ODISHA STATE BOARD OF PHARMACY
D. Pharm - II Examination - 2014 (II)
PHARMACOLOGY & TOXICOLOGY (THEORY)
Time - 3 Hours Full Marks - 80
__________________
(Answer any five questions including question no-1)
1. A. Fillin the blanks
1x10
i. _______ is the prime drug in treatment of Leprosy.
ii. Streptomycin is mainly used in the treatment of _______.
iii. Deficiency of Niacin causes _______ .
iv. Cardiac glycosides are used in treatment of _________.
v. Heparin in used in the treatment of ________ .
vi. A diuretic also used in the treatment of Glaucoma is ________ .
vii. Methotrexate is used in treatment of ________.
viii. Acetyl choline is not effective by _________ route.
ix. Verapamil and Nifedipine are __________
x. Natorphine is principally used in the treatment of _______
B. Define the terms
2x5
(i) Pharmacodynamics
(ii) Analeptics
(iii) Tolerence
(iv) Purgatives & Antacids
(v) Triple response
2. Write short notes on any two
7.5 x2
(a) Proton pump Inhibitors
(b) Drugs used in Asthma
(c) Metronidazole
3. Explain general anaesthetics, briefly describe the different stages of general anaesthesia. Write a note on Barbiturates.
2+5+8
4. Define and classify opioid analgesics. Write the pharmacological action. uses and adverse effects of Morphine.
6+9
5. A. Role of Alkylating agents and Antimetabolites in Cancer.
7.5
B. Pharmacological actions & uses of Atropine
7.5
6. Write the mode of action, uses and adverse effects of
3×5
(a) Penicyjllins
(b) Dapsone
(c) Rifampicin
7. Define and Classify Antimalarials ? Write a note on Pharmacological action, adverse effects & uses ofchloroquine.
6+9
ANSWER TO 2014
1. A.
(i) Dapsone
(ii) Tuberculosis
(iii) Pelegra
(iv) Congestive heart failure
(v) Thrombus/clot as anticoagulast
(vi) Acetazolamide
(vii) Cancer
(viii) Oral
(ix) Calcium channel blockers
(x) Morphine poisoning
B. Define the terms
(i) Pharmacodynamics
Ans.
It is the study of effect of drug on the body. It includes study of mechanism of action of drug.
(ii) Analeptics
Ans.
They stimulate the central nervous system and in large doses, they cause generalized convulsion.
(iii) Tolerence
Ans.
It is a dose related term. It occurs when higher dose of a drug is required to show same effect.
(iv) Purgatives & Antacids
Ans.
Purgatives action. It is a drug which promote defectation. It is used in the treatment of constipation. Antacids - These are the drugs which neutralise gastric acid.
(v) Triple response
Ans.
Triple response - On intradermal injection, histamine produces a triple response which consists of local redness (flush) and local oedema (wheal).
2.
(a) Proton pump Inhibitors in
Ans.
Proton pump inhibitors : These are the drugs which inhibit proton pump (H + K+ ATpase) in the parietal cells of GIT.
Ex-Omeprazole, Pantoprazole, Rabeprazole, Lansoprazole.
They inhibit acid secretion & are useful in peptic ulcer.
Use : (1) Peptic ulcer, (2) Zollinger Syndrome, (3) Gastro esophageal reflux disease
Adverse effect : headache, dizziness, nausea
(b) Drugs used in Asthma
Ans.
Drugs used in Asthma - Bronchial asthma is characterised by periodic spasm of bronchial smooth muscles, increased secretion and edema of bronchial mucosa. Because of the spasm, large volume of air remains locked in the alveoli. This decreases tidal air and vital capacity leading to dyspnea.
Classification of drugs : Drugs used for the treatment of bronchial asthma can be classified as
1. Bronchodilators
a) Sympathomimetics (Adrenaline Ephedrine , Isoprenaline Orciprenaline Salbutamol)
b) Methyl xanthines (Theophy Iline)
c) Anticholinergics ( Atropine, Ipratropium bromide)
2. Mast cell stabilisers (Disodium chromoglycate, Ketotifen)
3. Corticosteroids (Beclomethasone dipropionate.)
(c) Metronidazole
Ans.
Mechanism: The nitro group in metronidazole serves as on electron acceptor. Reduced etronidazole is cytotoxic to entamoeba.
Pharmacokinetic:
It isorally absorbed well and distributed throughout tissues reaching body fluids. It can cross placenta. It is excreted in saliva and urine.
Side effect:
Metallic, bitter taste in mouth, Urethra burning, Dark colour urine
Use:
(i) Both mtestinal and extra intestinal amoebiasis
(ii) Gingivitis
(iii) Giardiasis
(iv) Trichomoninasis
3. Fxptain general annesthetics, briefly describe the different stages of general anaesarthesin. Write a note on Barhbiturates.
Ans.
Gieneral anaesthetics depress the central nervous system and produce loss of consciousness. General anacsthesia is the controlled, reversible depression of the function activities of the central nervous system producing loss of sensation and consciousness. the stages of anaesthesia vary for all agent producing general anaesthesia.
Stage I (Cortical stage) : Analgesia is produced, consciousness persists, but the patient is sleepy due to depression of the higher cortical centres.
Stage II (Excitement) : Loss of consciousness occurs, but depression of higher centres involving the brain stem and the cerebellum leads to excitement and delirium.
Stage III (Surgical Anaesthesia) : The activity of spinal cord reflexes is minimized, and skeletal muscle relaxation is obtained. In this stage most of the operations are performed.
Stage IV (Meduillary Paralysis) : Respiratory failure and vasomotor collapse occur due to depression of vital functions of the medulla and the brain stem.
Classification :
Volatile: general anaesthetics: (inhalation anaesthetics)
(a) Liquids: Diethy! ether, Chloroform, Halothane, Enflurance, Ethyl chloride, Trichloroethylene, Methoxyflurane, Fluorexene.
(b) Gases: Cyclopropane, Nitrous oxide, Ethylene.
2. Non volatile general anaesthetics: (intravenous Anaesthetics)
(a) Ultra short acting Barbiturates Thiopental sodium; Methohexital.
(b) Non-barbiturates
(i) Eugenol derivative: Propandid
(ii) Phecyclidine derivative: Ketamine
(iii) Steroid: Althesin
(iv) Etomidate Barbiturates :
Barbiturates are derivatives of barbituric acid: (malonylurea) which is obtained by the condensation of urea and malonic acid.
Barbituric acid itself doves not possess hypnotic activity But hypnotic activity is produced, if the hydrogen at Position 5 are replaced by alkyl or aryl groups.
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Classification of barbiturates :
1. Long acting (Phenobarbitone, mephobarbitone)
2. Short acting (Butobarbitone, Secobarbitone, Pentobarbitone)
3. Ultrashort acting (Thiopentone, Hexobarbitone,Methohexitone)
Pharmacological actions :
(i) Central nervous system : Barbiturates produce all degrees of CNS depression like mild sedation, hypnosis and general anaesthesia.
a. Sleep : Barbiturate-induced sleep resembles natural sleep. But it decreases the time spent on ‘rapid eye-movement sleep’. Also there is hangover effect after awakening. ,
b. Analgesic effect : Barbiturates do not receive pain without producing unconsciousness. But they enhance the analgesic effect of salicylates and paraamino phenol derivatives.
c. Anaesthetic effect : Thiobarbiturates and some ultra short acting oxybarbiturates produce anaesthesia on intravenous administration.Ex: Thiopentone
d. Anticonvulsant effect : Barbiturates like phenobarbitone which have a phenyl group at the Sth carbon atom have anticonvulsant effect.
e. Respiration : Respiration is not affected at sedative or hypnotic dose. Large dose administered intravenously may produce death due to central respiratory paralysis.
(ii) Gastrointestinal tract : Intestinal motility is not affected at a normal dose, but gastric secretion may be depressed.
(iii) Uterus : Force and frequency of uterine contractions are depresssed at toxic dose.
(iv) Kidney : No effect at normal dose, but anaesthetic dose decreases urinary output due to decrease in glomerular filtration and release of ADH.
(v) Liver : No effect at normal dose but anaesthetic ; dose may produce hepatic dysfunction.
Absorption, fate and excretion :
Barbiturates can be administered by oral and parenteral routes. They are distributed in all tissues and fluids. They cross placental barrier and also are excreted in milk. They are chiefly metabolised in the liver and to a small extent in kidney and brain. Excretion is through urine both in free form and as glucuronic acid conjugate.
Adverse reactions :
1. Intolerance like nausea, headache and diarrhoea,
2. Foetal respiratory depression if administered during labour.
3. Drug automatism due to repeatedly taking the drug owing to forgetfulness. .
4. Tolerance because of increased inactivation in the liver.
5. Dependence and withdrawal symptoms.
Therapeutic uses :
1. Sedation in case of anxiety or tension.
2. Hypnosis to relieve insomnia.
3. Anticonvulsant effect in case of tetanus or status epilepticus.
4. Pre-anaesthetic medication and to produce basal anaesthesia.
5. Potential of analgesics like salicylates.
6. In psychiatric practice and in neonatal jaubdice.
4. Define and classify opioid analgesics. Write the pharmacological action. uses and adverse effects of Morphine.
Ans.
Narcotic
(i) These are opioid analgesics.
(ii) They act centrally
(iii) They are habit forming.
(iv) Example: Morphine, Heroine
(v) They can be natural, Semisynthetic or Synthetic
Non-Narcotic
(i) | These are non steroidal anti-inflammatory drugs (NSAIDs).
(ii) | They act peripherally.
(iii) They are not habit forming.
(iv) Example : Ibuprofen, Paracetamol.
(v) They are all synthetic.
Classification of Opioid analgesics :
1. Natural opium alkaloids
a) Phenantherene derivatives (Morphine ,Codeine)
b) Benzylisoquionoline derivatives (Papaverine, Noscapine)
2. Semisynthetic derivatives of Opium alkaloids : Herioin Dihydromorphine Apomorphine 3. Synthetic substitutes of opium alkaloids : Pethidine Methadone Butorphanol . Pentazocine Nalbuphine Buprenorphine
Pharmacological actions :
1. Analgesia : Morphine relieves severe pain like visceral pain and trauma. The mechanisms are :
i. it elevates the threshold for painful stimulus.
ii. it alters the emotional reaction to pain.
iii. it produces sleep which also elevates the threshold.
2. Central nervous system : Morphine produces euphoria in presence of pain. But in the absence of pain, it produces dysphoria. With an increased dose, it produces sleep.
3, Respiration : Morphine produces depression of respiration by
a) directly depressing the respiratory centre
b) decreasing the sensitivity of respiratory centre to carbondioxide.
4. Pupil : Morphine produces constriction of pupil (miosis). This effect is blocked by atropine. Morphine addicts have constricted pupil (pin point pupil).
5. Emetic action : In small doses, morphine produces vomiting due to the stimulation of chemoreceptor trigger zone (CTZ).
6. Antitussive effect : Morphine suppresses cough by depressing the cough centre.
7. ADH Secretion : Morphine produces release of ADH. This results in decrease of urinary output.
8. Gastrointestinal tract : Morphine decreases peristaltic propulsive movements. It produces spasm of intestinal smooth muscles and sphincters. It also increases absorption of water. All these effects lead to constipation.
9. Biliary tract : Morphine produces spasm of Sphincter of oddi. This produces increase in intrabiliary pressure. Atropine antagonises this effect.
10. Other smooth muscles —
(i) Morphine increases the tone of detrusor muscle Of urinary bladder and produces urinary urgency.
(ii) It increases tone of ureter and decreases its peristalsis.
11.Cardiovascular System : Normal dose of morphine produces no effect on heart or circulation. But hypotension may be produced at toxic dose.
Absorption, fate and excretion :
Absorption of morphine from gastrointestinal tract is slow and incomplete. Quick effect is produced on subcutaneous injection. It is partly bound to plasma proteins. It is metabolised by conjugation with glucuronic acid. It is almost completely excreted in urine within 24 hours.
Adverse reactions :
1. Central effects like dysphoria and mental clouding.
2. Gastrointestinal symptoms like nausea, vomiting and constipation.
3. Intolerance like tremor, delirium and skin rashes.
4. Acute morphine poisoning characterised by respiratory depression pin point pupil, cyanosis, reduced body temperature, hypotension, shock and coma.
5. Depression of foteal respiration.
6. Tolerance and drug depednece.
Therapeutic uses :
1. Asan analgesic for the relief of severe pain.
2. For producing sedation and sleep.
3. As pre-anaesthetic medication.
4. Inthe treatment of acute left ventricular failure.
5. For the treatment of diarrohea.
6. Asan antitussive.
5.A. Role of Alkylating agents and Antimetabolites in Cancer.
Ans.
Malignant tumours are called concers. They are characterised by
(i) uncontrolled proliferation
(ii) defifferentiation
(iii) invasiveness
(iv) metastasis
The drugs used in treatment of cancer are called anticancer drugs.
Classifications:
(a) Cytotoxic Agents .
(1) Alkylating agents .
(a) Nitrogen mustards: Cyclophosphamide , Chlorambucil
(b) Ethylene imines: Triethylene melamine (TEM) | Thio - TEPA
(c) Alky sulphonate: Busulphan, Treoshulphan
(d) Nitrosoureas: Commustine, Lornustine
(e) Triazines: Triazines, Dacarbazine, Procarbazine .
2. Antimetabolites -
(a) Folate antagonist: Ex.: Methotreaxate
(b) Purine antagonist: 6-thio guanine .
(c) Pyrimidine antagonist: 5-fluorouracil .
3. Antibiotics:
Actinomycin D, Mitomycin C , Doxorubicin . Bleomycin
4. Plant derivatives
(a) Vinca alkaloids: Vincristine, Vinblastine
(b) Epipodophylilotoxins: Etoposide
(c) Taxanes: Paclitaxel
(d) Compothecins: Rubitecan
5. Platinum compounds: Cisplatin
B. Hormones and hormone antagonists .
(a) Hormones: Estrogens Progestines Androgens Glucocorticoids ’
(b) Hormone antagonisis Finasteride Flutamide Formestane Tamoxifen
(c) Radioactive tsotopes: 131I, 32P, 198Au
(d) Enrymes:
Crisantaspase or L-asparaginase
Mechanism of alkylating agents:
They introduce alkyl groups to nucleophilic moicties in DNA or RNA such as phosphate, sulfhydryl, hydroxyl, carboxyl etc. This cross links in between the strands of DNA which prevents the cell division and protein synthesis. Hence they kill the cells and are called cytotoxic agents.
Mechanism of Antimetabolites:
They are analogues of cither purine or pyrimidine bases of DNA or RNA. Hence they are incorporated in the DNA instead of the pure bases and inhibit cell division and protein synthesis. Methotrexate is a folate antagonist which also inhibits the DNA synthesis.
B. Pharmacological actions & uses of Atropine
Ans.
(a) CNS: Prevents motion sickness Release ADH from pituitary gland
(b) CVS: Increase heart rate which returns to normal
(c) Respiratory system: Inhibit secretion of nose, mouth, pharynx and bronchi.
(d) GIT : decrease tone, motility and peristalsis of GIT, decrease GI secretions.
(e) Smooth muscles of ureters. urinary bladder, gall bladder Spasmolytic Smooth muscle relaxation
(f) Glands: Decrease secretions
(g) Eye: Causes dilation of pupil (mydriasis) does not alter intra occular pressure, relaxes ciliary muscle, cause paralysis of accomodation which leads to impaired near vision.
(h) Skin: Decrease sweet secretion increase body temp and cause dry skin. Uses of atropine
(i) anti spasmodic
(ii) anti-ulcer
(iii) pre-anasesthetic
(iv) organophosphate poisoning
(v) anti-parkinsonian
(vi) mydriatic
6. Write the mode of action, uses and adverse effects of
(a) Penicillins
Ans.
Penicillins :
Classification : (Generation wise)
(a) Ist generation : Pencilling G Pencillin V
(b) 2nd generation : Ampicillin, Amoxicillin
(c) 3rd generation : Carbenicillin, Propenicillin
(d) 4th generation : mezlocillin, azlocillin
Source wise classification :
(a) Natural : Benzyl pencillin
(b) Semisynthetic : Ampicillin Amoxicillin
Mechanism of action :
Penicillin is a bactericidal drug. It acts by inhibiting the synthesis of bacterial cell wall. This action is produced by inhibiting the synthesis and cross linkage of peptidoglycans.
Adverse reactions / Toxicity :
The adverse reactions of penicillin are :
(i) Intolerance which includes allergic and anaphylactic reactions. Allergy which the major problem with penicillin may occur in the form of skin rashes, renal disturbances and hemolytic anemia. The manifestations of anaphylaxis are cardiovascular collpase, bronchospasm and angioedema.
(ii) Superintection with Klebsiella, Aerobacter and Candida,
(b) Dapsone
Ans.
DIAMINO DIPHENYL SULFONE (DDS, Dapsone) :
Dapsone is chemically related to sulfonamides. It is bacteriostatic. It acts by competitively inhibiting the use of PABA and inhibits synthesis of folic acid required for bucterial growth.
Adverse reactions.
1. Sensitisation of skin leading to exfoliative dermatitis,
2. Hemolysis in patient with G-6-PD deficiency.
3. Blood dyscrasias like agranulocytosis.
4. Hypothyroidism and goitre.
Dose: Tablets of dapsone administered at a dose + of 100 mg. daily.
Use : antileprosy
(c) Rifampicin
Ans.
It is semisynthetic derivative of rifamycin B (isolated from Streptomyces mediteranei). It is bactericidal and it acts by inhibiting DNA dependent RNA polymerase. It is well absorved on oral administration. It is widely distributed in tissues. It is metabolished to desacety] rifampicin. This metabolite is equally tuberculocidal and undergoes enterohepatic circulation.
Use : (i) anti-bubercular (ii) antileprosy.
7. Define and Classify Antimalarials ? Write a note on Pharmacological action, adverse effects & uses of chloroquine.
Ans.
Antimalarial Drugs :
These are the drugs used in treatment of malaria.
(a) Chemical classification :
1. Cinchonaalkaloids: Quinine ,
2. 4-aminoquinolines: Chloroquine, Hydroxychloroquine, Amodiaquine
3.’ 8-aminoquinolines: Pamaquine, Primaquine, Pentaquine
4. Acridines: Mepacrine
5. Biguanides: Progunail,Chlorproguanil, Cycloguanil
6. Diamidopyrimidines: Pyrimethamine
7. Artemisinin derivatives: Artesunate, Artemether
8. Miscellaneous: Mefloquine, Halofantrine
(b) Therapeutic classification :
(i) Causal prophylactics : They are primaquine, proguanil and pyrimethamine. These drugs prevent the maturation of sporozoites in the liver. So the liberation of merozoites from the liver is prevented.
(ii) Suppressives : They are quinine, chloroquine, mepacrine, proguaniland pyrimethamine. These drugs prevent the rupture of erythrocytes . The liberation of merozoites is prevented. This prevents fever and chill.
(iii) Radical curative : They are pamaquine, primaquine and pentaquine. These drugs eradicate exoerythrocytic phase. So relapse of fever is prevented.
(iv) Gametocides : Most of the antimalarial: drugs have gametocidal effect. Destruction of gametocytes prevents a fresh individual from getting malarial infection. Ex: Primaquine .
Chloroquine :
It is a 4 aminoquinoline derivative. It has a suppressive effect like quinine. It acts by inhibiting the incorporation of phosphate into RNA and DNA of plasmodia Chloroquine inhibits haem polymerase and hence inhibit the conversion of toxic haem to neutral haemazoin. This accumulates the toxic haem to kill the parasite. The other actions of chloroquine are ,
(i) Effectiveness against giardiasis, taeniasis and extraintestinal amoebiasis.
(ii) Anti-inflammatory and antihistaminic effect.
(iii) Local anaesthetic and anticholinesterase activity.
(iv) Depressant effect on myocardium.
Absorption, fate and excretion :
Chloroquine is well absorbed from gastrointestinal tract. It is distributed in liver, spleen, kidney and lungs. It is metabolised in the liver and eliminated in urine.
Adverse Reactions :
(i) Intolerance in the form of skin rashes, bleaching of the scalp hair, eye lashes and eyebrows.
(ii) Visual disturbances like loss of accommodation, blurred vision, diplopia, difficulty in focussing eyes and lenticular opacities (collecfively called chloroquine retinopathy).
Use
(1) antimalarial
(2) anti-amoebic
___________
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