Thursday, September 23, 2010

4.3 Medications - Everything to Know

Physician's Notebooks 4 - See Homepage

Chapter 3: Medication (Update 18 July 2018)
     Chapter content in order of presentation - use search & find or scroll down to subject.
Medication is used for what?
 Book References & Med Naming
Each medicine has at least 2 names
Toxicity vs. Allergy & Hypersensitivity
Oral Medication - Swallowing vs Mouth Absorption
Interactions with Food or Drink or Other Medications
Other Ways to Take Medicine
Enhancing Med Effect by Right Behavior
Principle of Lowest Dose for Symptom Relief
Taking Medication on a Long-term Daily Basis
My Latest Self-Testing: Phenobarbital 30 mg Pills
Surface Receptor:Tolerance, Resistance, SuperSensitivity
Mood Elevate & Endorphin Effect Drugs
Experiments with Stimulants 
Histamine & Antihistamine H-1 Blocker
The Steroids
Corticosteroids IV & Oral
Corticosteroid Injection for Pain
Aspirin and the Anti-Inflammatory Response
Acetaminophen a.k.a.Tylenol
Tranquilizer, Sedative, Sleep Pill
Anti-Nausea Med
Medicines for GERD, Esophagus, Stomach & Duodenum Pain
Antibiotic Against Infection
Augmentin, Trimethoprim, Clindamycin
Topical Medication for,Scaling,I tching, Callus, Psoriasis
Summing Up - The 7 Principles
End note, Suffixes, Medicine Taste and Storage Life
Hands-on Dosing of the Anti Vitamin-K Anticoagulant, Coumadin, or Warfarin

Medication is used for what? To relieve symptom (acetaminophen, or Tylenol for headache), to normalize body state (anti-hypertensive for high blood pressure), to cure disease (antibiotic against infection) ... . When used to cure disease, it may be to eradicate its cause (penicillin against gonorrhea germ), reverse deficiency sign or symptom (insulin in diabetes), or tilt internal balance in favor of health (adrenal corticosteroid for hyper immune states)
   Depending on purpose, a medication may be used single dose (symptom relief) or repeatedly as a course.

Book References & Med Naming: To survey Pharmacology, I advise Goodman & Gilman's The Pharmacological Basis of Therapeutics (Latest ed). For focusing on particular medication in U.S., use Physician's Desk Reference (PDR, yearly from Medical Economics, Oradell NJ 07649 USA). For finding every medicine by common, brand name and foreign name, Martindale: The Extra Pharmacopoiea (Pharmaceutical Press, 1 Lambeth High St., London SE17JN, UK; tel. + international access code, UK & London codes 735-9141 or fax –7629)

Each medicine has at least 2 names – one or more, commercial or brand name, to advertise product, and, other, generic, to describe its chemical structure or tell something about its workings (eg, Achromycin & Sumycin for the antibiotic tetracycline, Vistaril and Atarax for the anti-histamine hydroxyzine). And then there is single-name medicine actually a drug combination (eg, Septra antibiotic is sulfamethoxazole and trimethoprim in fixed ratio in one pill; Augmentin is 250, 500, 875 mg amoxicillin & 125 mg clavulinic acid).

Toxicity vs. Allergy & Hypersensitivity
Toxicity is a dose-related bad effect. Each individual's response to dose varies. Usual toxicity is the wanted-effect overdone (too sleepy from sleep pill overdose) or normally unnoticed effect that becomes serious with overdose (peptic ulcer from aspirin irritation of stomach). Allergy/hypersensitivity is due to initial, unpredictable bad reaction that a tiny dose of medication may provoke, like a skin rash or internally (low red blood cells as anemia). Allergy occurs suddenly, with patient having previously received the medication without problem. (Patient may not be aware of past exposure) Hypersensitivity is due to abnormal level of enzyme from genetic or medication cause (eg, swelling around mouth from aspirin's effect on the enzyme cyclo-oxygenase). Often it is hard to tell an allergy from a hypersensitivity because both show same symptom (hives & swelling around mouth) not related to dose. If you get toxic reaction to a drug, you took too much and should lower the dose. But allergy or hypersensitivity is a warning to stop taking the drug for life or you may die on second or third time you use it.

Oral Medication – Swallowing vs. Mouth Absorption
Most pills can be absorbed via mouth by chewing-up or holding in mouth under tongue. Limitations on medication that stay in mouth are: imipramine (Tofranil) a popular tricyclic antidepression med is bitter, stinging (for about 5 minutes after) and then numbing (for an hour) on the tongue and palate; it is a quite unpleasant effect. Opioids like pentacozine can be quite bitter. Some medications have an effect that needs passage into stomach or intestines so best not absorbed in mouth (med for GI upset, cholesterol-lowering med and vitamins and iron).
   Held-In-mouth route has rapid effectiveness. With swallowing a pill, the medication effect may be neutralized by food or drink. And a swallowed medication initially is absorbed in stomach or intestine and goes directly to the liver, and that may negate part of its good effect while one absorbed in mouth goes to the jugular and subclavian veins  or mouth artery (and directly to brain) and via veins to heart and its first pass is from left side of heart so it gets more quickly to the organ that needs the effect in high concentration. This also protects the liver from toxic effect.

Powder: Especially in Japan, some medications come in powder form, eg, ascorbic acid (Vit.C) and codeine phosphate. Generally, powders are inconvenient but I found the powdered ascorbic acid is very useful to impart a sour-sweet flavor to drinks and also to be used to help swallow a lot of pills when you don't have water or other fluid drink. Powder codeine is useful to take with the drinks like tea or coffee.

Interactions with Food or Drink or Other Medications
Swallowing medication singly on empty stomach will avoid bad, unpredictable interaction between one oral medication and another, or with food. Large list of drug-drug interactions may be found in the manufacturer’s insert of the Physicians' Desk Reference. Best to consider every other drug as having potentially bad interaction affect.

Other Ways to Take Medicine:
Absorption from suppository in any body opening is unpredictable. Skin patch med is popular for hormone and motion sickness. I do not prefer it because user has poor control of dose or mixing.
Skin ointment rubbed in for local itch or eczema, or ear or eye drop is good way of delivering corticosteroid to local area and avoiding toxicity of taking orally. Do it just after shower to warm and moist skin. Useful for local allergy, itch, chronic skin inflammation and its pain, and to reverse callus especially on sole of feet.

Enhancing Medication Effect by Right Behavior
If you take acetaminophen (Tylenol) to relieve headache in stuffy room, enhance its relief of headache by freshening air. Or if you take cough medicine, don't expect good effect if you insist on continuing to smoke or being around smoker. Or with tranquilizer or sleep medication, don't expect rapid effect if you watch anxiety-provoking TV or read hate mail before sleep. When taking medication to relieve symptom, if possible, lie quietly with minimum of stimulation for 30 minutes after you swallow pill or put under tongue.

Principle of Lowest Dose for Symptom Relief
There is overkill in instruction on how much medication to take for symptom relief. Everyone thinks they have to take 2 Tylenols for headache or fever. One pill, half a pill or even a quartered pill may do as well and less risk to liver. Also when low dose gives relief, you can repeat at shorter, more frequent intervals. For single-dose symptom relief, start with lowest dose (You determine by experiment on yourself) which can be a quartered pill made with cutter. And if possible take it under tongue.

Taking Medication on a Long-term Daily Basis
As mentioned, a medication may be taken on a single-dose only to relieve a symptom, like taking aspirin for headache. Or it may be taken on a daily basis continuously for years to improve/prevent/relieve or cure a disease, like anti-convulsive for epilepsy. A third way of taking medications is as we use antibiotics daily for a limited number of days of an infection. 
Here I want to advise based on my book-learning and my personal experience about taking long-term medication every day. Of course, there are a few of these medications like anti-convulsive for epilepsy where once you start it you should usually never stop it even for a day while you have the epilepsy because it is no fun to get an epileptic fit and also it can be very dangerous. However, most long-term medications can be stopped for a day or 2 or 3 with no problem. Most of us get such a medication get it by prescription. Usually the prescription is for a month or 2 and when we are about to run out of the pills, we try to anticipate that by going to the doctor and getting the new prescription before our pills ran out. There is nothing much wrong by doing it this way and it is common sense but for many of such medications (for hypertension, for cortico-steroids treating auto-immune disease) there is no harm and potentially a little good to allow yourself to first run out of your medication and then because you have no pill the next day become reminded that you have no prescription and go and get one. In this case, you usually end up going a few days without your usual medication. And with the exception of anti-convulsives and medications against high blood sugar if you do it this way you will get the advantage of, at intervals, (Of course always check it with your prescribing physician) tapering off the medication and then building up again in your system. For most such medications this can be good for your system because, 1, it prevents overdoses, and, 2, it keeps your body cells sensitive to the medication you are taking, ie, in the case of hypertensive medication, if you take it continuously for months or years, you gradually become tolerant to its effect. But if you are intermittently allowing it to stop for even a few days you will prevent this tolerance. This is good for pain medications. For example, I take codeine regularly for the enjoyment of its effect and I allow myself to run out of the prescription purposely to prevent the undo tolerance that would occur if I took it continuously for a year.

Especially with a medication you may use for life for single-dose relief of symptom (pain-killer, tranquilizer, sleep pill) I do self testing. For example, with tranquilizer like Valium, which is often advised as 5 mg pill, but is available as 2 or 1 mg, the self-test should answer 4 questions: What is smallest dose that has good effect you seek? How long does it take after swallowing pill or putting it under tongue before it begins? How long does the effect last? Finally, are there any other effects, especially unwanted ones?
   Self-testing requires getting a supply of the medication in low dose pill, using pill cutter, choosing convenient time, and doing single dose test under ideal condition. Start with control test. (Doing it without actually taking the test medicine) Then, first night, start lowest dose and then increase stepwise (eg, with a 2 mg Valium pill, start with control, then ½ a pill, 1, 1½ pills …)
Ideal control condition for self-test is 1) No food or beverage or other medicine for at least 4 hrs previous and 2) An observation period in the 15 minutes before taking medication, and 3) Lay-down-in-dark observation period of the 15 minutes and take the medication. Have timer and tape recorder at hand, and record observation relating to the questions at 15-minute intervals in relation to taking medication (before and after).
   Each person will have different response. So one person may find he needs 5 mg Valium to get effect another gets same at 2 mg.
My Latest Self-Testing: Phenobarbital 30 mgm Pill:  Phenobarbital is an old fashioned, slow-acting barbiturate that was used as a tranquilizer but today its main use is against epileptic seizures. I am interested in it as a suicide drug for self administration in oldsters. (The famous hippie leader Abbie Hoffman committed suicide using 150 phenobarbital pills -- 15 or 30mg?) It is easy to get, has gentle, reversible effect but its pill/kill ratio is very high. I chose the 30 mg pill because it is the highest dose I could get prescribed as a single pill without raising suspicion of suicidal intent. My experiment is very simple: at a convenient time when I plan to relax at least several hours at my company's flat, being sure to have an empty stomach (No food or drink >4 hours) I have been advancing the number of phenobarbital pills I take by one 30 mg pill at a time; so, I started with 1 pill and now I have just reached 12 pills (360mgm; according to authorities, this is considered a very high single dose although nowhere near suicidal dose) at one time. The pills are allowed to dissolve in my mouth (dissolve easily; fairly tasteless) and partially swallowed or absorbed. So far I have noted a mild to moderate analog effect (ie, with increasing pill dose). I have experienced sudden, unpredictable dozing off (these dozing-offs have not lasted to more than an hour and a half and if they happen when you are taking a bath or driving a car or other machine, it could be catastrophic. Also, they can really get in a way of your work.) That started at around 200-mg and has become very obvious at 360-mg. I am stopping the experiment at 360-mg single dose. I am rather surprised to say that the mental effect is very, very mild. I find no problem doing mental work and staying awake when I'm not normally sleepy. This could be a great advantage for an anti epileptic drug. But it's negative for something that's used as a tranquilizer or suicide medication. 
   I do not advise anyone to do this experiment unless they have close medical supervision. 
   But keep in mind that this is an effect on 85-y/o high opioid user and may not be typical for the average younger patient who is not taking other medication.
Surface Receptor: Tolerance, Resistance, SuperSensitivity
A medication's effects come by its interacting with surface receptors located on the outer cell wall. A receptor can be imagined as a keyhole into which a key in the form of a drug molecule fits. The unlocked keyhole pushes a button that starts the drug's effect.
Tolerance is one such effect. Most obvious with sleep pill. First time it works fine, but as you continue every day the effect gets less. Then if you stop taking the pill for several days, the effect strengthens but will weaken if you again use it daily. It is due to a lesser number of surface receptors because of frequent contact with the drug.
   Those who take aspirin for the slightest pain will find they need more and more to relieve less and less. Eventually they will come to say “Aspirin does not work for me.” But someone who rarely takes pill for pain will find single aspirin rapidly relieves migraine.
   An extreme variant of tolerance is resistance. Here, a drug that once worked well stops working. Most frequently seen with antibiotic against bacteria, the resistance is due either to a new strain of the bacteria that lacks surface receptor for the particular drug or to selection of a strain that has an enzyme which blocks the drug effect. In both cases the resistance is due to overly prolonged use of the drug in the individual that develops the resistance. Super sensitivity is the opposite. In one who is super-sensitive to a medication its cell surface receptors are markedly increased, most often because of use of ‘blocker’ to the class of medicine. For example, propranolol (Inderal) blocks (beta blocker) the heart-rate-speeding, bronchial tube-dilating effect of the natural hormone adrenaline. Propranolol taken regularly for more than several days will cause marked increase in beta-type cell-surface receptor in heart and bronchial tube and make the heart and bronchi super-sensitive to normal adrenaline level in blood. If the propranolol is suddenly stopped, the patient who has been taking it will become suddenly super-sensitive to even tiny amount of adrenaline and will experience unpleasant rapid heart rate and palpitation, which may go into life-threatening arrhythmia. Also seen as insomnia after sudden stopping sleep pill or huge appetite after stopping slimming pill.
   The most disturbing side effect of medication is due to cell-surface receptor change. For example, the worst allergic reaction happens because a previously taken medication has stimulated one's immune regulation cells to produce cell-surface receptor that on re-contact with molecules of the medication acts like a Pandora box key, unlocking release of histamine and other chemicals to produce severe allergic and inflammatory reaction.
   The lesson of receptors should reinforce the advice: “Use medication sparingly for good reason, starting in low dose to relieve symptom or cure disease, and limit course of treatment."

Mood Elevate & Endorphin Effect Drugs
Imipramine (Tofranil) was the top selling anti-depression med before Prozac. Tofranil comes as 10 and 25 mg pill and usual dose for depression starts at 75 mg a day. I self-tested swallowing a 25 mg on empty stomach at 4 AM on several tests. Quietly resting in bed without external stimuli, I noted a first pleasure effect at 30 minutes after swallowing the pill. By 2 hours, it built, reaching peak and plateau at 4 hrs, and slowly wearing off by 13 hrs. Also, I noted it was easy to go to sleep in the several hours after. (Keep in mind at that time years ago I had never taken Tofranil before so I was quite sensitive to its effects. Today I'm quite tolerant and they would not be the same) Since then, over years, from a 25 mg Tofranil, I consistently experience a pleasant day.
   For a while, a few years ago I used a 25 mg Tofranil to a max dose of one 25-mg every other day to get the pleasant day. In addition to improved sleep and ease of reposing, the several effects I note are: 1) A mild elevation of my pain threshold which means that my usual aches & pains are more bearable; 2) A numbing effect on mucous membranes which, if the pill is left in my mouth and not swallowed, can be quite unpleasant, but in my trachea & bronchi, esophagus and urinary bladder relieves my irritating nighttime in-bed coughs, my gastro-esophageal reflux discomforts and allows me to be less bothered by feeling of frequent need to urinate that many old men have; and 3) an improved pleasure of sexual orgasms with no affect on my libido (feeling of lust). Older men with prostate enlargement may note that the usual pressure against urinating worsens in the several hours after taking Tofranil. Also be careful of the sleep effect if you drive a car or operate machinery. Finally  my impression is that Tofranil increases inadvertent absent minded.forgetting. Note, I stopped taking Tofranil  a few years ago because I found that the opioids better satisfied my needs for a recreational drug. I noted no withdrawal side effects and easily stopped on a dime so to speak and now do not use it.
   Note: It is important to keep in mind that we all have somewhat different reactions to the same medication based on individual differences in body chemistry. For example, although I personally find Tofranil very useful to make a good day, I recently did an experiment in which myself and another person each took a 25 mg pill at the same moment and noted the effect for the next 24 hrs. The other person quickly noted the, to her, unpleasant effect of drowsiness starting within 30 minutes and plateauing at 3-5 hrs after the medication. The lesson here is that with all medication but especially one that affects the mind, always test the minimal dose on yourself before following a doctor's instruction on taking a medication.
   Also, I have noted what seems to be a tendency to absent-minded losings that coincide with Tofranil days that I suspect may be an effect of causing absent-minded overlooking.

Experiments with Stimulants
Methylphenidate (MP; Ritalin, Methylin) is a stimulant that produces an adrenaline-like effect in brain – alertness and energy. Its most frequent use is in child with Attention Deficit Hyperactivity Disorder, but it is also popular with fashion model to keep slim and for student wishing to do well on test. It comes as 5 mg or 10 mg scored pill easily cut in half. Advised dose is 5 or 10 mg, as much as 3 x a day. I started my experiment with 10 mg at 4 AM in bed. MP has potential elevation of BP and increase in HR, I noted these. It is a worrisome effect.
Dry mouth began at +30 minutes.
First psychic effect +30 minutes was dilation of my time sense. (My time seemed to pass at a slower rate than actual clock time; common effect of psychic drug) Also, I noted a start of euphoria with vocal volubility. (Even alone, I felt like talking; typical side effect of MP)
The MP pill at 10 mg level is a powerful euphoric with mild endorphin (deep pleasure feeling beneath skin) release, and the effect lasted several hours, peaking between 1 and 2 hrs, at which point I was on an outer edge of control (“Flying high!”). Had I been with people, I would have been obnoxious. Playing back the tape of my talk then, I hear myself singing loudly and talking to myself as I thought then in a witty way but listening to it now, it sounds merely stupid. Euphoria started 5 AM, an hour after taking the pill, lasted to late afternoon but by 5:30 PM, I found myself irritable and depressed.
   Ten mg was clearly too much for me.
   So I tried 5 mg. Its effect was smoother. The BP elevation showed +5 systolic and no heart rate increase and I experienced a dry mouth.
   Methylphenidate, at 5 mg, seems useful for making the mind sharp, for avoiding drowsiness, and for keeping high motivation. But I do not think it is worth the risk of hemorrhagic brain stroke from its high blood pressure effect or heart attack from cardiac arrhythmia effect.
Libido and sexual orgasm is not affected by MP.

Cafergot and Caffeine Experiment: Cafergot contains a mix of 100 mg caffeine (caffeine content of 1 cup strong black coffee) and 1 mg ergotamine tartrate (uterine and artery wall muscle constricting agent). It is used against migraine, 1 pill at 30 minutes until relief or max 6 pills. I swallowed 1 pill at 4 AM.
At that dose the Cafergot acted as a powerful endorphin releaser with 1st effect at +18 min, and coming on with electric-shock orgasmic intensity. By +30 min, I felt pleasure, energy & desire to get out of bed and do morning chore. The endorphin feeling pulsated out of chest and down extremities like a good orgasm radiates from groin.
   I noted appetite suppression and no desire for morning coffee.
   I continued energetic, productive all morning with high-touch energy.
   The effect faded by 3 PM (11 hrs for the pill).
   I do not advise cafergot because of its known constrictive effect on the coronary arteries; it risks acute myocardial infarction. Migraine is better treated with acetaminophen and in difficult cases by the specific remedies neurologists advise.

Histamine & Antihistamine H-1 Blocker
Histamine is stored in the skin, around the bronchial tubes, in the GI tract lining, in the basophil white blood cells and is also found in the brain as a neurotransmitter that protects from excess drowsiness.
   Certain drugs (opioid), some injected chemicals (dye used in x-ray), other chemicals produced by body cells in disease (interferon), and antigen-antibody reactions may cause histamine-release into the blood, sometimes suddenly and in massive amount. Then we see typical histamine effect – skin hives (pale plaque with surrounding reddening spot and intense itching); blocked nostril, runny nose, and sinus pain; bronchial tube constriction that causes asthma; and extra stomach acid that could cause peptic ulcer.
   Early-on, it occurred to researchers that a chemical which could block histamine at cell-site of action might be useful in preventing or reversing symptom of histamine release, particularly the stuffy nose of colds & allergies, the wheezing of asthma, the itching and occurrence of hives, and the development of peptic ulcers.
   The first antihistamine (H-1 blocker) mostly showed effect against cold and sinus symptom, and was marketed in the 1940's as cure for the common cold. This turned out exaggeration. It has since become part of Over-the-Counter (OTC) drug mixture against symptoms of the common cold, usually with acetaminophen or aspirin. 
   Effectiveness of antihistamine as remedy to relieve the histamine effect has been poor. The problem is that once the blood cells have released histamine, it is too late to use antihistamine; ideally, it needs to be taken before the symptom, in order to prevent it.
   The antihistamines are actually chemicals that share that effect. Rather than antihistamine symptom, many are primarily tranquilizer (hydroxyzine), some are anti-psychotic (promethazine) and anti-spasmodic (diphenhydramine) and weight-gain appetite (cyproheptadine, or Periactin). All have side effect of drowsiness. Because of this, the passing years saw the development of new generations of H-1 blocker antihistamine under new names.
   The new wave of H-1 blocker has replaced drowsiness with side effects like deadly heart arrhythmia (causing at least one new name to go off market). And the cost is high.
   Taking antihistamine for its named effect wastes time and money.

The Steroids all derive from the chemical steroid nucleus which you may remember from chapter on lipids section on cholesterol.

The steroids we run into here as medications are of 2 types: sex steroids from ovary and testes, and corticosteroids from adrenal cortex glands. Sex steroids affect feminization and masculinization; male sex steroids are used by menopausal women and old men to stimulate sex desire and help erection in the men, and synthetic male sex steroids are used by sports persons to build muscles. I do not approve these uses because of their many serious complications.

Corticosteroids IV & Oral are steroids (a 4-ringed chemical structure seen above in the figure) made in the adrenal glands and also maybe made outside the body. Several chemical types are produced: one type is against the immune system and prevents the inflammation and the pain and swelling from it, and prevents rejection of organ transplant; and the other type conserves sodium ion (Na+) preventing its loss in urine. This explains the overdose effects - body swelling especially the face and loss of immunity with easy infections. It also explains how corticosteroids relieve certain symptoms of illness - stop allergic symptoms, relieve pain and swelling of inflammation and reduce tumor growth. A number of famous diseases - multiple sclerosis, lupus erythematosus and other hyper-immunity type diseases as well as tumors are relieved by corticosteroids and I deal with these under each of the illnesses. Here I want to focus practical self-help use for a layperson.
   First, the most powerful way to give corticosteroids is IV infusion, methylprednisolone 1 gram over 2 hours each day for 3 to 5 days. This treatment once a month is being used to prevent the advance of multiple sclerosis. I experienced it to prevent rejection of a corneal transplantation. Two important side effects were a temporary diabetic state (blood glucose up to 250 mg% just after the infusion) and a mild hallucinatory state (Looking up at the ceiling I saw pink elephants and other bizarre shapes). These effects did not bother me because I expected them due to my medical knowledge and they were temporary. (But could be serious for an actual diabetic or for a mentally unstable person)
   Then, corticosteroids are taken as pills (usually prednisone). The problem with the oral treatment relates to its duration. Up to a month, the high glucose and sometimes mental effects are tolerable but for a longer time they can become terrible. Also the corticosteroids worsen osteoporosis and can end in bone fractures and vertebral bone collapse. Again the key is foreknowledge. Oral corticosteroids are usually given for a disease like lupus erythematosus during bad periods when the disease acts up and they should be tapered off (slowly stopped) after a month or two.
   A third way to use corticosteroids is as an ointment (Creams are not as good). Here I have much experience and find great use. 1) In all itchy skin allergies or hypersensitivities including poison ivy, I use beta methasone 0.12%. Best to rub it into moist, warm skin, like after a shower or bath, and one time usually immediately relieves the red itchy skin rashes that are not due to infections.
   Also it has been good for my severe foot callus (Because it is anti-proliferative for cells) applied to the sole of the feet for 1 hour under the Saran wrap once a day for 7 days and the good effect has been permanent (It cured the condition)
   Corticosteroid Injection for Pain  Finally, corticosteroids are used as injections into joints and back against pain. Usually this is a last resort treatment when nothing has worked and surgery is not an option. Corticosteroid injections for pain rarely work well. One injection may seem to give temporary relief but mostly this is placebo effect. More importantly, they may cause complications of the pain (eg, recent epidemic of fungal meningitis for corticosteroid injections in back for lumbosacral pains).

Aspirin and the Anti-Inflammatory Response
Aspirin at low dose (30 mg) reduces blood platelet aggregation and slows blood clotting. At high standard headache dose (325 mg) it also reduces fever and is good against inflammation, and muscle & bone pains. Fever is body temperature above 37 degrees C (99 degrees F) caused by infectious or inflammatory disease (to separate it from elevated temperature of brain or heat stroke, which should not be treated with aspirin because of the risk of Reye('s) syndrome ).
   Concerning Aspirin's Side Effects - Arachidonic Acid (ArA) the source of Prostaglandins: The ArA is released from cells in response to trauma and irritation and chemicals. The cyclo-oxygenase enzymes act on ArA and convert it to Prostaglandins. There are two cyclo-oxygenases, COX-1 and COX-2. Both function chemically in the same way (They speed reactions that convert ArA to Prostaglandin G) but COX-1 is produced constantly at low level in all cells without stimulus while COX-2 only gets produced and released in cells subjected to trauma and chemical stimulants. Stomach and blood platelets do not produce COX-2; they depend upon COX-1 only. COX-2's main effect is to stimulate inflammation. The COX enzymes are the key to Prostaglandin (PG) production. Anything that inhibits their action will dam up and stop the downstream chemical reactions of Prostaglandin and therefore increase levels of prostaglandin and so prevent or treat inflammation, fever, headache. Aspirin even in small dose blocks COX-1 and COX-2, and this explains aspirin's good effect against inflammation (by blocking COX-2) as well as its bad effect (by blocking COX-1) causing peptic ulcer of stomach and duodenum, and preventing blood clotting to the extent of causing too much bleeding.
Non Steroid Anti Inflammatory Drugs (NSAIDs; Advil et al) are, strictly, any anti-inflammatory without corticosteroid, but usage seems to have dictated that aspirin and Tylenol, or acetaminophen, are in a class by themselves) Aspirin and the other NSAIDs except Tylenol also block COX 1 and COX 2, which also relieves the pain of inflammation and also lowers fever. But aspirin alone affects blood clotting by being anti-platelet. That explains Aspirin's popularity. In my opinion, the NSAIDs other than Tylenol are a waste of money because they are not superior to Tylenol and have their own bad side effects.

 Aspirin & Salicylate
Aspirin's good effect against head, muscle and joint ache, against fever, against inflammation and protection against blood clot in artery and vein depends on its two structural elements: salicylate and its bonded acetyl radical (–OCOCH3).
    The acetyl radical –OCOCH3 is connected to the salicylate in Aspirin. It makes “acetyl salicylic acid,” or ASA. Chemists among you will recognize Acetic Acid in the acetyl, and gourmets will recognize vinegar, in its 5% solution. Aspirin can be synthesized stewing Willow bark or Meadowsweet with vinegar.
The salicylate part of aspirin (and other salicylate drugs like Pepto Bismol, Doan’s Little Pills, Oil of Wintergreen massage lotion) accounts for some of its anti-inflammation and much of its anti-pain and anti-fever effect, but non-aspirin salicylates are weak COX-1 blockers and so have almost no effect on blood clotting. Of the salicylates, only Aspirin blocks platelet aggregation, decreasing blood clot risk in heart and other organs but increasing bleeding risk in susceptible person with peptic ulcer, diverticulosis and aging brain blood vessels. This effect of aspirin has been shown to be due to the acetyl end of its molecule inserting itself into a cleft in the COX-1 molecule and literally “gumming up its works”, preventing its catalytic action that produces thromboxane in blood platelets, which is the cause of the platelet aggregation on rough spot in artery and vein. Aspirin is uniquely different from all NSAIDs in this effect on COX-1 because it is a permanent effect (ie, once acetyl has gummed up the enzyme, it can't be reversed so the particular enzyme molecule is ruined throughout the c.10-day lifetime of its platelet). The other NSAIDs inhibit COX-1 production by a different molecular mechanism that is reversible. Thus, in contrast to aspirin, the effect of NSAIDs on platelets is transient while aspirin's effect on blood clotting from single small dose lasts the 10 or so days that it takes new platelets to replace old and therefore aspirin can be taken every other or every third day and still maintain protective effect against heart attack, stroke and blood clot to lung.
  Here are points about aspirin dosage against heart disease and stroke and emboli. Dose as low as averaging 30 mg a day can inhibit platelet aggregation and may be protective. With such low dose, side effects should be virtually nil. (Warning: many clinicians still prefer minimum dose of 81 mg a day but no strong evidence is against 30 mg a day dose) With doses less than 160 mg a day, it takes several days for aspirin’s full effect on blood platelets but that can be obviated by making your first dose 160 mg and then reducing to average 30 mg a day. For good anti pain effects, however, single doses up to 500mg maybe tried.
Reye('s) Syndrome of deadly liver toxicity occurs in child and adolescent given aspirin as treatment for fever and ache from influenza and other virus illness. Do not give aspirin to child!

Acetaminophen a.k.a. Tylenol
also Paracetamol in UK & Commonwealth and by shortening of N-acetyl-p-aminophenol, APAP or apap. It has replaced aspirin as the non prescription drug against fever and ache because no effect on blood platelet or peptic ulcer.
   Single dose of APAP for ache or fever is 325 mg. The 24-hr dose should not exceed 1000 mg for fear of toxic hepatitis. Pills come as 325 mg standard, and 500 mg extra-strength. You save money buying generic name (The bottle printing may be “Non-Aspirin Tablet", or "Non-Aspirin Bufferin”) rather than brand name; both equally effective. The pill is scored (crevice down center) easily halved or quartered with a cutter. The APAP works well against moderate inflammation based on my self use.
   Toxicity of APAP is dose dependent. When APAP is good it is very good; but above threshold it can be horrid. Damage is to the liver and, to lesser extent, kidney. Toxin is produced from APAP by enzyme present in liver or kidney. At safe dose of APAP, its toxic product is neutralized by antioxidants. But these are present in limited amount (By taking 2 grams vitamin C as antioxidant, you may protect self against the liver toxicity) and, once used up, the toxic product starts damaging liver cells. Toxicity is worsened by ethyl alcohol. Thus, heavy drinker may get toxic effect from normally safe dose of APAP. My advice is: first try half of 325 mg pill and limit max 24-hr dose to 500 mg. APAP is part of popular narcotic opioid Rx combination like Vicodin, which has 333 mg APAP per pill or 10 cc elixir. This promotes un-noticed use of APAP that in long term could destroy your liver.

First of all, what is and what is not NSAIDs? From nonsteroid anti-inflammatory drugs, you would expect every drug that relieves inflammation except corticosteroid should be NSAIDs. But I do not call aspirin by itself, and acetaminophen (apap, Tylenol, Paracetamol) an NSAID.
   The NSAIDs are salicylates without the acetyl or, if not salicylates, close chemical cousins.

   The NSAID Loxonin a.k.a. Loxoprofen is a newly released NSAID I have personal experience with and find to be superior to other NSAIDs in its ability to relieve pain especially menstrual pain. Two warnings: Do not take at the same time as the antibiotic ciprofloxacin because of the tendency for seizures with that combination. Do not take with warfarin (coumadin) because it interferes with anti blood clotting effect. Loxonin is available by prescription in Japan but may not yet be available in US.

Tranquilizer, Sedative, Sleep Pill
Tranquilizer is exampled by the diazepam (Valium) family. I self-experimented and find the 2 mg dose gives little if no affect for me! At higher dose - 5 to 10 mg - it increases potential for accident or absentminded losses of valuable possession, for inattentiveness or drowsiness, and also makes forgetfulness. 
   The ideal tranquilizer should eliminate anxiety without causing daytime sleepiness, forgetfulness, inattentiveness, and without making dis-inhibiting aggressiveness; and without hangover irritability. Since much anxiety is connected to depression about deteriorating health, poor brain function (Worry about going crazy, Alzheimer's, brain tumor), and paranoid angst (Will you be harmed by people who hate you?), I want mood elevation in my ideal tranquilizer. Try 25 mg imipramine (Tofranil taken on empty stomach); or, if you can't get that, take acetaminophen, do a 30-minute repose in chair and then drink cup of black caffeine coffee savoring it in mouth. It will give alert, tranquility.

Sleep pill ideally ought to make sleep by 15 to 30 min after swallowed, give pleasant sleep of 4 to 8 hrs and allow for alert awakening bright-eyed without being forgetful, inattentive or irritable, and ready to enjoy the day. Flurazepam (Dalma-te, -ne) 10 mg fills that slot based on my self-experiment. But I rarely if ever use sleeping pill. Recently, I needed to be hospitalized flat on my back for several weeks and I found the nighttime extremely boring because I'm not in a habit of sleeping for long periods. Solanax (aka Alprazolam) 0.4mg taken around midnight has given me a dreamless, pleasant, up to 5-hour-or-so sleep (with brief awakenings to pee) with no bad after effects. I recommend it for similar situations. 

Anti-Nausea Medicine
Nausea and vomiting can be useful for getting rid of rotten food or poison, or with acute surgical abdomen where eating is a no-no. So your first thought after noting nausea is to check out possibilities. If rotten food, you’ll belch bad stuff and need to vomit. If poison and you just swallowed some, you want to vomit it out. If infectious food-born gastroenteritis, it starts very severe followed by diarrhea but is better within 24 hours. If acute surgical condition, you want to be in hospital.
   Nausea could be first sign you - a woman - are pregnant. If you are going to keep it, no medicine is best, because drug may harm fetus.
   The time for anti-nausea medicine is: withdrawing from addiction, or with psychological nausea, or after vomiting has emptied stomach as shown by bile-stained vomit. Metoclopramide (Primperan, Reglan) contains 3.84 mg active drug. Self-experiment shows dissolving it under tongue or chewing and holding in mouth for absorption relieves nausea in 15 min and also headache that often accompanies it in migraine. It has pleasant mild endorphin & drowsy effect making it good sleep pill for those with nausea.

Medicines for GERD, Esophagus, Stomach & Duodenum Pain
Low esophagus pain from stomach reflux due to faulty sphincter (“Gastro-Esophageal Reflux Disease” or GERD) is in midline over lower edge of breastbone and extends up into chest. Low esophagus and upper stomach pain is worse in the hour or two after a heavy or poorly digested meal and brought on worst by dozing in chair. Stomach pain extends into right upper abdomen. Duodenum pain is in upper abdomen on right but may extend down to navel.
   Stomach or duodenal peptic ulcer or irritation pain is gnawing and comes on or worsens as stomach empties (4 hrs after eats), and may be quickly relieved by food or antacid.
   Pepto-Bismol is for upper abdominal GI pain from Reflux or peptic ulcer. It combines antibacterial, antacid, analgesic and anti-inflammation effect and works well. The bismuth subsalicylate in Pepto Bismol does not irritate stomach and does not cause bleeding as aspirin does; it also helps non-GI complaint like headache with stomach upset. But just standing up and drinking a glass of cold water is the best remedy for GERD.

Histamine-2 receptor (H2)-blockers (Zantac, Tagamet) stop acid production by stomach and are treatment of peptic ulcer and gastritis, and are now over the counter (OTC). Of the two, Zantac has lesser side effect while Tagamet could adversely affect sex in old men. 
   A class of acid production blocker called proton-pump inhibitor (PPI; Omeprazol, Omepral) has improved on Zantac. It too is OTC. Neither the H2 blocker or the proton-pump inhibitor will relieve acute pain of G-E Reflux or Peptic Ulcer. Instead it prevents or may shorten it. But use PPI only for short course because its long term use can badly affect many other acid-base reactions in the body.
Warning: An analysis of data on German patients, published recently by the American journal JAMA Neurology, found that the patients who regularly use PPIs were 44 percent more likely to develop dementia in older age compared with patients who were not receiving those medications.
   Low abdominal pain (navel or below) is best diagnosed before treating to be sure it is not surgical. Non-surgical pains are relieved within hour by a bowel movement.

Antibiotic Against Infection
Antibiotics kill or inhibit germs. Most are anti-bacterial but, recently, antivirals like acyclovir (Zovirax) and antifungals like Terbinafine (Lamisil) are being used.
   My Principle of antibiotic use: “Hit ‘em hard and heavy, and finish ‘em off quickly.” It means start antibiotic at highest safe dose to kill all infectious germs quickly! Worst way to use antibiotic is to give low dose for prolonged period. It is a recipe for germ resistance or allergy.
   The following are ones I have found very useful:
Augmentin is combination of Amoxicillin in various doses (250, 500, 750 & 875 mg) with Clavulinic Acid 125 mg. The combination allows the wide spectrum anti-bacteria effect of Amoxicillin, and the Clavulinic Acid prevents rapid bacteria resistance to Amoxicillin and adds a new antibacterial effect. It is the best combination and can be safely used in max dose as Augmentin 875 for 3-day course. (For me, I take every 8 hours on empty stomach with big glass water for 10 doses. If relief of all symptoms, then I stop; if partial relief, then I continue for 2 or 3 more days but not more than 1 week.  If no relief after 3 days, I stop and test for different diagnosis)

Clindamycin is an all-purpose, very powerful antibiotic as 150 mgm capsules and I do 72-hr course of starter dose 600 mg then 450 mgm (3 caps) every 6 to 8 hrs on empty stomach with glass of cold water. It is ideal for bacterial infection in mouth and skin. I had good result in treatment of infection of abscess tooth before I could get to a dentist. Also doing courses of it at several months in a year is a good way to rid your body of bacteria (I do it 3 times a year to clear my body of them) and it is very good to prevent killer infections like bacterial endocarditis in at-risk persons with heart valve abnormalities or with immune function disease. Also against bacterial bioterrorism like anthrax or plague. In all uses, limit to max 3 days course because longer use risks deadly super infection with deadly diarrhea bacteria.
Ciprofloxacin is a good, recently developed antibiotic that has the advantage of a single 500 mg dose a day (First day double dose) for 5-day course and will get rid if most bacterial upper respiratory infections (If you note yellow sputum or nose or eye discharge, you most probably got bacteria infection). It is also good against bioterrorism bacteria. Precaution is not to mix it with Loxonin (loxoprofen) NSAID because it could cause a seizure and not to mix with Warfarin (Coumadin) that is given to lower blood clotting because it interferes with the anti blood clotting effect.
Topical Antibiotic: Genta(mi)cin ointment 0.1% is good addition to cleaning of cuts or infected skin and alcohol or iodine tincture and then band aid. Note, it is often a combination with beta metasone corticosteroid ointment.

Topical Medication for Scaling, Itching, Callus, Psoriasis
Inflammation on skin which expresses as itching, redness, and local swelling sometime as rash; or from insect bite or fungus infection of athlete's foot, contact dermatitis or allergy. For itching from these conditions, adrenal corticosteroid ointments (fluocinolone acetonide 0.025%, Synalar in U.S., Flucort in Japan; alternatively 0.12% beta methasone) is virtually a miracle drug. It stops almost any itchy inflammation (including inside nostril) within minutes and rarely requires more than 1 application. Corticosteroid ointment is also good for painful callus on heels and soles and all hyperkeratosis like psoriasis. Applied with Gentamicin (In Japan, combination as Linderon VG ointment) under Saran Wrap for 1 hour for 7 days, it will give remission.

Severe athlete’s feet is best treated with Lamisil (terbinafine) an antifungal that works well by mouth; 250 mg a day for 30 days. it needs M.D. Rx.  I have done several courses on myself with no side effects. But before starting get a dermatologist to confirm the fungal presence by skin or callus scraping and special microscopic stain diagnosis.

Eye drops are excellent for local diseases of eyes. For inflammation, beta methasone and for antibiotic, as mentioned, a floxacin. One drop each, 3 times a day the usual.

Summing Up - the 7 Principles

Enhance Medication Effect: If you swallow the medication, do it on empty stomach (4 hrs after last food or drink and 1 hr before next, if possible) with big glass water. With skin topical, apply to recently cleaned, warm, moist skin.

Minimal Dose: Start with lowest possible and observe for effect after 30 minutes.

Single-Dose: For relief of symptom; as much as possible, rely on one dose held in mouth or chewed or else swallowed on empty stomach. Self-Experiment to Find Ideal Single Dose: Check effect of single-dose med you will regularly use to relieve symptom by observing, under standardized, controlled condition, the effect of single dose, progressively increased until ideal effect.

Tolerance: Remember that the more frequently you take a medication, the less effective it will be and the greater risk of allergy. Therefore, use it for good indication, for well defined effect in effective dose, and with lowest frequency that gets desired effect.

Limiting Medication to Well-Learned One: For each type effect (anti-pain, anti-itch, etc.), learn about a good one and use it well.

 Your learning should be a gradual, life-long process not limited to this or any single book. Also make use of self-experiment and observation of use of the drug. Keep actively learning and this chapter will become more practically useful to you.

Keep a Critical, Analytic Attitude Toward Data: Never believe absolutely. All data should be considered provisional. Do not be swayed by one observation. With positive good effect (eg, you cannot sleep because of common cold symptoms, and you take one Tylenol and immediately fall asleep), consider it may be chance and say “Well, all I can say is that one Tylenol did not prevent the good effect."

End note, Suffixes, Tastes of Med and Storage Life
Pay attention to suffixes of medicine names. In the heart-cardiovascular set you have -ol or -al for the beta blockers, -(p)ril for the ACE Inhibitors, -artan for the ACE blockers, -ide for the Na salt-losing diuretics, -xin for the digitalis heart strengtheners, and one can go on and on. Keep your ears open among the medicines.
  Medicine taste and consistency can be useful: most opioids are bitter on the tongue, Tofranil is unpleasantly numbing to mouth and tongue, aspirin is mildly acid sour; Valium (diazepam) is tasteless and falls apart to powder, beta blocker and Vit. B12 slightly sweet; omeprazol the protein pump inhibitor is brick-like and no taste. Find out taste of your medications. It can be useful when you visually mistake one pill for another and put it in mouth by mistake or when someone is trying to feed you medicine against your knowledge.
  Storage Life of Medications: Today most medications come as plastic bubble-top sheets of 10 or 21; some still come bare in a bottle. All should have an expiration date on sheet or bottle. My experience with sheet medicine comes from Tofranil. This mood elevator has a striking effect one cannot miss. I am still using Tofranil from sheets I bought more than 15 years ago and the medication still works well. From that I generalize that plastic bubble-top sheet medicine has a human lifetime storage life.
Hands-on Dosing of the Anti Vitamin-K Anticoagulant:  Recently I had the chance to self experiment with what is the quickest, best loading dose for the popular anticoagulant Coumadin, a.k.a. Warfarin. Its most popular pill is 1 mgm and the measure of proper dosing is to get a blood INR test of 2. The quickest way to do it, I found, is to take five 1 mgm Coumadin pills at once under tongue (may be chewed) and then continue on a daily dose 1 mgm three times a day equally divided dose (every 8 hours). This will achieve an effective INR within the first 24 hours and then you may adjust the dose as you please. Also it is important when you take Coumadin to be aware of tendency to easy bleeding so do not blow your nose hard or cough hard, and try as much as possible to avoid the small hard traumas - like straining too hard at stool, or banging head by accident (use long front visor cap).

                     END OF CHAPTER. To read on next, now, click 4.(4-5) Pain? Opium Drugs?


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