pcol 2 post labs finals

PHARMACOLOGY LAB 2

POST LABSHONEYLENE B. PALOMA

DRUG DISSOLUTION

Is the process by which solid substances enters in solvent to yield a solution.

Is the process by which a solid substance dissolves.

Fundamentally, it is controlled by the affinity between the solid substance and the solvent.

The rate of dissolution of solid substances is determined by the rate of diffusion of a very thin layer of saturated solution that forms instantaneously around the solid particle.

Drug dissolution

Physical characteristics of the dosage form Wettability of the dosage unit Penetration ability of the dissolution

medium swelling process Disintegration Deaggregation of the dosage forms Stirring rate (in vitro)

Factors affecting dissolution

Schematics illustration of dissolution process of solid dosage forms

Drug in Blood and Other Fluids and Tissues

Solid dosage forms

Disintegration Granules or Aggregates

Deaggregation Fine particles

Dissolution (minor)

very limited dissolution

Dissolution (major) limited

dissolutionDissolution (major)

Best dissolutionDrug in vitro or in vivo

Absorption (in vivo)

It is the rate of dissolution of a pure pharmaceutical active ingredient, when conditions, such as surface area, temperature, agitation or stirring speed, pH, and ionic strength of the dissolution medium is kept constant.

This parameter allows the screening of the drug candidates and aids in the understanding their solution behavior under various biophysiological conditions.

Intrinsic dissolution rate

Defined as all the kinetic processes that occur to a drug subsequent to its systemic absorption.

By definition, the components of disposition are distribution and elimination.

Drug Disposition

Denotes the partitioning of a drug among the numerous locations where a drug may be contained within the body.

The process of reversible transfer of a drug to and from the site of measurement and the peripheral tissues.

An example is distribution between blood and muscle. The pathway for return of drug need not be the same as that leaving the circulation.

Drug distribution

For example,

The drug completes a cycle, ENTEROHEPATIC CYCLE, a component of distribution.

Drug distribution

BILEDRUG

EXCRETED GALL

BLADDERStored in and released

SMALL INTESTINE

Transited into

CIRCULATIONReabsorbed back

Effect of pH on drug dissolution The rate at which

drugs act when taken orally and dissolve in the stomach and other regions of the gastrointestinal tract is an important factor in determining how quickly a drug can be absorbed into the bloodstream and carried to where it needs to act.

When dissolving in aqueous media, drugs dissolve faster if they can ionize because the ionized form has higher water solubility. Thus, a higher total drug concentration is reached in the diffusion layer, increasing the concentration gradient for dissolution.

Effect of pH on drug dissolution Since gastrointestinal

pH is region dependent, and ionizable drug solubility is a function of pH, drug dissolution and precipitation can impact drug.

The local physiological pH has a tremendous influence on dissolution rate, and consequently, could have a big influence on drug absorption.

Effect of pH on drug dissolution Stomach fluids are

acidic with pH in the range 1 to 3.5, whereas the small intestines have pH in the range 5.5 to 7.5. A weak acid drug has a lower solubility and dissolution rate in the stomach and a higher solubility and dissolution rate in the small intestines. The opposite is true for weak base drugs.

Salts of weak acids and bases often have faster dissolution rates than the parent acid or base. The faster dissolution rate is a reflection of higher water solubility of the salt because of a local pH effect; the salt effectively acts as its own buffer and facilitates ionization and dissolution. The type of salt influences dissolution rate.

Effect of differences in the pH of gastrointestinal fluids on the absorption of a drug which requires

a low pH to dissolve.

AGAIN, remember! The LOW pH of gastric

fluids favors rapid dissolution of weak bases but it is unfavorable for the dissolution of weak acids.

Also, the effects of pH on dissolution rate - limited absorption are opposite to the effects of pH on the absorption of weak acids and bases from solution.

In other words, weak acids are more rapidly absorbed at higher pH when given in solid form (unless the pH is so high that dissolution is no longer absorption rate - limiting) while weak acids given in solution are more rapidly absorbed at low pH.

Station 1 - Ampoules with files, needles of different size (gauge), syringes, vials.

Notes: Needles of 26 gauge used for intradermal, subcutaneous route. 23 gauge for intramuscular 21-20 for injecting iv: for giving or withdrawing blood 19,18 15,16 for blood donation purposes Bevels - short (iv) long (im) Before giving an injection wash hands Open packet carefully without touching nozzle Breaking an ampoule - file and break, discard in bin Use one needle for removing from vial another for injecting, do not leave needle in the vial (infection) Fixing the needle to syringe, checking, removing air bubbles, taking exact quantity

ROUTES OF ADMINISTRATION

Station 2 – oranges (model for IM route), eggplant (model for sc route)

For SC, pinch up the skin, needle should be 45 degrees angle, bevel should face up. After injection rub the area. Intradermal injection is more superficial (a bleb will be formed).


Drugs given sc - insulin, adrenaline, im - procaine penicillin, B complex injections, tetanus toxoidintradermal - Manteux, penicillin (for sensitivity testing), BCG vaccine


Volumes which can be given by subcutaneous route - 1ml, intramuscular route - 5ml (in gluteal region)

Volume should be less if patient is very thin and emaciated, child, elderly.

With larger volumes absorption is not proper. Do not inject in gluteal region in a child until child starts walking. Inject into lateral part of thigh.



Heparin should not be administered by intramuscular injection due to the risk of haematoma

Injury to nerves- paresis of muscles can occur. Never give injection (im) to child with suspected poliomyelitis.


ROUTES OF ADMINISTRATIONStation 3 – Model of Hand with vein (made of

latex glove stuffed with cotton and a tube filled with red ink placed under the latex on top of the cotton)

Drugs should not be added to blood and blood products. e.g - hypertonic mannitol - irreversible crenation of RBC, Dextrans - rouleaux formation



Continuous infusion - aminophylline, dopamine, cisplatinIntermittent infusion - amoxicillin, ampicillinAddition via drip tubing – gentamicinBolus - thiopentone sodium (avoid extravasation)



Do not use plastic tubing for glyceryl trinitrate, paraldehydeProtect from light – nitroprussideLayering effect of potassium chloride due to density. Shake thoroughly after adding.Mixing should be done before connecting to the giving set (to mix thoroughly).

Respiratory stimulants

Analeptic Stimulant

A diuretic is any substance that promotes the production of urine.

Sometimes called “water pills,” diuretics help remove water, sodium, and chloride from the body.

Diuretics may be used to treat a number of heart-related conditions, including high blood pressure, heart failure, kidney and liver problems, and glaucoma. Thiazide diuretics, such as Esidrix or Zaroxolyn, can be used to lower blood pressure, or to treat edema in heart failure.

Diuretic activity

Diuretic activityLoop diuretics remove excess fluid by causing your kidneys to make more urine. This results in the removal of water and salts. Loop diuretics include torsemide, furosemide, bumetanide, and ethacrynic acid.

Take your diuretic with food if it upsets your stomach. Some diuretics cause loss of the minerals potassium, calcium, and magnesium from the body.

Other diuretics, like triamterene (not with hydrochlorothiazide), lower the kidneys’ ability to remove potassium, which can cause high levels of potassium in the blood stream (hyperkalemia).

Drug – Food Interactions

Too much potassium can be harmful and can cause an irregular or rapid beating of the heart.

When you use diuretics that can increase potassium in your body, avoid eating large amounts of foods high in potassium, such as bananas, oranges, and green leafy vegetables, and salt substitutes that contain potassium.


They can raise the level of potassium even higher. Tell your doctor if you are taking salt substitutes with potassium or potassium supplements because they can add to the amount of potassium in your body.


Digoxin and other cardiac glycosides - furosemide and spironolactone increase the effect of digoxin, and digoxin may become toxic if hypokalaemia occurs. Monitor plasma potassium and give supplements if necessary.

Aminoglycosides (eg amikacin, apramycin, dihydrostreptomycin, framycetin, gentamicin, kanamycin, neomycin, paromomycin, streptomycin, tobramycin) - may show increased ototoxicity with furosemide

Drug – Drug Interactions

Cephalosporins - increase nephrotoxicity may occur when used with furosemide

Sulphonamides - allergic reactions to sulphonamides (or potentiated sulphonamides) may occur when they are used with diuretics

ACE inhibitors - increased risk of developing hyperkalaemia when given with potassium-sparing diuretics (Spironolactone, amiloride)


Corticosteroids - in the presence of furosemide or thiazide diuretics there is an increased risk of developing hyperkalaemia, and the efficacy of the diuretic may be reduced.

Non-steroidal anti-inflammatory drugs (NSAIDs) - may reduce the diuretic efficacy of spironolactone or amiloride and increase the risk of hyperkalaemia developing.


Propranolol, atenolol - if hypokalaemia develops there is an increased risk of ventricular arrhythmias with these drugs.

Other, less frequently prescribed drugs that interact with diuretics include : Acetazolamide, Aspirin, Calcium salts, Chlorpropamide, Glipizide, Glibenclamide, Lidocaine, Oestrogens, , Quinidine and Tolbutamide.


(from the Greek erythros, meaning red) is redness of the skin or mucous membranes, caused by hyperemia of superficial capillaries. It occurs with any skin injury, infection, or inflammation.

Erythema nodosum is a type of skin inflammation that is located in a part of the fatty layer of skin. Erythema nodosum results in reddish, painful, tender lumps most commonly located in the front of the legs below the knees. The tender lumps, or nodules, of erythema nodosum range in size from a dime to a quarter.

Erythema

Erythema

Erythema nodosum

HYPERSENSITIVITY REACTIONS

Allergy is a hypersensitivity (oversensitivity) to a particular substance, and always involves the immune system.

Patch testing is a way of identifying whether a substance that comes in contact with the skin is causing inflammation of the skin (contact dermatitis).

There are two types of contact dermatitis: irritant contact dermatitis and allergic contact dermatitis.

Importance of Sensitivity Tests

An irritant substance is one that would cause inflammation in almost every individual if it was applied in sufficiently high concentration for long enough.

An irritant reaction is caused by the direct contact of an irritant substance with the skin and does not involve the immune system.


An allergic reaction is specific to the individual and to a substance (or a group of related substances) called an allergen.

All areas of skin that are in contact with the allergen develop the rash. The rash will disappear if you avoid contact with the substance.


Patch testing can help to differentiate between the two. The test involves the application of various test substances to the skin under adhesive tape that are then left in place for 48 hours.

The skin is then examined a further 48 hours later for any response. This can help the doctor decide which allergens you are allergic to and identify those that could be aggravating your dermatitis. The doctor will then be able to advise how you can avoid the allergens.


It is the body's attempt at self - protection; the aim being to remove harmful stimuli, including damaged cells, irritants, or pathogens, and begin the healing process.

Inflammation does not mean infection, even when an infection causes inflammation. Infection is caused by a bacterium, virus or fungus, while inflammation is the body's response to it.

Inflammation

Wound healing is a natural restorative response to tissue injury. Healing is the interaction of a complex cascade of cellular events that generates resurfacing, reconstitution, and restoration of the tensile strength of injured skin.

Healing is a systematic process, traditionally explained in terms of 4 overlapping classic phases: hemostasis, inflammation, proliferation, and maturation. While platelets play a crucial role in clot formation during hemostasis, inflammatory cells débride injured tissue during the inflammatory phase.

Inflammation

Epithelialization, fibroplasia, and angiogenesis occur during the proliferative phase. Meanwhile, granulation tissue forms and the wound begins to contract. Finally, during the maturation phase, collagen forms tight cross-links to other collagen and with protein molecules, increasing the tensile strength of the scar.

Inflammation

Nonsteroidal Antiinflammatory Drugs (NSAIDs)• reduce pain associated with inflammation

• are not steroids (e.g. cortisone)• include aspirin and salicylates• are useful in the management of

o headache (nonmigraine) o muscle aches and pain, o Dysmenorrhea o joint pain of osteoarthritis

Nonsteroidal Antiinflammatory Drugs (NSAIDs)Inflammation is characterized by local swelling (edema) redness (erythema, vasodilation) warmth pain

Intermediated by prostaglandins (G2, H2, E2, F2ά)

NSAIDs Mechanism of ActionInhibit inflammation and reduce pain byblocking the synthesis of prostaglandins

Stabilize cell membranes to prevent further

leakage of substances (edema)

NSAIDs Adverse Effects Nausea Gastrointestinal distress, ulceration,bleeding Vomiting CNS stimulation Headache Vertigo Mental confusion Hypersensitivity reactions (rash, fever) Hepatic damage (elevated serum enzymes)

NSAIDs Special ConsiderationsAspirin sensitive patients may develop

anaphylactic reactions angioedema asthmaChronic toxicity is the same as for aspirin tinnitus gastrointestinal bleeding black tarry stools

Chronic Salicylate ToxicitySalicylism is a constellation of symptoms

that occur in some patients with the chronic use

oflarge doses of aspirin and other salicylates

Nausea Vomiting Headache Tinnitus (ringing in the ears) Hyperglycemia Delirium

Acute Salicylate PoisoningAccidental ingestion of a large dose bychildren or attempted suicide may produce

» Depression of respiratory centers Respiratory acidosis CNS depression Sweating Dehydration, electrolyte imbalance Hypotension & vasodilation Coma Death

is a weak acid. It is also known as acetaminophen, APAP, chemically named N-acetyl - p - aminophenol. It is a widely used OTC analgesic and antipyretic.

Paracetamol is the International Nonproprietary Name (INN). Australian Approved Name (AAN), and British Approved Name (BAN). While acetaminophen is the US adopted name (USAN) and Japanese Adopted name (JAN).

Paracetamol

Paracetamol

Acetaminophen Weak prostaglandin synthetase inhibitor

Useful for reducing fever and headache (nonmigraine)

Should not substitute for antiinflammatory drugs

Does not affect platelet aggregation/clotting

May be used as an aspirin substitute in aspirin-sensitive patients

Acetaminophen MOA

It reduces levels of prostaglandin metabolites in urine bit does not reduce synthesis of prostaglandins by blood platelets or by the stomach mucosa.

Weak inhibitor of both COX-1 and COX-2. Analgesic activity of paracetamol is due

to its metabolite NAPQI that act on TRPA1 – receptors in the spinal cord to supress the signal transduction from the superficial layers of the dorsal horn, to alleviate pain.

Acetaminophen NAPQI n–acetyl–p–benzoquinone imine

A toxic metabolite, normally produced in small amounts, and almost immediately detoxified in the liver.

Causes severe damage to the liver Death may result from liver failure

several days after overdose

Acetaminophen TRPA1 – receptors transient receptor

potential cation channel, subfamily A, member 1, a protein that in humans is encoded by the TRPA1 gene.

This is an ion channel located on the plasma membrane of many human and animal cells.

This ion channel is best known as a sensor for environmental irritants giving rise to somatosensory modalities such as pain, cold and itch.

Interactions

Alcohol: If you drink three or more alcoholic drinks every day, ask your doctor if you should use medicines with acetaminophen or other pain reliever/fever reducers. Acetaminophen can cause liver damage. The chance for severe liver damage is higher if you drink three or more alcoholic drinks every day

PARACETAMOL

PK: Rapidly absorbed with peak levels usu

reached within 30 – 120 mins Vd is 0.8 to 1 L/Kg Elimination is mainly by liver

conjugation (90%) to nontoxic glucuronides or sulfates

Elimination half – life is 1 – 3 hours after a therapeutic dose but may be greater than 12 hours after an overdose.

PK principles of Paracetamol:

Acetaminophen Adverse Effects

Acute toxicity Nausea Vomiting Hepatoxicity (elevated serum enzymes) Acidosis Respiratory depression

Special CautionAspirin and acetaminophen in children and teenagers who have active viral infections(flu or chicken pox) may result in Reye’ssyndrome, potentially life-threatening

Reye’s syndrome rare but serious condition that causes swelling in the liver and brain.

Garlic has been used medicinally for at least 3,000 years, but until recently its benefits were considered little more than folklore. Medical studies have shown that garlic can lower cholesterol, prevent dangerous blood clots, protect LDL cholesterol and the endothelial lining of the arterial system against oxidation, reduce blood pressure, prevent cancer, and protect against bacterial and fungal infections.

Garlic

For anti-bacterial or anti-viral effect, raw garlic is better than cooked. Both raw and cooked garlic seem to have cardiovascular, decongestive and anti-cancer benefits.

Eating more than three raw cloves a day can cause gas, bloating, diarrhea and fever in some people. Cooked garlic is gentler on the stomach.

Garlic

Although garlic is generally considered safe for regular use in your diet or as a supplement, there are some possible side effects. Many people may get bad breath from oral garlic use. In addition, some people may get heartburn, nausea, vomiting, diarrhea, gas, or body odor.

People who are undergoing surgery should stop taking garlic two weeks prior to the surgery, as garlic may prolong bleeding. You should also avoid if you suffer from a bleeding disorder, or gastrointestinal problems .

Garlic

Raw garlic is more likely to cause side effects than other forms. In addition, garlic may interact with many medications.

It may decrease the effectiveness of drugs for bleeding disorders, HIV/AIDS, tuberculosis, and a number of other conditions.

Garlic may even reduce the effectiveness of birth control pills that contain estrogen (NIH, 2011).

Garlic

http://www.nlm.nih.gov/medlineplus/druginfo/natural/300.html

Because garlic may slow blood clotting, it may increase the risk of bleeding when taken with other supplements that have similar properties.

These include fish oil, ginger, ginkgo, turmeric, vitamin E, and willow (NIH, 2011). Always consult a health professional before taking garlic supplements or significantly increasing the amount of garlic you eat

Garlic

http://www.nlm.nih.gov/medlineplus/druginfo/natural/300.html

Putting garlic on the rectum will make one’s temperature high.

This is done traditionally, to treat pinworms from the body.

The garlic clove contains a very high amount of sulphur; sulphur is one of the best minerals to be used as an oxygen carrier. Oxygen is the breath of life and sulphur will carry the oxygen in the body directly to the infected area. Germs cannot live in a good supply of oxygen, therefore, the infection is cleared quickly.

Garlic

Garlic contains at least 33 sulfur compounds like aliin, allicin, ajoene, allylpropl, diallyl, trisulfide, sallylcysteine, vinyldithiines, S-allylmercaptocystein, and others. Besides sulfure compounds garlic contains 17 amino acids and their glycosides, arginine and others.

Garlic

Pyrexia is found among people who take Garlic, especially for people who are female, 50-59 old, also take medication Ascorbic acid, and have Multiple sclerosis. We study 1,209 people who have side effects while taking Garlic from FDA and social media. Among them, 38 have Pyrexia.

http://www.ehealthme.com/

Garlic -- Recent Study

Garlic -- Recent Study

They are one of the most frequently prescribed drugs. Their use is complicated by the presence of adverse effects, poor compliance, high cost and self medication.

Many unnecessary prescriptions are given in common cold, self limiting diarrhoeas due to patient pressure to prescribe. Rapid acceptance of newer agents by doctors further complicates matters leading to resistance.

Antimicrobial Agents

Case 1: A 35 year old man came with history of

yellowish purulent urethral discharge for two days. Gram's stain of urethral exudate showed gram negative diplococci. Patient said that he was allergic to penicillin.

He was prescribed: Clarithromycin 2 gm

orally single dose


Case 1: The patient has urethritis caused by N.

gonorrhea.

Tx: Azithromycin, Doxycycline


Case 2: A 18 year old girl came with fever, headache

and abdominal pain for 3 days. The blood culture was positive for Salmonella.

She was advised: Complete bed rest for 3 weeks Chloramphenicol cap. 500 mg q.i.d. x 1 day

followed by 250mg t.d.s x 6 days Vitamin B Complex tab. 1 t.d.s x 7 days Vitamin C tab. 500mg o.d. x 7 days


Case 2:

◦ Chloramphenicol may inhibit the response of RBC to vitamin B12, may decrease absorption of vitamin B12.


Case 3: A 13 year old boy (30 Kg) with recurrent

mild pain abdomen was found to be clinically normal. The stool examination revealed ascaris and a few hook-worm ova.

He was prescribed: Piperazine citrate tab. 3gm at night Pyrantel pamoate tab. 400 mg.


Case 3:

◦ Pyrantel pamoate is not effective against treatment of roundworms like Ascaris if NOT combined along with Mebendazole. Dose: 75 mg/kg twice daily for 2 days

◦ Dose for piperazine citrate is too high. Paralyzes parasites

Pyrantel pamoate and piperazine citrate should not be combined because the mode of action are antagonistic.


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