notes

1. POST LABS
HONEYLENE B. PALOMA

3.  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.

4.  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)

5. 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
dissolution
Dissolution
(major)
Best
dissolution
Drug in vitro or in vivo
Absorption (in vivo)

6.  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.

7.  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.

8.  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.

9.  For example,
 The drug completes a cycle, ENTEROHEPATIC
CYCLE, a component of distribution.
BILE
DRUG
EXCRETED
GALL
BLADDER
Stored in and released
SMALL
INTESTINE
Transited into
CIRCULATION
Reabsorbed back

10.  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.

11.  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.

12.  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.

14. Effect of differences in the pH of gastrointestinal
fluids on the absorption of a drug which requires
a low pH to dissolve.

15.  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.

16. 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

17. 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 toxoid
intradermal - Manteux, penicillin (for
sensitivity testing), BCG vaccine

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

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

20. ROUTES OF ADMINISTRATION

21. ROUTES OF ADMINISTRATION
Station 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

22. ROUTES OF ADMINISTRATION
Station 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)
Continuous infusion - aminophylline, dopamine,
cisplatin
Intermittent infusion - amoxicillin, ampicillin
Addition via drip tubing – gentamicin
Bolus - thiopentone sodium (avoid
extravasation)

23. ROUTES OF ADMINISTRATION
Station 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)
Do not use plastic tubing for glyceryl
trinitrate, paraldehyde
Protect from light – nitroprusside
Layering effect of potassium chloride due to
density. Shake thoroughly after adding.
Mixing should be done before connecting to
the giving set (to mix thoroughly).

27.  Respiratory stimulants

31.  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.

33. Loop 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.

35.  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).

36.  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.

37.  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.

38.  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

39.  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)

40.  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.

41.  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.

42.  (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.

45. HYPERSENSITIVITY REACTIONS

46.  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.

47.  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.

48.  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.

49.  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.

50.  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.

51.  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.

52.  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.

54. 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

55. Nonsteroidal Antiinflammatory
Drugs (NSAIDs)
Inflammation is characterized by local
 swelling (edema)
 redness (erythema, vasodilation)
 warmth
 pain
Intermediated by prostaglandins (G2, H2,
E2, F2ά)

56. NSAIDs Mechanism of Action
Inhibit inflammation and reduce pain by
blocking the synthesis of prostaglandins
Stabilize cell membranes to prevent further
leakage of substances (edema)

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

58. NSAIDs Special Considerations
Aspirin sensitive patients may develop
 anaphylactic reactions
 angioedema
 asthma
Chronic toxicity is the same as for aspirin
 tinnitus
 gastrointestinal bleeding
 black tarry stools

59. Chronic Salicylate Toxicity
Salicylism is a constellation of symptoms that
occur in some patients with the chronic use
of
large doses of aspirin and other salicylates
 Nausea
 Vomiting
 Headache
 Tinnitus (ringing in the ears)
 Hyperglycemia
 Delirium

60. Acute Salicylate Poisoning
Accidental ingestion of a large dose by
children or attempted suicide may produce
» Depression of respiratory centers
 Respiratory acidosis
 CNS depression
 Sweating
 Dehydration, electrolyte imbalance
 Hypotension & vasodilation
 Coma
 Death

61.  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).

63. 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

64. 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.

65. 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

66. 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.

67.  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


68.  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.

69. Acetaminophen Adverse
Effects
Acute toxicity
 Nausea
 Vomiting
 Hepatoxicity (elevated serum enzymes)
 Acidosis
 Respiratory depression

70. Special Caution
Aspirin and acetaminophen in children and
teenagers who have active viral infections
(flu or chicken pox) may result in Reye’s
syndrome, potentially life-threatening
Reye’s syndrome  rare but serious condition
that causes swelling in the liver and brain.

71.  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.

72.  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.

73.  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 .

74.  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).

75.  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

76.  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.

77.  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.

78.  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/

82.  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.

83.  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

84.  Case 1:
 The patient has urethritis caused by N.
gonorrhea.
 Tx: Azithromycin, Doxycycline

85.  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

86.  Case 2:
◦ Chloramphenicol may inhibit the response of RBC to
vitamin B12, may decrease absorption of vitamin
B12.

87.  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.

88.  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.