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INSULIN | High Alert Medicines | What Pharmacists should know?

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Digoxin structure | Pharmacokinetics | Pharmacodynamic | Indications| Contraindications | Adverse drug reactions | Clinical implications.

                                        DIGOXIN
INTRODUCTION
Digoxin is obtained mainly from Digitalis lanata; it consists of sugars and the aglycone digoxigenin. Digoxin has positive inotropic and negative chronotropic activity. It is used for atrial fibrillation and congestive heart failure. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small.
 Digitalis is an example of a cardio-active , in other words a steroid which has the ability to exert a specific and powerful action on the cardiac muscle in animals, and has been used in the treatment of heart problems ever since its discovery in 1775.
Digoxin is the primary cardiac glycoside in clinical use. Digoxin is used for the treatment of congestive heart failure (CHF) because of its inotropic effects on the myocardium and for the treatment of atrial fibrillation because of its chronotropic effects on the electrophysiological system of the heart. The role of digoxin in the treatment of each of these disease states has changed in recent years as a better understanding of the pathophysiology of these conditions has been gained and new drug therapies have been developed. The treatment of chronic CHF, angiotensin I converting enzyme inhibitors (ACE inhibitors) and diuretics are the primary pharmacotherapeutic agents with angiotensin II receptor antagonists, spironolactone, and β-blockers playing key roles.For the treatment of acute or severe heart failure, agents that decrease cardiac preload (diuretics, nitrates) or afterload (vasodilators) and ACE inhibitors (decreases both preload and afterload) are used in conjunction with potent intravenously administered inotropic agents (dobutamine, dopamine, adrenergic agonists) to balance the current cardiovascular status of the patient.
 In either the acute or severe heart failure situations, digoxin can be used when a mild inotropic or oral agent is needed.
STRUTURE

PLASMA CONCENTRATION-RESPONSE RELATIONSHIP
<0.5mcg/L:-   no clinical effect
0.7 mcg/L:-  some positive inotropic
0.8-2 mcg/L:-  optimum therapeutic range
2-2.5 mcg/L:-  increased risk of toxicity
>2.5  mcg/L:-  GI,CVS and CNS toxicity
PHARMACOKINATICS
ABSORPTION
Digoxin is well absorbed in the gastrointestinal intestinal tract, and there is no massive hepatic first pass effect. Digoxin's oral bioavailability (70%-80%), even though considerable  metabolism of digoxin in GI by hydrolysis in the acidic environment of the stomach or by digestion by intestinal bacteria. Therefore, when give with antibiotics it increase their bioavailability.
DISTRIBUTION
Digoxin has a large volume of distribution, due to its affinity toward skeletal and cardiac muscles, intestines and kidney. Digoxin has a distinct distribution time 6-8 hrs and thus its disposition is best described by a two-compartment model. Adipose tissue is not a reservoir for digoxin; therefore, dosing should be based on the estimated lean body mass. Binding to plasma proteins, mostly albumin, averages 20-30%. Digoxin incompletely distributes across the placental membrane .
METABOLISM
A small amount of digoxin is metabolized by the liver and approximately 8% undergo an enterohepatic cycle. The eliminationhalf-life of digoxin is long. Therefore, in the absence of a  loading dose, the time required to reach steady state, after the initiation of a repeated administration regimen, is around 5 to 7 days.
ELIMINATION
Most of the digoxin is eliminated unchanged by the kidneys. Renal clearance of digoxin exceeds by glommerular filtration, thus indicating a tubular secretion component. Tubular secretion is mediated by the multidrug active transporter, p-glycoprotein. This p-glycoprotein may be inhibited by some drugs such as quinidin etc. Renal impairment also decreases the clearance of digoxin, and may cause accumulation to toxic levels if dosage is not adapted thoroughly.
HALF LIFE
36–48 hr (↑ in renal impairment)



MECHANISM OF ACION
Digoxin inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium. The sodium calcium exchanger (NCX)in turn tries to extrude the sodium and in so doing, pumps in more calcium. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Digoxin also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.

INDICATION
 Digoxin is used to treat  heart failure, usually along with other medications. It is also used to treat certain types of irregular heartbeat (such as chronic atrial fibrillation). Treating heart failure may help maintain your ability to walk and  exercise and may improve the strength of your  heart. Treating an irregular heartbeat can decrease the risk for   blood clots, an effect that may reduce your risk for a heart attack or  stroke Paroxysmal atrial tachycardia.

CONTARAINDICATIONS
Hypersensitivity;
Uncontrolled ventricular arrhythmias;
AV block (in absence of pacemaker);
Idiopathic hypertrophic subaortic stenosis;
Constrictive pericarditis;
Known alcohol intolerance (elixir only).
Lactation: Similar concentrations in serum and breast milk result in subtherapeutic levels in infant, use with caution

ADVERSE DRUG REACTION

CNS: fatigue, headache, weakness.
EENT: blurred vision, yellow or green vision
CV: ARRHYTHMIAS, bradycardia, ECG changes, AV block, SA block
GI: anorexia, nausea, vomiting, diarrhea
Hemat: thrombocytopenia
Metabolic: electrolyte imbalances with acute digoxin toxicity
* CAPITALS indicate life-threatening. Underline indicates most frequent.


PRACTICAL IMPLECATION
Using population averages it is possible to predict plasma concentration from specific dosage particularly since the time to reach the steady state is long. Population value are only average and  individual value may very. A number of disease and drugs effect digoxin disposition such as congestive hear failure, hapetic and renal disease all decrease elimination of digoxin. The hypothyroidism increases the plasma concentration and increase the sensitivity of heart to digoxin. hypokalemia ,  hypocalcaemia, hypomagnesaemia also increase the sensitivity of heart.

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General Principles of Rational Drug Prescribing

Rational Prescribing:

Rational Prescribing

 Definition:

 rational prescribing is to prescribe the drug to treat a particular health problem safely effectively and at affordable cost

Steps in Rational Prescribing:

Like another process in medicine writing a prescription should be based on a series of rational steps

Step 1: RATIONAL DIAGNOSIS:

Prescription based on the desire to status for patient psychological needs for some type of therapy is often unsatisfactory and may result in an adverse effect

A specific diagnosing should be made before moving to the next the diagnosing should be shared with the patient National diagnosing is Amen step two rational prescribing it is done by

• Physical Examination
• Lab Data

STEP 2: PATHOPHYSIOLOGY:

If the disorder is well understood the prescriber is a much better position to offer effective therapy.

for example, if the patient is of rheumatoid arthritis there is an increased level of mediators of inflammation of the prescriber has sufficient knowledge about the mediators then it is easy for him to prescribe the best drug-like selecting the right NSAIDS And at a dose at right time at right interval this is most important for treatment purpose.

The patient should be provided with an appropriate amount of information about the pathophysiology.

STEP 3: GOALS OF TREATMENT:

Therapeutic objective or goal of treatment should be chosen for each of the pathophysiological condition

The goal should be short term and long term.

For example

Rheumatoid arthritis

Short Term Goals:

• Relief of pain
• Reduction in inflammation

Long term Goals:

• Prevention of disease
• Prevent recurrence
• Prevent complications

If the patient is of rheumatoid arthritis then the relief of pain by the reduction of the inflammatory process is one of the major therapeutic goals that identify the drug group which will be considered.

STEP 4: DRUG OF CHOICE SELECTION:

First of all, prepare the list of the available option, one or more drug group will be suggested for each therapeutic goal.

The selection of the drug of choice from the drug group will be based on specific characteristics of the patient in a clinical presentation like age or other conditions in other drugs being taken or important in selecting the drug of choice for the management of present complaints.

For example:

if a patient is resistant to a drug in the past we should not use their drug again.

Similarly, the cost of the drugs should also be considered is safety and suitability should also be kept in mind.

STEP 5:DOSE REGIMEN:

The dose regimen should be based on the pharmacokinetics of the drug patient.

If the patient is suffering from the organ disease which causes the elimination of drugs selected adjustment and dose regimen are needed.

For the drugs like Ibuprofen which is mainly excreted by the kidney renal function test must be assessed

STEP 6:MONITORING OF DRUG THERAPY:

Monitoring of drug therapy should be:

1.Active Monitoring:

Done by the physician in the form of

1. Lab Reports
2. LFTs

2.Passive Monitoring:

Done by the patient himself. The patient must be aware of changes that are bringing about the drugs.

Inactive monitoring, the physician must inform the patient about the effect the drug can bring about changes and laboratory reports and various signs and symptoms that can be brought about by a particular drug.

For Example:

In treating infection the physician must tell the patient about the time required for the treatment so that the patient may not stop the medication before the date.

Similarly, the patient must be aware that gastrointestinal bleeding may occur in treating rheumatoid arthritis which requires immediate attention.

STEP 7: DRUG INFORMATION AND EDUCATION:

The prescriber and other members of the Healthcare Team should be prepared to repeat extend and reinforce the information transmitted to the patient as often as necessary.

The most toxic the drug prescribed the greater the importance of his educational program.

The importance of informing in involving the patient in each of the above steps must be recognized.

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Pharmacodynamic Drug-drug Interactions

I Pharmacodynamic interaction:

PHARMACODYNAMIC INTERACTIONS

In pharmacodynamic DI there is a change in a personal response on the administration of a drug is a significant factor in PDI. These changes are particularly tough to categorize given through several different mechanisms. 

This wide variety also means that in all but the most understandable cases it is important to examine and know these mechanisms. The well-founded feeling exists that there are more unidentified interactions than known ones. At some point the medications straightforwardly vie for specific receptors e.g. beta-2 agonists, for example, salbutamol and beta-blockers, for example, propranolol yet regularly the response is more roundabout and includes the impedance with physiological systems. These communications are a great deal less simple to group about than those which are pharmacokinetic.

Epidemiology:

The purpose of this to focus on hospital admissions which are caused by a specific type of ADR that can be expected to be preventable in almost all cases. The use of multidrug can increase the risk of DD. Aging of the population and the increasing number of available drugs show the importance and awareness of DI in both clinical and forensic works.

The incidence of combinations of the drug having serious ADI was generally low i.e 0.71%  but it was noted for the two individually drugs studies a common anticoagulant warfarin 33% and new-generation antidepressant venlafaxine 46%. The toxicity of serotonin and adverse cardiovascular effects were the most prominent possible adverse outcomes.

Polypharmacy is common in the children's hospital in the United States and has been known as a major risk factor for exposure to potential drug-drug interactions. In hospital admission, the reported incidence of drug-drug interaction ranges from 0% to 2.8% in a review which includes nine studies all of which had some design faults. In Harvard medical practice AE is 8% whereas in US OPD have 10% DI out of 50 patient.

Risk factor:

The risk factor in a patient includes i.e polypharmacy, multiple prescribers, multiple pharmacies, genetic, specific population such as females, malnutrition, critically ill patient, and narrow therapeutic index drugs. One-third of the population was visible to polypharmacy, and 6% were showing to potential DI for 1 year. Patient factors related to improved possibility of potential DI were high age or a high number of concurrent drugs used and a high number of prescribers [16].

The outcome of drug interaction:

• loss of therapeutic effect.
• Toxicity.
• an unexpected increase in pharmacology activity.
• Beneficial effect.
• Chemical or physical interaction

Factor contribution to the occurrence of drug-drug interaction:

• pharmacokinetic interaction.

• multiple pharmacological effects.

• Multiple prescribers.

• Use of otc medication.

• Patient non-compliance.

• Drug abuse.

Pharmacokinetic interaction:

Significantly change the PK profile and result in the DI in the situation that interferes with the distribution, absorption, metabolism, or excretion of drugs. Such interaction has the potential to decrease the suitability or rise the danger of toxicities of influenced specialists.

Multiple pharmacological effects:

 Most of the drugs utilized as a part of the current treatment can impact numerous physiological frameworks. There are two medications are direct together that will frequently influence a portion of the same system. The potential medication association between the medications, they're regularly the propensity just to be worried about the essential impact of the medication is included and to ignore the auxiliary exercises they have.

Consolidate treatment with a phenothiazine antipsychotic e.g. chlorpromazine, a tricyclic energizer e.g. amitriptyline, and an antiparkinson operator e.g. trihexyphenidyl is a started in some patient. It has considered the different primary effects of each agent. However, the anticholinergic activity of all three possesses. Any of the medications might be slight in the anticholinergic impact; the added substance impacts of the three specialists might be critical.

Multiple prescribers:

It is exceptionally fundamental for some individuals to check more than one doctor and to be seeing at least one authority notwithstanding a family doctor is very common for a patient e.g. dental specialists, podiatrists who might be recommending the medicine. It is extremely troublesome for one prescriber to know about all the solution that has been recommending by others for a specific patient and such circumstance consummation could emerge.

For instance, one doctor may endorse a pharmaceutical competent for bringing about sluggishness or tiredness e.g. certain antihistamine, opioid analgesic for a patient for whom another physician has prescribed an antianxiety agent of an excessive depressant effect with possible consequences. The patients have seen the different physician he or she frequently will have the remedy apportioned by a similar drug store. In this manner, the drug specialist can assume an imperative part of the identification and counteractive action of medication-related problems.

Use of otc drug:

 Many people hide the use of OTC drugs while possible for numerous drug used in little

era may have the same API but work inversely then incite side

effects. Usually, when using prescribed drugs along with OTC e.g. aspirin, antacids, and

decongestant, etc measured having incompliance to patients. The interaction also may result from the simultaneous utilization of at least two items accessible without a remedy.

Increase the risk of an excessive response to these agents with two nonprescription products promoted for different purposes contain the same active ingredient in the same situation. Acetaminophen is included in many products for its action is antipyretic and analgesic and is included nonprescription sleep-aid formulation. They purchase for the different conditions may contain the same active ingredients that the patient is unaware of the products and therefore with the use of products increased risk of the problem they might assume to be safe because they do not require a prescription.

Patient non-compliance:

For a variety of reasons, many patients do not take the medication in the manner intended by the prescription. Some patient does not receive proper instruction from the prescriber and pharmacist as to how and when taking their medication. In some cases the patient is particularly involving that have taken to the other medication, confusion about the instruction may develop even though the patient may have understood them initially.

It is understandable that the older patient who may have may be taking five or six medication at several time a day at a different time can become confused or forget to take their medication, although these occurrences are by no means unique to the geriatric population, In the situation involving in the noncompliance usually a result in a patient are not taking enough medication, some circumstances could lead to use excessive of the medication that why increasing the drug interaction.

 For example, some patient has forgotten a dose of the medication, then in the next time, double medication can be taken. Some other patients may act on the assumption that if one tablet dose that has been prescribed provides partial but not complete relief of symptoms, a two tablet dose will be even more effective.

Drug abuse or misuse:

Some drugs are individual to manhandle or intentionally abuse medications may likewise prompt to an expanded frequency of medication connection. The antianxiety specialists, opioid pain-relieving, and amphetamines are among the operator frequently manhandled, and the wrong utilization of these medications can bring about various issues, including an expanded potential for medication communication.

Mechanism of drug-drug interaction:

Altered bioavailability:

This alteration may occur when the amount of object drug reaches the systemic circulation which is interfered with by perpetrator drugs. This only occurs when orally drug administered and absorption or first-pass metabolism is changed. The drug which has low oral bioavailability is mostly effected but those who have high bioavailability are less effected e.g. Alendronate has low oral bioavailability. Alendronate co-administration with calcium decrease bioavailability and the result is no absorption of Alendronate. On other hand co-administration of dabigatran with verapamil increase bioavailability and can result in an increased risk of bleeding .

Altered metabolism:

Changes in the metabolism of a drug is very important causes of unexpected drug interaction. These occur when as a result of changing in drug clearance or oral bioavailability. There is some enzyme family that is involved in drug metabolism i.e CYP450 which is the most important for drug metabolism. In this one drug induce these enzyme for other drug so metabolism is affected.

Inhibition of CYP450 increase the conc of some drugs by decreasing its metabolism

e.g. clarithromycin is a strong antagonist of CYP3A catalyst simvastatin metabolism. Thus increasing the risk of myopathy as observed. Drug inhibition of CYP450 is also used as a therapeutic monitoring tool e.g. ritonavir an antiviral agent which is a strong inhibitor of CYP3A which reduces the metabolism of other protease inhibitors and thus increasing their effectiveness in treating HIV.

Induction of a CYP450 decreasing the conc of some drugs by increasing their metabolism e.g. carbamazepine is a strong inducer of CYP3A that increases the metabolism of the combined oral contraceptive, thus increasing the risk of unwanted pregnancy.

Prodrug:

Most of the drugs are depends upon CYP450 for conversion to their active state. As this is usually depending upon a single enzyme pathway. Prodrugs are particularly prone to change in metabolism. Inhibition of such enzyme may lead to prevent the conversion of prodrugs to active drugs which may lead to inappropriate conc of the active drug and therapeutic failure e.g tamoxifen is metabolized by CYP2D6 to its active form endoxifen and concomitant therapy with strong CYP2D6 inhibitor paroxetine has been associated with the increased death rate in breast cancer.

Altered distribution:

This occurs when the conc of the drug at the side of the action is altered without necessarily changing its circulation conc. This is a particular problem with those drugs which target the intracellular or central nervous system. Most drugs cause more alteration in the cell membrane transport of other drugs e.g. verapamil inhibits efflux transporters i.e P-glycoprotein increasing the conc of substrates such as digoxin and cyclosporine. Probenecid block anion transport result in increasing the conc of substrates such as methotrexate and penicillins. DI involved in transport is less understood as compared to DI involving metabolism.

Altered clearance:

This can also occur when excretion or metabolism of the OD is effected by a perpetrator drug. OD with a narrow therapeutic index drug is mainly effected, as modest changes in conc may be clinically imported. Perpetrator drugs known to strongly affect drug metabolism are more likely to cause large conc in alterations and hence clinical consequence as observed.

Altered excretion:

Some of the drugs are eliminated from the body in the unchanged form usually in the urine or with biliary tract in the stool. Changes in the drug clearance may result due to effects on renal tubular function or urine PH e.g. probenecid decrease the renal clearance of anionic drugs such as methotrexate and penicillin.

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How to study pharmacognosy

Here is an Easy Way To Learn and memorize Most important drugs in Pharmacognosy

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RESINS
DRUGS	SYNONYMS	B.SOURCE	FAMILY	HABITAT	CHEMICAL CONSTT.	USES
ROSIN Or COLOPHON Distillation of Volatile oil from Oleoresin Obtained from Pinus palustris Y	Yellow resin, Rosin, Colophony Resin, Abietic anhydride, Amber resin	Pinus palustris	Pinaceae	Pakistan, China , India, Italy, Spain, Greece, USA	MAINLY:- Resin Acid Resenes Fatty acid Esters α-β- ϒ Abietic Acid OTHERS:- DihydroAbietic Acid DehydroAbietic Acid	As a stiffening Agent in Ointment Plasters Cerates As Diuretic in Vets In Manufacturing of Varnishes Printing inks Wood polishes Fire works
CANNABIS Dried flowering tops	Indian hemp, Indian Cannabis, Marihuana, Marijuana , Bhang, Ganja, Hasach, Cannabis indica	Cannabis sativa	Cannabinaceae	Native to India. Cultivated in Pakistan Afghanistan, iran, central America, Bangladesh, USA, S.Africa, Asia Minor	RESINS (15-20%) Cannabinol Tetrahydro Cannabinol Cannabidiol Cannabidiol carboxylic Acid Cannabigerol Cannabichromene	Tonic Intoxicant Stomachic AntiSpasmodic Analgesic Norcotic AntiConvulsant AntiAnxiety Anti Tussive agentr
GLYCORESINS
PODOPHYLLUM Dried Roots and Rhizome	May Apple, Mandrake root, American  Mandrake, Indian Apple,  Podophyllum Rhizome, Rhizoma  Podophylli	Podophyllum hexandrum Podophyllum peltatum	Berberidaceae	Canada , USA	RESINS (6-12%) Podophyllotoxin PicroPodophyllin	AntiCancer Purgative Cytotoxic
DRUGS	SYNONYMS	B.SOURCE	FAMILY	HABITAT	CHEMICAL CONSTT.	USES
JALAP Dried Tuberious Roots	Jalap root, Mexican  Jalap, Radix  Jalapae	Exogonium purge Ipomoea purga	Convolvulaceae	Indigenous to Mexico. Found in India, West Indies, south America	RESINS (8-12%) Jalapin β- methyl esculetin Ipurganol	Hydrogogue  Cathartic Drastic Purgative
IPOMOEA	Mexican scamony, Orizaba jalap, Ipomoea radix,	Ipomoea orizabensis	Convolvulaceae	Native to Orizaba, Mexico	Resins 10-20% Mainly: Methyl pentoside Phytosterole Ipurolic acid Convulvulinic acid Others: Scopoletin Volatile oil Sitosterole Ca Oxalate	Cathartic Hydrogogue
COLOCYNTH	Maraghonae, Bitter apple Bitter cucumber, Colocynth pulp, Colocynthis, Fructus colocynthis, Indrayan ,	Citrullus colocynthis	Cucuribitaceae	Syria Cyprus N.Africa Turkey Spain India Pakistan	Citrullol Chloroform soluble resin Pectin Mainly: Colocynthin Colocynthetin Albuminoids cucurbitacine	Powerful Cathartic Anticancer cytotoxic
OLEORESINS
TURPENTINE	Olium, Terbinathae Tarpine Rectified oil of turpentine	Pinus palustris Pinus longifolia Pinus elliotii Pinus radiata	Pinaceae	Pakistan India France USA	α pinene β Pinene	As counter irritant Rubifcient Inhalation Vicks As disinfectant Insecticide Source of vitamin Paint Varnishes

DRUGS	SYNONYMS	B.SOURCE	FAMILY	HABITAT	CHEMICAL CONSTT.	USES
CAPSICUM (Dried ripe fruit)	Chillies, Mirch, Cayenne pepper, Red pepper, Spanish Pepper, Capsicum Fruit,	Capsicum frutescens Capsicum annuum	solanaceae	Native to America India S.Europe Japan Mexico Srilanka	Oleoresins Mainly: Capsaicin Homo-capsaicin Dihydrocapsaicin Nor-  Dihydrocapsaicin Homo- Dihydrocapsaicin Carotenoids Capsacutin capsico	As Stimulant C-irritant Rubefacient In sorethroat Scarlattina Hoarseness Dyspepsia Yellow fever carminative stomachic Dyspepsia Flatulence Rheumatism lumbago
OLEOGUM RESIN
ASAFOETIDA (Root and Rhizome)	Asafoda Gum Asafoetida Asant Henng (Hindi) Hingo (sankirt) Inja (Pashto) Devils Dung Food Of the God Org-gardening	Ferula assafoetida Ferula foetida Ferula rubricaulis	Umbelliferae	Native to Iran Found in Turkestan Afganistan	Volatile Oil 4-20% Gum 25% Resins 40-65% Main Oil Isobutyl propanyl disulphide Umbelliferone Asarsinotannol	Carminative Expectorant Antispasmodic Laxative As Flavoring Curries Enemas In Hysteric & Epileptic In Cholera Asthma Bronchitis Whopping Cough
Myrrh (Stem)	Co	Comiphora molmol Commiphora absyssinica	Burseraceae	Native to Somalia Arabian Pennisula Ethopia Nubia Yemen Africa	Resins 25-40% Gum 5761% Volatile Oil 7-17% Elemol Furanodiene Isofuranogermacrene Curzerenone Lindestrene Protocatechuric acid pyrocatechin	Carminative Religons ceremony Local stimulant Antiseptic Stomachic Tooth poweder Toothachne Mouth wash Astringent Embalming

Balsams
DRUGS	SYNONYMS	B.SOURCE	FAMILY	HABITAT	CHEMICAL CONSTT.	USES
STORAX (Trunk)	Styrax, Prepared storax, Styrax Preparatus, Sweet oriental gum	Liquidamber orientalis Liquidamber styraciflua	Hammelidaceae	Levant Storax Native to Asia minor American storax in Hondrus	Alcobal 50% αβ. Storesins Balsamic acid30-47% Cinnamyl cinnamate Or Styracin, Phyenyl Propyl Cinnammate, Benzyl cinnamte, Ethyl free cnnamic acid, Styrene, Vaniline + V oil	Stimulant Expectorant Parasiticide Protectant Antiseptic Pharmacological preparation, Balsam &benzoin Inhalation
PERU BALSAM By Incision Of the Stem	Peruvian balsam, Indian balsam, China oil, Black balsam, Honduroas balsam, Balsam Of Peru	Myroxylon pereirae Myroxylon balsamum	Leguminosae	Columbia, Venezuela, Central America, Cuba, Florida, Srilanka, Pacific Coast EI Slavador	Balsamic Esters Benzyl Cinnamate Benzyl Benzoate Styracin , And Resins Peru Resinotannol Cinnamate	Miticide To Aid in healing Of indolent wounds Scabicide Parasiticide Skin Ulcer therapy Local Protectant, Rubifacient As Antiseptic, Expectorant Vulmerable Diseases
TOLU BALSAM (By Incison of the stem)	Tolu Balsam, Thomas balsam, Balsam of tolu Resin Tolu, Opobalsam , Balsamum Tolutanum,	Myroxylon balsamum	Leguminosae	Columbia West indies Cuba Venezuela And Peru	Resins 80% Resin alcohol Cinnamic and Benzoic Acid Armoatic Acid Others: Benzyl benzoate Benzyl cinnamate Vanilline Styrene Eugenol	Expectorant Stimulant, Antiseptic, In Cough Mixture as benzoin tincture, As flavoring In Confectionery

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