They are used as a pain releiver.
Adverse effects:
• Diarrhea
• Hemolytic anemia (rare)
Sunday, April 10, 2011
Oxicam derivatives
Action:
Meloxicam is relatively COX-2 selective.
Therapeutic uses:
(Similar to that of Acetic acid derivatives)
Pharmacokinetics:
These have usually longer half lives. Piroxicam and its metabolites are excreted in the urine whereas meloxicam and its metabolites are excreted equally in the urine and feces.
Adverse effects:
It may cause GI disturbances.
Meloxicam is relatively COX-2 selective.
Therapeutic uses:
(Similar to that of Acetic acid derivatives)
Pharmacokinetics:
These have usually longer half lives. Piroxicam and its metabolites are excreted in the urine whereas meloxicam and its metabolites are excreted equally in the urine and feces.
Adverse effects:
It may cause GI disturbances.
Sulindac
It is used for:
• Rheumatoid arthritis
• Ankylosing spondylitis
• Osteoarthritis
• And acute gout.
• Rheumatoid arthritis
• Ankylosing spondylitis
• Osteoarthritis
• And acute gout.
Indomethacin
It is used for:
• Acute gouty arthritis
• Ankylosing spondylitis
• And osteoarthritis of the hip.
• Acute gouty arthritis
• Ankylosing spondylitis
• And osteoarthritis of the hip.
Propionic acid derivatives
Mechanism of Action:
These are reversible inhibitors of cyclooxygenase.
Action:
These inhibit the synthesis of prostaglandins but not that of leukotrienes.
Pharmacokinetics:
It is absorbed orally. It has the ability to bind to plasma albumin. It undergoes hepatic metabolism and excreted by the kidney.
Therapeutic Uses:
It is used as anti-inflammatory mostly in the chronic treatment of rheumatoid arthritis and osteoarthritis. It is also anti-pyretic and anti-inflammatory.
Adverse effects:
• Headache, tinnitus and dizziness.
• GI disturbance ranging from dyspepsia to bleeding.
These are reversible inhibitors of cyclooxygenase.
Action:
These inhibit the synthesis of prostaglandins but not that of leukotrienes.
Pharmacokinetics:
It is absorbed orally. It has the ability to bind to plasma albumin. It undergoes hepatic metabolism and excreted by the kidney.
Therapeutic Uses:
It is used as anti-inflammatory mostly in the chronic treatment of rheumatoid arthritis and osteoarthritis. It is also anti-pyretic and anti-inflammatory.
Adverse effects:
• Headache, tinnitus and dizziness.
• GI disturbance ranging from dyspepsia to bleeding.
Aspirin and other salicylates
Mechanism of Action:
Action:
Analgesic:
There is sensitization of nerve endings to the action of bradykinin, histamine and other chemical mediators by PGE2, thereby, reduce pain.
It is used to relieve low to moderate pain coming from integumental structures rather than that coming from viscera.
Anti-pyretic:
Anti-Inflammatory:
Aspirin reduces inflammation in which PG acts as mediators.
Respiratory Actions:
It causes increased alveolar ventilation and increased respiration.
Aspirin reduces pain at subcortical sites also.
Action:
Analgesic:
There is sensitization of nerve endings to the action of bradykinin, histamine and other chemical mediators by PGE2, thereby, reduce pain.
It is used to relieve low to moderate pain coming from integumental structures rather than that coming from viscera.
Anti-pyretic:
Aspirin stops PGE2 production. Also there is heat dissipation (of febrile subjects) as a result of peripheral vasodilatation and sweating and in this way it acts as anti-pyretic.
Anti-Inflammatory:
Aspirin reduces inflammation in which PG acts as mediators.
Respiratory Actions:
It causes increased alveolar ventilation and increased respiration.
If the dose exceeds the therapeutic range it may cause some side effects.
Gastrointestinal effects:
Aspirin causes epigastric distress, ulceration or hemorrhage.
Effect on platelets:
It causes reduced platelet aggregation.
Actions on kidneys:
It may cause retention of water and sodium resulting in edema and hyperkalemia.
Pharmacokinetics:
Absorption:
Salicylates are well absorbed through the undamaged and normal skin. On the other hand, unionized form of salicylates are passively absorbed by the stomach and small intestine.
Distribution:
They can pass through the Blood brain barrier except diflunisal.
Metabolism:
Elimination:
Plasma half life of salicylates is 3.5 hours. Salicylate is converted by the liver to water soluble conjugates. It is at last cleared by the kidney.
Doses:
Low doses act as Analgesic
High doses act as Analgesic and anti-inflammatory
Therapeutic Uses:
1. It is used as Anti-pyretic and analgesic.
2. Salicylic acid is also used topically for the treatment of corns, calluses and epidermophytosis.
3. It is also used prophylactically for the heart.
4. It may also help in the reduction of colon cancer.
Adverse effects:
1. GI disturbance.
2. Prolonged bleeding time due to the inhibition of the platelet aggregation.
3. Reduced respiratory activity.
4. Hypersensitivity reactions.
5. Reye’s syndrome.
6. Salicylates in toxic quantities may cause hyperthermia due to uncoupling of oxidative phosphorylation.
Gastrointestinal effects:
Aspirin causes epigastric distress, ulceration or hemorrhage.
It causes reduced platelet aggregation.
It may cause retention of water and sodium resulting in edema and hyperkalemia.
Absorption:
Salicylates are well absorbed through the undamaged and normal skin. On the other hand, unionized form of salicylates are passively absorbed by the stomach and small intestine.
Distribution:
They can pass through the Blood brain barrier except diflunisal.
Metabolism:
Plasma half life of salicylates is 3.5 hours. Salicylate is converted by the liver to water soluble conjugates. It is at last cleared by the kidney.
Doses:
Low doses act as Analgesic
High doses act as Analgesic and anti-inflammatory
Therapeutic Uses:
1. It is used as Anti-pyretic and analgesic.
2. Salicylic acid is also used topically for the treatment of corns, calluses and epidermophytosis.
3. It is also used prophylactically for the heart.
4. It may also help in the reduction of colon cancer.
Adverse effects:
1. GI disturbance.
2. Prolonged bleeding time due to the inhibition of the platelet aggregation.
3. Reduced respiratory activity.
4. Hypersensitivity reactions.
5. Reye’s syndrome.
6. Salicylates in toxic quantities may cause hyperthermia due to uncoupling of oxidative phosphorylation.
Classification of Anti-Inflammatory Drugs
1. Non-steroidal anti-inflammatory drugs:
a. Salicylates:
Aspirin, Methyl salicylate
b. Propionic Acid Derivatives:
Ibuprofen, Naproxen, Fenoprofen, Ketoprofen, Flurbiprofen, Oxaprozin
c. Acetic Acid Derivatives:
Indomethacin, Sulindac, Etodolac
d. Oxicam Derivatives:
Piroxicam, Meloxicam
e. Fenamates:
Mefenamic Acid, Meclofenamate
f. Other Agents:
Diclofenac, Ketorolac, Tolmetin, Nabumetone, Diflunisal
2. COX-2 Selective NSAIDs:
Celecoxib, Lumiracoxib, Etoricoxib
3. Drugs for Arthritis:
a. Drugs for anti-cytokine therapy
Etanercept, Infliximab, Adalimumab, Anakinra
b. Methotrexate
c. Leflunomide
d. Chloroquine and hydroxychloroquine
e. d-Penicillamine
f. Gold salts
4. Drugs used to treat Gout:
Colchicine, Allopurinol, Uricosuric agents such as Probenecid and Sulfinpyrazone
a. Salicylates:
Aspirin, Methyl salicylate
b. Propionic Acid Derivatives:
Ibuprofen, Naproxen, Fenoprofen, Ketoprofen, Flurbiprofen, Oxaprozin
c. Acetic Acid Derivatives:
Indomethacin, Sulindac, Etodolac
d. Oxicam Derivatives:
Piroxicam, Meloxicam
e. Fenamates:
Mefenamic Acid, Meclofenamate
f. Other Agents:
Diclofenac, Ketorolac, Tolmetin, Nabumetone, Diflunisal
2. COX-2 Selective NSAIDs:
Celecoxib, Lumiracoxib, Etoricoxib
3. Drugs for Arthritis:
a. Drugs for anti-cytokine therapy
Etanercept, Infliximab, Adalimumab, Anakinra
b. Methotrexate
c. Leflunomide
d. Chloroquine and hydroxychloroquine
e. d-Penicillamine
f. Gold salts
4. Drugs used to treat Gout:
Colchicine, Allopurinol, Uricosuric agents such as Probenecid and Sulfinpyrazone
Phentolamine
Mechanism of action:
It competitively blocks α adrenergic receptors. It causes inhibition to the response to serotonin.
It causes weak activation of the muscarinic receptors in GI tract and H1 and H2 histaminic receptors in the stomach.
Action:
It causes vasodilatation by
1. Blocking α adrenergic receptors
2. Nonadrenergic activity on vascular smooth muscles
This causes a decrease in peripheral vascular resistance and elevated venous capacitance.
It causes cardiac stimulation through blockade of α2 adrenergic receptors and reflex effect.
It also causes stimulation of salivary, lacrimal, pancreatic and respiratory tract secretions.
Pharmacokinetics:
It has a relatively short duration of action.
Therapeutic uses:
It is used effectively in the diagnosis of Pheochromocytoma and hypertensive crisis caused by Pheochromocytoma.
It is also used in Raynaud’s phenomenon and frost bite.
It is also used for erectile dysfunction.
It can be used to prevent dermal necrosis.
Adverse effects:
It may cause severe tachycardia, angina pectoris, arrhythmia and diarrhea.
Precautions:
It should be used with caution in patients with
1. Peptic ulcer
2. Coronary artery disease
It competitively blocks α adrenergic receptors. It causes inhibition to the response to serotonin.
It causes weak activation of the muscarinic receptors in GI tract and H1 and H2 histaminic receptors in the stomach.
Action:
It causes vasodilatation by
1. Blocking α adrenergic receptors
2. Nonadrenergic activity on vascular smooth muscles
This causes a decrease in peripheral vascular resistance and elevated venous capacitance.
It causes cardiac stimulation through blockade of α2 adrenergic receptors and reflex effect.
It also causes stimulation of salivary, lacrimal, pancreatic and respiratory tract secretions.
Pharmacokinetics:
It has a relatively short duration of action.
Therapeutic uses:
It is used effectively in the diagnosis of Pheochromocytoma and hypertensive crisis caused by Pheochromocytoma.
It is also used in Raynaud’s phenomenon and frost bite.
It is also used for erectile dysfunction.
It can be used to prevent dermal necrosis.
Adverse effects:
It may cause severe tachycardia, angina pectoris, arrhythmia and diarrhea.
Precautions:
It should be used with caution in patients with
1. Peptic ulcer
2. Coronary artery disease
Prazosin, Terazosin and Doxazosin
Mechanism of action:
It selectively blocks postsynaptic α1 adrenergic receptors.
Actions:
It causes the dilatation of the resistance vessels as well as capacitance vessels. This results in reduced blood pressure in upright position.
Its long term use may cause water and salt retention. This effect can be reduced by using diuretics.
Therapeutic uses:
1. It is used for mild to moderate chronic hypertension. It is even more useful on combination with diuretic or propranolol.
2. It is also used for acute congestive cardiac failure.
3. To relieve urinary obstruction (Terazosin).
Adverse effects:
It may cause dizziness, headache, lassitude, nasal congestion, postural hypotension, retention of salt and fluid.
It selectively blocks postsynaptic α1 adrenergic receptors.
Actions:
It causes the dilatation of the resistance vessels as well as capacitance vessels. This results in reduced blood pressure in upright position.
Its long term use may cause water and salt retention. This effect can be reduced by using diuretics.
Therapeutic uses:
1. It is used for mild to moderate chronic hypertension. It is even more useful on combination with diuretic or propranolol.
2. It is also used for acute congestive cardiac failure.
3. To relieve urinary obstruction (Terazosin).
Adverse effects:
It may cause dizziness, headache, lassitude, nasal congestion, postural hypotension, retention of salt and fluid.
Phenoxybenzamine
Mechanism of action:
It gets bind to α-adrenergic receptors causing the irreversible blockade of these receptors.
It blocks reuptake of norepinephrine by the presynaptic adrenergic nerve terminals.
In addition to α-adrenergic receptors blockade, it also causes blockade of histamine (H1), acetylcholine and serotonin receptors.
Actions:
It inhibits vasoconstriction caused by catecholamine resulting in decrease of total peripheral resistance and blood pressure.
It decreases blood pressure in upright position or as a result of reduced blood volume. In these situations sympathetic tone is elevated.
It causes an elevation of cardiac output as a result of reflex effects and by some blockade of presynaptic α2 receptors present in cardiac sympathetic nerves.
Pharmacokinetics:
It is well absorbed orally. It has plasma half life of about 12 hours.
Therapeutic uses:
They are used for regulating hypertension in Pheochromocytoma.
It is also used to relieve spasm of the vessels in Raynaud’s phenomenon.
It is used to alleviate urinary blockage in patients of spinal cord injury and prostatic hypertrophy (by partial reversal of contraction of the smooth muscles)
It is also used to regulate autonomic hyperreflexia caused by spinal cord transaction.
Adverse effects:
It may cause fatigue, sedation, miosis, nasal stuffiness, nausea and vomiting local tissue irritation by injection and hyperventilation.
Dosage:
It is given orally in the dose of 10-20 mg /day; The dose may be increased up to 200 mg, gradually.
It is also given by IV infusion in the dose of 1 mg/kg diluted in 5% dextrose or 0.9% saline.
It gets bind to α-adrenergic receptors causing the irreversible blockade of these receptors.
It blocks reuptake of norepinephrine by the presynaptic adrenergic nerve terminals.
In addition to α-adrenergic receptors blockade, it also causes blockade of histamine (H1), acetylcholine and serotonin receptors.
Actions:
It inhibits vasoconstriction caused by catecholamine resulting in decrease of total peripheral resistance and blood pressure.
It decreases blood pressure in upright position or as a result of reduced blood volume. In these situations sympathetic tone is elevated.
It causes an elevation of cardiac output as a result of reflex effects and by some blockade of presynaptic α2 receptors present in cardiac sympathetic nerves.
Pharmacokinetics:
It is well absorbed orally. It has plasma half life of about 12 hours.
Therapeutic uses:
They are used for regulating hypertension in Pheochromocytoma.
It is also used to relieve spasm of the vessels in Raynaud’s phenomenon.
It is used to alleviate urinary blockage in patients of spinal cord injury and prostatic hypertrophy (by partial reversal of contraction of the smooth muscles)
It is also used to regulate autonomic hyperreflexia caused by spinal cord transaction.
Adverse effects:
It may cause fatigue, sedation, miosis, nasal stuffiness, nausea and vomiting local tissue irritation by injection and hyperventilation.
Dosage:
It is given orally in the dose of 10-20 mg /day; The dose may be increased up to 200 mg, gradually.
It is also given by IV infusion in the dose of 1 mg/kg diluted in 5% dextrose or 0.9% saline.
Mecamylamine
Pharmacokinetics:
It is well absorbed orally. Its duration of action is about 5-12 hours. It is eliminated by renal tubular secretion.
Therapeutic uses:
It is used in hypertension.
Adverse effects:
Mecamylamine results in sedation, tremor and mental deviations.
It is well absorbed orally. Its duration of action is about 5-12 hours. It is eliminated by renal tubular secretion.
Therapeutic uses:
It is used in hypertension.
Adverse effects:
Mecamylamine results in sedation, tremor and mental deviations.
Trimethophan
They cause blockade of nicotinic cholinergic receptors itself. They do not occupy ion channels.
Therapeutic uses:
It is used in
1. hypertensive crisis,
2. for controlled hypotension to reduce bleeding in operation during surgery,
3. acute pulmonary edema to decrease pressure pulmonary vasculature.
Therapeutic uses:
It is used in
1. hypertensive crisis,
2. for controlled hypotension to reduce bleeding in operation during surgery,
3. acute pulmonary edema to decrease pressure pulmonary vasculature.
Hexamethonium
They cause blockade ganglion receptors by occupying sites in or on the ion channels that are regulated by nicotinic cholinergic receptors. They do not occupy cholinergic receptor itself.
Competitive ganglion blockers
Mechanism of action:
They cause non-depolarizing competitive blockage of ganglia. They compete with acetylcholine at postsynaptic nicotinic receptors.
Actions:
Since the ganglia of sympathetic as well as parasympathetic nervous system are cholinergic so these agents obstruct the outflow through these systems.
Blockade of sympathetic outflow causes a decrease in firmness of the arterioles resulting in the reduced peripheral vascular resistance leading to postural or orthostatic hypotension.
Blockade of parasympathetic outflow causes:
1. A prominent reduction in the motility of the GI tract.
2. Dry mouth
3. Cycloplegia with a decrease in accommodation.
4. Precipitation of urinary retention in men with prostatic hypertrophy.
Adverse effects:
Mostly autonomic effects
They cause non-depolarizing competitive blockage of ganglia. They compete with acetylcholine at postsynaptic nicotinic receptors.
Actions:
Since the ganglia of sympathetic as well as parasympathetic nervous system are cholinergic so these agents obstruct the outflow through these systems.
Blockade of sympathetic outflow causes a decrease in firmness of the arterioles resulting in the reduced peripheral vascular resistance leading to postural or orthostatic hypotension.
Blockade of parasympathetic outflow causes:
1. A prominent reduction in the motility of the GI tract.
2. Dry mouth
3. Cycloplegia with a decrease in accommodation.
4. Precipitation of urinary retention in men with prostatic hypertrophy.
Adverse effects:
Mostly autonomic effects
Clonidine
Mechanism of action:
It causes activation of α2 receptors in the vasomotor center of brain that causes a decrease in sympathetic outflow to the peripheral vascular bed.
Actions:
Its intravascular injection causes a direct activation of peripheral α-adrenergic receptors resulting in a short time elevated systolic and diastolic pressure. After this, there is a reduction of cardiac output and cardiac rate resulting in the fall of blood pressure.
It causes a decrease in plasma renin activity.
It causes an elevated vagal discharge along with promoted baroreceptor reflex sensitivity.
It causes a reduction of renal vascular resistance but does not affect renal blood flow.
It causes sodium and water retention and that is why they are taken along with diuretics.
Pharmacokinetics:
It is well absorbed orally and is excreted by the kidney.
Therapeutic uses:
It is used for hypertensive patients especially in patients of renal impairment.
Adverse effects:
Sedation, drowsiness, drying of the nasal mucosa, fluid retention, headache and sweating,
Dosage:
It may be given in the dose of 0.2-1.2 mg/day. Its transdermal patches can give dose for up to 1 week.
It causes activation of α2 receptors in the vasomotor center of brain that causes a decrease in sympathetic outflow to the peripheral vascular bed.
Actions:
Its intravascular injection causes a direct activation of peripheral α-adrenergic receptors resulting in a short time elevated systolic and diastolic pressure. After this, there is a reduction of cardiac output and cardiac rate resulting in the fall of blood pressure.
It causes a decrease in plasma renin activity.
It causes an elevated vagal discharge along with promoted baroreceptor reflex sensitivity.
It causes a reduction of renal vascular resistance but does not affect renal blood flow.
It causes sodium and water retention and that is why they are taken along with diuretics.
Pharmacokinetics:
It is well absorbed orally and is excreted by the kidney.
Therapeutic uses:
It is used for hypertensive patients especially in patients of renal impairment.
Adverse effects:
Sedation, drowsiness, drying of the nasal mucosa, fluid retention, headache and sweating,
Dosage:
It may be given in the dose of 0.2-1.2 mg/day. Its transdermal patches can give dose for up to 1 week.
Methyldopa
Mechanism of action:
Methyldopa is changed into α-methylnorepinephrine, which replaces norepinephrine in adrenergic nerve granules. This α-methylnorepinephrine, interacts with presynaptic central α2-adrenergic receptors, on release by nerve stimulation. On interaction it causes a decrease in sympathetic outflow and total peripheral resistance resulting in reduction of arterial pressure.
Methyldopa also blocks dopa decarboxylase resulting in the reduction of the stores of norepinephrine in the sympathetic nervous system leading to a decrease in blood pressure.
Actions:
This causes a decrease in renal vascular resistance, which is probably due to weak vasoconstrictor effect of α-methylnorepinephrine in renal vessels than norepinephrine.
It does not affect the blood flow to the important organs.
Pharmacokinetics:
Its onset of action is 120 minutes and duration of action is 17-25 hours.
Therapeutic uses:
It can be used for mild to moderately serious hypertension. It is especially useful for hypertensive patients, who are pregnant or have renal insufficiency.
Adverse effects:
Sedation, lassitude, Hemolytic anemia, orthostatic hypotension, rebound hypotension on sudden withdrawal, depression
Contraindications:
It is contraindicated in
1. pheochromocytoma
2. during the administration of MAO inhibitors
3. acute hepatic disease
Dosage:
It is given orally in the dose of 1-2 gm in divided doses.
Methyldopa is changed into α-methylnorepinephrine, which replaces norepinephrine in adrenergic nerve granules. This α-methylnorepinephrine, interacts with presynaptic central α2-adrenergic receptors, on release by nerve stimulation. On interaction it causes a decrease in sympathetic outflow and total peripheral resistance resulting in reduction of arterial pressure.
Methyldopa also blocks dopa decarboxylase resulting in the reduction of the stores of norepinephrine in the sympathetic nervous system leading to a decrease in blood pressure.
This causes a decrease in renal vascular resistance, which is probably due to weak vasoconstrictor effect of α-methylnorepinephrine in renal vessels than norepinephrine.
It does not affect the blood flow to the important organs.
Pharmacokinetics:
Its onset of action is 120 minutes and duration of action is 17-25 hours.
Therapeutic uses:
It can be used for mild to moderately serious hypertension. It is especially useful for hypertensive patients, who are pregnant or have renal insufficiency.
Adverse effects:
Sedation, lassitude, Hemolytic anemia, orthostatic hypotension, rebound hypotension on sudden withdrawal, depression
Contraindications:
It is contraindicated in
1. pheochromocytoma
2. during the administration of MAO inhibitors
3. acute hepatic disease
Dosage:
It is given orally in the dose of 1-2 gm in divided doses.
Saturday, April 9, 2011
ACE inhibitors
Mechanism of action:
They block the converting enzyme peptidyl dipeptidase that hydrolyzes and causes the conversion of (decapeptide) angiotensin I to (octapeptide) angiotensin II, resulting in the decrease of vasoconstrictor effect of angiotnesin II.
It also causes an increase of bradykinin, which has a vasodilator activity.
Actions:
1. They cause a decrease in total peripheral resistance and mean arterial blood pressure and either no change or an increase in cardiac output.
2. They do not result in reflex sympathetic stimulation and can be used safely and effectively in patients with ischemic heart disease.
Therapeutic uses:
They can be used for:
1. Mild to moderate essential hypertension and renovascular hypertension
2. Chronic congestive heart failure
3. Left ventricular systolic dysfunction
4. They can also be used in diabetic proteinuria
Adverse effects:
Headaches, dizziness, acute renal failure, hyperkalemia, dry cough, wheezing, skin rashes, angioedema
Contraindications:
1. aortic constriction
2. renal disturbance
3. pregnancy and lactation
4. bilateral renal artery constriction
They block the converting enzyme peptidyl dipeptidase that hydrolyzes and causes the conversion of (decapeptide) angiotensin I to (octapeptide) angiotensin II, resulting in the decrease of vasoconstrictor effect of angiotnesin II.
Actions:
1. They cause a decrease in total peripheral resistance and mean arterial blood pressure and either no change or an increase in cardiac output.
Therapeutic uses:
They can be used for:
1. Mild to moderate essential hypertension and renovascular hypertension
2. Chronic congestive heart failure
3. Left ventricular systolic dysfunction
4. They can also be used in diabetic proteinuria
Adverse effects:
Headaches, dizziness, acute renal failure, hyperkalemia, dry cough, wheezing, skin rashes, angioedema
Contraindications:
1. aortic constriction
2. renal disturbance
3. pregnancy and lactation
4. bilateral renal artery constriction
Saralasin
It is a partial agonist. It is a peptide analogue of angiotensin II.
Mechanism of action:
It competitively inhibits of angiotensin II receptors.
Actions:
1. it blocks the vasoconstrictor and aldosterone releasing effects of angiotensin II and reduces blood pressure in increased renin states e.g. in renal artery constriction.
2. Due to its weak agonist activity it may increase Blood pressure by rapid administration to persons without increased circulating angiotensin II.
Adverse effects:
Its adverse effects are almost same to those of ACE inhibitors.
Contraindicated:
They are contraindicated in for pregnant woman.
Mechanism of action:
It competitively inhibits of angiotensin II receptors.
Actions:
1. it blocks the vasoconstrictor and aldosterone releasing effects of angiotensin II and reduces blood pressure in increased renin states e.g. in renal artery constriction.
2. Due to its weak agonist activity it may increase Blood pressure by rapid administration to persons without increased circulating angiotensin II.
Adverse effects:
Its adverse effects are almost same to those of ACE inhibitors.
Contraindicated:
They are contraindicated in for pregnant woman.
Minoxidil
Mechanism of action:
It causes dilatation of arterioles by unclosing of potassium channels. This opening of potassium channels causes hyperpolarization leading to relaxation of smooth muscles. This relaxation of smooth muscles results in the reduction of total peripheral vascular resistance. So, the blood pressure is reduced.
Actions:
Minoxidil may cause palpitations and reflex tachycardia.
It may increase the plasma renin activity caused by reflex sympathetic activity or decrease by certain unknown mechanism.
It may cause sodium and water retention.
Pharmacokinetics:
It is well absorbed orally. It is metabolized in the liver. Its duration of action is about 1-3 days.
Therapeutic uses:
1. Moderate to serious hypertension
2. severe hypertension associated with disturbance of renal function
3. topically can be used as an activator of hair growth for baldness
Adverse effects:
Headache, Tachycardia, angina, sweating, Excessive hair growth, fluid retention causing volume overload
It causes dilatation of arterioles by unclosing of potassium channels. This opening of potassium channels causes hyperpolarization leading to relaxation of smooth muscles. This relaxation of smooth muscles results in the reduction of total peripheral vascular resistance. So, the blood pressure is reduced.
Minoxidil may cause palpitations and reflex tachycardia.
It may increase the plasma renin activity caused by reflex sympathetic activity or decrease by certain unknown mechanism.
It may cause sodium and water retention.
Pharmacokinetics:
It is well absorbed orally. It is metabolized in the liver. Its duration of action is about 1-3 days.
Therapeutic uses:
1. Moderate to serious hypertension
2. severe hypertension associated with disturbance of renal function
3. topically can be used as an activator of hair growth for baldness
Adverse effects:
Headache, Tachycardia, angina, sweating, Excessive hair growth, fluid retention causing volume overload
Hydralazine
Mechanism of action:
It results in vasodilatation by activating guanylate cyclase in the smooth muscles of the arteries. The stimulant is thought to be nitric oxide (NO), which comes from the local oxidation.
Actions:
It causes a decreased diastolic blood pressure more than systolic blood pressure.
Pharmacokinetics:
It is absorbed orally. Its half life ranges from 1.5-6 hours.
Therapeutic uses:
It is used for moderate to serious hypertension
It is used for acute and chronic congestive heart failure.
Adverse effects:
It may cause headache, dizziness, malaise, flushing, angina, anorexia, nausea, sweating.
Contraindications:
It is contraindicated in patients with coronary artery disease and lupus erythematosus.
Dosage:
It is given in the dose of 40-200 mg/day.
It results in vasodilatation by activating guanylate cyclase in the smooth muscles of the arteries. The stimulant is thought to be nitric oxide (NO), which comes from the local oxidation.
Actions:
It causes a decreased diastolic blood pressure more than systolic blood pressure.
Pharmacokinetics:
It is absorbed orally. Its half life ranges from 1.5-6 hours.
Therapeutic uses:
It is used for moderate to serious hypertension
It is used for acute and chronic congestive heart failure.
Adverse effects:
It may cause headache, dizziness, malaise, flushing, angina, anorexia, nausea, sweating.
Contraindications:
It is contraindicated in patients with coronary artery disease and lupus erythematosus.
Dosage:
It is given in the dose of 40-200 mg/day.
Sodium Nitroprusside
It directly causes relaxation of the peripheral vessels.
Mechanism of action:
It causes the release of nitric oxide (NO). NO is a relaxing factor. NO stimulates guanylyl cyclase in vascular smooth muscle leading to vasodilatation.
When it acts on arterioles it causes a reduction in total systemic vascular resistance leading to a fall in blood pressure.
Actions:
It causes relaxation of smooth muscles of both arteries and veins resulting in the immediate vasodilatation with reflex tachycardia.
Cardiac rate is promoted in the supine position and reduced in the standing position. Cardiac rate is increased reflexly.
It results in reduced oxygen demand of the heart muscles caused by promoted venous capacitance.
It regulates the blood to the kidneys and there is a slightly promoted renin secretion.
Pharmacokinetics:
It is rapidly metabolized as its half life is about 2 minutes. Its metabolism causes the production of cyanide ions. It is eliminated by the kidney.
Therapeutic uses:
1. It is used in hypertensive crisis as it has the ability of reducing the blood pressure in standing as well as supine position.
2. It is used for reducing bleeding during surgery
3. It is used in ventricular unloading in acute congestive heart failure.
4. It is used for acute myocardial infarction
Adverse effects:
It may cause headache, excessive hypotension, tachycardia, agitation, palpitation, restlessness, nausea, cyanide ions poisoning (which can be treated by using sodium thiosulfate), disorientation, muscle spasms and convulsions.
Dosage and administration:
It is given by continuous IV infusion in the dose of 0.5-1.0 μg/kg/min.
Mechanism of action:
It causes the release of nitric oxide (NO). NO is a relaxing factor. NO stimulates guanylyl cyclase in vascular smooth muscle leading to vasodilatation.
When it acts on arterioles it causes a reduction in total systemic vascular resistance leading to a fall in blood pressure.
Actions:
It causes relaxation of smooth muscles of both arteries and veins resulting in the immediate vasodilatation with reflex tachycardia.
Cardiac rate is promoted in the supine position and reduced in the standing position. Cardiac rate is increased reflexly.
It results in reduced oxygen demand of the heart muscles caused by promoted venous capacitance.
It regulates the blood to the kidneys and there is a slightly promoted renin secretion.
Pharmacokinetics:
It is rapidly metabolized as its half life is about 2 minutes. Its metabolism causes the production of cyanide ions. It is eliminated by the kidney.
Therapeutic uses:
1. It is used in hypertensive crisis as it has the ability of reducing the blood pressure in standing as well as supine position.
2. It is used for reducing bleeding during surgery
3. It is used in ventricular unloading in acute congestive heart failure.
4. It is used for acute myocardial infarction
Adverse effects:
It may cause headache, excessive hypotension, tachycardia, agitation, palpitation, restlessness, nausea, cyanide ions poisoning (which can be treated by using sodium thiosulfate), disorientation, muscle spasms and convulsions.
Dosage and administration:
It is given by continuous IV infusion in the dose of 0.5-1.0 μg/kg/min.
Diazeoxide
It is a benzothiazide.
Mechanism of action:
Diazoxide causes activation of the ATPase sensitive potassium channels resulting in the hyperpolarization of the vascular smooth muscles leading to the relaxation of the arterioles (smooth muscles) leading to reduced systemic vascular resistance resulting in diminished blood pressure.
It causes a promoted cardiac rate and cardiac output along with a fall in both of the systolic and diastolic pressure due to its vasodepressive action. This vasodepression is most importantly due to arteriolar dilatation, however venous dilatation is also effective in causing vasodepression.
It also causes relaxation of the other smooth muscles.
It also blocks the release of insulin from pancreatic β-cells. It can cause salt and water retention resulting in weight gain.
Therapeutic uses:
1. It is used in hypertensive crisis (IV).
2. It is used in hypoglycemia due to hyperinsulinemia (Oral).
Pharmacokinetics:
Most of the drug gets bind with protein. Its plasma half life is about 25-60 hours. The drug is eliminated by renal tubular secretion and biotransformation.
Adverse effect:
It may cause Angina, edema, serious hypotension which may lead to stroke and myocardial infarction or Hyperglycemia.
Contraindications:
It is contraindicated in patients of
1. Diabetes mellitus
2. Congestive heart failure
Dosage:
In the beginning 75-100 mg; but if necessary dose may increase up to 150 mg every 5 minute until blood pressure comes to normal.
Mechanism of action:
Diazoxide causes activation of the ATPase sensitive potassium channels resulting in the hyperpolarization of the vascular smooth muscles leading to the relaxation of the arterioles (smooth muscles) leading to reduced systemic vascular resistance resulting in diminished blood pressure.
Actions:
It causes a promoted cardiac rate and cardiac output along with a fall in both of the systolic and diastolic pressure due to its vasodepressive action. This vasodepression is most importantly due to arteriolar dilatation, however venous dilatation is also effective in causing vasodepression.
It also causes relaxation of the other smooth muscles.
It also blocks the release of insulin from pancreatic β-cells. It can cause salt and water retention resulting in weight gain.
Therapeutic uses:
1. It is used in hypertensive crisis (IV).
2. It is used in hypoglycemia due to hyperinsulinemia (Oral).
Pharmacokinetics:
Most of the drug gets bind with protein. Its plasma half life is about 25-60 hours. The drug is eliminated by renal tubular secretion and biotransformation.
Adverse effect:
It may cause Angina, edema, serious hypotension which may lead to stroke and myocardial infarction or Hyperglycemia.
Contraindications:
It is contraindicated in patients of
1. Diabetes mellitus
2. Congestive heart failure
Dosage:
In the beginning 75-100 mg; but if necessary dose may increase up to 150 mg every 5 minute until blood pressure comes to normal.
Guanethidine
Mechanism of action:
Its neurotransmission is almost similar to the process of norepinephrine.
It replaces norepinephrine in the transmitter vesicles resulting in the reduction of norepinephrine in the nerve endings. This causes the inhibition of the release of norepinephrine from the sympathetic nerve endings.
Actions:
As it causes the replacement of norepinephrine, so firstly, mild cardiac stimulation and minor form of hypertension that lasts for short duration, occurs.
This is followed by bradycardia and hypotension (orthostatic type of hypotension occurs mostly as it decreases vasoconstrictor reflexes.)
It promotes tissues sensitivity to catecholamines.
Therapeutic uses::
In combination with diuretic and vasodilator it can be used for moderate to severe type of hypertension.
Adverse effects:
Weakness, Orthostatic hypotension, Diarrhea
Contraindications:
It is contraindicated in patients of
1. Pheochromocytoma
2. Serious coronary artery disease
3. Cerebrovascular insufficiency
4. While using MAO inhibitors
Its neurotransmission is almost similar to the process of norepinephrine.
It replaces norepinephrine in the transmitter vesicles resulting in the reduction of norepinephrine in the nerve endings. This causes the inhibition of the release of norepinephrine from the sympathetic nerve endings.
Actions:
As it causes the replacement of norepinephrine, so firstly, mild cardiac stimulation and minor form of hypertension that lasts for short duration, occurs.
This is followed by bradycardia and hypotension (orthostatic type of hypotension occurs mostly as it decreases vasoconstrictor reflexes.)
It promotes tissues sensitivity to catecholamines.
Therapeutic uses::
In combination with diuretic and vasodilator it can be used for moderate to severe type of hypertension.
Adverse effects:
Weakness, Orthostatic hypotension, Diarrhea
Contraindications:
It is contraindicated in patients of
1. Pheochromocytoma
2. Serious coronary artery disease
3. Cerebrovascular insufficiency
4. While using MAO inhibitors
Reserpine
It is a plant alkaloid derived from the roots of plant Rauwolfia Serpentina.
Mechanism of action:
Reserpine works to prevent neuronal and chromaffin granule transporters by Mg2+/ATP dependent transport mechanism.
As a consequence accumulation of catecholamine transmitters by adrenergic transmitter vesicles is prevented resulting in great depletion of transmitters in both central and peripheral neurons that can remain for days to weeks. Monoamine oxidase has the ability of degrading norepinephrine in the cytoplasm.
It also exerts a direct vasodilating effect on vascular smooth muscles when administered intra-arterially.
Actions:
1. It causes sedation due to depletion of biogenic amines centrally.
2. It decreases cardiac rate, cardiac output and blood pressure.
3. It may also decrease peripheral vascular resistance.
4. It partially prevents cardiovascular reflexes.
Its effects appear to be irreversible.
Pharmacokinetics:
The drug is absorbed poorly from the G.I. Tract. It has slow onset of action and long duration of action.
Therapeutic uses:
1. In combination with thiazide diuretics it is used to treat mild to moderate hypertension and is mostly used in condition when no other anti-hypertensive agent showing affect.
2. Insomnia
3. It was used to treat snakebites
4. Insanity
Adverse effects:
Drowsiness, Sedation, lassitude, depression, bradycardia, diarrhea, Gastric acid secretion, Nasal congestion, Nausea, vomiting
Contraindications:
• Peptic ulcer
• Parkinsonism
• Pheochromocytoma
Precautions:
It must be used with caution in patients of depression as it may aggravate this condition.
Mechanism of action:
Reserpine works to prevent neuronal and chromaffin granule transporters by Mg2+/ATP dependent transport mechanism.
As a consequence accumulation of catecholamine transmitters by adrenergic transmitter vesicles is prevented resulting in great depletion of transmitters in both central and peripheral neurons that can remain for days to weeks. Monoamine oxidase has the ability of degrading norepinephrine in the cytoplasm.
Actions:
1. It causes sedation due to depletion of biogenic amines centrally.
2. It decreases cardiac rate, cardiac output and blood pressure.
3. It may also decrease peripheral vascular resistance.
4. It partially prevents cardiovascular reflexes.
Its effects appear to be irreversible.
Pharmacokinetics:
The drug is absorbed poorly from the G.I. Tract. It has slow onset of action and long duration of action.
Therapeutic uses:
1. In combination with thiazide diuretics it is used to treat mild to moderate hypertension and is mostly used in condition when no other anti-hypertensive agent showing affect.
2. Insomnia
3. It was used to treat snakebites
4. Insanity
Adverse effects:
Drowsiness, Sedation, lassitude, depression, bradycardia, diarrhea, Gastric acid secretion, Nasal congestion, Nausea, vomiting
Contraindications:
• Peptic ulcer
• Parkinsonism
• Pheochromocytoma
Precautions:
It must be used with caution in patients of depression as it may aggravate this condition.
Reserpine
It is a plant alkaloid derived from the roots of plant Rauwolfia Serpentina.
Mechanism of action:
Reserpine works to prevent neuronal and chromaffin granule transporters by Mg2+/ATP dependent transport mechanism.
As a consequence accumulation of catecholamine transmitters by adrenergic transmitter vesicles is prevented resulting in great depletion of transmitters in both central and peripheral neurons that can remain for days to weeks. Monoamine oxidase has the ability of degrading norepinephrine in the cytoplasm.
Mechanism of action:
Reserpine works to prevent neuronal and chromaffin granule transporters by Mg2+/ATP dependent transport mechanism.
As a consequence accumulation of catecholamine transmitters by adrenergic transmitter vesicles is prevented resulting in great depletion of transmitters in both central and peripheral neurons that can remain for days to weeks. Monoamine oxidase has the ability of degrading norepinephrine in the cytoplasm.
Adrenergic neuron blocking drugs
These drugs decrease the delivery of catecholamines such as norepinephrine to adrenergic receptors.
Norepinephrine:
It is an adrenergic neurotransmitter. It is stored in the granular organelles. It is secreted by adrenal glands.
Synthesis:
It is produced in sympathetic adrenergic neurons and attaches to adrenergic receptors.
1. It elevates blood pressure and breathing rate.
2. It elevates blood sugar.
3. It causes a decline in the activity of the intestines.
Norepinephrine:
It is an adrenergic neurotransmitter. It is stored in the granular organelles. It is secreted by adrenal glands.
Synthesis:
It is produced in sympathetic adrenergic neurons and attaches to adrenergic receptors.
Actions:
1. It elevates blood pressure and breathing rate.
2. It elevates blood sugar.
3. It causes a decline in the activity of the intestines.
Classification of Anti-hypertensive drugs
1. Adrenergic neuron blocking drugs:
Bethanidine, Methoserpidine, Reserpine, Syrosingopine, Guanthedine
2. Antihypertensive direct vasodilators:
Diazoxide, Dihydralazine, Hydralazine, Minoxidil, Sodium nitroprusside
3. Centrally acting sympatholytic antihypertensive drugs:
Clonidine, Guanabenz, Guanfacine, Labetol, α-methyldopa
4. Ca2+ channel blockers:
a. Diphenylalkylamines:
Verapamil
b. Benzothiazepines:
Diltiazem
c. Dihydropyridines:
Amlodipine, Felodipine, Isradipine, Nicardipine, Nifedipine, Nisoldipine, Nitrendipine
5. Diuretics:
Bumetanide, Furosemide, Hydrochlorthiazide, Methyclothiazide, Polythiazide, Quinthazone, Spironolactone, Triamterene, Trichlomethiazide
6. Drugs acting on Renin angiotensin system:
a. ACE inhibitors:
Benazepril, Captopril, Enalapril, Fosinopril, Lisinopril, Moexipril, Perindopril, Quinapril, Ramipril, Trandolapril
b. Angiotensin II receptor antagonist:
Candesartan cilexetil, Losartan, Saralasin, Valsartan
7. Drugs acting on Serotonin receptors:
Ketanserin, Urapidil
8. Ganglionic blocking agents:
Mecamylamine hydrochloride, Pentamethonium bromide, Pentolinium, Trimethaphan camsylate
9. Monoamine oxidase inhibitor:
Pargyline hydrochloride
10. Peripheral anti-adrenergic drugs:
a. α-blockers:
Phenoxybenzamine, Phentolamine,
b. α1-blockers:
Doxazosin, Prazosin, Terazosin
c. β-blockers:
Atenolol, Metoprolol, Nadolol, Propranolol, Timolol
d. α and β blockers:
Labetalol
11. Plant products:
Cryptenamine acetates, Reserpine, Veratridine
12. Miscellaneous:
Bretylium
Bethanidine, Methoserpidine, Reserpine, Syrosingopine, Guanthedine
2. Antihypertensive direct vasodilators:
Diazoxide, Dihydralazine, Hydralazine, Minoxidil, Sodium nitroprusside
3. Centrally acting sympatholytic antihypertensive drugs:
Clonidine, Guanabenz, Guanfacine, Labetol, α-methyldopa
4. Ca2+ channel blockers:
a. Diphenylalkylamines:
Verapamil
b. Benzothiazepines:
Diltiazem
c. Dihydropyridines:
Amlodipine, Felodipine, Isradipine, Nicardipine, Nifedipine, Nisoldipine, Nitrendipine
5. Diuretics:
Bumetanide, Furosemide, Hydrochlorthiazide, Methyclothiazide, Polythiazide, Quinthazone, Spironolactone, Triamterene, Trichlomethiazide
6. Drugs acting on Renin angiotensin system:
a. ACE inhibitors:
Benazepril, Captopril, Enalapril, Fosinopril, Lisinopril, Moexipril, Perindopril, Quinapril, Ramipril, Trandolapril
b. Angiotensin II receptor antagonist:
Candesartan cilexetil, Losartan, Saralasin, Valsartan
7. Drugs acting on Serotonin receptors:
Ketanserin, Urapidil
8. Ganglionic blocking agents:
Mecamylamine hydrochloride, Pentamethonium bromide, Pentolinium, Trimethaphan camsylate
9. Monoamine oxidase inhibitor:
Pargyline hydrochloride
10. Peripheral anti-adrenergic drugs:
a. α-blockers:
Phenoxybenzamine, Phentolamine,
b. α1-blockers:
Doxazosin, Prazosin, Terazosin
c. β-blockers:
Atenolol, Metoprolol, Nadolol, Propranolol, Timolol
d. α and β blockers:
Labetalol
11. Plant products:
Cryptenamine acetates, Reserpine, Veratridine
12. Miscellaneous:
Bretylium
Hypertension
It is an arterial disease accompanied by abnormally high blood pressure. It is also called as “Hyperpiesis” or “Hyperpiesia”.
Systolic pressure:
Persistent systolic blood pressure at about 140 mmHg or greater
Diastolic pressure:
Persistent diastolic blood pressure at about 90 mmHg to 110 mmHg
After effects of hypertension:
1. Congestive cardiac failure
2. Myocardial infarction
3. Renal damage
4. Other cerebrovascular disorders.
Wednesday, April 6, 2011
Levigation
Definition:
Levigation is the process of grinding an insoluble substance to a fine powder.
Or
Levigation is the grinding to a powder of a moist or hard substance.
Explanation:
The material is introduced into the mill together with water in which the powdered substance remains suspended and flows from the mill as a turbid liquid or thin pastes. According to the amount of water employed. There is no loss of material as dust nor injury or annoyance to the workmen.
Further any (substances) soluble impurities in the substance are dissolved and the product thereby purified.
Advantages of levigation:
The greatest advantages of levigation is the facility it affords for the subsequent separation of the products into various grades of fitness because of slower. Subsidence of the finer particles from suspension.
The turbid liquid flows into the first of a series of tanks and is allowed to stand for a time. The coarsest and heaviest particles quickly subside leaving the finer material suspended in the water which is drawn from above the sediment into the next tank.
The liquid is passed from tank to tank remaining in each longer than it remained in the proceeding since the finer and higher the particles the more time is necessary for this deposition. In some cases a dozen or more tanks may be used and the process then becomes exceedingly slow.
The term levigation is now often applied to more sedimentation a substance being simply stirred up in water without previous wet grinding.
Levigation is the process of grinding an insoluble substance to a fine powder.
Or
Levigation is the grinding to a powder of a moist or hard substance.
Explanation:
The material is introduced into the mill together with water in which the powdered substance remains suspended and flows from the mill as a turbid liquid or thin pastes. According to the amount of water employed. There is no loss of material as dust nor injury or annoyance to the workmen.
Further any (substances) soluble impurities in the substance are dissolved and the product thereby purified.
Advantages of levigation:
The greatest advantages of levigation is the facility it affords for the subsequent separation of the products into various grades of fitness because of slower. Subsidence of the finer particles from suspension.
The turbid liquid flows into the first of a series of tanks and is allowed to stand for a time. The coarsest and heaviest particles quickly subside leaving the finer material suspended in the water which is drawn from above the sediment into the next tank.
The liquid is passed from tank to tank remaining in each longer than it remained in the proceeding since the finer and higher the particles the more time is necessary for this deposition. In some cases a dozen or more tanks may be used and the process then becomes exceedingly slow.
The term levigation is now often applied to more sedimentation a substance being simply stirred up in water without previous wet grinding.
Calcination
Definition:
The process of heating a substance to a high temperature but below the melting point or fusing point causing loss of moisture reduction or oxidation and dissociation. Into simpler substances, the term was originally applied to the method of driving off carbon dioxide from limestone to obtain lime.
Calcination is also used to extract metals from ores.
Or
To heat a substance to a high temperature but below the melting point or fusing point causing loss of moisture, reduction or oxidation and the decomposition of carbonates and other compounds.
Explanation:
Calcination also referred to as calcining a thermal treatment process applied to ores and other solid materials in order to bring about a thermal decomposition phase transition or removal of a volatile fraction. The calcinations process normally takes place at temperatures below the melting point of the product materials.
Calcination is to be distinguished from roasting. In which more complex gases, solids reactions takes place between the furnace and the solids.
Calcination reactions:
Calcinations reaction usually takes place at or above the thermal decomposition temperature or transition temperature. This temperature is usually defined as the temperature at which the standard energy of reaction for a particular calcination reaction is equal to zero.
Example:
Examples of chemical decomposition reactions common in calcination processes and their respective thermal decomposition temperature include
CaCO3 = CaO + CO2 : 484ºC
Occurance:
Calcination occur under layers of hot volcanic ash.
Physical properties:
The physical properties which involves bulk density, total pore volume, and the pore size distribution of the calcines prepared under different conditions were determine by using a Mercury porosimeter.
It was found that the physical properties of calcines were dramatically affected by the calcinations conditions, at high calcination temperature, because of sintering and shrinking affects, a decrease in properties. An increase in bulk density and average pore radius were observed.
The process of heating a substance to a high temperature but below the melting point or fusing point causing loss of moisture reduction or oxidation and dissociation. Into simpler substances, the term was originally applied to the method of driving off carbon dioxide from limestone to obtain lime.
Calcination is also used to extract metals from ores.
Or
To heat a substance to a high temperature but below the melting point or fusing point causing loss of moisture, reduction or oxidation and the decomposition of carbonates and other compounds.
Explanation:
Calcination also referred to as calcining a thermal treatment process applied to ores and other solid materials in order to bring about a thermal decomposition phase transition or removal of a volatile fraction. The calcinations process normally takes place at temperatures below the melting point of the product materials.
Calcination is to be distinguished from roasting. In which more complex gases, solids reactions takes place between the furnace and the solids.
Calcination reactions:
Calcinations reaction usually takes place at or above the thermal decomposition temperature or transition temperature. This temperature is usually defined as the temperature at which the standard energy of reaction for a particular calcination reaction is equal to zero.
Example:
Examples of chemical decomposition reactions common in calcination processes and their respective thermal decomposition temperature include
CaCO3 = CaO + CO2 : 484ºC
Occurance:
Calcination occur under layers of hot volcanic ash.
Physical properties:
The physical properties which involves bulk density, total pore volume, and the pore size distribution of the calcines prepared under different conditions were determine by using a Mercury porosimeter.
It was found that the physical properties of calcines were dramatically affected by the calcinations conditions, at high calcination temperature, because of sintering and shrinking affects, a decrease in properties. An increase in bulk density and average pore radius were observed.
Tuesday, April 5, 2011
Wonders of Placebo
Placebo refers to a drug having no active ingredient for therapy and which is given to benefit the patient psychologically such as it can be a simple glass of water but the patient is told that this water contains medicine. It is related to positive thinking. Placebo is still a wonder for scientific community.
Data on placebos is holding such an attention that many physicians in America (one study estimates 50 percent) secretly give placebos to unsuspecting patients.
In a study it was found that amond 435 patients of headache reported by branded placebo users, 64% were reported as improved 1 hour after pill administration compared with only 45% of the 410 headaches reported as improved among the unbranded placebo users. So they found that branding of a drug even have more effect on the treatment of a particular disease.
It has been found that placebo works even better, if a doctor give this to a patient.
References:
Harvard Medical School (2010, December 23). Placebos work -- even without deception. ScienceDaily. Retrieved April 5, 2011, from http://www.sciencedaily.com /releases/2010/12/101222173033.htm
Moerman, D. E.; Jonas, W. B.; Deconstructing the Placebo Effect and Finding the Meaning Response. Annals of Internal Medicine, 2002, Vol. 136, No. 6. Pages 471-476.
Data on placebos is holding such an attention that many physicians in America (one study estimates 50 percent) secretly give placebos to unsuspecting patients.
In a study it was found that amond 435 patients of headache reported by branded placebo users, 64% were reported as improved 1 hour after pill administration compared with only 45% of the 410 headaches reported as improved among the unbranded placebo users. So they found that branding of a drug even have more effect on the treatment of a particular disease.
It has been found that placebo works even better, if a doctor give this to a patient.
References:
Harvard Medical School (2010, December 23). Placebos work -- even without deception. ScienceDaily. Retrieved April 5, 2011, from http://www.sciencedaily.com /releases/2010/12/101222173033.htm
Moerman, D. E.; Jonas, W. B.; Deconstructing the Placebo Effect and Finding the Meaning Response. Annals of Internal Medicine, 2002, Vol. 136, No. 6. Pages 471-476.
Sunday, April 3, 2011
Ondansetron
It is a serotonin receptor antagonist.
Mechanism of action:
It has been shown to inhibit 5-HT3 receptors both centrally and peripherally and thus showing its anti-emetic activity.
It has been found that the chemotherapy causes degradative changes in the GI tract such as small intestine that causes the increased release of serotonin which then stimulates vagal and splanchnic nerves which leads to vomting center of the brain inducing vomiting.
The same stimulation has been found in the area postrema.
Ondansetron stops acute chemotherapy induced emesis by the inhibition of visceral afferent stimulation from the vomting center which may be:
1. Indirectly at the level of the area postrema
2. Directly inhibiting serotonin activity within the area postrema and chemoreceptor trigger zone.
Therapeutic uses:
It is used for Nausea and vomiting, which may be due to:
1. Cancer chemotherapy
2. Postoperative
3. Radiation induced.
Administration and dosage:
It can be administered orally or IV. The usual oral dose for cancer chemotherapy induced vomiting is 8 mg 30 minutes prior to chemotherapy induced vomiting.
Adverse effects:
It may cause headache, dizziness, restlessness and diarrhea (in some patients it may cause constipation). Fever and injection site reactions have also been reported.
Mechanism of action:
It has been shown to inhibit 5-HT3 receptors both centrally and peripherally and thus showing its anti-emetic activity.
It has been found that the chemotherapy causes degradative changes in the GI tract such as small intestine that causes the increased release of serotonin which then stimulates vagal and splanchnic nerves which leads to vomting center of the brain inducing vomiting.
The same stimulation has been found in the area postrema.
Ondansetron stops acute chemotherapy induced emesis by the inhibition of visceral afferent stimulation from the vomting center which may be:
1. Indirectly at the level of the area postrema
2. Directly inhibiting serotonin activity within the area postrema and chemoreceptor trigger zone.
Therapeutic uses:
It is used for Nausea and vomiting, which may be due to:
1. Cancer chemotherapy
2. Postoperative
3. Radiation induced.
Administration and dosage:
It can be administered orally or IV. The usual oral dose for cancer chemotherapy induced vomiting is 8 mg 30 minutes prior to chemotherapy induced vomiting.
Adverse effects:
It may cause headache, dizziness, restlessness and diarrhea (in some patients it may cause constipation). Fever and injection site reactions have also been reported.
Phenothiazine
These are also dopamine receptor antagonists.
Mechanism of action:
It is thought to affect the chemoreceptor trigger zone causing the blockage of dopamine receptors in the chemoreceptor trigger zone. It causes the inhibition of apomorphine induced vomiting.
Therapeutic uses:
It is effective in the treatment of nausea and vomiting which may be post operative or due to toxins or chemicals. It can be used in the treatment of acute migraine attacks and nausea and vomiting coming after the attacks.
It is also used as an antipsychotic drug.
Administration and dosage:
It can be administered orally or parenterally. The usual dosage of prochlorperazine is about 5 or 10 mg, 3-4 times daily.
Pharmacokinetics:
The onset of action of prochlorperazine is 30-45 minutes. The duration of action of prochlorperazine tablets is about 2.5-4.5 hours.
Adverse effects:
It may cause extrapyramidal reactions, tardive dyskinesia, hypotension and drowsiness.
Mechanism of action:
It is thought to affect the chemoreceptor trigger zone causing the blockage of dopamine receptors in the chemoreceptor trigger zone. It causes the inhibition of apomorphine induced vomiting.
Therapeutic uses:
It is effective in the treatment of nausea and vomiting which may be post operative or due to toxins or chemicals. It can be used in the treatment of acute migraine attacks and nausea and vomiting coming after the attacks.
It is also used as an antipsychotic drug.
Administration and dosage:
It can be administered orally or parenterally. The usual dosage of prochlorperazine is about 5 or 10 mg, 3-4 times daily.
Pharmacokinetics:
The onset of action of prochlorperazine is 30-45 minutes. The duration of action of prochlorperazine tablets is about 2.5-4.5 hours.
Adverse effects:
It may cause extrapyramidal reactions, tardive dyskinesia, hypotension and drowsiness.
Dimenhydrinate
It is an ethanolamine H1-receptor antagonist.
Mechanism of action:
Dimenhydrinate is thought to inhibit acetylcholine. It inhibits vestibular stimulation. (Vestibular and reticular systems stimulates nausea and vomiting in motion sickness.)
Therapeutic uses:
It is used to treat motion sickness. It is also used in Meniere’s disease and some of the other vestibular disturbances. It has been used in the allergic conditions also.
Administration and Dosage:
It can be administered orally, IM or IV. In motion sickness 50 mg of the drug is taken 30 minutes before motion. For vomiting 50-100 mg is taken 4-6 times in 24 hours.
Pharmacokinetics:
Its duration of action is 2.5-6 hours. It is widely distributed in the body cavities. It can cross the placenta. It is metabolized in liver and excreted through urine.
Adverse effects:
It may cause drowsiness, headache, dryness of the mouth and respiratory passages.
Mechanism of action:
Dimenhydrinate is thought to inhibit acetylcholine. It inhibits vestibular stimulation. (Vestibular and reticular systems stimulates nausea and vomiting in motion sickness.)
Therapeutic uses:
It is used to treat motion sickness. It is also used in Meniere’s disease and some of the other vestibular disturbances. It has been used in the allergic conditions also.
Administration and Dosage:
It can be administered orally, IM or IV. In motion sickness 50 mg of the drug is taken 30 minutes before motion. For vomiting 50-100 mg is taken 4-6 times in 24 hours.
Pharmacokinetics:
Its duration of action is 2.5-6 hours. It is widely distributed in the body cavities. It can cross the placenta. It is metabolized in liver and excreted through urine.
Adverse effects:
It may cause drowsiness, headache, dryness of the mouth and respiratory passages.
Metocloprmamide
It is a substituted benzamide and is D2-receptor antagonist.
Mechanism of action:
It acts by blocking dopamine D2-receptor in the chemoreceptor trigger zone in the brain. It also causes increased action of the acetylcholine at muscarinic nerve endings in stomach resulting in more peristalsis and emptying of the upper part of the stomach.
Therapeutic uses:
It is primarily used in nausea and vomiting. It is also used in emptying of the stomach.
Administration and dosage:
It can be administered orally, IM or IV in the dose of 10 mg three times a day.
Adverse effects:
It causes antidopaminergic side effects i.e. twisting of the neck towards one side due to muscle spasm, diarrhea, sedation and extra pyramidal symptoms that are the main adverse effects of dopamine receptor blockers characterized by symptoms very similar to Parkinson’s disease and include tremor.
Mechanism of action:
It acts by blocking dopamine D2-receptor in the chemoreceptor trigger zone in the brain. It also causes increased action of the acetylcholine at muscarinic nerve endings in stomach resulting in more peristalsis and emptying of the upper part of the stomach.
Therapeutic uses:
It is primarily used in nausea and vomiting. It is also used in emptying of the stomach.
Administration and dosage:
It can be administered orally, IM or IV in the dose of 10 mg three times a day.
Adverse effects:
It causes antidopaminergic side effects i.e. twisting of the neck towards one side due to muscle spasm, diarrhea, sedation and extra pyramidal symptoms that are the main adverse effects of dopamine receptor blockers characterized by symptoms very similar to Parkinson’s disease and include tremor.
Classification of anti-emetic agents
1. Classification according to action:
a. Dopamine D2-receptor antagonists:
Metoclopromide, Domperidone, Phenothiazines (e.g. chlorpromazine, thioridazine)
b. Sedative-hypnotics:
Barbiturates, Benzodiazepines.
c. Anti-histamines:
Promethazine, Cyclizine, Dimenhydrinate, Diphenhydramine.
d. 5-HT3 (serotonin) receptor antagonists:
Ondansetron, Tropisetron, Granisetron.
e. Anti-cholinergic:
Scopolamine
f. Demulcents:
Gum acacia, Gum tragacanth.
g. Miscellaneous:
Aprepitant, Diphenidol hydrochloride
2. Classification according to specific causes:
a. Motion sickness:
Anti-cholinergic drugs, Anti-histamines
b. Nausea and vomiting due to other causes:
i. Vomiting by cytotoxic drugs:
Phenothiazines, metoclopramide, serotonin antagonists
ii. Vomiting induced by pregnancy:
Anti-histamines, Vit. B6 alongwith anti-histamine such as meclizine
iii. Vertigo:
Cyclizine, Phenothiazine, Cinnarizine
a. Dopamine D2-receptor antagonists:
Metoclopromide, Domperidone, Phenothiazines (e.g. chlorpromazine, thioridazine)
b. Sedative-hypnotics:
Barbiturates, Benzodiazepines.
c. Anti-histamines:
Promethazine, Cyclizine, Dimenhydrinate, Diphenhydramine.
d. 5-HT3 (serotonin) receptor antagonists:
Ondansetron, Tropisetron, Granisetron.
e. Anti-cholinergic:
Scopolamine
f. Demulcents:
Gum acacia, Gum tragacanth.
g. Miscellaneous:
Aprepitant, Diphenidol hydrochloride
2. Classification according to specific causes:
a. Motion sickness:
Anti-cholinergic drugs, Anti-histamines
b. Nausea and vomiting due to other causes:
i. Vomiting by cytotoxic drugs:
Phenothiazines, metoclopramide, serotonin antagonists
ii. Vomiting induced by pregnancy:
Anti-histamines, Vit. B6 alongwith anti-histamine such as meclizine
iii. Vertigo:
Cyclizine, Phenothiazine, Cinnarizine
Vomiting
It is the forcible throwing of contents of stomach up through mouth as a result of involuntary spasms of the muscles of the stomach. It is also called emesis.
The chemoreceptor trigger zone as well as vomiting center of the medulla oblongata is involved in the emesis.
Following illustration is helpful in this context.
Causes of vomiting:
Vomiting may have from one of the following causes:
1. Motion sickness
2. Intestinal obstruction
3. Disease or disorder of the inner ear
4. Some kind of injury to the head
5. Appendicitis
6. Adverse effects or direct effects of certain drugs
7. Pregnancy
8. Renal failure
After effects of vomiting:
In severe cases vomiting may result in dehydration, malnutrition, or rupturing of the esophageal wall.
Therapeutic strategies:
Its treatment is directly towards the cause or origin of vomiting. It is beneficial to drink a lot of clear water or any other fluids so that the chances of dehydration will not be there.
On the other hand, medicines can also be used.
The chemoreceptor trigger zone as well as vomiting center of the medulla oblongata is involved in the emesis.
Following illustration is helpful in this context.
Vomiting may have from one of the following causes:
1. Motion sickness
2. Intestinal obstruction
3. Disease or disorder of the inner ear
4. Some kind of injury to the head
5. Appendicitis
6. Adverse effects or direct effects of certain drugs
7. Pregnancy
8. Renal failure
After effects of vomiting:
In severe cases vomiting may result in dehydration, malnutrition, or rupturing of the esophageal wall.
Therapeutic strategies:
Its treatment is directly towards the cause or origin of vomiting. It is beneficial to drink a lot of clear water or any other fluids so that the chances of dehydration will not be there.
On the other hand, medicines can also be used.
Nausea
It is the disturbance of the stomach which accompanies the feeling to vomit.
Nausea directly is caused from irritation of the nerve endings present in the stomach or duodenum, which stimulates nausea and vomiting control centers present in the brain.
Causes of nausea:
The most common causes of nausea are
1. Indigestion:
The nausea caused by indigestion is due to eating too rapidly or emotional stress.
2. Motion sickness:
This is caused by the disturbance in the balance organs of the inner ear i.e. semicircular canals of the ear. The messages for disturbance go to the lower brain.
3. Pregnancy:
Nausea directly is caused from irritation of the nerve endings present in the stomach or duodenum, which stimulates nausea and vomiting control centers present in the brain.
Causes of nausea:
The most common causes of nausea are
1. Indigestion:
The nausea caused by indigestion is due to eating too rapidly or emotional stress.
2. Motion sickness:
This is caused by the disturbance in the balance organs of the inner ear i.e. semicircular canals of the ear. The messages for disturbance go to the lower brain.
3. Pregnancy:
Saturday, April 2, 2011
Streptokinase
It is an extracellular protein.
Production:
It is obtained from cultured medium of group C-β hemolytic streptococci.
Mechanism of action:
It causes the conversion of plasminogen to plasmin. It causes the degradation of fibrinogen.
It also results in the breakdown of factor V and VII.
Pharmacokinetics:
Its half life is half an hour. It is administered within 4 hours of myocardial infarction and is infused for 1 hour.
Therapeutic uses:
It is used for reopening of occluded shunts, arterial and deep vein thrombosis and acute myocardial infarction (in addition with aspirin this effect is increased).
Dosage:
Its loading intravenous dose is 2, 50,000 units. Then it will be given as a continuous infusion of 100,000 units per hour for 24-72 hours.
Adverse effects:
It may cause hemorrhage. In severe cases of hemorrhage, aminocaproic acid can be given as an antidote.
Hypersensitivity reactions can also be developed such as rashes, fever and anaphylaxis. Antibodies developed due to streptococcal infection in some peoples may neutralize fibrinolytic properties of streptokinase. These antistreptococcal antibodies may cause fever, allergy and treatment ineffectiveness. In that case of treatment ineffectiveness more amount of streptokinase is to be administered.
Fever and shivering have also been observed in 1-4% of patients.
Production:
It is obtained from cultured medium of group C-β hemolytic streptococci.
Mechanism of action:
It causes the conversion of plasminogen to plasmin. It causes the degradation of fibrinogen.
It also results in the breakdown of factor V and VII.
Pharmacokinetics:
Its half life is half an hour. It is administered within 4 hours of myocardial infarction and is infused for 1 hour.
Therapeutic uses:
It is used for reopening of occluded shunts, arterial and deep vein thrombosis and acute myocardial infarction (in addition with aspirin this effect is increased).
Dosage:
Its loading intravenous dose is 2, 50,000 units. Then it will be given as a continuous infusion of 100,000 units per hour for 24-72 hours.
Adverse effects:
It may cause hemorrhage. In severe cases of hemorrhage, aminocaproic acid can be given as an antidote.
Hypersensitivity reactions can also be developed such as rashes, fever and anaphylaxis. Antibodies developed due to streptococcal infection in some peoples may neutralize fibrinolytic properties of streptokinase. These antistreptococcal antibodies may cause fever, allergy and treatment ineffectiveness. In that case of treatment ineffectiveness more amount of streptokinase is to be administered.
Fever and shivering have also been observed in 1-4% of patients.
Alteplase
It is a single chain recombinant tissue plasminogen activator.
Production:
Initially, produced from cultured melanoma cells taken from humans and now it is obtained with recombination technology.
Mechanism of action:
It is fibrin selective or clot selective.
It gets bind more strongly to plasminogen, which is bound to fibrin in thrombus or hemostatic plug, causing its activation.
Due to fibrin selectivity its low dosage has very less effect on other proteins.
Therapeutic uses:
It is effective in large type of pulmonary embolism. It is also used for myocardial infarction and acute ischemic stroke. Therapy must be started within 3 hours of stroke symptoms.
It has better ability to dissolve chronic type of clots.
Pharmacokinetics:
Its half life is 5 minutes.
Dosage:
It is administered as 100 mg dose in which 10 mg is given quickly by IV injection and the remaining is given in 90 minutes (1mg/minute).
Adverse effects:
It may cause hemorrhage.
Production:
Initially, produced from cultured melanoma cells taken from humans and now it is obtained with recombination technology.
Mechanism of action:
It is fibrin selective or clot selective.
It gets bind more strongly to plasminogen, which is bound to fibrin in thrombus or hemostatic plug, causing its activation.
Due to fibrin selectivity its low dosage has very less effect on other proteins.
Therapeutic uses:
It is effective in large type of pulmonary embolism. It is also used for myocardial infarction and acute ischemic stroke. Therapy must be started within 3 hours of stroke symptoms.
It has better ability to dissolve chronic type of clots.
Pharmacokinetics:
Its half life is 5 minutes.
Dosage:
It is administered as 100 mg dose in which 10 mg is given quickly by IV injection and the remaining is given in 90 minutes (1mg/minute).
Adverse effects:
It may cause hemorrhage.
Thrombolytic drugs
These drugs cause the conversion of plasminogen to plasmin causing fibrinolysis leading to dissolution of clots and reperfusion.
Plasmin may also degrade other factors like factor V, VIII and XII.
Note: Clots become more stable as the time passes. So treatment in the beginning is more helpful.
Therapeutic uses:
Previously it was mostly used in serious pulmonary embolism and central deep vein thrombosis but now less commonly used because of increased ability of bleeding.
They are also used to remove clots from catheters and shunts.
Administration:
They are usually administered intravenously.
Adverse effects:
It may cause hemorrhage.
Sometimes dissolution of clots may lead to increased local thrombi leading to increased platelaet aggregation and thrombosis. This incidence can be reduced buy giving aspirin and heparin along with thrombolytic drugs.
Contraindication:
It is contraindicated in pregnancy and in the patients of healing wounds.
Plasmin may also degrade other factors like factor V, VIII and XII.
Note: Clots become more stable as the time passes. So treatment in the beginning is more helpful.
Therapeutic uses:
Previously it was mostly used in serious pulmonary embolism and central deep vein thrombosis but now less commonly used because of increased ability of bleeding.
They are also used to remove clots from catheters and shunts.
Administration:
They are usually administered intravenously.
Adverse effects:
It may cause hemorrhage.
Sometimes dissolution of clots may lead to increased local thrombi leading to increased platelaet aggregation and thrombosis. This incidence can be reduced buy giving aspirin and heparin along with thrombolytic drugs.
Contraindication:
It is contraindicated in pregnancy and in the patients of healing wounds.
Dipyridamole
It is an anticoagulant. It is a phosphodiesterase inhibitor. It is given in combination with aspirin.
Mechanism of action:
It causes inhibition of cyclic nucleotide phosphodiesterase leading to increased intracellular level of cAMP resulting in decreased Thromboxane A2 synthesis.
It may also stop the reuptake and metabolism of adenosine and potentiates prostacyclin effect to decrease platelet binding to thrombogenic surfaces leading to decreased platelet aggregation.
Therapeutic uses:
It is a coronary vasodilator. It is also used prophylactically in angina pectoris.
Adverse effects:
Headache
Mechanism of action:
It causes inhibition of cyclic nucleotide phosphodiesterase leading to increased intracellular level of cAMP resulting in decreased Thromboxane A2 synthesis.
It may also stop the reuptake and metabolism of adenosine and potentiates prostacyclin effect to decrease platelet binding to thrombogenic surfaces leading to decreased platelet aggregation.
Therapeutic uses:
It is a coronary vasodilator. It is also used prophylactically in angina pectoris.
Adverse effects:
Headache
Eptifibatide and tirofiban
These are Anti-coagulants. Eptifibatide is a cyclic peptide and tirofiban is a non-peptide.
These bind to platelet GP IIb/IIIa receptors at the site that interacts with arginine-glycine-aspartic acid sequence of fibrinogen.
These are almost similar to abciximab in pharmacological aspects.
These bind to platelet GP IIb/IIIa receptors at the site that interacts with arginine-glycine-aspartic acid sequence of fibrinogen.
These are almost similar to abciximab in pharmacological aspects.
Abciximab
It is a chimeric (hybrid) monoclonal antibody.
Mechanism of action:
In this hybrid monoclonal antibody i.e. constant regions of human immunoglobulin and Fab fragments of murine monoclonal antibody gets bind to platelet GP IIb/IIIa receptos leading to blockage of the binding of fibrinogen and von Willebrand factor resulting in inhibition of aggregation.
Administration:
It is administered intravenously with aspirin and heparin.
Note: After stoppage of therapy platelet function gradually returns to normal.
Therapeutic uses:
It is used for the prevention of cardiac ischemia.
It is also recommended for patients with unstable angina.
Adverse effects:
It may cause bleeding disorders. Thrombocytopenia may also be caused.
Mechanism of action:
In this hybrid monoclonal antibody i.e. constant regions of human immunoglobulin and Fab fragments of murine monoclonal antibody gets bind to platelet GP IIb/IIIa receptos leading to blockage of the binding of fibrinogen and von Willebrand factor resulting in inhibition of aggregation.
It is administered intravenously with aspirin and heparin.
Note: After stoppage of therapy platelet function gradually returns to normal.
Therapeutic uses:
It is used for the prevention of cardiac ischemia.
It is also recommended for patients with unstable angina.
Adverse effects:
It may cause bleeding disorders. Thrombocytopenia may also be caused.
Ticlopidine and clopidogrel
These are thienopyridine derivatives. They cause blockage of platelet aggregation.
Mechanism of action:
ADP gets bind to receptors on platelets resulting in activation of GP IIb/IIIa receptors, which is important for platelet binding to fibrinogen and to each other. Ticlopidine and clopidogrel cause interference in binding of ADP to receptors on platelets.
Pharmacokinetics:
The drugs get strongly bind to plasma proteins after ingesting orally. Metabolism takes place extensively in the liver by cytochrome P450 system releasing active metabolites.
Maximum activity reached in 3-6 days. Its elimination takes place through kidney and feces.
Therapeutic uses:
These are effective in the prevention of cerebrovascular disease, cardiovascular disease and peripheral vascular disease.
These are used for insertion of stents in myocardial infarction.
Adverse effects:
It may cause prolonged bleeding. Thrombocytopenic purpura is also another adverse effect. Ticlopidine may also cause neutropenia.
Clopidogrel may also cause abdominal pain, chest pain and flulike symptoms.
Dosage:
Ticlopidine is taken orally in the 250 mg, tablet form BD with food.
The maintenance dose of clopidogrel is 75 mg per day.
Drug interactions:
Food causes interference in the absorption of ticlopidine but not of clopidogrel.
These drugs can stop activity of cytochrome P450 and that is why they may interfere with the metabolism of drugs such as tolbutamide, phenytoin, warfarin, and tamoxifen, if taken together.
Mechanism of action:
ADP gets bind to receptors on platelets resulting in activation of GP IIb/IIIa receptors, which is important for platelet binding to fibrinogen and to each other. Ticlopidine and clopidogrel cause interference in binding of ADP to receptors on platelets.
The inhibitory effect is irreversible and this effect remains as long as the platelet life.
Pharmacokinetics:
The drugs get strongly bind to plasma proteins after ingesting orally. Metabolism takes place extensively in the liver by cytochrome P450 system releasing active metabolites.
Maximum activity reached in 3-6 days. Its elimination takes place through kidney and feces.
Therapeutic uses:
These are effective in the prevention of cerebrovascular disease, cardiovascular disease and peripheral vascular disease.
These are used for insertion of stents in myocardial infarction.
Adverse effects:
It may cause prolonged bleeding. Thrombocytopenic purpura is also another adverse effect. Ticlopidine may also cause neutropenia.
Clopidogrel may also cause abdominal pain, chest pain and flulike symptoms.
Dosage:
Ticlopidine is taken orally in the 250 mg, tablet form BD with food.
The maintenance dose of clopidogrel is 75 mg per day.
Drug interactions:
Food causes interference in the absorption of ticlopidine but not of clopidogrel.
These drugs can stop activity of cytochrome P450 and that is why they may interfere with the metabolism of drugs such as tolbutamide, phenytoin, warfarin, and tamoxifen, if taken together.
Aspirin
Mechanism of action:
Aspirin causes the inhibition of COX-1by irreversible acetylation of serine residue on its active site and by causing a developmental failure of thromboxane A2 synthetase leading to the inhibition of Thromboxane-A2 synthesis.
Aspirin causes the inhibition of COX-1by irreversible acetylation of serine residue on its active site and by causing a developmental failure of thromboxane A2 synthetase leading to the inhibition of Thromboxane-A2 synthesis.
In the whole process, Thrombin, collagen and ADP results in stimulation of platelets causing activation of platelet membrane phospholipids leading to the liberation of arachidonic acid from membrane phospholipids. COX-1 converts arachidonic acid to prostaglandin H2 which is then metabolized to thromboxane-A2 which is then released into plasma to cause a change in the shape of the platelets, release of their granules and promoting the clustering of platelets necessary for rapid formation of hemostatic plug.
Dosage:
For myocardial infarction prophylactically it is used as 325mg/day.
Adverse effects:
It may cause hemorrhage leading to hemorrhagic stroke or GI bleeding.
Aspirin also causes chemical mediators to influence positively on anti-aggregating properties of prostacyclin (PGI2) leading to further blockage of platelet aggregation.
The inhibitory effect apparently occurs in portal circulation where it is relatively faster. The effect occurs for 7-10 days.
Therapeutic uses:
It is used prophylactically for short duration of cerebral ischemia so that the incidence of myocardial infarction is reduced.
It is used in combination with other drugs such as heparin or clopidogrel.It is used prophylactically for short duration of cerebral ischemia so that the incidence of myocardial infarction is reduced.
Dosage:
For myocardial infarction prophylactically it is used as 325mg/day.
Adverse effects:
It may cause hemorrhage leading to hemorrhagic stroke or GI bleeding.
Anti-thrombotic drugs
These are platelet aggregation inhibitors (through a decreased formation or effect of chemical signals).
Mechanism of action:
In a series of reactions, when a vessel is injured, finally activation of membrane glycoprotein (GP) receptors takes place leading to binding of several adhesive proteins i.e. von Willebrand factor, fibronectin and fibrinogen.
Most important of GP-receptors is GP IIb/IIIa receptors upon which binding of fibrinogen takes place, through platelet activators like TXA2, ADP or thrombin, on two separate platelets resulting in the platelet cross linking and platelet aggregation leading to thrombus formation.
These drugs either cause inhibition of cyclo-oxygenase-1 (COX-1) or block GP IIb/IIIa receptors.
Mechanism of action:
In a series of reactions, when a vessel is injured, finally activation of membrane glycoprotein (GP) receptors takes place leading to binding of several adhesive proteins i.e. von Willebrand factor, fibronectin and fibrinogen.
Oral anticoagulants
Warfarin is a vitamin K antagonist. It antagonizes the cofactor functions of vitamin K.
Firstly, it was used as rodenticide.
Mechanism of action:
Factors like II, VII, IX, and X and certain natural anticoagulants such as protein C require vitamin K as cofactor for their synthesis.
These factors undergo vitamin K dependent posttranslational modification resulting in the carboxylation of glutamic acid residue which is converted into γ-carboxyglutamic acid residue by vitamin K dependent carboxylase. This residue gets bind to calcium ions, which is important for interaction between coagulation factors and platelet membranes.
The reduced form of vitamin K cofactor (active hydroquinone form) is changed into vitamin K epoxide during reaction. Vitamin K cofactor is regenerated by vitamin K epoxide reductase.
Warfarin inhibits this enzyme leading to inactive coagulation factors due to lack of γ-carboxyglutamyl chain.
It is used for prophylaxis therapy of pulmonary embolism and venous thrombosis.
Pharmacokinetics:
It is readily absorbed by oral ingestion. 99% bind to plasma albumin leading to stoppage of its movement to CSF, breast milk and urine. Its onset of action is 8-12 hours.
It can cross placenta.
It is metabolized by cytochrome P450 system and its half life is variable ranging from 40-60 hours. Elimination is done through urine and feces after conjugation with glucuronic acid.
Dosage:
It is given in the dose of 2-5 mg for one week daily.
Adverse effects:
It may cause hemorrhage. In this case, dose must be adjusted. It can be controlled by intravenous administration of vitamin K. Plasma concentrates of the blood factors may be employed in severe cases. It may also cause rashes, diarrhea and alopecia.
Drug Interactions:
Food may delay its absorption.
Drugs having higher attraction for albumin binding sites such as sulfonamides can displace warfarin leading to short duration of increased activity.
Contraindications:
It is contraindicated in pregnancy as it is teratogenic and can lead to abortion.
Antidote:
Vitamin-K
Firstly, it was used as rodenticide.
Mechanism of action:
Factors like II, VII, IX, and X and certain natural anticoagulants such as protein C require vitamin K as cofactor for their synthesis.
These factors undergo vitamin K dependent posttranslational modification resulting in the carboxylation of glutamic acid residue which is converted into γ-carboxyglutamic acid residue by vitamin K dependent carboxylase. This residue gets bind to calcium ions, which is important for interaction between coagulation factors and platelet membranes.
The reduced form of vitamin K cofactor (active hydroquinone form) is changed into vitamin K epoxide during reaction. Vitamin K cofactor is regenerated by vitamin K epoxide reductase.
Warfarin inhibits this enzyme leading to inactive coagulation factors due to lack of γ-carboxyglutamyl chain.
Therapeutic Uses:
It is used for prophylaxis therapy of pulmonary embolism and venous thrombosis.
Pharmacokinetics:
It is readily absorbed by oral ingestion. 99% bind to plasma albumin leading to stoppage of its movement to CSF, breast milk and urine. Its onset of action is 8-12 hours.
It can cross placenta.
It is metabolized by cytochrome P450 system and its half life is variable ranging from 40-60 hours. Elimination is done through urine and feces after conjugation with glucuronic acid.
Dosage:
It is given in the dose of 2-5 mg for one week daily.
Adverse effects:
It may cause hemorrhage. In this case, dose must be adjusted. It can be controlled by intravenous administration of vitamin K. Plasma concentrates of the blood factors may be employed in severe cases. It may also cause rashes, diarrhea and alopecia.
Drug Interactions:
Food may delay its absorption.
Drugs having higher attraction for albumin binding sites such as sulfonamides can displace warfarin leading to short duration of increased activity.
Contraindications:
It is contraindicated in pregnancy as it is teratogenic and can lead to abortion.
Antidote:
Vitamin-K
Danaparoid
It is a complex of sulfates of heparin, dermatan and chondroitin. It acts through antithrombin III. It is anti-factor Xa and to a lesser extent it is also inhibitor of thrombin.
Extraction:
It is obtained from porcine mucosa.
Administration and elimination:
It is administered subcutaneously and is eliminated through kidneys.
Therapeutic uses:
Prophylactically, it is used in deep vein thrombosis in hip replacement surgery.
It is effective in Type-II, heparin induced thrombocytopenia.
Adverse effects:
Allergic reactions such as anaphylaxis or asthma may develop. Hemorrhage may occur.
Excess danaparoid can be displaced by plasmapheresis.
Extraction:
It is obtained from porcine mucosa.
Administration and elimination:
It is administered subcutaneously and is eliminated through kidneys.
Therapeutic uses:
Prophylactically, it is used in deep vein thrombosis in hip replacement surgery.
It is effective in Type-II, heparin induced thrombocytopenia.
Adverse effects:
Allergic reactions such as anaphylaxis or asthma may develop. Hemorrhage may occur.
Excess danaparoid can be displaced by plasmapheresis.
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