Skip to main content
UploadLanguage (EN)Support
BusinessMobileSocial MediaMarketingTechnologyArt & PhotosCareerDesignEducationPresentations & Public SpeakingGovernment & NonprofitHealthcareInternetLawLeadership & ManagementAutomotiveEngineeringSoftwareRecruiting & HRRetailSalesServicesScienceSmall Business & EntrepreneurshipFoodEnvironmentEconomy & FinanceData & AnalyticsInvestor RelationsSportsSpiritualNews & PoliticsTravelSelf ImprovementReal EstateEntertainment & HumorHealth & MedicineDevices & HardwareLifestyle
Uploaded byNikithaGopalpet
PPTX, PDF9,486 views

2nd unit anti-hypertensive agents ppt

The document provides a comprehensive overview of anti-hypertensive agents, detailing types of hypertension, ideal characteristics, classifications, and mechanisms of action of various drug classes, including ACE inhibitors and calcium channel blockers. It also discusses the pharmacokinetics, adverse drug reactions, and therapeutic uses of specific medications such as captopril, enalapril, and lisinopril, emphasizing their roles in managing high blood pressure and related conditions. The content is intended for pharmacy students and covers essential medicinal chemistry concepts related to the treatment of hypertension.

Education◦
Downloaded 78 times
2ND UNIT ANTI-HYPERTENSIVE AGENTS Prepared by G. Nikitha, M.Pharmacy Assistant Professor Department of Pharmaceutical Chemistry Sree Dattha Institute Of Pharmacy Hyderabad 1 Subject: Medicinal Chemistry-II Year: B.Pharmacy 3rd Year Semister: 1st Semister
CONTENTS  Introduction.  Types of Hypertension  Ideal Characteristics  Classification  Mechanism of action .  SAR.  Structure  Synthesis.  Adverse Drug Reactions .  Uses.  References 2
INTRODUCTION  Hypertension is defined as an increase in the arterial blood pressure above normal.  It is the most common disorder affecting the heart and blood vessels.  The blood pressure (Bp) is said to be normal, if the systolic Bp is 120mm Hg and diastolic is 80mm Hg i.e, 120/80 mm Hg.  An individual is said to be pre hypertensive if systolic pressure is 121-139 mm Hg or diastolic pressure is 81-89 mm Hg.  An individual is said to be hypertensive if his systolic pressure is ≥ 140 mm Hg or diastolic pressure is ≥ 90 mm Hg. 3
Bp in mm Hg Diagnosis Systolic Diastolic 120 80 Normal Bp 121-139 81-89 Pre hypertensive 149-159 90-99 Stage-1 Hypertension ≥160 ≥100 Stage-2 Hypertension 4
TYPES OF HYPERTENSION Hypertension is divided into two types. 1. Primary (Essential) Hypertension:  In majority of cases, hypertension is of unknown cause and is known as primary or essential hypertension. Even though a definite cause is not known in primary hypertension the following factors may contribute to the elevation of Bp. a. Dietary intake of more sodium and less potassium. b. Decrease in vascular synthesis of nitric oxide that is responsible for vasodilatation. c. In some cases, primary hypertension may be hereditary. d. Advancement of age may also be responsible for primary hypertension. 5
2. Secondary Hypertension:  In some cases, hypertension may be secondary to other diseases. a. Endocrine Disorder b. Kidney Disorder c. Muscular Disorder 6
IDEAL CHARACTERISTICS  It should have specific site of action.  It should control blood pressure  It should be stable in light and heat  It should not cause cardial, renal or cerebral damage  It should be inexpensive 7
CLASSIFICATION  The potential of a substance or drug to lower the blood pressure to less than 140/90 mm Hg in hypertension patients is termed as antihypertension activity. 1. ACE Inhibitors: 8 Captopril Enalapril
9 Lisinopril Perindopril Ramipril
10 Quinapril Benazepril
2. Angiotensin II Receptor (AT1) Antagonist: 11 Losartan Candesartan Valsartan
12 Telmisartan Irbesartan
3. Calcium Channel Blockers: 13 Verapamil Diltiazem Nifedipine Amlodipine
14 Felodipine Nicardipine Nimodipine Bepridil
4. Centrally Acting Sympatholytic Drugs: 15 Clonidine Methyldopate Guanabenz
5. Direct Vasodilators: a. Arterial Vasodilators: 16 Diazoxide Minoxidil Hydralazine
b. Arteriovenular Vasodilators: 17 Sodium nitropruside
6. Adrenergic neuron blocking Drugs: 18 Reserpine Guanethidine
7. α-blockers or α-adrenergic blockers: a. Non Selective Antagonists: 19 Phenoxybenzamine Phenotolamine
b. Selective Antagonists: 20 Prazosin Terazosin Tamsulosin
8. β-Adrenergic Receptor Antagonists or β-blockers: a. Non Selective Antagonists: 21 Propranolol Timalol
22 Pindolol Sotalol Nadolol
b. Selective Antagonists: 23 Atenolol Metoprolol Esmolol Acebutalol
9. Diuretics: 24 Hydrochlorothiazide Chlorthalidone Indapamide
10. Potassium Sparing Diuretics: 25 spironolactone Amiloride
ACE INHIBITORS 26
 Angiotenion antagonists block the actions of angiotension II either by inhibiting its synthesis (ACE inhibitors) or by inhibiting its action at the receptors (angiotension II receptor antagonists). 27
Mechanism of Action: Angiotension Converting Enzyme (ACE) is involved in the 1. Conversion of Angiotenion I to Angiotenion II which is a potent vasoconstrictor. Angiotenion II stimulates the synthesis of aldosterone which causes increased reabsorption ofsodium and water fluid retention cardiac output blood pressure. 2. Degradation of bradykinin which is a potent vasodilator. Thus, the inhibition of ACE by ACE inhibitors leads to vasodilatation followed by decrease in Bp due to decreased formation of Angiotenion II which in turn leads to reduced aldosterone synthesis and increase bradykinin levels. 28
SAR: 1. Presence of carboxylic acid on N-ring is essential for the compound. 2. Presence of larger nitrogen containing heterocyclic rings will enhance the potency of the compound by increasing its lipophilicity. 3. The zinc binding groups are essential for stabilization they may be either sulfhydryl (-CH2SH) as in captapril, caroxylate ( ) as in Lisinopril or phosphate ( ) groups as in fosinopril. 29
4. Presence of sulfuhydryl group leads shorter duration of action because it facilitates the formation of dimmers and disulfides eg: Captopril 5. Presence of carboxylate or phosphinate group facilitates the esterification process, thus producing orally active prodrugs. R1 is generally a methyl group to resemble the side chain of alanine. 6. When R1 is n-butylamine in dicarboxylate containing compounds it resembles the lysine side chain and the compound is orally active thus eliminating the need for it to be a Prodrug eg: Lisinopril. 7. When the stereochemistry of the drug (ACE inhibitors) is in accordance with the stereochemistry of L-amino acid in normal substrate the drug exhibits maximum activity. 30
Captopril Structure: IUPAC:1-[-2-methyl-3-sulfanyl propanoyl] pyrrolidine-2-carboxylic acid Properties: It is white or almost white crystalline powder, soluble in dilute sodium hydroxide, potassium hydroxide, water, methanol, methyl chloride. 31 Molecular formula: C9H15NO3S
Pharmacokinetics:  It is well absorbed oral administration. Food delays the absorption of captopril but not other drugs. Therefore captopril should be taken one hour before meal. Captopril has faster onset of action but lesser duration of action compared to Enalapril and Lisinopril. It is metabolized in the liver and excreted in urine. Adverse Drug Reactions:  dry cough (should go away after you stop taking captopril),  dizziness, shortness of breath, skin rash,  a change in the way that foods taste  Head ache, nausea, bowel upset  Fetal toxicity, neutropenia (abnormal decrease in neutrophil count), Angioedema (swelling of lips, tongue)  Acute renal failure, in patients with renal artery stenosis.  Weight gain  Hypotension is seen in CHF patients and patients on diuretics. 32
Therapeutic Uses:  Used in the treatment of hypertension, congestive heart failure (CHF) and left ventricular (LV) dysfunction.  Used in the treatment of myocardial infarction.  Used in the treatment of diabetic and non-diabetic nephropathy.  It is also used to treat kidney disease in people with diabetes. Dose:  25-50 mg b.i.d orally. 33
 Enalapril Structure: IUPAC:1-[-2-{-1-ethoxy-1-oxo-4-phenylbutan-2-yl] amino} propanoyl]pyrrolidine-2-carboxylic acid Properties: White or off white crystalline powder, soluble in water, alcohol, methanol, insoluble in methylene chloride, Freely soluble in DMF. 34 Molecular formula: C20H28N2O5
Pharmacokinetics:  Oral route of administration, metabolized in the liver as it is a Prodrug which is metabolically transformed into enalaprilat, mainly eliminated through renal excretion, where approximately 94% of the total dose is excreted via urine or feces as either enalaprilat or unchanged parent compound. Adverse Drug Reactions:  Dizziness, head ache  weakness  skin rash  cough, nausea, blurred vision  disturbance in taste, hypotension, branchaspasm 35
Therapeutic Uses:  Enalapril oral tablet is used to treat high blood pressure, heart failure, and asymptomatic left ventricular dysfunction.  Enalapril may be used as part of a combination therapy. That means you need to take it with other drugs. Dose:  5-20 mg OD Orally. 36
Lisinopril Structure: IUPAC:6-amino-2-{[-1-carboxy-3-phenylpropyl] amino} hexanoyl]pyrrolidine-2-carboxylic acid Properties: White crystalline powder, insoluble in acetone, ethanol, soluble in water, sparingly soluble in methanol. 37 Molecular formula: C21H31N3O5
Pharmacokinetics:  Oral route of administration, it is not metabolized and is excreted as the unchanged drug, entirely eliminated exclusively in the urine. Adverse Drug Reactions:  Headache, dizziness, nausea, vomiting  persistent cough  low blood pressure, chest pain  diarrhea, loss of appetite, stomach pain,  Skin irritation 38
Therapeutic Uses:  Lisinopril oral tablet is used to treat high blood pressure and heart failure. It’s also used to improve your chance of survival after a heart attack.  This drug may be used as part of a combination therapy. That means you may need to take it with other drugs. Dose:  5-40 mg OD Orally. 39
Benazepril hydrochloride Structure: IUPAC:3-{[-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}-2-oxo-1H- benzazepin-1-yl]acetic acid hydrochloride Properties: White crystalline powder, soluble in water, ethanol, methanol 40 . Hcl Molecular formula: C24H29ClN2O5
Pharmacokinetics:  Oral route of administration, metabolized in liver, i.e Cleavage of the ester group (primarily in the liver) converts benazepril to its active metabolite; benazeprilat. Benazepril and benazeprilat are conjugated to glucuronic acid prior to urinary excretion. Adverse Drug Reactions:  dizziness, headache, drowsiness, anxiety, lightheadedness, confusion, fever  cough, nausea,  vomiting, constipation,  tired feeling,  sleep problems (insomnia),  flushing (warmth, redness, or tingly feeling),  Itching or Skin rash. 41
Therapeutic Uses:  Benazepril is used to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.  Benazepril is an ACE inhibitor and works by relaxing blood vessels so that blood can flow more easily. Dose:  20 to 40 mg/day orally as a single dose or in two equally divided doses. 42
Quinapril Hydrochloride Structure: IUPAC: 1-[-2-{[-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino} propanoyl]-quinoline-2-carboxylic acid hydrochloride Properties: White to off-white amorphous powder that is freely soluble in aqueous solvents 43 .Hcl Molecular formula: C25H31ClN2O5
Pharmacokinetics:  Oral route of administration, metabolized in liver, i.e de-esterified to the active quinaprilat or dehydrated to form the inactive PD109488. PD109488 can undergo O-deethylation to form another inactive metabolite, PD113413, eliminated through urine. Adverse Drug Reactions:  Headache, dizziness, fatigue  coughing, chest pain, low blood pressure (hypotension)  nausea or vomiting  stomach pain, diarrhea  gasping for air  muscle pain  skin rash, back pain 44
Therapeutic Uses:  Quinapril is used to treat high blood pressure and heart failure. Dose:  Usual Adult Dose for Hypertension Initial dose: 10 or 20 mg orally once a day in patients not on diuretics Maintenance dose: 20 to 80 mg orally per day, administered as a single dose or in two equally divided doses  Usual Adult Dose for Congestive Heart Failure Initial dose: 5 mg orally twice a day Maintenance dose: 20 to 40 mg orally per day administered in two equally divided doses 45
CENTRALLY ACTING SYMPATHOLYTIC DRUGS 46
 Drugs belonging to this class act by inhibiting the sympathetic nervous system by central action.  They stimulate α-adrenergic receptors of the vasomotor centre in medulla there by reducing non adrenaline release and sympathetic activity leading to fall blood pressure. 47
Clonidine hydrochloride Structure: IUPAC:N-(2,6-dichlorophenyl)-1H-imidazol-2-amine hydrochloride Properties: White crystalline powder, soluble in alcohol, slightly soluble in chloroform, insoluble in water. 48 .Hcl Molecular formula: C9H10Cl3N3
Pharmacokinetics:  Upon oral administration, Clonidine is rapidly absorbed with nearly 100% bioavailability. It is well distributed in the body and undergoes partial metabolism in liver. The major route of excretion of both changed and unchanged Clonidine is through urine and to some extent through faeces. Adverse Drug Reactions:  Nausea, vomiting, constipation, dry mouth, anorexia.  Itching or burning sensation in eyes.  Heart failure, bradicardia.  Drowsiness, anxiety, sleep disturbances, headache, dizziness, hallucinations.  Gynaecomastia (excess growth of male mammary glands, raynaud’s syndrome transient hyperglycaemia.  upper respiratory tract infection 49
Therapeutic Uses:  Clonidine is used as an antihypertensive agent for controlling hypertensive crisis.  It is used in the prophylactic treatment of migraine, headache, menopausal flushing.  It is used to treat glucoma, insomnia, neuropathic pain.  It is used in growth retardation, as it stimulates the release of growth hormones from pituitary gland. Dose:  An initial dose of 0.1 mg OD gradually increased to 0.3 mg by oral route. 50
Guanabenz acetate Structure: IUPAC:2{[(2,6dichlorophenyl)methylidene]amino}guanidine acetic acid Properties: White crystalline powder, slight odor, soluble in alcohol, chloroform, propylene glycogen. 51 Molecular formula: C10H12Cl2N4O2
Pharmacokinetics:  Oral route of administration, metabolized in liver, eliminated through urine. Adverse Drug Reactions:  dry mouth, upset stomach,  drowsiness, dizziness, headache, coma  weakness  decreased sexual ability  fainting, swollen ankles or feet  increased or decreased heartbeat, irregular heartbeat  Respiratory problems, hypotension, frequent urination  Blurred vision, muscle pain, dry eyes, back pain 52
Therapeutic Uses:  Guanabenz is used to treat high blood pressure. It is in a class of medications called centrally acting alpha2A-adrenergic receptor agonists.  Guanabenz works by decreasing your heart rate and relaxing the blood vessels so that blood can flow more easily through the body. Dose:  4 to 8 mg orally twice a day, whether used alone or in combination with a Thiazides diuretic.  The maximum dose studied is 32 mg twice a day 53
Methyldopate hydrochloride Structure: IUPAC:ethyl-2-amino-3-(3,4-dihydroxy phenyl)-2-methyl propanoate hydrochloride Properties: White crystalline powder, hygroscopic in nature, soluble in water, insoluble in organic solvents. 54 .Hcl Molecular formula: C12H18ClNO4
Synthesis: 55
Mechanism of Action:  It is a Prodrug which converts to an active metabolite α-methyl noradrenaline in the adrenergic neurons.  The active metabolite of the drug acts centrally by stimulating α2- adrenergic receptors in the vasomotor center of the medulla therapy reducing the sympathetic activity and noradrenaline release leading to decrease blood pressure. 56
Pharmacokinetics:  Methyldopate is absorbed rapidly but incompletely after oral administration. It is transported to the brain by amino acid transporter where it converted to its active metabolite, α-methyl noradrenaline. The plasma half life of the drug I 2 hours but the antihypertensive effect lasts for about 24 hours. The drug is excreted partly as metabolites (sulphate conjugate) and partly in an unchanged form in urine. Adverse Drug Reactions:  dry mouth  Drowsiness, headache, depression, night mares, parkinsonism  weakness  loss of energy, or fluid retention in legs, feet, arms, or hands  Hepatotoxicity, constipation  Sexual impotence, gynecomastia  Sedation, forgetfulness 57
Therapeutic Uses:  Methyldopate is used in the treatment of moderate hypertension in combination with diuretics.  Since it does not affect renal blood flow and GFR, it is used in hypertension associated with renal impairment.  It is especially useful in pregnant women due to its safety and efficacy.  However due to its severe adverse effects and availability of other safer drugs, its use has now declined. Dose:  250 mg b.i.d initially gradually increased to 500 mg by oral route. 58
DIRECT VASODILATORS 59
 They act directly on arteries or veins to reduce the blood pressure which are classified as 60
a. Arterial Vasodilators:  Diazoxide, Minoxidil, Hydralazine are the potassium channel openers used as antihypertensive drugs.  They cause direct relaxation of arteries but not veins.  However their usage as a single drugs is discouraged because the relaxation of blood pressure by relaxation of vascular smooth muscles is opposed by sympathetic activity i.e release of adrenaline, a vasoconstriction. 61
Diazoxide Structure: IUPAC: 7-Chloro-3-methyl-benzothiadiazine 1,1-dioxide Properties: White or almost white and fine crystalline powder soluble in dilute solutions of alkali hydroxides, in dimethylformamide, slightly soluble in alcohol, but insoluble in water. 62 Molecular formula: C8H7ClN2O2S
Pharmacokinetics:  It is well absorbed on oral and parental administration. The onset of action is rapid and duration of action is about 5-20 hours. It is highly bound to plasma proteins. It undergoes the hepatic metabolism and renal excretion. Adverse Drug Reactions:  Tachycardia, hypotension  Fluid retension, hyperglycemia, hyperuricaemia (abnormal increase of uric acid in blood).  Angina and myocardial infarction occurs in patients with ischemic heart disease.  nausea, vomiting, stomach pain, loss of appetite,  diarrhea, constipation; or decreased sense of taste 63
Therapeutic Uses:  It is used in hypertensive emergencies as an alternative to sodium nitropruside.  It is used to arrest premature labour.  It is used for temporary treatment of hypoglycaemia secondary to insulinoma (insulin producing tumours of the β-cells of pancreatic islets). Dose:  150 mg by rapid i.v injection. 64
Minoxidil Structure: IUPAC: 6-piperidin-1-ylpyrimidine-2,4-diamine 3-oxide Properties: It is a white or almost white crystalline powder, which is slightly soluble in water, soluble in methanol and in propylene glycol. 65 Molecular formula: C9H15N5O
Pharmacokinetics:  Minoxidil is well absorbed from GIT on oral administration it is converted to an active metabolite in the liver by glucoronide conjugation excreted through urine. Adverse Drug Reactions:  Headache,  Fluid retention, Palpitations  Angina, pulmonary hypertension, cardiac temponade, tachycardia.  Hypertrichosis (excess hair growth) 66
Therapeutic Uses:  Minoxidil is used in the treatment of hypertension, unresponsive to other drugs. It given in combination with β-blockers and diuretics.  Minoxidil is used in the topical treatment of alopecia (baldness). Dose:  1.5 mg OD initially gradually increased to 40 mg by oral route. 67
Hydralazine hydrochloride Structure: IUPAC: 1-hydrazinylphthalazine hydrochloride Properties: It is a white or almost white crystalline powder, which is slightly soluble in methylene chloride, but soluble in water and slightly soluble in alcohol. 68 .Hcl Molecular formula: C8H9ClN4
Pharmacokinetics:  Hydralazine Hcl is absorbed from GIT on oral administration. It is metabolized in liver by acetylation. It is excreted as metabolites and very small amount of the drug is excreted unchanged in urine. Adverse Drug Reactions:  Head ache, nausea, vomiting, dizziness, anorexia,  Diarrhea, nasal congestion, fever  Skin rashes, palpitation, polyneuritis  Tachycardia, angina, myocardial ischemia.  loss of appetite, weight loss, chest pain 69
Therapeutic Uses:  Hydralazine Hcl is used in the treatment of hypertension, which is not controlled by diuretics or β-blockers. It is preferred drug in hypertensive emergencies in pregnant women. It always given in combination with diuretics and β-blockers.  Hydralazine Hcl is sometimes used in the management of CHF in combination with nitrates. Dose:  25-50 mg OD by oral route. 70
b. Arteriovenular Vasodilators: Sodium nitropruside Structure: IUPAC: sodium pentacyanonitrosyl ferrate Properties: It is a reddish-brown powder or crystals, which are freely soluble in water, but slightly soluble in alcohol 71 Molecular formula: C5FeN6Na2O
Pharmacokinetics:  I.V route of administration, metabolized in liver i.e sodium nitropruside is converted to cyanide (CN) and NO by RBC in the blood vessels. The toxic CN is metabolized in liver (by rhodanase) to less toxic thiocyanates which is excreted very slowly in the urine. Adverse Drug Reactions:  Headache, nausea, vomiting, convulsions, psychosis, dizziness  Hypotension, hypothyroidism and methaemoglobinaemia  abdominal pain, apprehension, sweating, muscle twitching  palpitations, restlessness,  retching,  chest discomfort,  slow or fast heart rate,  Rash, flushing or irritation at the infusion site. 72
Therapeutic Uses:  It is used in the treatment of hypertensive emergencies. It is used only for a brief period until the blood pressure is lowered.  To produce controlled hypotension at the time of surgery.  In acute myocardial infarction to enhance LV function. Dose:  500 mg powder dissolved in 500 ml of 5% dextrose in water and administered at a rate of 0.25-1.5 μg/kg/min by i.v infusion. 73
ADRENERGIC NEURON BLOCKING DRUGS 74
These drugs inhibit the functioning of sympathetic nervous system by acting on the postganglionic adrenergic nerve endings. 75
Reserpine Structure: IUPAC: methyl-11,17-dimethoxy-18-(3,4,5-trimethoxybenzoyloxy)- 1,4-diazapentacyclo-henicosa-16-carboxylate Properties: White or cream to slightly yellow crystals or crystalline powder, odorless with a bitter taste, Freely soluble in chloroform , methylene chloride, glacial acetic acid; soluble in benzene, ethyl acetate; slightly soluble in acetone, methanol, alcohol, ether, and in aq solutions of acetic and citric acids. 76 Molecular formula: C33H40N2O9
Pharmacokinetics:  Reserpine is readily absorbed on oral and parenteral route of administration. The drug entirely metabolized. The antihypertensive effect persists even after the drug has been completely eliminated from the body through urine. Adverse Drug Reactions:  Diarrhea, gastrointestinal cramps, increased gastric acid secretion, excessive salivation  Nasal congestion, sedation, nightmares, mental depression, gynaecomastia, impotence in males and reduction in fertility in females and Parkinsonism, thrombocytopenia. 77
Therapeutic Uses:  Reserpine is used in the treatment of moderate hypertension. It is used in combination with diuretics. But due to its effects on CNs, its use has declined. Dose:  0.25 mg OD, by oral route. 78
Guanethidine monosulphate Structure: IUPAC: 3-[2-(azocan-1-yl)ethyl]guanidine sulphate Properties: White crystalline powder, strong characteristic odor, soluble in water, slightly soluble in alcohol, insoluble in chloroform, ether. 79 Molecular formula: C10H24N4O4S
Pharmacokinetics:  Oral route of administration. Guanethidine is converted by the liver to three metabolites, which are excreted in the urine. The metabolites are pharmacologically less active than the parent compound, which are excreted in the urine. Adverse Drug Reactions:  Drowsiness, dizziness, anxiety, depression  Diarrhea, nausea, vomiting, dry mouth, blurred vision, weight gain, slow heart  nightmares 80
Therapeutic Uses:  It is indicated for the treatment of moderate and severe hypertension, either alone or as an adjunct, and for the treatment of renal hypertension, including that secondary to pyelonephritis, renal amyloidosis, and renal artery stenosis. Dose:  At first, 10 or 12.5 milligrams (mg) once a day. Then, your doctor may increase your dose to 25 to 50 mg once a day. 81
ΒETA -ADRENERGIC RECEPTOR ANTAGONISTS OR Β-BLOCKERS 82
 These drugs used for the treatment of hypertension, ischemic heart disease, arrhythmias.  All the β-blockers are synthetic agents (Compounds) completely inhibit the action of adrenergic agonists on β-receptors.  Blockage of β-receptors reduces the heart rate; cardiac output consequently blood pressure is reduced. 83
Timolol Structure: IUPAC:1-(tert-butylamino)-3-{[4-(morpholin-4-yl)-1,2,5- thiadiazol-3-yl]oxy}propan-2-ol Properties: White, odorless, crystalline powder, slightly soluble in water; freely soluble in ethanol , Timolol hemihydrates , sparingly soluble in chloroform. 84 Molecular formula: C13H24N4O3S
Pharmacokinetics:  Oral, ophthalmic rote of administration metabolized in the liver by the cytochrome P450 2D6 enzyme, with minor contributions from CYP2C19. 15-20% of a dose undergoes first-pass metabolism. Despite its relatively low first pass metabolism, timolol is 90% metabolized. Four metabolites of timolol have been identified, with a hydroxy metabolite being the most predominant. Timolol and its metabolites are mainly found excreted in the urine. Adverse Drug Reactions:  Blurred vision, double vision, burning of eyes, eye redness, watery eye,  Head ache, drowsiness, nausea, insomnia (sleep problems)  Weakness, ringing in ears, dry mouth,  Diarrhea, loss of appetite, stomach upset  Skin rashes, cough 85
Therapeutic Uses: Used in the treatment of  Hypertension  Glaucoma  Arrhythmias Dose: For the treatment of hypertension.  Initially, 10 mg PO twice daily, alone or with a diuretic. The usual dose is 10 to 20 mg PO twice daily. Maximum dose is 60 mg/day, divided in 2 doses. For the treatment of Glaucoma  Instill 1 drop of a 0.25% solution in affected eye(s) twice daily. For the treatment of migraine prophylaxis.  Initially, 10 mg PO twice daily. May give maintenance dose of 20 mg PO once daily. Dosage range: 10 to 30 mg/day PO. 86
Reference books  Text book of Medicinal chemistry volume-1-3rd edition by V.Alagarasamy.  Text book of Medicinal chemistry volume-2-3rd edition by V.Alagarasamy.  Medicinal chemistry by Rama Rao Nadendla.  Medicinal Chemistry- 4th edition by Ashutosh Kar 87
THANK YOU 88