1. Evaluation of the effect of placebo
Dr. Raz Mohammed
Lab. 6

2. Definition
Placebo is defined as a substance that has no known specific pharmacological activity against the condition being treated. Placebos can be therapeutically beneficial to some patients when they give rise to the placebo effect.

3. Placebo medication is a dosage form of material which is similar in appearance to an actual medication but contains only substances without pharmacological activity.
Placebo Effects:
A remarkable phenomenon in which a placebo, an inactive substance like sugar, distilled water, or saline solution, can sometimes improve a patient's condition because the person has the expectations, belief, or hope that it will be helpful.

4. Factors that influence the response to placebos:
Type of the patient
The doctor’s attitude
Doctor-patient relationship
Type and even the color of the drug preparation

5. Symptoms and conditions that respond to placebo
Occasionally placebos are given to patients who are continuously complaining of some symptoms who are thought to be exaggerating and pain is usually involved.
Pain (severe pain)
Depression and anxiety
Gastric and duodenal ulcers
Chronic fatigue syndrome

6. Pain
The placebo administration may prove to be a useful treatment in some specific cases where recommended drugs cannot be used. For example, burn patients who are experiencing respiratory problems cannot often be prescribed opioid (morphine), as it can cause further respiratory depression. In such cases placebo injections (normal saline) are useful in providing real pain relief to burn patients if those are conscious, are told they are being given a powerful dose of painkiller.

7. Mechanism of action of Placebo
The mechanism in which placebos produce symptomatic relief is not known.
Research on the placebo effect has focused on the relationship of mind and body.
One of the most common theories is that the placebo effect is due to a person's expectations. If a person expects a pill to do something, then it's possible that the body's own chemistry can cause effects similar to what a medication might have caused.
But some researchers believe that when a placebo is given to a patient, the brain releases endorphins, which are natural pain killers the brain produces.

8. Placebos are also used in clinical trials (research).
For determination of placebo effect, there are two ways:
Single blind trials; only the researcher knows which medication the patient receives.
Double-blind trials; neither the researcher nor the patient knows which medication the patient receives.
The purpose of such a design is to eliminate or minimize the bias (unfair judgment) of the observer in evaluation of the responses of the patient.

9. Procedure
The students should be divided into three groups. A volunteer in each group takes one of the following:
Cyproheptadine
placebo

10. Cyproheptadine Side effects:
Is a first-generation antihistamine used to treat allergic reactions, stimulate the appetite and may lead to weight gain, which is helpful for underweight people. Also used to treat sneezing, itching, watery eyes, runny nose, and other symptoms of allergies.
Side effects:
Dizziness
Blurred vision
Constipation
Dry mouth, throat, or nose
Nausea
Nervousness
Restlessness

11. Cyproheptadine
Onset: min
Peak: 1-2 hr
Duration: 8 hr

12. Then the observer should fill the following sheet:
The observer score sheet:
Time………………………………..
Date:………………………………..
Observer:…………………………...
Environment:
………………hours since medication.
……………… time of the last meal.

13. Condition of the student at the start of interview.
A. …….awake B. ……drowsy
A. …….Normal appetite B. .….Increased appetite
A. ……… standing B………... sitting
A. ……….restless B…………lethargic
……….. Normal oral mucosa B……… Dry mouth
A…………Normal vision B………. Blurred vision

14. Response to the initial greeting by observer (e. g
Response to the initial greeting by observer (e.g. response to good morning or other greeting)
A. ………….answers greeting
B………….. ignores greeting
A. ………….. looks at observer
B. ……….. ignores observer
Response of patient to the question “ how do you feel?”
A. ………….smiles B. …………. frowns
A. …………Answers B. …………. Doesn’t answer

15. Collection of data
Refer to sample sheets for method of scoring. Observer scoring sheet:
A score of 10 is assigned to the scoring sheet at the start and indicates no changes. Add 1 point to those for each A box checked and subtract 1 point for each B box checked.
The maximum score is therefore 20 and the minimum is zero.
Compare drug scores with placebo scores. Placebo increases scores and cyproheptadine decreases scores.

16. Local anesthetics Dr. Raz Mohammed Lab 9

17. Local anesthetics Definition
A local anaesthetic can be defined as a drug which reversibly prevents transmission of the nerve impulse in the region to which it is applied, without affecting consciousness.

18. Structural classification of local anaesthetics
Local anaesthetics generally have a lipid-soluble lipophilic aromatic group and a charged, hydrophilic amide group.
The bond between these two groups determines the class of the drug,
and may be amide or
ester.

19. Types of local anesthetics
Ester
Procaine………short duration of action
Cocaine……….medium duration of action
Tetracaine……..long duration of action
Benzocaine……topical use only

20. Amides
Lidocaine………medium duration of action
Prilocaine………medium duration of action
Bupivacaine……long duration of action
Etidocaine………long duration of action

21. Clinically significant differences between esters and amides
The ester linkage is more easily broken than the amide bond so the ester drugs are less stable in solution and cannot be stored for as long as amides.
Amide anaesthetics are also heat-stable and can therefore be autoclaved; esters cannot.
The metabolism of most esters results in the production of para-aminobenzoate (PABA) which is associated with allergic reaction. Amides, in contrast, very rarely cause allergic phenomena.
For these reasons amides are now more commonly used than esters.

22. Mechanism of action of LA
Local anaesthetics reversibly block impulse conduction along nerve axons from the periphery to the CNS.
This occurs through specific binding of the local anaesthetic molecules (in their ionised form) to sodium channels by blockade of voltage-gated sodium channels and reduce the influx of sodium ions, so preventing depolarization of the membrane and blocking conduction of the action potential.
This effect is mediated from within the cell; therefore the local anaesthetic must be unionized to cross the cell membrane before it can exert its effect.

23. Mechanism of action of LA
The small, myelinated nerve fibers that conduct impulses for pain, temperature, and autonomic activity are most sensitive to actions of local anesthetics.

25. Clinical use Topical local anesthesia is used for eye, ear, dental,
throat, for cosmetic surgery and injection into the epidural
or subarachnoid spaces surrounding the spinal cord.
L.A requires an agent of rapid penetration of the skin or
mucosa and limited tendency to diffuse away from the site
of application.

26. Benzocaine:
It can be applied directly to wounds and ulcerated surfaces,
It is especially useful for anesthesia of large surface
areas within the oral cavity.
because of its poor solubility in aqueous fluid, tends to
remain localized at the site of application for a long time
and produces a sustained local anesthetic effect and is
not readily absorbed into the systemic circulation.
It is available in form of aerosol spray, gel, ointment,
cream& paste

27. Pharmacokinetics of LA
Absorption and distribution
LA drugs are administered to the areas around the nerves to be blocked – which include skin, subcutaneous tissues, intrathecal and epidural spaces.
Some of the drug will be absorbed into the systemic circulation: how much will depend on the vascularity of the area to which the drug has been applied and intrinsic effects of the drug or its additives on vessel diameter.

28. By adding the vasoconstrictor epinephrine to the local anesthetic, the rate of anesthetic absorption is decreased. This both minimizes systemic toxicity and increases the duration of action.
The distribution of the drug is influenced by the degree of tissue and plasma protein binding of the drug. The more protein bound the agent, the longer the duration of action as free drug is more slowly made available for metabolism.

30. Metabolism and excretion
Ester and amide anaesthetics differ in their metabolism. Esters (except cocaine) are broken down rapidly by plasma esterases to inactive compounds and consequently have a short half life. Cocaine is hydrolysed in the liver. Ester metabolite excretion is from the kidney.
Amides are metabolised hepatically by amidases. This is a slower process, so their half-life is longer and they can accumulate if given in repeated doses or by infusion.

31. Why inflammation reduces the action of local anesthetics?
This is partly because most of the anesthetic is ionized & therefore unable to cross the cell membrane to reach its cytoplasmic- site of action on the sodium channel. As the pH is reduced the fraction of unionised local anaesthetic is reduced and consequently the effect is delayed and reduced.
The pH of infected tissue differs from the physiological pH it may be as low as 6.4 in infected tissue.
2. Increase blood flow in inflamed tissues may speed the removal of local anesthesia from injection site.
3. Inflammatory exudates may also inhibit local anesthesia directly by enhancing nerve conduction.