drowsiness. Usually drugs with hepatic effects will inhibit the p-450 enzyme, but the barbiturates INDUCE the p-450 enzyme. Alcohol markedly potentiates CNS depressant actions; port wine is a good sedative “Brandy would work too.” The barbiturates are DEA controlled substances (schedule II or III).
Sedating antidepressants such as TCAs can be used for chronic facial pain, and have also been prescribed for insomnia, but with the following side effects: orthostatic hypotension, dedation, and anticholenergic effects (dry mouth, blurred vision, constipation, prostatic problems).
Zolpidem is Ambien. It is considered a benzodiazepine by the FDA, class IV. Ambien is very, very unlikely to produce dependence, habituation, or tolerance.
There is a receptor in the CNS that recognizes GABA. When it binds to GABA it results in a chloride influx and thus has inhibitory effects on neuronal firing. Benzodiazepines act on a specific receptor for benzodiazepine, separate from the GABA receptor. When benzodiazepine binds its receptor, the same thing happens as when GABA binds its receptor; there is a net influx of chloride and a stabilizing effect because of the decrease in neuronal firing, resulting in drowsiness. Benzodiazepines also help in treating seizure disorders because of their stabilizing effects on neuronal transmission. There is cooperativity between GABA and benzodiazepine. Ambient works on ANOTHER analogous receptor (separate still from both the GABA and benzodiazepine receptors), called omega-1.
Ambien does not produce any other effects aside from normal sleep. Zolpidem (Ambien) has no significant effect on mean percentage of time in each stage of sleep, compared to normal. There is no significant effect on REM activity. Duration of sleep is increased in insomniacs. No evidence of developing tolerance (1 month dosing) and no evidence of rebound insomnia (more difficult to fall asleep after ceasing tx with Ambien). Ambient is classified as a schedule IV drug, meaning that although tolerance is a remote possibility, the drug is not absolutely free of the potential to cause tolerance.
Ambien is only approved for treatment of insomnia. Zolpidem adverse reactions don’t seem to be too significant as compared to a placebo. For headache and nausea, in short-term trials, Ambien shows no significant difference from a placebo. In long term trials, drowsiness is a little higher than the placebo, but very good as compared to other drugs. Amnesia occurs very rarely with Ambien, unlike with benzodiazepines (which can be used in dentistry to produce quality amnesia after a dental extraction, for example).
This is an ad for the Ambien derivative, Sonata. Prescriptions for sonata should not exceed a one month supply… this is different than Ambien, which is usually given 10-14 days.
Do these drugs really promote sleep onset? Zolpidem (Ambien) is very good compared to Halcion or some of the other long-acting benzodiazepines. This is the virtue that allowed ambient to become more popular. Flurazepam has an active metabolite, the elderly are prone to residual daytime drowsiness.
There is a hormone produced by the pineal gland, melatonin, which acts on a melatonin receptor in the Pons, and can induce sleep. As you age, melatonin production declines markedly, thus the elderly have a hard time sleeping. Pts can buy otc melatonin, usually combined with other vitamins. Melatonin can also be used by pts who anticipate jet-lag; it is not considered a drug.
- Chloral hydrate,
- sedating antihistamines (diphenhydramine),
- barbiturates,
- alcohol (“night cap”),
- paraldehyde,
- beta-adrenergic blockers,
- tricyclic antidepressants,
- buspirone,
- glutethimide
We must be able to differentiate Neuropathic pain from pain associated with an infection, trauma, suturing pain, or extraction pain. These are not pains invoked by a neuropathic mechanism. Neuropathic pain involves nerves, or neurogenic pain (including damaged peripheral nerves, ie. damage during a local nerve block injection, or if you nick a nerve during surgery). Neuropathic pain involves some dysfunction of the nervous system, including both the central and autonomic (particularly the sympathetic) nervous systems. Sometimes the pain occurs as a sharp, shooting or burning pain; “burning mouth/ burning lip” syndrome is often linked to neuropathic pain. This occurs usually in the absence of tissue damage.
Other labels for neuropathic pain include: reflex dympathetic dystrophy (RSD), diabetic neuropathy, central pain syndromes (ie. something is wrong in the thalamus or a pain relay center, often the only tx is for a neurosurgeon to interrupt neurothalamic tracts surgically), trigeminal and postherpetic neuralgia. Very frequently in diabetic pts, especially type I insulin dependent diabetics, diabetic neuropathy occurs, this alters your pt’s pain perception considerably.
Complex Regional Pain Syndrome (CPRS) is a new emphasis on the way to define chronic pain syndromes, the old term was “causalgia”.
Type I: pain is disproportionate to the event that is provoking the pain, it is more severe. A term such as hyperalgesia can be used to describe it, and should be in your pt record (don’t just write mild or moderate or severe).
Type II: pain is exaggerated, but there is also continuing pain. Not the type of acute pain that will last a few days, but continuing pain as in low back pain (one of the most frequent reasons a pt goes to an MD).
Hyperalgesia is an increase in the intensity and interpretation of a normally painful stimuli. The pain is mediated by the CNS, either C-fibers, A-delta fibers, or NMDA receptors.
When there is injury, we get inflammation from the release of prostaglandins, and we treat this with an NSAID or peripherally acting agent. However, when we have chronic pain it involves the neurons. Clearly because there is a neuronal pathway, giving agents to alter the neuronal firing may be successful in treating the pain. This includes many of the anti-convulsives, or anti-epileptics. These drugs do have an accepted role as adjuncts in this kind of pain, because we’re dealing with neurons that are firing extensively. In sympathetic mediated pain (SMP) there is something wrong with the sympathetic nervous system, and the release of catecholamines, particularly norepinephrine, at nerve endings triggers a particular type of pain. It can be treated by sympatholytics, to block the sympathetic outflow. Chronic pain with complex mediators involves other parts of the nervous system also, maybe the limbic system (heavily mediated by seratonin) where the interpretation and emotional aspect of pain resides. Obviously, using drugs designed to alter norepinephrine in the CNS, including the tricyclic antidepressants (TCAs), the anti-convulsants, and trans-electrical nervous stimulation (TENS, in which a device stimulates nerves blocks the gates of pain pathways, usually used for pts with intractable pain who do not respond to drugs). So there are a very diverse array of strategies available depending on the strategy of your diagnostic skills.
Notice that there are quotation marks around “analgesics” because the drugs listed here are not truly analgesics, but are commonly used as adjuncts in treating pain. These include the Tricyclic Antidepressants (TCAs), of which Amitriptyline, and Desipramine and Imipramine are common. Dr. Inesi will cover these more specifically later this quarter. The TCAs were originally designed to be used by psychiatrists to counter depression, but because they affect norepinephrine reuptake, they can be used to treat neuropathic problems. They are not used alone, but as adjuncts.
Another class is the anticonvulsants, including Carbamazepine (Tegretol), which used to be widely used in dentistry for facial pain syndromes. It has been declining in popularity because it promotes bone marrow depression with chronic use. Because of this, if Tegretol is to be used for chronic pain, it is essential to moniter the pt’s blood chemistry.
Local anesthetics, including Mexiletine (an antiarrhythmic drug) can be used as an adjunct in treating chronic pain syndromes.
The neuroleptics are very popular in Europe, less so here in the USA. These are drugs that interrupt many of the sensory pathways, having nothing to do with norepinephrine, or dopamine or glutamate, (we don’t understand the mechanism) but they are not likely to be used in dentistry.
The controversy is substantial with regard to the muscle relaxants. When dealing with chronic myofacial pain syndrome, there is a perception that the facial muscles are contracting and maybe a muscle relaxants would help… much of the evidence shows that for these syndromes muscle relaxants are no better than placebos.
Corticosteroids may only help if there is an inflammatory cause of pain. These drugs are devoid of analgesic actions, but can help with pain because of their anti-inflammatory action.
Sympatholytic drugs (Prazosin and Phenoxybenzamine) are alpha blockers and probably have no use, but we should add to the list Clonidine (Catapres). Clonidine is a central acting sympatholytic drug, having a significant effect on the alpha-2 receptor and as a result there is interference with sympathetic outflow.
The antidepressants are used in the management of depression, but as used in dentistry to deal with chronic pain syndromes we deal mostly with the TCAs (amytriptyline and nortriptyline are the prototypes). The TCAs are old agents, 40-50 years. They do produce anti-depressant effects that can help if a pt is depressed over their pain. Side effects include the fact that they are powerful anti-muscarenic drugs, like atropine. So we see severe xerostomia, bladder dysfunction, and constipation. If a person is taking these drugs chronically for acute pain, rampant caries is associated with the TCAs. The Serotonin Specific Reuptake Inhibitors (SSRI) will be discussed later, but the prototype is Prozac. SSRIs block serotonin reuptake, are better tolerated compared to the TCAs, but there is little evidence that they are any better than placebos. There are anecdotal reports of efficacy, but no serious studies have been done to quantify their effects as analgesic adjuncts (not to be confused with these drugs effectiveness at fighting depression, at which they are very effective).
Pay attention to the side effects associated with use of the TCAs (of which Amitriptyline is the prototype, and Nortriptyline is secondary). Severe xerostomia, bladder dysfunction, constipation and sedation are common.
What do our esteemed colleagues from the National Institute of Health in Bethesda think about antidepressants for chronic orofacial pain? “Many putative dental and surgical treatments for TMDs have not withstood scientific scrutiny.” The effects of antidepressants on TMJ dysfunction are almost always based on anecdotal accounts and don’t stand up in scientific studies.
It has been found, and published in JAMA (1998), that “neither acupuncure nor amitriptyline (TCA) was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy.” Until somebody refutes this, this is what we call evidence-based dentistry.
Gabapentin (Neurontin) was developed and approved for the tx of seizures in adults. However, there are increasing reports in the literature that Neurontin is effective in sympathetic dystrophy. It takes from 2 hours to 12 days for pain relief. In neuropathic and myofascial pain, it has been found to decrease the pain associated with post herpetic neuralgia. So this drug is approved as an anti-epileptic drug, but used as monotherapy for post herpetic neuralgia. It’s been effective against migraine headaches as well. Side effects include dizziness, sleepiness, and some motor ataxia and nystagmus, but very minor. The doses must be high, however, sometimes as far as 2-3.6 grams per day… so its not very potent.
Gabapentin is effective in treating shingles pain, quality of life is improved- it is palliative. Gabapentin is effective in the treatment of pain and sleep interference associated with PHN. Mood and quality of life also improve with gabapentin therapy- it is a first-line therapy for these pains.
When a pt has had pain for over a year, over 90% will have persistence of pain in the elderly. So there is an age related incidence of pain. Again, when we’re talking about acute pain, we’ll think of the NSAIDs, peripheral agents, acetaminophen, and the opiate class. When we come to chronic pain, you’re going to go over the line and look at adjuncts; we don’t want pts to be on chronic opiate therapy year after year because of the risks of drug tolerance and dependence.
Gabapentin has been shown to be effective for treating the pain associated with diabetic peripheral neuropathies, which occurs in 45% of patients with diabetes (mostly type I). Gabapentin is effective as monotherapy! That means that you don’t need an analgesic.
The prevalence of neuropathy may be present in up to 60% of diabetics. In non-insulin dependent diabetes mellitus (NIDDM), or type II, the duration of neuropathy will be increased.
When we’re looking at trigeminal neuralgia (TN), it often masquerades as pulpitis, facial pain, cluster headaches, secondary pains associated with tumors, etc. So the differential diagnosis of TN requires some clinical skill and maybe a med consult. If there are orofacial manifestations of that condition, then the issue is choosing the appropriate drugs.
Carbamazepine (Tegretol) is traditionally used to treat TN, and is very effective. However, side effects include blood dyscrasias, agranulocytosis; monitering of blood chemistry is essential.
Phenytoin (Dilantin) is an anticonvulsant drug, can be used alone or in conjunction with other drugs, and is less effective than Tegretol.
Baclofen (Lioresal) acts on the spinal cord pathways and apparently interferes with GABA neurons in the spinal cord, and has fewer side effects but is less effective.
Neurologists can also treat TN by other methods such as glycerol injections, radiofrequency thermocoagulation , and microvascular decompression, but these are things that even neurosurgeons are not inclined to do.
This is an ad for Clonidine HCl. Those of us who remember our pharmacology will remember that Clonidine (brand name Catapres) is a drug used for HTN. It is a central acting alpha-2 receptor agonist… what does this have to do with pain? This drug is very effective because of its alpha-2 agonist activity in the CNS, and manages neuropathic pain well. It is approved for the treatment of neuropathic pain “in combination with epidural opioids, provides enhanced relief of severe neuropathic pain in cancer patients- pain not adequately relieved by opioids alone.” Clearly, this means that anesthesiologists will use this to treat the excruciating pain associated with cancer via intra-thecal injection (into the spinal fluid of the spinal canal).
There are still physicians who prescribe muscle relaxant drugs such as Cyclobensaprine (Flexeril), Methocarbamol (Robaxin), and Carisprodol (Soma) to manage chronic facial pain syndromes. THESE DRUGS HAVE LITTLE EFFICACY IN CHRONIC OROFACIAL OR HEAD PAIN!!!
Although it is effective as an acute muscle relaxant, Diazepam (Valium) in “40 mg or more (muscle relaxant doses) over the long term is unlikely to be efficacious.”
Although I keep telling you that lidocaine is not an analgesic, but a local anesthetic, the fact is that in intractable pain (that doesn’t respond to anything else) lidocaine is approved for treatment. So when nothing seems to work, block the peripheral nerve and then give I.V. lidocaine. This is obviously something out of the realm of general dentists.
One last word about behavioral and relaxation approaches in managing chronic pain. The hard evidence is not there concerning the efficaciousness of relaxation, hypnosis and biofeedback. But, “…data are insufficient to conclude that one technique is more effective than another for a given condition.”
Major drugs: Morphine, Methadone, Meperidine, Fentanyl, Butorphanol, Pentazocine… none of these drugs are commonly used in dentistry! So its kind of a misrepresentation of what’s important to you as practitioners, so we’ll look at a different set of drugs. The narcotic class, which also includes all of the opioids and opiates are used to relieve moderate to severe pain- this is controversial because the Cox-2 inhibitors (Vioxx and Celebrex) are also indicated for moderate to severe acute pain. The COX-2 inhibitors are of the non-inflammatory class (NSAIDs) yet have the same therapeutic window as the narcotics. This is important, because when you’re dealing with pain and you can’t characterize it as mild, moderate or severe, its always best to see if the pt will respond to an NSAID. But for some reason, in dentistry, regardless of the nature of the pain, pts are being given prescriptions for Vicodin (which is an acetominophen, hydrocodone preparation) or Tylenol III (which is acetominophen plus codeine). Your options are much greater than that! So moderate to severe pain is really the indication for the opioid analgesics, not mild pain.
These drugs are also used in medicine to control diarrhea because there are opiate receptors in the gut and if you occupy those receptors you can reduce peristalsis, such drugs are usually used acutely (we’ll cover these in later lectures). Cough suppression; many of the otc agents have opiate like action on the cough center in the medulla oblongata, and that’s a reasonable strategy but these have nothing to do with analgesia.
More and more we’re seeing this in the clinic, a pt could be on a maintenance dose of methadone, this is an oral opiate analgesic- 400mg/day, because he’s a former heroin addict and he’s now taking this maintenance opiate therapy, this is really a massive dose of methadone and has importance as to how you will manage the patient.
Analgesic is defined as a drug that relieves pain without impairing sensory modality. The reality is that the ideal analgesia doesn’t exist because of all the central acting analgesics carry the same warning, they cause sedation and drowsiness and obviously affect sensory modality. We must be careful after prescribing such a drug and sending them on their way to drive an automobile because their motor sensory functions will be impaired; sedation and drowsiness.
The word “narcotic” goes back to 1914 federal legislation, and is defined as a drug that produces a stupor or sleeplike state. Narcotics include opium derivatives, called opiates, derived from the opium poppy (the codeines, the morphines, the heroins). The synthetic ones are called opioids. The words are used interchangeably, however.
Now what do our esteemed authorities at the ADA in Chicago advise dentists with regard to managing their patients? “Because the pain commonly encountered in dental practice is of the acute type, tolerance of, and physical and psychological dependence on opioids are so rare as to be of little concern… The dentist should use opioid medications in sufficiently large doses for high quality management of acute pain without fear that patients will develop dependence. The one exception may be patients with a history of drug abuse. For these patients, nonopioid analgesics or perhaps an agonist-antagonist opioid should be prescribed initially.”
There are many physicians and dentists who abuse, for instance, Vicodin- they over prescribe it and the DEA gets after them. How many doses, and at what dose-level becomes an issue. The one exception with regard to prescribing opiates is when a pt has a history of drug abuse, particularly heroin; do these pts have a vulnerability to a codeine or a Vicodin with hydrocodone in it. Probably you will not precipitate drug seeking behavior, but a lot of the faculty will advise you not to give these former drug abusers a narcotic- go to another agent. The literature is not very supportive of this, there is not any really strong evidence that you’ll induce a renewed craving for heroin but its an issue that you’ll hear discussed by the faculty.
The tri-cyclic anti-depressants, which are used as adjuncts in the management of chronic, particularly neuropathic pain, have nothing to do with opiate receptors. These act instead on norepinephrine re-uptake at the pre-synaptic terminal.
The opiate receptors exist in the CNS on neurons, they are membrane receptors, and the most important one is the “mu receptor”. It is the mu receptor that mediates almost all of the therapeutic effects of the opiate agents.
Textbooks refer to agents like codeine and hydrocordone as mu-receptor agonists. When the opiate binds to the mu receptor, a variety of things happen; Ca++ entry is blocked, potassium channels are opened up. Its mediated through a cyclic AMP coupled to an adenylate cyclase. But the main thing that occurs is that there appears to be a decreased release of neurotransmitters; these ionic intracellular events alter that neuron so that the release of neurotransmitters is blunted or blocked. The net effect is that the neuron loses its excitability. So here we have an agonist, the drug that is producing blockade of pain is acting as an agonist on its receptor. The net effect of the agonist is to decrease the firing of that neuron in the pain pathway, which is essential.
The so-called penta-peptides such as the endorphins and enkephalins also bind to the mu receptor, they are the ligands. The kappa receptor and delta receptor are not really understood as far as the patho-physiology of pain, although some drugs do bind more selectively to the kappa receptor. But the medicinal agents used to manage moderate to severe pain are mu-receptor agonists. Clearly at that same receptor, if we wanted to block it we could give a drug like naloxone, which is a mu-antagonist and would block it without producing any analgesic effect; this is a pure competitive receptor antagonist.
Morpine is a natural opium derivative and is used as a prototype of the entire class. The important part is that it has an inhibitory effect on pain. It causes drowsiness, decreased mental alertness and sedation. So it’s not an ideal agent. This also applies to the codeine and hydrocodone; we cannot separate the analgesia properties from the drowsiness and decreased mental alertness. What is the risk of repressing respiratory centers? This probably does not occur anywhere near therapeutic dosages. In the acute setting in oral surgery, if you’re injecting I.V. Demerol and the dose is not correct you’ll get respiratory arrest. The effect on the heart is minimal. The other effects you see listed here can be translated into therapeutic effects for other things like diarrhea.
The stimulatory effects are paradoxical. Most importantly, if a pt is abusing an opiate drug, he/she will have pinpoint pupils (miosis). Paradoxically, some pts will show euphoria. This is especially true for the parenteral opiates, it may be a desirable effect; if you get euphoria coupled with analgesia the pt feels a lot better. This leads to the issue if you have drug seeking behavior. Sometimes the pt will seek the use of a narcotic for its euphoric effects. Other effects on the bladder, for example, are important because the pt may have difficulty urinating.
Codeine is one of the mainstays in dentistry, although not alone… you’ll always write a prescription in combination with acetominophen or other compounds. Codeine is really a weak analgesic, it produces constipation, has a weak effect at producing respiratory depression, and has a variable effect at producing addiction liability. When you’re using codeine, even for a fairly long regimen, you’re not likely to get dependence, but you’re also not getting a profound analgesic effect like you would with Demerol or a different drug. So some of these drugs have an advantage over codeine, but there is a linkage between usage and side effects such as constipation. By the way, if a pt says they’re “allergic to codeine” it usually means that they don’t like the side effects, such as constipation. Allergies to the opiates are very rare as compared to the NSAIDs.
Oxycodone is presently undergoing scrutiny by the DEA because there is a popular sustained release oxycodone product called oxycontin, and is widely prescribed in medicine. Oxycontin is now a very popular street drug, so is under scrutiny by the Feds. Street value may be above that of heroin.
Propoxyphene has variable effect on constipation, doesn’t repress respiration, and has little abuse liability. It was widely promoted to dentists, and is called Darvon. Propoxyphene is closely related to methadone. So chemists were looking for the narcotic benefits of methadone without the side effects. What they ended up with was a weak analgesic. Propxyphene alone will not manage pain any better than a placebo. However, if you prescribe Darvocet (Darvon plus Acetominophen… whenever you see –cet at the end of a drug it means that it includes acetominophen) it is effective.
Half-life is an important determinant of duration of action. Generally there is a good linkage between the biologic half-life and its pharmacologic therapeutic duration of action. Codeine can be given orally, its therapeutic duration of action is only 4-6 hours. Its got a half-life of three hours. So if you prescribe it, its usually a t.i.d. or q.i.d. drug (taken 3-4 times a day). Methadone, which is always used as maintenance therapy in a former heroin addict, where they don’t want the pt injecting I.V. heroin but the habit is maintained by taking oral methadone. The half-life is 23 hours, so its usually taken once a day. Naloxone and Naltrexone are both opiate receptor antagonists, competitive receptor antagonists. Naloxone must be given by injection- in your emergency kit in your dental office you will have a carp of this. It has a very short half-life so you must use more than one dose. Naltroxone however is orally effective and has a half-life of 24 hours.
NSAIDs don’t produce many of the side effects as the opiates and are not addictive. From a graph measuring relief from severe cancer pain, 225mg Ketoprofen (an NSAID available otc) is comparable to intramuscular (injection) morphine (10mg).
Here’s the issue, one drug is acting on the opiate receptor, another is acting as a COX-1, COX-2 inhibitor, and yet the analgesic effect on severe cancer pain is the same. So why use an opiate instead of an NSAID?
The opiate drugs give you the added euphoria that NSAIDs don’t. So analgesia is one thing, but how the pt feels is important.
Native American Indians are more susceptible to morphine depression of respiration than are Caucasians. We now know that codeine is metabolized to a certain degree to morphine, the analgesic effects of codeine may be modulated by the production of a morphine metabolite. Turns out that there’s a difference between Caucasians and other ethnic groups in the ability of the liver to convert codeine to morphine, so analgesia differs. So you may have to consider a pt’s failure to respond to analgesics based on racial pharmacokinetic differences. This is a major area of drug research today.
- Respiratory depression: not really, you’d have to use massive oral doses to get this
- Sedation
- Interactions with CNS depressant drugs: act as synergists
- Constipation: very real with codeine, any dose lasting 2-4 days will have a change in bowel habits
- Nausea, vomiting: rare
- Endocrine disturbances
- Tolerance to analgesic effect
- Physical dependence
- Abuse potential
Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving.
Physical dependence is a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonists.
The 5 C’s which define addiction: Chronic, impaired Control over drug use, Compulsive use, Continued use despite harm, Craving
Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects over time. You must escalate the drug in order to get the same therapeutic effect.
Opiate Antagonists include Naloxone (Narcan), which must be given by injection. It binds to opiate receptors and can reverse opiate side effects. This can be an antidote to opiate overdose. Naltrexone (Revia) is given once a day orally, and blocks physical dependence to morphine, heroin and other opiates. However, there is severe liver damage with prolonged use.
Tramadol (Ultram) is a central acting analgesic, its not an opiate or an NSAID. It is indicated for moderate to severe pain. For adults only. Interacts with MAO inhibitors. It was the #1 used drug in Europe for a while and since its not an opiate, you don’t need a DEA narcotic prescribing license number.
We can see that when a pt is given Tramadol for pain in combination with Flurbiprofen, there is very good analgesia.
You need to know the components of Tylenol I, II, III, Percocet, Darvocet, Vicodin, Vicoprofen, Ultracet. Ultracet is brand new, and combines tramadol (centrally acting, non-opioid) with acetaminophen (peripherally acting). So you’ve got a lot of choices regarding pain management.
Percocet exists with varying oxycodone concentrations (7.5mg and 10 mg). You can see by the “C” with “II” in it that Percocet is a controlled substance II, which means that you need a triplicate prescription form. Oxycodone has a greater addiction liability, so that’s why Percocet is classified as a schedule II drug.
Usually the contraindications have to do with hypersensitivity to the components. YOU MUST NOT GIVE DEMEROL IF THE PT IS TAKING MAO INHIBITORS, YOU WILL KILL THE PATIENT. It is a lethal drug interaction.
It will be a very rare condition when you will want to prescribe hydrocodone alone. It requires a triplicate prescription form, and no refills are allowed. Hydrocodone alone is an addictive substance, it can produce very rapid tolerance and dependence. If you see hydrocodone in a fixed combination with another drug like acetaminophen, the dose is low enough that it usually means it will be a schedule III. If you look at schedule III drugs, you are allowed refills but the pt must be reevaluated every six months. That’s important for a physician treating chronic pain with opiates, for our case we’re always dealing with short-term pain of about five days.
This accounts for about 20% of lung cancer cases. This is still associated with smoking, but is the most common type to occur in non-smokers & women. Histological classification includes two forms: 1) bronchial-derived adenocarcinoma (i.e.: derived from bronchial mucosa), 2) bronchioloalveolar carcinoma (i.e.: derived from terminal bronchioles – specialised cells located here). Adenocarcinoma lesions are located more peripherally, are smaller, and vary histologically (glandular appearance≫ papillary lesions≫solid mass). 80% of these tumours contain mucin producing glands (i.e.: Histological landmark: gland formation / mucin production by tumour cells).
This type of cancer is most commonly associated with HPOA.
This type of tumours probably represent SSC / adenocarcinoma, but because their cells are so undifferentiated – that they can no longer be recognised in the above category. Some of these tumour cells contain intracellular mucin, some cells are multinuclear (giant cell carcinoma), some have cleared cells (clear cell carcinoma), some have spindle shaped cells (spindle cell carcinoma).
Natural History of Lung Cancer
For a 1cm carcinoma large enough to be seen on a CXR it takes about 7.5-10yrs, given that the average time for cells to double is 3-4mths. 1cm carcinoma contains about 1 billion cells, and represents ¾ of its life time – so mostly undetectable (before it gets to 1cm).
General points:
5% of Lung Cancers are detected in asymptomatic phase (i.e.: good prognosis)
95% of Lung Cancers are detected in symptomatic phase (i.e.: poor prognosis, metastatic disease)
Modes of spread
Usually, carcinoma of the lung begins as an area of thickening or piling up of bronchial mucosa. Over time it appears warty and elevates/erodes the lining epithelium. From here a variety of pathways can be followed:
fungate into bronchial lumen to produce intraluminal mass
penetrate beneath the bronchial mucosa into the peribronchial tissue -->mediastinum
grows within the parenchyma and produces a large intraparenchymal mass
These are all local lesions. Metastatic lesions include:
High blood supply areas including:
Complications include:
Lymph node involvement may compress the SVC as it is a low pressure vessel hence easier to compress
Neural involvement: compress phrenic nerve (diaphragmatic paralysis), recurrent laryngeal nerve (vocal cord paralysis), brachial plexus (upper limb paralysis / sensory loss), cervical sympathetic chain (60% of Pancoast tumours)
These syndromes are associated with bronchogenic carcinoma. There might not be a casual relationship established. For example: if a patient has been diagnosed with bronchogenic carcinoma of a particular histological type, then you also find these syndromes. These syndromes have been caused by systemic effects of the bronchogenic carcinoma, but are not caused by metastatic disease.
For example: tumours producing ACTH / ADH are usually small cell carcinomas, while tumours producing hypercalcaemia are SCCs. Other systemic manifestations of bronchogenic carcinoma is Lambert-Eaton myasthic syndrome – which causes muscle weakness due to autoimmune antibodies (elicited by tumour ionic channels) against neuronal calcium channels. HPOA is a connectiev tissue disorder associated with bronchogenic carcinoma.
-resonates between 2 structures (one with a single triple bond, the other with two double bonds); is gaseous and marketed in high pressure canisters; nonflammable but supports combustion; Guedel signs work well for nitrous.
-good analgesic, low potency
-relatively insoluble, Oswald coefficient= 0.47
-used in dentistry; 20% concentration results in analgesia, typically dentists used concentrations between 30-50%. Maximum useful dose before pt will enter stage 2 is about 60% (pt gets excited and difficult to control in stage 2). 70% is the maximum allowable concentration, valves are rigged so that you can’t get a greater than 70% concentration of nitrous.
-incomplete anesthetic, can’t reach stage 3 even if you went to 100% nitrous oxide
-induction/emergence is fast and pleasant, benign in many ways—no respiratory irritation, no salivation, no depression of circ. System, not toxic to kidney… BUT nitrous oxidizes vitamin B12 and can cause a deficiency, it inhibits an enzyme called methionine synthetase and can lead to megaloblastic anemia.
-not metabolized, compatible with other drugs
-does not cause neuromuscular blockade, which is something we’d like to occur
-in surgery nitrous is often mixed with something else such as halothane, thus called balanced anesthesia
-reduces MAC from other agents, so they become more potent in the presence of nitrous oxide.
-can also mix nitrous with other kinds of agents such as barbiturates, muscle relaxers, often used as psychosedation in dentistry (to control anxiety)
If you use nitrous oxide in your office, you must have scavenging equipment available. N2O is heavier than air and so will accumulate near the floor and hangs around. The people most at risk are the practitioner and his/her staff because they are exposed more frequently. Dentists who use N20 have higher than average congenital abnormalities in their offspring. Male dentists who used N20 in their offices, have wives who aren’t exposed but their children are still more likely to have birth defects. Female practitioners and staff who are exposed to N2O are more prone to have miscarriages.
The strong analgesic effect of nitrous oxide seems to involve the substantia gelatinosa (spinal cord), causes endorphin release. We know this because we can block this analgesic effect with naloxane, a blocker of the receptors there.
So in summary, nitrous oxide is a nearly ideal due to absence of side effects, but lacks potency and efficacy. It’s a good analgesic, and does not cause muscle relaxation. Its an ideal additive to other agents. It can cause a condition called malignant hyperthermia (MH) a very rare but serious thing to be described at the end of the lecture.
(C3H6): this is a simple hydrocarbon, and not used anymore as an anesthetic because its flammable and explosive. It has a very strong effect at sensitizing the myocardium to catecholamines and causes sympathetic stimulation, this can lead to arrhythmias. If cyclopropane is given with epinephrine, this is a very powerful stimulus for arrhythmias, and in fact is used in lab animals to induce arrhythmias so that people can study how to fix them.
(CHCl3): pretty good anesthetic but not used anymore due to toxicity to the liver/ kidney. Also, chloroform is a carcinogen.
: Used more than 100 years ago as a GA, problem is that its flammable and hard to handle, and produces a pungent odor. Causes profound analgesia at sub anesthetic concentrations; you can go to stage 1 and do minor surgery. Very good muscle relaxant.
Hallmark of ether is that its essentially benign to the cardiovascular system… all GA’s depress the myocardium (negative inotropic effects), but ether maintains cardiac output by causing release of catecholamines to stimulate the heart. Does not produce arrhythmias, so is compatible with epinephrine. Not toxic to liver/ kidney. The problems are that it is irritating to the pt and has difficult and slow induction and emergence properties due to the high Oswald coefficient of 12. Follows Guedel signs perfectly because the Guedel signs were designed to describe ether!
: The first of the more modern agents, it is a halogenated hydrocarbon. (Halogens are Cl, F, Br, I)—all the GA’s from now on will be halogenated. Has 3 F- attached, was synthesized by the Brits in the 1950s. Halothane is still widely used and is a standard for halogen compounds.
-Very potent (MAC=0.75)
-very fat soluble
-strong myocardial depressant, negative inotropic effect; relaxes sm. Muscle, decreased TPR
-depresses sympathetic NS, no catecholamine release
-HALLMARK: causes hypotension
-does NOT follow guedel signs
-must monitor bp for depth of anesthesia
-baroreceptor reflex depression
-overall hypotension, bradycardia, decreased C.O.
-NOT compatible with epinephrine, danger of arrhythmia, sensitizes to catecholamines
-poor analgesic, often used with nitrous oxide
-inadequate muscle relaxant so usually given with a muscle relaxant
-15% metabolized in liver, concern of liver toxicity (“halothane hepatitis”)… this is rare, and often occurs only after repeated exposures to halothane. In any case halothane is contraindicated in pts with liver problems.
-moderately fast acting, Oswald coefficient= 2.3
-cardiovascular depressant, respiratory depressant, can produce malignant hyperthermia (MH)
main use as analgesic during labor and obstetrics
-Oswald Coefficient = 13, slow induction/emergence; not used for induction/emergence but for maintenance
-can cause hypotension similar to halothane
-very fat soluble
-HIGHLY METABOLISED (60%) IN LIVER, F- released from liver metabolism; metabolised in the liver because high Oswald coefficient. Must limit dose and duration. Also toxic to kidney.
-excellent analgesic, similar in effect to ether
-excellent muscle relaxant; best among the halogenated compounds!
- Causes hypotension similar to halothane with low Oswald coefficient (faster acting; less potentMAC =1.7%).
- Similar to halothane in many ways but better in that its: faster, better analgesia, better skeletal muscle relaxation, less tendency for arrhythmias, less toxic (3% metabolized).
- Enflurane is the MOST RESPIRATORY DEPRESSANT AGENT so must have mechanical ventilation while using it—pt cant breathe on his/her own.
- Downside to this one is that it can cause EEG high-voltage discharges and seizures… bad stuff.
-THE MOST WIDELY USED AGENT IN THE USA
-improved version of enflurane
-safer than halothane or enflurane
-hypotension similar to halothane
-less potent than halothane but more than enflurane (MAC = 1.2%)
-elevated HR (tachycardia) and decreased TPR maintain cardiac output
-no arrhythmias or seizures
-little metabolized (0.5%), which is excellent! There’s little danger of toxicity
-pungent, can cause laryngospasm and coughing
-danger of malignant hyperthermia (MH)
-new agent as of 1992, same in structure as isoflurane, except Cl replaced by F; has 6 F-.
-similar clinical signs to isoflurane, but faster and less potent
-LOWEST OSWALD COEFFICIENT (0.42), similar to nitrous oxide (0.47)
-extremely fast induction and emergence, highly controllable
-least potent of halogenated agents (MAC= 6%)
-hypotension similar to halothane
-depresses myocardium
-cardiac output maintained by decreased TPR
-good muscle relaxant
-very pungent, cause upper airway irritation
-difficult induction and emergence, cant use with kids
-LEAST METABOLIZED OF HALOGENATED AGENTS (0.02%)
-not toxic to liver or kidney
-major advantages: speed controllability, rapid recovery
-NEWEST agent (1995)
-similar structure to desfluane, but CF3 attached to central C; has 7 F-s
-low Oswald coefficient= 0.69, similar to desflurane and nitrous oxide
-fast induction and emergence, highly controllable
-NON-PUNGENT, NON-IRRITATING, GOOD INDUCTION; used with kids!
-more potent than desflurane (MAC= 2%)
-cardiac output maintained by decreased TPR
-good muscle relaxer
-less stable than desflurane, maetabolism 100x greater than desflurane (2%)!!! And is less chemically stable!
-one metabolic product is “compound A” which is LETHAL TO RATS AT CLINICALLY USEFUL CONCENTRATIONS!! Toxic to liver and kidneys, and can damage DNA!
-degraded by soda lime (CO2 absorber in breathing circuit)
-main advantages: lack of pungency, speed, controllability
Every now and then (quite rarely), when a pt is given a GA (also has been associated with the use of succinyl choline with the anesthetic) the sarcoplasmic reticulum in the skeletal muscle cells become leaky.
This is a genetic condition. Calcium thus leaks out of the sarcoplasmic reticulum causes massive contraction and the calcium ATPases in the sarcoplasmic reticulum to turn on, full-speed. They do this and generate and enormous amount of heat. So the incidence in the US is 1 in 50,000 adults and 1 in 15,000 kids.
The treatment for MH is to immediately cease whatever operation is being done, MH is an emergency of the first order! Stop administration of anesthetic and hyperventilate the pt with 100% oxygen. Give intravenous dantrolene, which can plug the sarcoplasmic reticulum and reduce the calcium leakage. Then, you’ve got to do everything possible to fight the hyperthermia. Put the pt in ice, inject cold IV saline, lavage all body cavities with ice-water, and pray… often times the pt won’t make it. This can rarely occur with use of nitrous oxide!!! So we must be aware of this possibility.
You should be able to get an idea from the pt’s med history if they or their family is prone to this malignant hyperthermia.
1840s: Patients needing surgery (ie. Amputation of a limb) were given laudanum (opium mixed with wine) which would cause drowsiness, but was not a genuine anesthetic and did little to dull the pain. In operations at this time, speed was key because long surgeries would result in a blood rush to the limb being operated upon, causing shock and a blood deficit to the brain. Prolonged shock would cause death. Thus, without anesthetics, patients could not receive operations involving internal organs or complicated procedures.
Boston dentists, Morton and Wells, experimented with nitrous oxide (discovered by Humphrey Davie), which was discovered to be a laughing gas. Nitrous oxide was the first general anesthetic, and was not predictable because the effective dosage varies from patient to patient, and its effects vary from patient to patient. Wells attempted to spread the use of nitrous oxide as an anesthetic to the medical profession, and so lectured to a skeptical Dr. Warren (a prominent Boston physician) and his students, and was ridiculed. Morton continued to experiment with alternate anesthetics, and in 1846 discovered that purified ether worked as an anesthetic. Ether could also be used as a laughing gas, which would cause the medical community to be skeptical, so Morton decided to add a red dye to his purified ether and re-name it lipion (spelling?). On October 16 1846 at the Massachusetts general hospital, Morton uses his anesthesia to remove a small tumor from the neck of a patient, Gilbert Abbott. It is the most important occasion in the history of anesthesia. The surgeon is the revered Dr. Warren, and so it is Dr. Warren who transmits the discovery through the New England Journal of Surgery to the medical world. It is hailed as successful and widely used in the great medical centers of London, Paris, and Berlin.
James Young Simpson, an obstetrician in Edinburgh, Scotland, used ether to deal with childbirth pain. Ether was used as an analgesic in childbirth, not an anesthetic, to moderate the pain but not stop it. Ether, though, could cause nausea so severe that a patient could suffocate. Gaseous anesthetics are effective by being inhaled, then reaching the bloodstream and the brain. The church and much of the local medical profession opposed ether on the grounds that it was unnatural. Simpson and some of his assistants experimented with different chemicals attempting to find new anesthetics, and almost died from inhalation of “Dutch oil”, a poison.
On November 4, 1847, chloroform was discovered by Dr. Simpson to work as a laughing gas and anesthetic. Chloroform is denser than ether and so easier to transport. The trouble with chloroform was that it, too, was hard to predict with respect to the correct dosage needed per patient. Indeed, for untrained New England country doctor Mr. Micheson (spelling?), chloroform therapy killed a patient when it was used as an anesthetic for the removal of a toenail—although there is still debate as to whether it was the chloroform or the brandy used in attempts to wake her, that suffocated the patient. Horace Wells, the dentist involved with some of the original work with nitrous oxide as an anesthetic, later in life became addicted to chloroform and committed suicide after being incarcerated for throwing acid in the face of a prostitute while high on the drug. Indeed, addiction was not understood by the pioneers of anesthetics, which lead to the abuse of experimental chemicals and drugs by many of the very innovators who brought them into public medicinal usage.
With the advent of many more complicated surgeries brought about by the introduction of anesthesia, infection killed many of those operated upon because not enough was known or believed about microscopic germs.
In the 1880s, it was discovered that cocaine could cause local anesthesia in the eye or tip of the tongue due to the fact that there was no thick external skin to prevent the absorption of the drug into the tissue. It was later found by Dr. William Holstead that when cocaine was injected into tissues it was effective at blocking nerves (when administered within a millimeter or two of the targeted nerve). Holstead then, was a pioneer of regional anesthetic. He also found that injected cocaine could allow him to go for days without sleep, and became addicted… he eventually overcame his cocaine addiction by substituting morphine and went on to become the father of modern surgery due to his ability to proceed slowly—an innovation made available by the use of anesthesia on his patients.
Cyclo-oxygenase-1 (COX-1) isoenzyme: A.is increased by inflammation B. is predominant mode of action of indomethacin best of bad lot C. in increased by lipopolysaccharide ie G –ve endotoxin D. is NOT involved in gastric mucosal protection tis E. is increased by cytokinesClick Here For Answer with Discussion
Cardiac: 1) valvular incompetence / stenosis (obstruction from vegetations) ≫ cardiac failure, 2) myocardial ring abscess, with perforation of IV septum, aortic wall, conduction system, 3) suppurative pericarditis, 4) endocarditis on artificial valves can split open valves ≫ paravalvular leak.
Embolic: 1) brain – cerebral infarct, meningitis, abscess, 2) heart (MI), 3) spleen (abscess), 4) kidneys (abscess)
Immune complex generation: deposits in walls of vessels ≫ inflammatory reaction ≫ Osler’s nodes (painful), skin infarcts, Roth spots: fundal vasculitic lesions, Janeway lesions, splinter haemorrhages. Can also deposit in renal glomeruli (i.e.: these are vessels too) cause basement membrane damage ≫ ↓ GFR ≫ renal failure.
What are main reasons for death in people with infective endocarditis?
Valve dysfunction ≫ heart failure
Infarction of major organs due to emboli
Chronic valvular disease
Chronic renal failure
Infective endocarditis vegetation aneurises and ruptures
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Parathormone
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ADH
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Aldosterone
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Erythropoeitin
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Stimulates the marrow to create new RBC's
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Chronic renal failure can cause anemia
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This causes an anemia of under production
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Renin
Thin (aka - descending tubule, concentrated segment)
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1cm thick
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Bulk of water recovery occurs here
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More hypertonic at the end
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Supersaturation leads to precipitates
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Counter current - bodies way to create hypertonic environment, E- regulation. Large amounts of Na+ in peritubular tissue to bring H2O back into body.
Thick (aka - ascending tubule, diluting segment)
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There is a brush border with in the PCT - this increases the surface area
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Specialized cell - mitochondria - lines the inside tubular wall
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Sodium, potassium, chloride, urea
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Some things can go straight through to the PCT into the urine (alternate pathway)
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Creatine, hydrogen, uric acid can all go from the blood to the PCT (not using the glomerulus)
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Hydrogen can also go through the walls of the DCT into the urine
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Gall bladder
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Kidney - nephprocalcinosis
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Liver
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Renal artery - atherosclerosis
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Hepatic artery - atherosclerosis
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Costochondral calcification - physiologic calcification
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Suprerenal gland - triangle calcification due to hemorrhagic adenopathy
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Duodenum
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Pancreas
Conduction blocks…the only way we can see a block is through an ECG
SA block (sinus block/arrest/SSS) where SA node doesn’t fire
During the time when there is no SA signal is called asystole, after this the AV node will stimulate a beat, this is called a nodal escape beat or junctional escape beat (nodal = junctional)
AV Blocks
Left vagus goes to AV node & Right goes to SA node. Time b/t between P-wave & QRS is the AV delay. When this time is increased, it is due to increased vegal tone. (Dr. Christy thinks this can be due to excessive upper cervical adjusting.)
The purpose of the AV node is to hold the signal for a brief signal (.2 seconds), if it holds is too long there is a block
1° - presence of an excessive AV delay, All P-waves conducted,
lesion is in AV node, think UC problem
By itself is not life threatening, pts don’t know they have it
50% of people w/1° will develop 2°
2° - presence of some non-conducting p-wave
Problem can be in common bundle or in
It’s more serious when with common bundle
This can be fatal, will end up with asystole (p-waves will still be present)
A 1° block is not required to have a 2° (60% of pts with 1° will develop 2° blocks)
2 Types of 2° Blocks
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Mobitz I (Wenckebach), it is predictable, there is a pattern. = lesion is in AV node
The PQ interval (AV delay) is ever increasing, then there will be a non-conducting signal
4:3 block (4 p-waves for every 3 QRS); there must be a minimum of a 3:2 block to tell if it’s a Wenckebach
The common bundle will take over when needed
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Mobitz II (Non-Wenckebach) = lesion is in common bundle
Block site is infranodal,
there is no pattern as to which p-wave will not conduct
PVCs can happen in the middle of these
These are deadly; many believe this is what happens to young athletes who die on the field
If this is detected b/f an outpatient procedure they won’t do the procedure until further tests & care by a cardiologist
If you can’t see if it’s a Mobitz I or II, then assume it is II = non-Wenckebach
We determine if it Mobitz I or II to determine where the lesion is
3° - No P-wave is conducted, total heart block, in this case all signals for beats are from below AV node, but the heart is still beating
AV junction is the same as AV node
Ventricular Asystole
W/ a Type II Block (lesion is in Common Bundle), and it doesn’t let a signal get down, the next place is the bundle branch, but if they are blocked also, the only thing left is a spot in ventricular wall.
Ventricular asystole is not always so sinister. If it develops as a result of vagal storm such as with vomiting, the level of block is in the AV node and the disturbance may be relatively mild and transient (cam also happen with UC adjusting)
3° Block – Complete Block – Total heart block
None of the P-waves never get down to the ventricles; therefore every beat of the heart is an escape beat.
There will be a nice rhythmic p-waves, and a QRS that have a nice rhythm, but the two don’t correlate with each other
There is both atrial & ventricular depolarization, but they are not working together
Bacteraemia/Septacaemia vs Parasitaemia/Fungi/Viraemia
People are more aware of bacteraemia / septicaemia but do not forget parasitaemia/fungi/viraemia can also occur. These occur when parasites, fungi, viruses get into the blood stream. Our focus for this lecture is parasitaemia.
Blood culture vs Blood examination
A blood culture is when you take a sample of blood into a bottle (aerobic / anaerobic environment) and watch for any growth of organisms in a selective growth medium. A blood examination is when you take a sample of blood, put a drop of blood onto a slide and smear it ≫ prepare a slide.
When do take the blood specimens?
For parasites it does matter when the blood specimen is taken. Parasites are only present in blood when patients are febrile. Some parasites only appear at certain times of the day ≫periodicity of organism.
Sending specimens?
When you send the specimen and a blood examination is done, they prepare a thin + thick blood flim.
Examination of the blood film?
A series of options are available:
Blood film stain – giemsa, aendine
Concentration techniques
Inoculate animals – and see the result of this (i.e.: what clinical features animals show, work backwards from this)
Have specific antibodies to specific antigen in dipstick – and see if complex is formed (i.e.: this means antigen you are testing for is +ve)
Serology – look for IgM/IgG discrepancy between acute & convalescent period
Eosinophilia – detects filiariasis
Some times bacteria are diagnosed with blood examination. An example of this is relapsing fever – caused by spirochaetes (i.e.: you get relapsing pyrexic attacks), Borrelia recurrentis. Treatment of relapsing fever: tetracycline.
African Trypanosomiasisi (aka: African sleeping sickness): In West Africa: you get Tryp. Rhodesiense (carried by humans). In East Africa: you get Tryp gambiense. This disease is transmitted by blood sucking tsetse fly. After the bite, the flagellated form spreads to lymph nodes + CNS via blood (takes about 5 days).
Features: hard, red, skin ulcer at site of bite – heals in 2 weeks if not systemic. If systemic spread occurs ≫ lymphadenopathy + fevers. The fevers subside and reappear, this can occur for months. If CNS affected: drowsiness in day time (i.e.: “sleeping sickness”), slurred speech, difficulty walking. In the East African type – this can occur within 1 year. In West African type, it takes aout 3 years.
Dx: blood examination, look for characteristic parasite (trypomastigote – the flagellated form of bug).
Treatment: if CNS not involved use suramin. If CNS is involved use malarsoprol (extremely toxic).
- On an EKG when you see a really weird beat, know that it is not a sinus beat & it should be considered to be a ventricular beat (it has ventricular origin),
- Not all PVCs look alike
- Vent beats cannot be labeled (PQRST)
- When you have 2 different PVC’s they are multifocal PVC, this is very critical
- If you have 2 points of origin for vent contraction & those signals cross, it is considered ventricular fibrillation, which is quickly fatal
- When every third beat is a ventricular beat, it is called Trigemini
- When every other beat is a ventricular beat, it is called Bigemini
- When every 4th beat is a ventricular beat, it is called Quadgemini
- When there are 3 or more ventricular beats it is considered a vent rhythm
- When a heart depolarizes in one direction and repolarizes in another, then ischemia is present.
- When the P-wave is half the height of the QRS complex think atrial hypertrophy – P-Pulmonale
** When the heart depolarizes & repolarizes in different directions, then it is a strong sign of ischemia. (When t-wave is inverted from QRS) **
- ** When there are more than one hot spot on vent wall, it is called multifocal PVCs.
- ** Most common cause for axis deviation if chamber hypertrophy.
- - With enlargement of left atrium, the P-wave will be long & delayed (time for P-wave is increased. This is called P-Mitrale.
- - With enlargement of right atrium, the P-wave is tall & peaked. This is called P-Pulmonale.
- - Sick Sinus Syndrome when there is a delay b/t beats, due to SA node not firing (Stokes-Adams Attacks, is when this happens & pt. looses consciousness
- - Then nodal beats that were fired by AV node are called escape beats, these are still supraventricular ventricular beats
- - If the escape beats are not supravent (and are caused by the vents) it is not good
- - These pts suffer from vagtonia (increased vegal tone); the treatment in this case is a demand pacemaker.
- - This is almost the same as SA Block (a.k.a. Sinus Arrest)
- - These pts are placed on atropine to inhibit vegal stimulation
- - They probably have subluxations of upper cervical spine
Atrial Hypertrophy (enlargement of atrial chamber enlargement)
- Rt. Atrial Hypertrophy
- Due to Tricuspid Stenosis
- Pulmonary hypertension will develop causing the Rt. Vent to enlarge also, causing CHF (congestive heart failure)
- EKG will end up having a tall-peaked p-wave, this reflects an increase in the amplitude on the wall, and this is called P-Pulmonale
- The QRS complex still looks normal
- This is commonly seen in pts with COPD
- The atrial wall is quivering (not pumping any blood with it)
- The EKG will not have a P-wave, and instead there will be a quivery/shaky line
- On the axis: P (ind) – indeterminant
- The AV node will absorb one signal and send it down to the vent, but it can’t pick up one in a rhythmic pattern, therefore these pts will have arrhythmia. There are too many signals for the AV node to have a constant rhythm.
- The mechanism is sympathetico-tonia
- These pts may die b/c clots form in the atria due to pooled blood, most commonly in the retro-pharyngeal pocket in the atrium. When these clots leave the atrium, enter & leave the vent, and end up in the lungs or aorta
- These are found by a retro esophageal ultrasound.
- These is no effective medical treatment, pts are on beta-blockers & Ca channel blocking, warfarin -or- cumarin for clots, Cardio-version is another option for certain pts (pt is sedated & then the heart is shocked to get it back to sinus rhythm). Sex has also been shown to help as a treatment
- These pts generally feel sick, weak, tired, nausea
- These pts need to totally get off of all stimulants (caffeine…)
- These pts have been shown to have upper thoracic involvement; therefore chiropractic, osteopathic, & acupuncture could & should be promoted here
- The sympathetics are not as dense in the atrial wall as in vents
- Parasympathetics dominate in the atria
- If atrial wall is contraction is contracting <200x/min>
- If atrial wall is contraction is contracting >250x/min = fibrillation
- The heart maintains function, but the main fear is blood clot
Found in central Africa, Middle East, India, central Sth America
Transmitted by flies
Clinical features: hepatosplenomegaly + fevers
Dx: blood examination shows ‘cluster material’ within macrophages (i.e.: phagocytosis of protozoa has occurred)
Treatment: pharmacological treatment but have toxic effects
The Correct option is B
Discussion