WRITE DOWN THE RATIONAL OF FOLLOWINGS:

1. Aspirin in post myocardial infarction.ANS: By inhibiting the platelet aggregation aspirin lowers the incidence of reinfarction. TXA2 synthesis in platelet is inhibited in low doses. Aspirin reduces the transient ischaemic attack and lowers the incidence of stroke in such patients. But the risk of stroke in post MI patients is not reduced. Dose: 60-100 mg/dayBut it has been argued that high dose can reverse the beneficial effects concurrently inhibiting PGI2 synthesis in vessel wall.

2. Disulfuram in alcoholism:ANS: Disulfuram has been used as an aversion technique in chronic alcoholics who are motivated and sincerely desire to leave the habbit. It inhibits the enzyme aldehyde dehydrogenase probably after conversion into active metabolites. When alcohol is ingested after taking disulfuram, the concentration of acetaldehyde in tissue and blood rises and a number of highly distressing symptoms (aldehyde syndrome) are produced promptly. Due to which the person stops the drinking.

3. Folic acid in pregnancy: ANS: Folic acid is used in the pregnancy due to the increased demand to meet the metabolic functions of the body and prevents the anaemia in pregnancy. Folic acid is vital to support the healthy development of a baby’s brain and spinal cord. Before you are even aware that you’re pregnant, your baby’s brain and spinal cord are already forming. By having enough folic acid in your blood at this important time you help to ensure that they develop properly. Many women don't realise that taking folic acid can help to avoid the possibility of some very serious consequences.

4. Naloxone used for morphine poisoning:ANS: Naloxone is the drug of choice for morphine poisoning. It is N-alylnor-oxymorphine and a competitive antagonist on all type of opioid receptors. However, it blocks µ- receptors at much lower dose than those needed to block kappa and delta receptors. So, it blocks the effects of morphine completely.

5. Acetazolamide in mountain sickness:ANS: Acute altitude sickness usually occurs during the first few days at altitude, before respiratory acclimatization is complete. Thus at high altitudes, climbers hyperventilate in response to lower oxygen levels. This results in reduced carbon dioxide(an acid) and reduced oxygen level in the body.Herein, lies the rational for prophylaxis with acetazolamide inhibits renal carbonic anhydrase causing bicarbonate dieresis and extracellular acidosis.Acetazolamide has, however been shown repeatedly to lower blood pH, improve blood gas, and improve symptoms scores for acute mountain sickness.In nephron, CO2 is lipophilic and rapidly diffuse across the luminal membrane into the epithelial cell, where it reacts with water to form bicarbonate, a reaction catalyzed by cytoplasmic carbonic anhydrase. Acetazolamide increases CO2 levels in peripheral tissues and decrease CO2 levels in expired gas.It is usefull in treating established acute mountain sickness. Doses used have varied from 250mg to 1 gm, and probably 500mg daily as a sustained release preparation begun in nthe 24 hours before ascent is adequate.

6. Sublingual nitroglycerine tablets:ANS: When nitroglycerine is administered orally, most of each dose is destroyed on its first pass through liver. The sublingual route is used when terminating an attack or aborting an imminent one is the aim. The tablet may be crushed under the teeth and spread over the buccal mucosa. It acts within 1-2 min because of direct absorption into the systemic circulation bypassing the liver where 90% is metabolized.

7. Sodium intake is restricted in hypertension:ANS: salt is essential to our bodies. Normally the kidneys control the level of salt. If there is too much salt, the kidneys pass it into urine. But when our salt intake levels are very high, the kidneys can not keep up and the salt ends up in our bloodstream. Salt attracts water. When there is too much salt in the blood, the salt draws more water into the blood. More water increases the volume of blood which raises blood pressure. Almost 80% of the average person’s daily salt intake comes from processed foods. If we ate only natural foods and limited the use of table salt, we would be able to eliminate excess salt in our body.

A lower sodium diet is good for people who are older, who are of African American descent, or who have high blood pressure or diabetes. These folks should limit their sodium intake to no more than 2300-2400mg a day.people with heart failure or kidney disease are advised to keep their sodium intake under 2000mg per day.

8. Atropine is given in organophosphorus poisoning:ANS: Atropine is the specific antidote for anticholinesterase ( organophosphate) so, it is highly effective in counteracting the muscarinic symptoms, in higher doses it also antagonize the central effects. It does not reverse the peripheral muscular paralysis which is a nicotinic action. In all cases of anti-ChE (carbamate or organophosphate) poisoning must be promptly given atropine 2mg i.v. repeated every 10 min till dryness of mouth or other signs of atropinization appear. Continued treatment with maintainance dose may be required for 1-2 weeks.

9. Salicylates are not given in empty stomach:ANS: The most important adverse effect of salicylate is gastric mucosal damage and peptic ulceration especially when given in empty stomach. This is due to the inhibition of COX-1 mediated synthesis of gastroprotective prostaglandins i.e. PGE2, PGI2.deficiency of PGEs reduces mucus and HCO₃⁻ secretion tends to enhance acid secretion and may promote mucosal ischaemia leading to peptic ulceration and the chance of inhibition of PGs synthesis is more when given in empty stomach. So, these drugs are not used in empty stomach.

WRITE DOWN THE RATIONAL OF:10.Carbidopa and le vodopa combination:

ANS: Levodopa undergoes high first pass metabolism in gastrointestinal mucosa and liver. About 1% of administered levodopa that enters brain when used alone. Carbidopa is an extracerebral dopa decarboxylase inhibitors; they do not penetrate the blood-brain barrier and do not inhibit conversion of levodopa to dopamine in the brain. Administered along with levodopa, they increase its half-life in the periphery and make more of it available to cross blood-brain barrier to reach its site of action.

The benefits of the combination are:

i. The plasma half-life of levodopa is prolonged and its dose is reduced to approximately 1/4th.

ii. Systemic concentration of dopamine is reduced, nausea and vomiting are not prominent, therapeutic dose of levodopa can be attained quickly.

iii. Cardiac complications are minimized.iv. Pyridoxine reversal of levodopa effects does not occur.v. “on-off” effect is minimized since cerebral dopamine levels are

more sustained.vi. Degree of improvement may be higher; some patients, not

responding adequately to levodopa alone, also improve.

Combination of levodopa with carbidopa has been given the name

“co-careldopa”.

11. Furosemide with amiloride:ANS: furosemide is high efficacy loop diuretics and inhibits the Na⁺-k⁺-2Cl⁻ cotransport in ascending limb of loop of hanle. Potassium excretion is increased due to high sodium load reaching distal tubule.

Amiloride is non-seroidal organic bases which cause decrease potassium excretion, particularly when it is high due to large K⁺ intake or use of diuretic that enhances K⁺ loss i.e. furosemide. Unlike spironolactone their action is independent of aldosterone.They act on luminal membrane of distal tubule cells to inhibit elecrogenic Na⁺ reabsorption.

Therefore, by giving these two drung in combination the level of K⁺ can be maintained in the blood and the risk of hypokalemia is minimized.

12.Nifidipine and beta-blockers:ANS: Nefidipine is a calcium channel blocker which cause reflex tachycardia, increased contractility and cardiac output.

Beta-blockers cause ventricular dilatation.

By giving combination of these two drugs, following advantages can be achieved:

I. Reflex tachycardia due to CCBs is blocked by beta-blockers.II. The tendency of beta-blockers to cause ventricular dilatation is

counteracted by CCBs.III. The tende3ncy of beta-blockers to reduce total coronary flow is

opposed by CCBs.

13. Thiazide and spironolactone:ANS: Thiazidse diuretics cause hypokalemia by increasing the loss of potassium leading to weakness, fatigue, muscle cramps, cardiac arrhythmias. Decrease plasma potassium level also inhibits the release of insulin leading to hyperglycemia.

Spironolactone is a aldosterone antagonist. It blocks the receptor on which aldosterone acts. This leads to inhibition of reabsorption of sodium and inhibition of secretion of potassium in the late part of distal tubule resulting in i9ncreased excretion of sodium and retention of potassium in the body.

So, by giving these two drugs in combination, the level of potassium can be maintained in the body and the risk of hypokalemiaa is minimized.

14. Classify antipsychotic and antiepileptic. Explain pharmacological action and use of chlorpropamide and carbamazepine:

ANS: Psychoses are the severe psychiatric illness with serious distortion of thought, behavior, capacity to recognize reality and of perception (delusions and hallucinations). There is in explicable misperception and misevaluation; the patient is unable to meet the ordinary demands of life.

Anti-psychotic drugs are the agents having primary effects on psyche (mental process) and are used for treatment of psychiatric disorders.

CLASSSIFICATION OF ANTI-PSYCHOTIC DRUGS:

I. Phenothiazines: Chlorpromazine Triflupromazine Trifluperazine

II. Butyurophenones: Haloperidol Trifluperidol Penfluperidol

III. Thioxanthenes: Flupenthixol

IV. Other heterocyclics: Pimozide Loxapine

V. Atypical antipsychotics: Clozapine Risperidone Olanzapine Ziprasidone

Pharmacological actions of chlorpromazine:

a) CNS: effects differ in normal and psychotic individuals:In normal individuals chlorpromazine produces indifference to surroundings, paucity of thought, psychomotor slowing, emotional quietening, reduction in initiative and tendency to go off to sleep from which the subject is easily arousable. Spontaneous movements are minimized butr slurring of speech, ataxia or motor incoordination does not occur.

In a psychotic individual, chlorpromazine reduces irrational behavior, agitation and aggressiveness and controls psychotic symptomology. Disturbed thought and behavior are gradually normalized, anxiety is relieved. Hyperactivity, hallucination and delusions are suppressed.

b) ANS: chlorpromazine have varying degree of alpha adrenergic blocking activity. It also have a weak H₁-antihistamine and anti-5HT actions as well.

c) Local anaesthetics: chlorpromazine is as potent a local anaesthetic as procaine. However, it is not used for this purpose because of its irritant action.

d) CVS: high dose of chlorpromazine directly depress the heart and produce EEG changes. Chlorpromazine exerts some antiarrhythmic action, probably due to membrane stabilization. Arrhythmia may occur in overdose.

e) Skeletal muscle: neuroleptics have no effect on muscle fibres or neuromuscular transmission. They reduce certain types of spasticity; the site of action being in the basal ganglia or medulla oblongata. Spinal reflexes are not affected.

f) Endocrine: neuroleptics consistently increase prolactin release by blocking the inhibitory action of dopamine on pituitary lactotropes. This may result in galactorrhoea and gyaecomastia.

Uses of chlorpromazine:

i. Psychoses: Schizophrenia Mania Organic brain syndromes

ii. Anxietyiii. As anti-emeticsiv. Other uses:

To potentiate hypnotics, analgesics and anaesthetics. Tetanus, CPZ is secondary drug to achieve muscle relaxation. Alcoholic hallucinations.

CLASSIFICATION OF ANTI-EPILEPTICS:

i. Barbiturates: Phenobarbitone

ii. Deoxybarbiturate: Primidone

iii. Hydantoin:

Phenytoin Fosphenytoin

iv. Iminostilbene: Carbamazepine Oxcarbazepine

v. Succinimide: Ethosuximide

vi. Aliphatic carboxylic acid: Valproic acid Divalproex

vii. Benzodiazepines: Clonazepam Diazepam Lorazepam Clobazam

viii. Phenyltriazine: Lamotrigine

ix. Cyclic gaba analogue: Gabapentin

x. Newer drugs: Vigabatrin Topiramate Tiagabine Zonisamide

Uses of carbamazepine:a) Complex partial seizuresb) General tonic clonic seizurec) Simple partial seizured) Trigeminal and related neuralgiase) Manic depressive illness and acute mania.

15.Describe the pharmacotherapy of hypertension and gout:ANS: the general principles of antihypertensive therapy enunciated in JNC7 and WHO-ISH guidelines is as follows:

a) Except for stage-2 hypertension, starts with a single most appropriate drug which for majority of patients is thiazide. However, a beta-blocker, ACE inhibitor or CCB may also be considered.

b) Initiate therapy at low dose; if needed increase dose moderately. Thiazide dose should be 12.5-25mg/day hydrochlorthiazide or equivalent.

c) Majority of stage-2 hypertension are started on a 2 drug combination; one of which usually is a thiazide diuretic.

d) If only a partial response, add a drug from another complimentary class or change to low dose combination.

e) If no response, change to a drug from another class or low dose combination from another classes.

f) In case of side effect to the initially choosen drug, either substitute with drug of another class or reduce dose and add a drug from another class.

Drugs and their doses:

Hydrochlorthiazide- 12.5 mg OD Furosemide-20-80mg/day Atenolol-25-50mg OD Amlodipine-2.5-5mg OD Lisinipril-2.5-5mg OD Losarton-25-50mg OD

Pharmacotherapy of gout:

For acute gout:

a. NSAIDs: one of the strong anti-inlammatory drugs, e.g. indomethacin, naproxen, piroxicam, or etoricoxib is given in relatively high dose and quickly repeated doses. They are quite effective in terminating the attack.

b. Colchicines is neither analgesic nor anti-inflammatory, but it especially suppress gouty inflammation. It does not inhibit the synthesis or promote the excretion of uric acid. Thus, it has no effect on blood uric acid levels.

c. Corticosteroids: intraarticular injection of a soluble steroid suppress the symptoms of acute gout. Crystalline preparations should not be used. It is indicated in refractory cases and those not tolerating NSAIDs/ colchicines. E.g. prednisolone 40-60mg/day

For chronic gout:a. Uricosuric drugs:

Probenecid: uric acid is largely reabsorbed by active transport, while less of it is secreted; only 1/10th of filtered load is excreted in urine. Probenecid therefore, promotes its excretion and reduces its blood level.

Dose 0.25-0.5mg BD Sulfinpyrazone: it is a pyrazolone derivative related to

phenylbutazone having consistent uricosuric action, but is neither analgesic nor anti-inflammatory. At the usual therapeutic doses, it inhibits tubular reabsorption of uric acid.

Dose: 100-200mg BD.

b. Uric acid synthesis inhibitors: Allopurinol: allopurinol is the first choice drug in chronic gout.

It can be used in both over producers and under excretors of uric acid, particularly more serious case, with tophi or nephropathy.

Dose start with 100mg OD , gradually increase to maintenance dose of 300mg/day; maximum 600mg/day

16.Describe vasomotor reversal of dale:ANS: Rapid i.v. injection of adrenaline produces a marked increase in both systoloic as well as diastolic blood pressure (at high concentration α-response predominates and vasoconstriction occurs even in skeletal muscle). The blood pressure returns to normal within a few minutes and a secondary fall in mean BP follows. The mechanism is rapid uptake and dissipation- concentration of adrenaline decreases, This adrenaline concentration cannot stimulate alpha receptors but is enough to stimulate Beta receptors. Hence there is a secondary fall in blood pressure. So when rapid i.v. injection of adrenaline is given in combination with Alpha blockers, only fall in BP is seen which is called Vasomotor Reversal Of Dale.

17. Differentiate between:

A. Drug potency and drug efficacy:

Drug potency:

1) It is the relationship between the the dose of a drug and the therapeutic effect.

2) It refers to the drug's strength.

3) A drug is considered potent when a small amount of the drug achieves the intended effect.

4) It depends on both affinity and efficacy of drug.

5) It is a factor in choosing the dose of drug.

Drug efficacy:

1) It is the ability of a drug to produce the desired therapeutic effect.

2) It refers to the drug's effectiveness.

3) A drug is considered efficacious when a drug achieves the maximal responses that can be elicited by it.

4) It depends on both drug binding and drug bound receptor.

5) It is a decisive factor in choosing the drug.

B. Synergism and antagonism:

Antagonism

1) When one drug decreases or abolishes the action of another, they are said to be antagonistic and the phenomena is called antagonism.

2) In an antagonistic pair one drug is inactive as such but decreases the effect of other.

3) It can be represented as:

•Effects of drugs (A+B) <Effects of drug A+ Effects of drug B

4) Eg:

•Atropine - ACh

•Morphine - Naloxone

•Glucagon and insulin on blood sugar level.

Synergism:

1) When the action of one drug is facilitated or increased by the other, they are said to be synergistic and the phenomena is called synergism.

2) In a synergistic pair, both the drugs can have action in same direction or given alone one may be inactive but still enhance the action of the other when given together.

3) It can be represented as :

•Effects of drugs (A+B) =Effects of drug A+ Effects of drug B

•Effects of drugs (A+B) >Effects of drug A+ Effects of drug B

4) Eg :

•Aspirin + Paracetamol= as analgesic / anripyreti

•Ephedrine + Theophylline= as bronchodilator

•Amlodipine+ Atenolol = as antihypertensive

•Levodopa + Carbidopa = Inhibition of peripheral metabolism

C. Tubocurarine and succinylcholine

Tubocurarine:

1) It belongs to non- depolarizing or competitive blockers.

2) It work by competitively blocking the binding of acetylcholine to its receptors.

3) They bind to acetlycholine receptors as antagonist and leaves fewer receptors available for acetylcholine to bind.

Succinylcholine:

1) It belongs to depolarizing blockers.

2) It work by depolarizing the plasma membrane of muscle fibre.

3) They bind to acetylcholine receptor and cause depolarization by opening sodium ion channels just like acetylcholine does.

D. Respiratory alkalosis and respiratory acidosis:

Respiratory alkalosis:

1) When the pH value of body fluids become higher than 7.45 due to abnormalities in respiratory system then it is called respiratory alkalosis.

2) It is caused by hyperventilation of lungs.

3) In this, rate at which CO2 is eliminated from body fluids through the lungs increases.

4) It may be produced accidentally during excessive mechanical ventilation. Other causes include: psychiatric causes like anxiety , hysteria, stress ; CNS causes like stroke, subarachnoid haemorrhage, meningitis ; drugs like doxapram , aspirin , caffeine; high altitude; lung disease such as pneumonia; pregnancy.

5) Kidneys help to compensate for respiratory alkalosis by decreasing the rate of secretion of hydrogen ions into filtrate and reabsorption of bicarbonate ions.

Respiratory acidosis:

1) When the pH value of body fluids become lower than 7.35 due to abnormalities in respiratory system then it is called respiratory acidosis.

2) It is caused by hypoventilation of lungs.

3) In this, rate at which CO2 is eliminated from body fluids through the lungs decreases.

4) Its causes include : CNS problems such as myasthenia gravis, muscular dystropy ; traumas ;airway obstruction related to asthma or chronic obstructive pulmonary disease (COPD) exacerbation; hypoxia.

5) Kidneys help to compensate for respiratory acidosis by increasing the rate of secretion of hydrogen ions into filtrate and reabsorption of bicarbonate ions.

18. Write down the adverse drug reactions of the following:

a) Amphetamine:

More common Bladder pain

bloody or cloudy urine

difficult, burning, or painful urination

fast, pounding, or irregular heartbeat or pulse

frequent urge to urinate

lower back or side pain

Anxiety

dry mouth

lack or loss of strength

stomach pain

weight loss

Less common Cold or flu-like symptoms

cough or hoarseness

fever or chills

b) Lignocaine:

More common Flushing, redness of the skin

small red or purple spots on the skin

swelling at the site of application

unusually warm skin

Less common Bruising, burning, pain, or bleeding at the site of application

itching skin

c) Warfarin:

Abdominal or stomach pain with cramping

bleeding gums

blood in the urine

bloody stools

blurred vision

burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings

chest pain or discomfort

confusion

coughing up blood

difficulty with breathing or swallowing

dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position

excessive bruising

headache

increased menstrual flow or vaginal bleeding

nosebleeds

paralysis

peeling of the skin

prolonged bleeding from cuts

red or black, tarry stools

red or dark brown urine

shortness of breath

sweating

unexplained swelling

unusual tiredness or weakness

red, sore, or itching skin

sores, welting, or blisters

unusual drowsiness, dullness, or feeling of sluggishness

d) Furosemide:

Chest pain

chills

cough or hoarseness

fever

general feeling of tiredness or weakness

headache

lower back or side pain

painful or difficult urination

shortness of breath

sore throat

sores, ulcers, or white spots on the lips or in the mouth

swollen or painful glands

tightness in the chest

unusual bleeding or bruising

unusual tiredness or weakness

wheezing

e) Acetylcholine:

Hypotension

Bradycardia

Flushing, and sweating

Ocular side effects have rarely included corneal clouding, corneal decompensation, and corneal edema

Bronchospasm in a patient on concomitantmetoprolol therapy.

f) Aspirin:

 epigastric pain

Heartburn

Nausea and vomiting

Ulcers

Gastric mucosal lesions

Hemorrhage and peptic ulcers

Renal side effects include reduction in glomerular filtration rate (particularly in patients who are sodium restricted or who exhibit diminished effective arterial blood volume, such as patients with advanced heart failure or cirrhosis), interstitial nephritis, papillary necrosis, elevations in serum creatinine, elevations in blood urea nitrogen, proteinuria, hematuria, and renal failure.

Hypersensitivity side include bronchospasm, rhinitis, conjunctivitis, urticaria, angioedema, and anaphylaxis

Hepatotoxicity and cholestatic hepatitis

Central nervous system side effects include agitation, cerebral edema, coma, confusion, dizziness, headache, cranial hemorrhage, lethargy and seizures

g) Morphine in CNS:

 Respiratory depression

Apnea and to a lesser degree

Circulatory depression

Respiratory arrest

Shock and cardiac arrest

Constipation, nausea

Lightheadedness, dizziness

Sedation

Vomiting and sweating

Bradycardia, hypertension, hypotension, palpitations

Biliary pain, dyspepsia, dysphagia, gastroenteritis, abnormal liver function tests, rectal disorder, thirst

Nervous System: abnormal dreams, abnormal gait, agitation, amnesia, anxiety, ataxia, confusion, convulsions, coma, delirium, depression, dry mouth, euphoria, hallucinations, lethargy, nervousness, abnormal thinking, tremor, vasodilation, vertigo, headache.

h) Benzodiazepines:

Hypotension

Cardiac arrhythmias

Slow heart rate

Apnea

Respiratory depression

Nausea/vomiting

Blurred vision or double vision

19. Write down the use of acetazolamide in glaucoma:

An increase in pressure within the eye can lead to damage to the optic nerve at the back of the eye. When this occurs it is called glaucoma. Glaucoma can lead to a loss of vision if it is not treated. Treatment with acetazolamide helps to reduce eye pressure, and this helps to prevent further eye damage.

Acetazolamide works by blocking the action of an enzyme called carbonic anhydrase. Blocking this enzyme reduces the amount of fluid in eye i.e. aqueous humor and this helps to lower the pressure within the eye.

20. Write the drugs commonly used in the managemaent of myasthenia gravis and describe their mechanism of action ?

Ans. -Mysthenia gravis is an autoimmune disorder affects 1 in 10000 populations

-characterized by the development of antibodies directed to the nicotinic receptors at the muscle end plate and

-this results in the reduction of NM cholinoreceptors to 1/3rd of normal or less.

- structural damage to the neutomuscular junction results feel weakness and fatigue on repeated activity with recovery after rest.

Commonly used drugs to treat this disorder can be listed as-

1) Anticholineesterase : Neostigmine(preferred 15 mg QID), Physostigmine etc2) Corticosteroids: Prednisolone( 30-60mg od)3) Other immunosuppresants( eg. Azathioprine, Cyclosporine,etc.)

Other mechanisms4) Plasmapharesis( plasma exchange)5) Thymectomy( removal of thymus gland)

Short mechanism of action of drugs

1) Anticholineesterase : Neostigmine(preferred), Physostigmine etc

Reversibly binds at the esteric site of cholinesterase enzyme

Prevents the hydrolysis of Ach Increase the interaction between Ach-nicotinic receptor

2) Corticosteroids: Prednisolone

Inhibit the production of nicotinic receptor antibodies

Immunosuppresant action

May increase the synthesis of nicotinic receptors

3) Other immunosuppresantsImmunosuppresants inhibit the nicotinic receptor antibody by selectively suppressing the cell mediated immunity.

21. Why acetazolamide is used in Glaucoma?Ans: Acetazolamide is a carbonic acid anhydrase enzyme inhibitors.

Acetazolamide ( ─)

H2O + CO2 H2CO3 H+ + HCO3-

When acetazolamide (0.25 gm tablet 6-12 hourly) is administered orally, it reduces the formation

of aqueous humor by limiting the generation of bicarbonate in, because carbonic acid is the main

component of aqueous humor. Hence, along with other ocular hypertensive drug, it reduces the

intraocular pressure and thus used in the treatment of open angle glaucoma.