1. Rakesh Mahindra Baba Sheikh Farid Pharmacy college Kotkapura-151204 Classification of Drugs

2. 1.Neurotransmission in CNS & Types of Mental Disorders 2.General & Local Anesthetics 3.Anxiolytics & Hypnotics sedative 4.Antipsychotics 5.Anti Depressants & Antimanics 6.CNS stimulants 7.Alcohols 8.Opioid Analgesics & Antagonist 9.Drug Dependence & Drug Abuse 10.Antiepileptics 11.Drugs used in Neurodegenerative Disorders

3. Neurotransmission in CNS CNS neurotransmitter & their Receptors- 1.Acetylcholine 2.Biogenic Amines-Dopamine, Epinephrine,NE,5-HT, Histamine 3.Aminoacids Neurotransmitter-GABA, Glutamate/Aspartate, Glycine 4.Peptides as Nmitters-oxytocin, Tachykinins,Neurotensin, vasoactive, opioid-Endorphin,Dynorphin,Nociceptin & Neuropeptides-Y 5.Nitric oxide 6.Miscel-Endocannabinoids-Anandamide 7.Purine-Adenosine & ATP

4. Mental Disorders 4 Neurosis Psychoneurosis-Anxiety,Phobic, Obsessive compulsive,Hysteria,Panic Disorders,Reactive Depression Psychoses associated with delusions, illusions & Hallucinations- Organic Psychosis-Schizophrenia Affective Disorders- Mania-Depression-Manic Depressive Psychosis

5. General Anesthetics Loss of all sensation-Usually with ⇓ propagation of neural impulses.**Analgesiaa (pain relief) *Impairment of all skeletal muscle (ie causes motion lessness and allow smooth surgury) (needed to abolish fear and anxiety in patients during surgury) *Loss of motor reflexes*Reversible*Not therapeutic or diagnostic but facilitates surgery procedures 5

6. Classification Inhalation-1.Gases-Nitrous oxide 2.Volatile Liquids-Halothane,Enflurane,Isoflurane,Desflurane, Sevoflurane Intravenous-1.Ultrashort Acting Barbiturates-Thiopental Sodium,Thiamylal 2.Benzodoazepines-Mofazolam 3.Dissociative Anesthetics-Ketamine 4.Narcotic-Fentanyl 5.Miscellaneous-Propofol, Etomidate 6

7. Local Anesthetics Local anaesthetics (LAs) are drugs which upon topical application or local injection cause reversible loss of sensory perception, especially of pain, in a restricted area of the body. 7

8. Classification LA Injectable Anaesthetic Low potency, short duration -Procaine -Chloroprocaine Intermediate potency and duration-Lidocaine (Lignocaine)- Prilocaine High potency, long duration - Tetracaine (Amethocaine)-Bupivacaine-Ropivacaine -Dibucaine (Cinchocaine) Surface anaesthetic Soluble-Cocaine, Lidocaine, Tetracaine, Benoxinate Insoluble-Benzocaine,Butylaminobenzoate,Butamben,Oxethazaine

9. Ester-linked Las Cocaine, procaine, chloroprocaine, tetracaine, benzocaine. Amide-linked Las Lidocaine, bupivacaine, dibucaine, prilocaine, ropivacaine. Mepivacaine, Etidocaine, Articaine, Dyclonine, Proparacaine are other local anaesthetics, occasionally used in some countries. Some other drugs, e.g. propranolol, chlorpromazine, H 1 antihistaminics, quinine have significant LA activity, but are not used for this purpose because of local irritancy or other prominent systemic activity. Local anaesthesia can be produced by cooling as well, e.g. application of ice, CO 2 snow, ethylchloride spray. 9.

10. Anixolytics & Hypnotics Sedatives Barbiturates-Long Acting-Phenobarbitone Short Acting-Pentobarbitone,butobarbitone Ultra short Acting-Thiopentone, Methobarbitone Benzodiazepine-Hypnotics-Diazepam, Flurazepam, Alprazolam,Tamazepam, Nitrazepam, Triazolam Anti-anxiety-Diazepam, Alprazolam, Chlordiazepoxide, Lorazepam, Oxazepam Anticonvulsant-Diazepam,

11. Benzodiazepines Vs Barbiturates Alprazolam Clorazepate Oxazepam Quazepam Temazepam Triazolam Phenobarbital Thiopental Amobarbital -Methohexital- Pentobarbital Secobarbital

12. Antipsychotics Oral first Generation(typical) - Benperidol-Chlorpromazine-Flupentixol-Haloperidol- Levomepromazine –Pericyazine Perphenazine-Pimozide- Prochlorperazine-Promazine-Sulpiride-Trifluoperazine Oral second-generation (atypical) - Amisulpride-Aripiprazole-Clozapine-Olanzapine-Paliperidone- Quetiapine-Risperidone Antipsychotic depot injections * Aripiprazole-Flupentixol decanoate-Fluphenazine decanoate- Haloperidol-Olanzapine embonate-Paliperidone-Pipotiazine palmitate-Risperidone-Zuclopenthixol decanoate

13. Antidepressants & Antimanic Agents Depression- It is a mental illnesses characterized by pathological changes in mood (in contrast schizophrenia is disorder in thought) Two types of mood disorders 1)Unipolar disorders Depression - lacking enthusiasm Mania - excessive or unreasonable enthusiasm 1)Bipolar disorder (Alteration between manic depressive phase) How severe can depression be physiologically? Depression isn’t just a psychological state that can drive to suicide. It has physiological consequences too that can interfere with quality of life Insomnia (lack of sleep) - Weakens immune system, fatigue,Increases pain perception To suppress depression people do * Excessive eating > obesity related heart problem * Excessive alcohol → liver damage and withdrawal symptoms

14. . Classification of Antidepressants 1. Selective Serotonin Reuptake Inhibitors -SSRI’s- Sertraline,Fluoxetine,Fluvoxamine, Paroxetine,Citalopram,Escitalopram 2. Selective Serotonin-Norepinephrine Reuptake Inhibitors SNRI’s- Duloxetine,Venlafaxine,Milnacipran 3. Drugs block both NE & 5-HT Reuptake TCA Antidepressants- Imipramine,Clomipramine, Amitriptyline,Doxepin 4. Drug mainly block NE Reuptake -Desipramine, Nortriptyline,Protriptyline,Amoxapine, Reboxetine 5. Atypical Antidepressants- Trazodone,Nefazodone,Bupropion, Mirtazapine 6. MAO Inhibitors Nonselective - MAO-A & MAO-B-Tranylcypromine 7. Selective MAO-A Inhibitors-Moclobemide 8. Antidepressants of Natural Origin- St.john’s wort -Hyperforin

15. CNS stimulants Analeptic Stimulants -Doxapram-Nikethamide-Pentylene tetrazol-Strychnine- Picrotoxin-Bicuculline Psychomotor Stimulants Amphetamine-Methamphetamine-Methylphenidate- Pemoline-Ephedrine-Phentermine-Fenfluramine- Phenylpropanolamine Methylxanthines -Caffeine-Theophylline-Theobromine

16. Alcohols Alcohol can affect several parts of the brain, but, in general, contracts brain tissues, destroys brain cells, as well as depresses the central nervous system. Excessive drinking over a prolonged period of time can cause serious problems with cognition and memory Alcohol (ethanol, whiskey, ethyl alcohol, or grain alcohol) is probably the most widely used nonprescription sedative-hypnotic and antianxiety agent

17. Other form of Alcohols Absolute alcohol 99% w/w ethanol (dehydrated alcohol). Rectified spirit 90% w/w ethyl alcohol produced from fermented mollases, by distillation. Proof spirit It is an old term.  If whiskey is poured on gun powder and ignited and it explodes, then it was labelled to be of ‘proof strength’.  If water is mixed to it, gun powder will not ignite.  100% proof spirit is 49.29% w/w or 57.1% v/v alcohol.  Methylated spirit (industrial) Also called ‘ denatured spirit’ is produced by adding 5 parts of methyl alcohol to 95 parts of rectified spirit so as to render it unfit for drinking.  It is tinted blue by methylene blue dye for distinction.  It can be applied on the skin for antiseptic, cleaning and astringent purposes. 17

18. Opioid Analgesics & Antagonists PMN include Neurokinin,Bradykinin,5-HT, Histamine, Prostaglandin,protons,ATP & Vanilloid a.Peripheral Mediators- 1.Capsaicin vanilloid Receptors (TRPV-1) and others PM 2.Nociception-Endogenous Tachykinins/Neurokinin b.Endogenous Opioid Peptides- 1. beta-Endorphin 2.Enkephalins 3.Dynorphins 4.Nociceptin Subtypes Receptors are – 1.mu-Receptors 2.Delta 3.Kappa

19. Classification Agonists –Codeine-Tramadol-Hydrocodone-Morphine- Oxycodone-Hydromorphone-Fentanyl Partial Agonists - Pentazocine-Nalbuphine Buprenorphine- Butorphanol Antagonists – Naloxone

20. NSAID’S Classification A. Nonselective COX inhibitors (traditional NSAIDs) 1. Salicylates: Aspirin. 2. Propionic acid derivatives: Ibuprofen, Naproxen, Ketoprofen, Flurbiprofen. 3. Anthranilic acid derivative: Mephenamic acid. 4. Arylacetic acid derivatives: Diclofenac, Aceclofenac. 5. Oxicam derivatives: Piroxicam, Tenoxicam. 6. Pyrrolopyrrole derivative: Ketorolac. 7. Indole derivative: Indomethacin. 8. Pyrazolone derivatives: Phenylbutazone, Oxyphenbutazone. B. Preferential COX2 inhibitors-Nimesulide, Meloxicam, Nabumetone. C. Selective COX2 inhibitors-Celecoxib, Etoricoxib, Parecoxib. D. Analgesic antipyretics with poor anti-inflammatory action 1. Paraaminophenol derivative: Paracetamol (Acetaminophen). 2. Pyrazolone derivatives: Metamizol (Dipyrone), Propiphenazone. 3. Benzoxazocine derivative: Nefopam. 20

21. Classification Hydantoin derivatives-Phenytoin-Fosphenytoin Iminostilbenes-Carbamazepine (only antiepileptic used in pregnancy)-Oxcarbamazepine Valproic acid derivatives-Sodium valproate (valproic acid) Long acting barbiturates-Phenobarbitone-Methobarbitone Deoxy barbiturate-Primidone Succinimides-Ethosuximide-Methsuximide-Phensuximide Benzodiazepines-Clonazepam-Nitrazepam-Diazepam Carbonic anhydrase inhibitors (CAI)-Acetazolamide-Sulthiame GAMA- vinyl – GABA-Vigabatrin Phenyltriazine-Lamotrigine Amino acid derivatives-GABA pentin Monosacharide derivatives-Topiramate Nicotinic acid derivatives-Tiagabine Sulphonamide derivatives-Zonisamide Miscellaneous-Paraldehyde

22. Neurodegenerative Diseases Neurodegenerative diseases are characterized by the progressive and irreversible loss of selected neurons in discrete brain areas, resulting in characteristic disorders of movement, cognition, or both The neurodegenerative disorders include Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis 22

23. Drugs used in Parkinson’s disease Drugs Used in Parkinson's Disease include: 1.Levodopa-carbidopa 2.Dopamine agonists 3.Monoamine oxidase (MAO) inhibitors 4.Cathechol-O-methyl transferase (COMT( inhibitors 5.Anticholinergic agents 6.Amantadine 23

24. 2.Drugs prevent Dopamine Degradation- MAO-B inhibitors-Selegiline,Rasagiline 3.Drugs stimulate Dopamine Receptors-Dagonists- Ergot Derivatives-Bromocriptine,Cabergoline Non Ergot-Ropinirole,Pramipexole 4.Drug restore DA-Ach Balance-Centrally acting Antimuscarinic Drugs-Trihexyphenidyl,Procyclidine, Orphenadrine,Benztropine 24

25. Catechol-O-Methyltransferase Inhibitors-Tolcapone & Entacapone Drugs used in Huntington’s disease include: 1.Dopamine receptor antagonists Neuroleptics Drugs used in Tourette’s syndrome include: 1.Neuroleptics 2.Clonidine 3.Nn blocking drug 25

26. Drugs used in Huntington’s disease include: 1.Dopamine receptor antagonists Neuroleptics (haloperidol, chlorpromazine) antagonize the excessive dopaminergic activity in basal ganglia and are also helpful to improve motor function and to relieve paranoia[personality disorder] and delusional states that often accompany the disease. 2.Amine depleting drugs Reserpine, which can block the vesicular storage of dopamine (Benzodiazepines which potentiate central GABA activities should help but the results have been some what disappointing). SlideModel.com26

27. Drugs used in Tourette’s syndrome include: 1.Neuroleptics (haloperidol, olanzapine, etc.) 2.Clonidine (it is effective in some patients only) 3.Nn blocking drug (mecamylamine)

28. Drugs for Alzheimer’s Disease The ‘cholinergic hypothesis’ which states that a deficiency of acetylcholine is critical in the genesis of symptoms of AD.  Donepezil, galantamine and tacrine are cholinesterase inhibitors approved for treatment of AD. Donepezil and rivastigmine selectively inhibits cholinesterase in the CNS with less effect on cholinesterases in peripheral tissues.  These drugs can slow the deterioration of cognitive functions, even if they do not affect the underlying neurodegenerative process.  Adverse effects include insomnia, nausea, vomiting and diarrhea. 28

29. Drugs Affecting Renal & Cardiovascular System Related Autacoids 29

30. 1.Diuretics 2.Vasoactive Peptides 3.Renin-Angiotensin System & Inhibitors 4.Antihypertensive 5.Drugs in Angina Pectoris 6.Cardiac Arrhythmias 7.Heart Failure 8.Drug therapy in Dyslipidaemia 30

31. Classification b 1.Diuretics a. Thiazides and related agents b. Loop diuretics c. Potassium sparing diuretics 2. Sympatholytic drugs a. Centrally acting agent b. Adrenergic neuron blocking agent c. β adrenergic antagonist d. α adrenergic antagonist e. Mixed α and β adrenergic antagonist 3. Vasodilators a. Arterial vasodilators b. Arterial and venous vasodilators 4. Angiotensin converting enzyme inhibitors 5. Angiotensin II receptor antagonists 31

32. Diuretics Thiazides - Chlorothiazide Chlorthalidone Hydrochlorothiazide, Polythiazide Indapamide Metolazone Metolazone Loop Diuretics Bumetanide Furosemide Torsemide Potassium-Sparing Diuretics Amiloride Triamterene Aldosterone Receptor Blockers Eplerenone Spironolactone 32

33. β- Blockers Atenolol-25 to 100 Betaxolol-5 to 20 Bisoprolol2.5 to 10 Metoprolol 50 to 100 Metoprolol extended release 50 to 100 Nadolol 40 to 120 Propranolol 40 to 160 Propranolol long-acting 60 to 180 Timolol20-40mg/d 33

34. β- Blockers with Intrinsic Sympathomimetic Activity Acebutolol 200 to 800 mg/d Penbutolol 10 to 40 Pindolol 10 to 40 Combined α- Blockers and β- Blockers Carvedilol 12.5 to 50 Labetalol 200 to 800 34

35. Angiotensin-Converting Enzyme Inhibitors Benazepril 10 to 40 mg/d Captopril 25 to 100 Enalapril 5 to 40 Fosinopril 10 to 40 Lisinopril 10 to 40 Moexipril 7.5 to 30 Perindopril 4 to 8 Quinapril 10 to 40 Ramipril 2.5 to 20 Trandolapril 1 to 4

36. Angiotensin II Antagonists Candesartan 8 to 32 mg/d 1 Daily frequency Eprosartan 400 to 800 1 to 2 Irbesartan 150 to 300 1 Losartan 25 to 100 1 to 2 Olmesartan 20 to 40 1 Telmisartan 20 to 80 1 Valsartan-80 to 320

37. CCBs: Nondihydropyridines Diltiazem extended release 180 to 420 1 Diltiazem extended release 120 to 540 Verapamil immediate release 80 to 320 2 Verapamil long-acting 120 to 480 1 to 2 Verapamil controlled onset, extended release 120 to 360

38. CCB: Dihydropyridines Amlodipine 2.5 to 10 mg/d 1 usual daily Frequency Felodipine 2.5 to 20 1 Isradipine 2.5 to 10 2 Nicardipine sustained release 60 to 120 2 Nifedipine long-acting 30 to 60 1 Nisoldipine 10 to 40 1

39. α 1-Blockers Doxazosin 1 to 16 mg/d 1 usual daily frequency Prazosin 2 to 20 2 to 3 Terazosin 1 to 20 1 to 2

40. Central α2- Agonists and Other Centrally Acting Drugs Clonidine (0.1 to 0.8 mg/d 2 usual daily frequency Clonidine patch 0.1 to 0.3 1 weekly Methyldopa 250 to 1000 2 Reserpine 0.05 to 0.25 1 Guanfacine 0.5 to 2 1 Direct Vasodilators Hydralazine 25 to 100 2 Minoxidil 2.5 to 80 1 to 2

41. Effects of Nitroglycerin and Organic Nitrates on the Coronary Circulation. Epicardial coronary artery dilation: small arteries dilate proportionately more than larger arteries Increased coronary collateral vessel diameter and enhanced collateral flow Improved subendocardial blood flow Dilation of coronary atherosclerotic stenoses Initial short-lived increase in coronary blood flow, later reduction in coronary blood flow as M Ṿ o2 decreases Reversal and prevention of coronary vasospasm and vasoconstriction

42. Intraoperative Nitroglycerin Class I* High-risk patients previously on nitroglycerin who have active signs of myocardial ischemia without hypotension. Class II As a prophylactic agent for high-risk patients to prevent myocardial ischemia and cardiac morbidity, particularly in those who have required nitrate therapy to control angina. The recommendation for prophylactic use of nitroglycerin must take into account the anesthetic plan and patient hemodynamics and must recognize that vasodilation and hypovolemia can readily occur during anesthesia and surgery. Class III Patients with signs of hypovolemia or hypotension.

43. Effects of β -Adrenergic Blockers on Myocardial Ischemia Reductions in myocardial oxygen consumption Improvements in coronary blood flow Prolonged diastolic perfusion period Improved collateral flow Increased flow to ischemic areas Overall improvement in supply/demand ratio Stabilization of cellular membranes Improved oxygen dissociation from hemoglobin Inhibition of platelet aggregation Reduced mortality after myocardial infarction

44. for Perioperative Medical Therapy Class I β-Blockers required in the recent past to control symptoms of angina or symptomatic arrhythmias or hypertension; β-blockers: patients at high cardiac risk, owing to the finding of ischemia on preoperative testing, who are undergoing vascular surgery Class IIa β-Blockers: preoperative assessment identifies untreated hypertension, known coronary disease, or major risk factors for coronary disease Class III β-Blockers: contraindication to β-blockade SlideModel.com44

45. ResponseShort-Term EffectsLong-Term Effects Salt and water retentionAugments preloadPulmonary congestion, edema VasoconstrictionMaintains blood pressure for perfusion of vital organs Exacerbates pump dysfunction (excessive afterload), increases cardiac energy expenditure Sympathetic stimulationIncreases heart rate and ejection Increases energy expenditure Neurohormonal Effects of Impaired Cardiac Performance on the Circulation

46. Mechanical Disadvantage Created by Left Ventricular Remodeling Increased wall stress (afterload) Afterload mismatch Episodic subendocardial hypoperfusion Increased oxygen utilization Sustained hemodynamic overloading Worsening activation of compensatory mechanisms

47. Classification of Antiarrhythmic Drugs I (Membrane Stabilizers)-Fast channel (Na+) blockade Electro ‑ physiologic Decreased rate of max depolarization II ( β- Adrenergic Receptor Antagonists)- β ‑ Adrenergic receptor blockade. Decreased Vmax, increased APD, increased ERP, and increased ERP/APD ratio III (Drugs Prolonging Repolarization)-Uncertain: possible interference with Na+ and Ca2+ exchange IV (Calcium Antagonists)-Decreased slow channel calcium conductance Vmax-rate of Depolarization APD-Action potential Duration ERP-Effective Refractory Peroid.

48. Intravenous Supraventricular Antiarrhythmic Therapy Class I Procainamide (IA)—converts acute atrial fibrillation, suppresses PACs and precipitation of atrial fibrillation/flutter, converts accessory pathway SVT. 100 mg IV loading dose every 5 min until arrhythmia subsides or total dose of 15 mg/kg (rarely needed) with continuous infusion of 2 to 6 mg/min Class II Esmolol—converts or maintains slow ventricular response in acute atrial fibrillation. 0.5 to 1 mg/kg loading dose with each 50 μ g/kg/min increase in infusion, with infusions of 50 to 300 μ g/kg/min. Hypotension and bradycardia are limiting factors

49. . Class III Amiodarone—converts acute atrial fibrillation to sinus rhythm; 5 mg/kg IV over 15 min. Ibutilide (Convert)—converts acute atrial fibrillation and flutter. Adults (>60 kg): 1 mg given over 10 min IV, may be repeated once. Class IV Verapamil—slow ventricular response to acute atrial fibrillation, converts AV node reentry SVT. 75 to 150 μ g/kg IV bolus. Diltiazem—slow ventricular response in acute atrial fibrillation, converts AV node reentry SVT. 0.25 μ g/kg bolus, then 100 to 300 μ g/kg/hr infusion.

50. Anti-Ischemic Drug Therapy Ischemia during the perioperative period demands immediate attention by the anesthesiologist. The impact of ischemia may be both acute (impending infarction, hemodynamic compromise) and chronic (a marker of previously unknown cardiac disease, a prognostic indicator of poor outcome). Nitroglycerin is indicated in nearly all conditions of perioperative myocardial ischemia. Mechanisms of action include coronary vasodilation and favorable alterations in preload and afterload. Nitroglycerin is contraindicated when hypotension is present

51. . Perioperative β-blockade may reduce the incidence of perioperative myocardial ischemia via a number of mechanisms. Favorable hemodynamic changes associated with β-blockade include a blunting of the stress response and reduced heart rate, blood pressure, and contractility. All of these conditions improve myocardial oxygen supply/demand ratios. Calcium channel blockers reduce myocardial oxygen demand by depression of contractility, heart rate, and/or decreased arterial blood pressure. Calcium channel blockers are often administered in the perioperative period for longer-term antianginal symptom control.

52. Drug Therapy for Systemic Hypertension Current guidelines suggest seeking a target blood pressure of less than 140/85 mm Hg to minimize long-term risk for adverse cardiovascular morbidity and mortality. For patients with diabetes, renal impairment, or established cardiovascular diseases, a lower target of less than 130/80 mm Hg is recommended. Mild-to-moderate hypertension does not represent an independent risk factor for perioperative complications; however, a diagnosis of hypertension necessitates preoperative assessment for target organ damage. Patients with poorly controlled preoperative hypertension experience more labile blood pressures in the perioperative setting with greater potential for hypertensive or hypotensive episodes or both.

53. Pharmacotherapy for Acute and Chronic Heart Failure The signs, symptoms, and treatment of chronic heart failure are as related to the neurohormonal response as they are to the underlying ventricular dysfunction. Current treatments of chronic heart failure are aimed at prolonging survival, not just relief of symptoms. The low cardiac output syndrome seen after cardiac surgery has a pathophysiology, treatment, and prognosis that differ from those of chronic heart failure, with which it is sometimes compared.

54. Pharmacotherapy for Cardiac Arrhythmias Physicians must be cautious in administering antiarrhythmic drugs because of the proarrhythmic effects that can increase mortality in certain subgroups of patients. Amiodarone has become a popular intravenous antiarrhythmic drug for use in the operating room and critical care areas because it has a broad range of effects for ventricular and supraventricular arrhythmias. β-Receptor antagonists are very effective but underused antiarrhythmic agents in the perioperative period because many arrhythmias are adrenergically mediated due to the stress of surgery and critical illness. Managing electrolyte abnormalities and treating underlying disease processes such as hypervolemia and myocardial ischemia

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