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CLINICAL PHARMACY
 CEPHALOSPORINES “KEFLEX, VELOSEF”:
 They are very similar to broad-spectrum ampicillins, but they are resistant to
penicillinase.
 They are used instead of penicillin in staph. aureus infections.
 They interfere with glucose test in urine.
 ERYTHROMYCINS “MACROLIDE ANTIBIOTICS”:
 This is the drug of choice in patients sensitive to penicillins.
 The drug of choice for Legionaries disease and mycoplasma pneumonia.
 It can be used during pregnancy.
 The oestolate salt of erythromycin has greater blood level than the stearate salt, but it
may cause cholestasis, because the route of elimination of erythromycin is the liver (via
bile).
 LINCOMYCIN “LINCOCIN” – CLINDAMYCIN “DALACIN”:
 Macrolides type of antibiotic.
 Restricted only for anaerobic infections.
 They develop serious diarrhea and colitis (pseudomembranous colitis).
 VANCOMYCIN:
 It’s a bactericidal antibiotic against gm +ve bacteria.
 It’s used in the treatment of penicillin resistant infections.
 It’s used orally in the treatment of antibiotic induced pseudomembranous colitis.
 Because 1 gm provides adequate blood levels for 7 – 10 days, I.V. vancomycin is
especially useful in the treatment of anephric patients with gm +ve bacterial infections.
 TETRACYCLINE:
 They are bacteriostatic.
 They inhibit protein synthesis in bacteria.
 Most valuable to patients with mixed infections.
 There is cross-sensitivity and cross-resistance between all tetracyclines.
 Long acting tetracyclines are Doxycycline “Vibramycin” and Minocycline “Minocin”.
 Tetracyclines have the following side effects:
b. Gastrointestinal side effects.
c. Photosensitivity.
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d. Fanconi’s syndrome.
e. Tooth discoloration as a result of complex formation with calcium ions in children.
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 CHLORAMPHENICOL:
 It inhibits bacterial protein synthesis.
 It’s most valuable in the treatment of gm +ve and gm –ve infections – e.g. Salmonella,
Rickettsia and also against ampicillin resistant H. influenza.
 Adverse effects include:
f. Bone marrow depression and agranulocytosis.
g. Idiosyncratic aplastic anemia.
h. Gray Syndrome or Gray-baby syndrome (in new born).
Mechanism of action of antibiotics:
INHIBITION OF CELL WALL SYNTHESIS
Penicillins, cephalosporines, bacitracin,
cycloserine and vancomycin
INHIBITION OF CELL MEMBRANE FUNCTION
Amphotricin B, imidazoles, polymixins, colistin,
polyenes and nystatin.
INHIBITION OF PROTEIN SYNTHESIS
Chloramphenicol, erythromycines, lincomycin,
tetracycline and aminoglycosides.
INHIBITION OF NUCLEIC ACID SYNTHESIS
Quinolones, pyrimethamine, rifampin,
sulfonamides, trimethoprim and grieofulvin.
N.B. Sulfa drugs inhibit growth by means of competitive antagonism.
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Antineoplastic drugs are classified into:
1. Interfering with DNA, RNA and protein (anti-metabolite):
a. Methotrexate  Folic acid antagonist.
b. 6-mercaptopurine  Purine antagonists.
c. 5-fluorouracil  pyrimidine antagonists.
d. Cytorabine  pyrimidine antagonist.
2. Inhibiting protein synthesis:
a. L-asparaginase (Leukemia).
3. Interfering with the replication and translation of the DNA:
a. Nitrogen Mustard (Mechlorethamine).
b. Cyclophosphamide
c. Actinomycin D.
4. Interfering with mitotic spindle formation: (Vinca Alkaloid)
a. Vincristin.
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b. Vinplastin.
Another Classification:
 ALKYLATING AGENTS:
 These are highly reactive agents, which can alkylate or bind covalenty with cellular
components of DNA.
 They interfere with mitosis producing chromosomal damage, mutation and suppression
of normal immune response by interfering DNA cross-linkage.
 This group includes:
a. Mechlorethamine (nitrogen mustard) given I.V.
b. Chlorambucil (Leukeran) given orally.
c. Cyclophosphamide (Cytoxan) given orally or parentrally.
d. Melphalan (Alkeran) given orally.
e. Busulfan (Myleran) given orally.
 ANTIMETABOLITES:
 They interfere with the cell synthesis of essential components by competing with the
natural synthesis for the enzyme involved or synthesis of un-natural cell constituents.
 They include:
a. Methotrexate (Folic acid antagonist).
b. 6-mercaptopurine (Purine antagonist).
c. 5-fluorouracil (Pyrimidine antagonist).
d. Cytosine arabinoside (Cytorabine).
 VINCA ALKALOIDS:
 They block microtubular precipitation, which is necessary for mitosis – i.e. bind with the
tubulin so interfere with the assembly of spindle proteins during mitosis.
 They include:
a. Vincristin (Oncovin) used for acute lymphoblastic leukemia.
b. Vinplastin (Velban) used for Hodgkin’s disease.
 HORMONES:
 Corticosteroids (in lymphocytic leukemia).
 Androgens (in breast cancer).
 Estrogens (in prostatic carcinoma).
 Progestines (in endometrium carcinoma).
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 ANTIBIOTICS:
 They inhibit DNA synthesis.
 They are used in cancer of stomach, colon, pancreas, breast and bladder.
 They include:
a. Actinomycin D (Dactinomycin)
b. Mithramycin (Mithracin)
c. Doxorubicin (Adriamycin)
d. Mitomycin (Mutamycin)
e. These are cytotoxic drugs (antibiotics).
 MISCELLANEOUS GROUP:
a. Procarbazine (Natulane), which is used in treatment of Hodgkin’s disease.
b. Nitrosureas is used in gastrointestinal malignancy.
c. L-asparaginase (Elspar), which hydrolyses L-aspargin, thus inhibits protein
synthesis.
 RADIOACTIVE ISOTOPES:
These are isotopes of elements that emit , , and  (gamma) ionizing radiations. But only ,
and  radiation are used in cancer chemotherapy. They cause:
 Inhibition of mitosis.
 Inhibition of bone marrow.
 Fetal abnormalities and chromosomal mutation.
 Affection of reproductive system – i.e. amenorrhea in female and sterility in male.
 They include:
a. Iodine 131:
 It has a half-life time about 8 days as NaI
131
given orally.
 It emits  and  radiation.
 Used in hyperthyroidism and thyroid cancer.
b. Gold 198:
 It has a half-life time about 2 – 7 days and is given parentrally.
 It emits  and  radiation.
 Used to inhibit ascitic and pleural effusion caused by metastatic neoplasma.
c. Sodium Phosphorus
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:
 It has a half-life time 14.3 days and is given orally or I.V.
 It emits  radiation only.
 Used in treating Polycythaemia Vera because it follows the phosphate pool in
body and concentrated in bone marrow, spleen and lymph nodes.
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d. Cobalt
ANTIDEPRESSANTS
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 TRICYCLIC ANTIDEPRESSANTS:
 They enhance the effect of biogenic catecholamines (adrenaline and nor-adrenaline) as
a result of inhibiting their reuptake in their storage sites.
 They include:
e. Imipramine (Tofranil)  dibenzazepine.
f. Amitriptyline (Tryptizol)
g. Doxepin (Sinquan)
h. Desipramine (Norpramine) dibenzocycloheptadine.
i. Nortriptyline (Aventyl)
j. Protriptyline (Vivactyl)
 MAO-INHIBITORS:
 These increase the amount of biogenic catecholamines in the synaptic cleft, by inhibiting
their breakdown – i.e. inhibit MAO, which is essential for the breakdown of
catecholamines.
 They include:
a. Hydrazine derivatives – e.g. Phenelzine and Iproniazid.
b. Non-hydrazine derivatives – e.g. Tranylcypromine (Paranate) and Paragyline
(Eutonyl).
 L-TRYPTOPHAN:
It’s an essential amino acid for the synthesis of 5-hydroxy tryptamine (Serotonin).



GABA (gamma amino butyric acid) is the main inhibitory neurotransmitter in the brain.
i.e. prevent convulsions.
 Phenobarbital: enhances transmission of GABA.
 In vitamin B6 deficiency, GABA decreases and leads to convulsions.
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 ACETAMINOPHEN (PARACETAMOL)  HEPATIC TOXICITY
 Treated with N-acetyl cystine, given I.V. within the first 2 hours.
 Charcoal to reduce absorption.
 AMPHETAMINES (BASE): (gastric lavage)
 Acidification of urine to enhance excretion.
 Barbiturates or chloropromazine to control CNS stimulation.
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 -blocker to control hypertension.
 BARBITURATES (ACIDS):
 Alkalization of urine to enhance excretion.
 Forced diuresis and artificial kidney.
 I.V. administration of dextran in case of hypotension.
 BENZODIAZEPINES (NON-BARBITURATE HYPNOTIC):
 They are safe if given 50 – 100 times their therapeutic doses.
 NARCOTICS: 0.4 mg I.V. of Naloxone.
 SALICYLATES:
 Alkalization of urine.
 Gastric lavage with NaHCO
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.
 Hemodialysis in severe cases.
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These are drugs that cause hypnosis by suppression of the reticular activating system in the
brain.
Hypnotics are classified into:
 Barbiturate hypnotics.
 Non-barbiturate hypnotics which include:
a. Paraldehyde (used in renal failure).
b. Chloral hydrate (fastest hypnotic).
c. Benzodiazepines.
d. Glutathemide
e. Ethanol
f. Carbromal (Carbacol).
g. Methyprylone.
h. Morphine and related drugs.
 OVERDOSE OF BARBITURATES:
Is treated by artificial respirator, I.V. fluids, alkalization of urine, and hemodialysis.
 PARALDEHYDE:
It’s the hypnotic of choice in renal failure because it’s mainly excreted via the lungs.
 BENZODIAZEPINES:
 They enhance GABA transmission, and used as minor tranquilizers rather than
barbiturates.
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 They are not antidepressants, less addictive and much more safer.
 Fluorazepam is the hypnotic of choice in insomnia.
 Chlordiazepoxide is the fastest hypnotic used in anxiety.
 In alcohol withdrawal, diazepam, oxazepam and chlordiazepoxide are used.
 Oxazepam and Lorazepam produce non-active metabolite and could be used in elderly
people with renal insufficiency.
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 Non-narcotic analgesics – e.g. A.S.A. (Acetyl salicylic acid) and they act on the
thalamus.
 Narcotic analgesics – e.g. Morphine and they act on both thalamus and cortex.
 MORPHINE:
a. It’s an opium alkaloid.
b. It’s contraindicated in asthmatic patients, because it releases histamine and
serotonin. It’s also contraindicated in pulmonary heart disease.
c. Miosis caused by morphine is blocked by atropine (morphine causes severe miosis
and pin-point pupil).
d. It doesn’t affect uterine contraction.
e. Morphine and its isomer to be active should be in the (-) levo form.
f. In case of morphine poisoning, gastric lavage is very important since morphine and
its metabolites are excreted in stomach.
 NALOXONE (0.4 MG I.V.):
a. It’s pure narcotic antagonist without analgesic activity.
b. It’s used as antidote of narcotic analgesic.
 CODEINE:
a. It’s methyl morphine.
b. It’s weaker than morphine in analgesia (1/4 potency).
c. It has little respiratory depression effect.
d. It has little addiction.
e. Used as antitussive (cough sedative).
 HYDROCODONE AND OXYCODONE:
a. They are potent analgesic derivatives of codeine used as antitussives and
analgesics.
b. They have analgesic effect like morphine.
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c. They are addictive.
d. Can be used in the form of suppositories.
 HEROINE:
a. It’s Diacetyl-morphine.
b. It’s class I controlled substance used for experimental work only.
c. It’s 10 times more potent than morphine as analgesic.
d. It has less antitussive and constipating properties.
 LEVORPHANOL:
a. It’s 5 times more potent than morphine.
b. It has longer duration with narcotic agonist action.
c. The dextro-rotatory form of levorphanol is Dextromethorphan, which has an excellent
antitussive effect as codeine.
d. It has no analgesic effect, non-addictive.
e. It’s used I.V. in the treatment of morphine poisoning.
 ETHYL MORPHINE (DIONIN):
a. It’s the least analgesic narcotic.
b. It can be used in ophthalmic preparations.
 MEPRIDINE “DEMEROL OR PETHEDINE”:
a. It has 1/10 the analgesic activity of morphine.
b. It has shorter duration.
c. It has some respiratory depression.
d. No miosis.
e. No antitussive.
f. Has less constipation.
g. Has less addiction.
 PROPOXYPHENE “DARVON”:
a. It has less analgesic potency than codeine and has no addictive properties.
b. It’s structurally related to methadone but less potent.
c. 12 – 15 times less potent than morphine.
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 ACID LABILE + PENICILLINASE SENSITIVE:
a. Crystalline Penicillin.
b. Procaine Penicillin.
c. Benzathine Penicillin (L.A.)
d. Carbenicillin.
e. Ticarcillin
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 ACID STABLE + PENICILLINASE SENSITIVE:
a. Phenoxymethyl Penicillin (Penicillin V).
b. Benzyl penicillin (Penicillin G).
c. Ampicillin (-aminobenzyl penicillin).
d. Amoxicillin.
e. Carbenicillin indanyl.
 ACID LABILE + PENICILLINASE RESISTANT:
a. Methicillin.
 ACID STABLE + PRNICILLINASE RESISTANT:
a. Oxacillin.
b. Cloxacillin.
c. Dicloxacillin.
d. Naficillin.
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 All penicillins and their analogues exhibit cross sensitivity.
 Staphylococcus and pseudomonas groups produce penicillinase enzyme.
 Penicillin acts by inhibiting the bacterial cell wall synthesis.
 General structure of Penicillins:
a = -lactam ring
b = Thiozolidine ring




 Substitution of R- affects solubility.
 Salts that are water-soluble can be given orally.
 Esters – e.g. procaine and benzathine are poorly soluble and thus are given by I.M.
route only (long acting).
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It’s the reference standard – i.e. the antibiotic activity of 0.6 g of USP sodium penicillin G.
1 unit = 0.6 g
1600 unit = 1 mg penicillin G
500 000 units = 300 mg penicillin G
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Substitution of “R” affects the stability of the -lactam ring.
 ACID-LABILE AND PENICILLINASE SENSITIVE:
R = -CH2- (Benzyl Penicillin or Penicillin G)
R-CoNH
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 ACID-STABLE AND PENICILLINASE SENSITIVE:
R = - O – CH2- (Phenoxymethyl penicillin or Penicillin V)
R = -CHNH2- (-aminobenzyl Penicillin or Ampicillin)
R = HO- - - CHNH2 - (p-hydroxy--aminobenzyl penicillin or Amoxycillin)
 ACID-LABILE AND PENICILLINASE RESISTANT:
R = 1, 6-dimethoxy phenyl penicillin Or Methicillin
N.B. the side chain is rresistant to hydrolysis by penicillinase.
R = -carboxy benzyl penicillin or Carbenicillin
R = CH – O – C - - CH2 - -carboxy-3-thimyl methyl penicillin or Ticarcillin
N.B. both Carbenicillin and Ticarcillin are broad spectrum and effective against pseudomonas
and sensitive to penicillinase.
 ACID AND PENICILINASE RESISTANT:
R = Oxaxillin
R = Cloxacillin
R = Dicloxacillin
OCH
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R = Naficillin
Types of Insulin Preparations
Insulin Type Product Onset Duration
1. Fast acting Insulin  Acid regular insulin
 Neutral regular insulin
 Semilent insulin (suspension of small
particles
1 hour 5 – 12
hours short
acting
insulin
2. Intermediate acting
insulin
 Isophan insulin suspension
 Insulin zinc suspension
 Globin zinc insulin
 NPH & Lent
 Lent = 30% semilent + 70% ultralent
2 hours 12 – 24
hours
3. Long acting insulin  Protamine zinc insulin (PZI)
 Extended insulin Zn (ultralent, which
is a suspension of large particles)
6.8 hours > 36 hours
 MECHANISM OF ACTION OF INSULIN:
a. Enhances utilization of glucose by peripheral tissues.
b. Increases the storage of glucose in the form of glycogen in the liver and skeletal
muscles by enhancing glucose-6-phosphate formation by enhancing the Hexokinase
enzyme.
c. It’s anabolic, thus enhances protein synthesis.
d. Decreases fat catabolism and enhance lipogenesis.
e. Decreases Gluconeogenesis (i.e. conversion of amino acids into glucose).
N.B. the term “Single Peak” indicates insulin that displays a single protein peak when assayed
chromatographically.
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