PharmacologyPHARMA T 20 General Pharmacology Branches Of Pharmacology > Pharmacokinetics > Effect of body on drug > Pharmacodynamics > Effect of drug on the body Pharmacokinetics | Also known as ‘ADME’ study because it deals with four factors. ie A. Absorption B. Distribution C. Metabolism D. Exeretion A. Absorption > Movement of drug from site of administration to blood > Paranceter on which absorption of drug depends is lipid solubility of drug (single most important factor in absorption). Drug is absorbed in non-ionizable form as it is lipid soluble. > Pka is the pH of the medium at which 50% of the drug can eross the membrane and rest SOK. > When medium is same, drug can cross ~ Acidic drug can cross in acidic medium > Basic drug can cross in basic medium Bioavailability > Percentage of given dose which reaches the systemic circulation + Depends upon 2 factors: @) Absorption ») First pass metabolism (FPM) > Bioavailability «— F First pass metabolism ~ Bioavailability « absorption ~ IF we give a drug by IV route bio-availability is 1008, Plasma Concentration ~ Time Graph Pc -T + € max > maximum plasina concentration that can be re obtained with a particular dose T Ly (ave) > T max +> Time required to reach the maximum re plasma concentration AUC (Area under the curve):~ Tells the extent of absorption B. Distribution -» Amount of drug going to the tissues Volume of Distribution (Vd) > i Most important parameter that determines the loading dose of a drug: LD= Vd X Target PC LD = Loading dose PC lasmna concentrationMD = Clearance x Target PC 425 MD = Maintenance dose £ Plasma proteins bindnig (PPB) ie., more PPB less distribution. > Vd 0 Lipid soluble drug C. Metabolisen > To make drug water soluble = There are 2 phases of metabolisrn Phase | Phase Ul Catabolic Reactions Like ‘Conjugation Reaction = oxidation Molecules Attached To The Drug Like > Reduction > Glucuronide > Most important > Hydrolysis + Glutathione > Cyclization ete. = Acetyl > Methyl => Phase | & It reaction are carried out by enzymes that are microsomal and non- microsomal enayrmes ‘Microsomal Enzyme ‘Non ~Microsornal Enzymes = Can be induced or inhibited = Cannot be induced and cannot be inhibited Enzyme Inducing Drugs G - GriseoPulvin P ~ Phenytoin R = Rifampicin 5 - Smoking Cell - Carbamazepine (CBZ) Phone -Phenobarbitone Enayme inhibiting Drugs Vit - valproate K ~ Ketoconazole Can ~ Cimetidine Cause - Ciprofioxacin Enzyme - Erythromycin excRETION inhibitor ~ Isoniazid (INH) @ a meiem J + Glomerular filtration (GF) & Fama patna being me — Glomerular filtration does not depend upon water or lipid solubility of drug 5 Tubular Reabsorption: Depends on lipid solubility, so lipid soluble drug can be reabsorbed. Clinical Significance = For Aspirin or any acidic drug poisoning, we will make the urine alkaline, = For basic drug poisoning, we will make the urine acidic. F Dr Ciat Rng~ Tubular Secretion ~ Depends upon transporters which are saturable. Eg. Penicillin & Probenecid 426 Half Life -t% = 0693 x4 Order OF Kineties 2" Order Zero Order > Fraction is Constant > Amount is constant + Rate of elimination o PC ~ Rate of elimination = Constant > CL. = Constant cL ak > EK = Constant th aPC Drugs Following Zero Order Kinetics Zero W = Warfarin A = Alcohol / Aspirin T ~ Theophylline T = Tolbutamide Power — Phenytoin Pharmacodynamics Enayme Inhibition - Competitive/Non-competitive Ken V Max. Competitive 1 - Non Competitive * + me op) fi > Affinity ~ Ability of a drug to bind to a receptor > Intrinsic Activity ability to produce action after binding to receptor > Every drug has affinity but they may have different intrinsic activity (1A) > Based on A we have + types of drugs Intrinsic Activity (1A) ‘Agonist +2 Partial Agonist Otor Inverse Agonist Oto -2 Antagonist No or zero > Receptors 4. Inotropic Receptor ~ Fastest acting receptor Eg. -GABA-A Brain. Enzymatic Receptors ~ Tyrosine kinase Receptors eg, ~ Cytokine Receptors = IL receptors = Interferon receptors ~ Prolactin = Insulin PIG = Growth Hormone Intracellular Receptors > Nuclear Receptor superfamily + Slowest acting receptor Cytoplasmic Receptors ‘Nuclear Receptors C> Corticosteroids Glucocorticoids S + Sex Hormones: Mineralocorticoids Aw VitA D> vitD Tat 4. G~ Protein Coupled Receptors > Most of drug act by GPCR Dose Response Curve = DRC = Hyperbola in shape — Log DRC = Sigmoid in shape Three important Parameters 4) Potency 6) Efficacy ¢) Slope -+ Potency tells which drug produces more effect on lower dose Efficacy tells maximum effect of a drug. Tamia EC > Clinically efficacy is more important than potency Slope talls the safety of the drug as more is the slope less is the safety. Quantal DRC + Ie tells about effect of drug in population QUANTAL DRC > On Y-axis there is & of subjects responding + Therapeutic index (TI) of a drug LD = Lethal dose ED = Effective dose > Tlis index of racasure of safety. L0s0. 9% SUBJECTS Three conditions to be identified. 1. G-6-PD Deficiency Primaquine Eaton (apn Nitrofurantoin Furazolidone These drugs cause hemolysis in patients with G-6-PD deficiency. ¢ Do Giint Rat ony2. Metabolism By Acetylation Drugs that are metabolized by acetylation S — Sulphonaraides H = Hydralazine | 1 - INH P — Procainamide “These drugs can also cause SLE as an adverse effect. Succingl-Choline induced Apnoea > Shortest acting muscle relaxant because metabolism by pseudocholinesterase > Ifa patient has geneticaly defective enzyme called as atypical pseudocholinesterase, drug is not metabolized quickly and that can lead to apnea Clinical Trials > Drugs are tested in humans before they come into market. This is called as clinical trials: > Regulatory authority in US ~ FDA tm tndia ~ DCG! (Drug controller general of india) ~ Under CDSCO (Central Drug Standard Control Organization) > Clinical trials are divided into 4 phases: Phase | ~ Done in healthy people to know max. tolerable dose(MTD)> Dosing> PK> Safety Efficacy Phase Il — Done in 20-200 ate Safety Phase lll ~ Done in large no of patient upto 5000: (Multi centric trial) Safety Phase |V — Post marketing study done to see rare/long term side effect Controls in Clinical Trials ~ Placebo~ Inactive substance to which comparison is done. = Standard drug control: Done in phase Ill where new drug is compared with existing drugs. Drug Label > Name - Generic ~> Schedule H ( drags given on prescription) or OTC (over the counter drug) Abbreviation: 1P —_— Indian Pharmacopoeia BP British Pharmacopoeia USP = US Pharmacopoeia Confirm efficacy + MED (manufacturing date) ~ EXD (expiry date) + Shelf life of Drug = MED - EXD + Temperature Keep frozen» -20'C Keep cold > 2-8°C keep cool > 8-25°C (India) + 8-15°C (USA)‘Three Types OF Drugs 429 + Spurious Drugs - New company is trying to mimic or take advantage of already existing company. + Mis~Branded Drugs - Any information written on drug label is wrong + Contaminated Drug contains some harmful chemicals Fixed Dose Combination (FDC) > Advantages = Instead of taking 2 tablets, patient will take 2 tablet ~ Adverse effect of one drug may counter the adverse effect of another drug. ~ Efficacy may increase ~ Cost decreases > Disadvantages = We cannot change the relative ratio of the two drugs. = If patient is allergic to one drug, he will be allergic to whole group. ~ May be irrationally used. = May add to the cost if other drug is added unnecessarily. ‘Autonomic Nervous System (ANS) . ‘ = Nerve fibers that originate from cranio-sacral region > Major neurotransmitter is Ach. = also called cholinergic system = Pre-ganglionic fibers are long > Post ganglionic fibers are small nergic) > Nerve fibers that originate from thoraco-lumber region = Major neurotransmitter is nor-adrenaline (Exception is sweat gland where neurotransmitter is Ach) = Also called adrenergic systern > Pre-ganglionic fibers are small = Post ganglionic fibers are long Note:~ Neurotransmitter at all the ganglia in both parasympathetic & sympathetic is Ach and receptor is Nn Actions Of Parasympathetic And Sympathetic Nervous System Parasyrapathetic Nervous System | Sympathetic Nervous System Heart ua ttt Other + v Bronchus Bronchoconstriction Bronchodilators Gt Diarrhoea Constipation Bladder ‘tout ow out Flow Glands '} secretion secretion Pupil Miosis mydriasis Parasympathetic Nervous System > Major neurotransmitter is Ach = Receptors on which Ach works are: z Bo Cond Rei Gang$ Receptors ———, Nicotinic (N) Muscarinic (M) Ny - Ganglia M, ~ Stomach Ny = NMJ (Neuro-Muscular junction) M, - Heart (Require Optional Stimulation) M, ~All others Cholinergic Drugs, scared acting Directly acting (Ach Esterase inhibitor) ~ Pilocarpine (Mainly acts on pupil) -Methacholine (Mainly acts on myocardium) EE Reversible Irreversible Lipid soluble Water soluble ~ Physostigmine ~ Neostigmine (treat myasthenia gravis) DOC: Atropine poisoning = Pyridostignsine Used as eye drop in glaucona ~ Edrophonium (diagnosis myasthenia gravis) ~ Tensilon test Irreversible Organophosphates eo Carbamates = Malathion = Carbaryl (baygon) ~ Parathion ~ Propoxur > When these drugs are taken in excess they inhibit Ach-E which 14 Ny - Tachycardia, palpitations, hypertension (rare) | Nu > Muscle weakness M, ~ Acidity M,~ Bradycardia, Hypotension Overstinsulation in brain > coma M, — Miosis (Pin point pupils) = t Secretions causing Diarrhea, bronchoconstriction, lacrimnation Organophosphate and Carbamate Poisoning ~ Atropine is drug of choice. This can reverse the reaction of M,, M,, M, but not the action of Nw Atropine will be continued till the sign of Atropinisation occur. Most common sign ~ Mydriasis Most Reliable sign-in secretions > Atropine is not used for organochlorine (Endrin) poisoning. > OXIME - Can also be used in organophosphate poisoning, They are not used for carbamate poisoning They will reactivate AchE enzyme. 2 oximes- PAM - DAM PAM (Pralidoxime) - It only acts in periphery and does not enter brain. DAM (Diacetylmonoxime) - Acts in periphery as well as in brain. Anti-Cholinergic Drug According to the effects Stomach - M, is receptor blocked ~ Used for peptic ulcer eg. — Pirenzepine, Telenzepine Heart - M, Receptor blocked eg. - Atropine ~ used in | HR (Bradyeardia) and AV block (Drug of choice) Bronchus - M, blocked 2g. ~ Ipratropium - Tiotropium Bladder - M, blocked -> used in overactive bladder 29.8 ~ solifenacin ° ~ Oxybutynin F = Flavoxate T = Tolterodine Bladder ~ Darifenacin Side effect - Urinary Retention Eye - M, blocked Actions — Mydviasis = Cycloplegia 2g. Atropine ~ Drug of choice for refraction tests in children. tt is very long acting. (> 7 days) - Homatropine ~ Cyclopentolate ~ Tropicamide - Shortest acting drug used in adults for refraction test Used in Bronchial Asthma and COPD Poisoning + Organophosphate, carbamate. and early mushroom poisoning Drug of choice is Atropine = For Atropine/ Dhatura /Belladonna Poisoning ~ Drug of choice is Physostignaine. ‘Sympathetic Nervous System + Major neurotransmitter is Nor-Adrenaline Receptors ms, a + a,Receptor Present in- Blood vessels - vasoconstriction ~ Eye - Mydviasis — Prostatic Urethra - 4 outflow of urine (Contraction of urethra) +0, Recoptor — act like BRAKES - They stop the release of nor-adrenaline F Br Cebit Rs CyB, Receptor ~ Present in urinary bladder 432 Mirabegron ~ Stimulates p, and relaxes bladder. > B,Receptor ~ Heart Kidney (JG cells) where it secretes renin > B,Receptor - Lungs (Bronchus) = GIT (Relax GIT) + Bladder (Relaxes) - Muscle Spindle (Tremors) + Blood vessels (Vasodilation) » Drugs Acting On Sympathetic Nervous System: / Sympathomimetic Drugs ~ Adrenaline ~ Nor-adrenaline = Dopamine Dopamine It stimulates 5 receptors Receptors Dose of Dopamine for stimulation D. 2 1g/Kg/min. B 2-40 ug/kg/enin a 950 ng/Kg/min ~ It 15 drug of choice for SHOCK with oliguria. At High dose > 10 ug/Kg/min, it stimulate a, which cause vasoconstriction to treat the shock and also stimulation of D, causes vasodilation in the renal blood vescele and treat oliguria Nor-Adrenaline > Stimulates a, 0, B, receptors > Used in Shock. ~ How to monitor the effect of nor-adrenaline? © Nor-adrenaline increases the blood pressure. So we will sismply check the MAP (Mean Arterial Pressure) Adrenaline > Stimulates all receptors a, 0, , By > It is drug of choice for anaphylactic shock and cardiac arrest. ~> tn Anaphylactic Shock ~ Dose of Adrenaline ~ 2:4000 by LM route/Subeutaneous Route (IM preferred) ~ IF no response to 1* dose, repeat it within 40 min. ~ HF no response to 2% dose, then give adrenaline by IV route in a diluted concentration of 4:10,000. > In Cardiac Arvest ~ We start with IV route. if not possible through IV route then give by intra-cosseous route. If that is not possible then give by endotracheal route. = Dose = IV ~ 1:10,000 Sympatholytic Drug They may be a blockers and p blockers. > «Blockers = Non selective a, +2, blockers ~ Selective blockers ie. a, blockersNon Selective « Blockers Selective a3 Blockers Irreversible Prazosin -+ Phenoxybenzamine Terazosin > Used for pheochromocytoma Doxazosin Reversible Alfuzosin > Phentolamine, Tolazoline = These drugs are used for BPH and HTN. = DOC for cheese reaction and clonidine | > Also used for scorpion sting withdrawal Selective at blockers cause postural hypotension, which is also known as First Dose Hypotension. So to avoid First dose Hypotension o,, blockers are used. ¢g. - TAMSULOSIN, SILODOSIN (New drug). 5 Blockers Selective §, blockers (Cardio selective blockers) Selective > These drugs are relatively safe in Asthma, DM, PVD New —— - Nebivolol Exclusively — esmolol Beta — Betaxolol At ~ Atenolol Blocker — Bisoprolol Myo — Metoprolol Act ~ Acebutolol Cardium — Celiprolol Intrinsic Sympathomimetic Activity / Partial Agonistic Activity ‘Advantage of this activity is that these drugs cause lesser bradycardia as compared to other B blockers drugs Contain ~ Celiprolol Agonist - Alprenolal Partial — Pindolol Activity — Acebutolol MSA (Membrane Stabilizing Activity) / Local Anesthetic Property + Advantage of this property is that these B blockers are used in arrhythraias = Disadvantage is that they should not be used in glaucoma because they anaesthetize corneal membrane. > Drugs are Possess — Propranolol Membrane Stabilizer - Metoprolol or L — Labetalol A = Acebutolol Property ~ Pindolol + Acebutolol Comes in All 3 Mnemonics B- Blockers that are Contraindicated In Renal Failure A - Atenolol Nv - Nadolol (Longest acting) s - Sotalol + Esmolol is shortest acting p-blocker. it is metabolized by pseudocholinesterase. Third Generation ~ Blockers Labetalol ] a+ Blockers dona F Bo Gat Qe Gyof B= Blockers Cardiac uses Non cardiac uses - HTN Mainly non selective -blockers are used Angina Play ~ Performance anxiety Mi “The — Thyrotoxicosis - Arrhythmia G ~ Glaucoma - CHE A ~ Akathisia M = Migraine E ~ Essential tremors Adverse Effects OF B-Blockers Cardiac Non-Cardiac + HR so C/I in Bradycardia (Sick sinus syndrome) = Asthwaa 4 Conduction so C/I in AV Block -DM 4 Contractility so C/I in CHE -PvD Vasomotor Reversal Of Dale + This is a biphasic phenomenon. Py a, ~ Strong receptor thus more effect: ~ B, ~ Sensitive receptor thus stimulated at low dose too. > When adrenaline is given IV at high doses 2* BP will increase due to stimulation of a, > B, & then BP will decrease due to B, stimulation. > When adrenaline is given IV at high dose with o blocker, exaggerated fall of BP occurs called as Vasomotor Reversal of Dale. Glaucoma > increase in intra-ceular pressure ~ So to decrease the pressure there are 2 methods: 2.4 Production of Aqueous hurmour 2. t Excretion / outflow of Aqueous humour Drugs That Decrease the Production of Aqueous Humour > These drugs may act by stimulation of a, or by blocking B receptors 2. a Agonist ~ Adrenaline/ Dipivetrin, Apraclonidine 2. B Blockers ~ Timolol > Increased outflow of aqueous humour may be of 2 types: 1. Trabecular outflow Increased by mioties like pilocarpine 2. Uveoscleral outflow — increased by PGF. like latanoprost ~ Latanoprost is drug of choice for open angle glaucoma Adverse effects of Anti-glaucoma drugs: 4, Miotic drugs like Pilocarpine, Physostigmine > Cataract ~ Stenosis of nasolacrimal duct 2. PGF, like latanoprost > Pigmentation of ivis/ Heterochromia tridis + Growth of eye lashes/ Hypertrichosis = Macular edema3. Apraclonidine > Causes lid Retraction 4. Brimonidine > Causes brain suppression mainly in infants. 5. Adrenaline > Adrenaline given as eye drops gets oxidized & converted to Adrenochrome which can deposit as black colored pigment on the conjunctiva Pupil , ; ; n = Stimulation of M, cause Pupil contraction’ Miosis > circular rauscle Acie T “Miesis = Stimulation of a, cause Pupil dilatation / Mydriasis > radial wauscles ms + Myde + Parasympathoraimetics cause active miosis fee = Sympathomimetie cause active mydriasis ay Mybe = M, blocker ~ Mydriasis ° = a, blocker ~ Miosis % Mists = This is passive when a drug block the receptor and produces action on pupil. Rabbit Experiments Eye Moura Rabbit Eye Experiment = The eye drop is given in the rabbit eye. Effect of drug is seen and we have to identify the drug, So 4 drugs are given +1. Parasyrapathornimetic drug like acetylcholine 2. Sympathomimetic drug like adrenaline 3. Parasympatholytic drug like atropine 4A + We will check sequentially Corneal reflex (CR) If absent» LA {f Present then check Light Reflex (LR) If Absent > Anti-Cholinergic drug like Atropine if Present than we will check the size of pupil eae > Parasympathetic drug Mydriasis > Sympathetic drug Rabbit lleum Experiment — in this test baseline contractions are present. After adding the drug we need to identify, if first drug was stimulant or depressant and then 2% whether stimulant or depressant. Stimulants act through Depressants, act through Ach receptors Bacl, receptors, Cacl, Receptors Sympathetic Receptors Kel, Papaverine As works on. Works on cholinergic receptor Adrenaline effect canbe Effect can't be cholinergic receptor but effect can't be blocked by blocked by B blockers blocked by B its effect cane blocked anti-cholinergic blockers by anti-cholinergic.Depressant tele we, eh washed L wte uke > Firstly see the drug is stinnulant or depressant. If itis stimulant, then see whether the effect can be blocked by Ach blocker or not, if effect is blocked then the unknown (pink) is Ach. IF it is not blocked (black) then unknown is Bacl, or Cacl, ~ Similarly in Depressants, se whether the effect s blocked by B blockers or not. If effect is blocked (pink) then itis a sympathetic drug. IF tis not blocked (black) then it is Kel or papaverine. Cardio ~ Vascular Systern Congestive Heart Failure Acie Chronic Acute CHE Drugs Used For T/t of Acute CHF 2. Diuretics - | Fluid by Loop diuretics (preferred) 2. Inotropic ~ t Pumping 3 Types of notropies can be used. 4. Drugs that stinulate B, Receptor ~ Dopamine = Dobutamine ~ (soprenaline = Nor ~ Adrenaline 6. Phosphodiesterase inhibitors/ Inodilators = Inaravinone = Milrinone © Cardiac glycosides / Digitalis group of drugs: = Two Important mechanisnn of action are:~ 1) inhibits Na ~ K purap 4 Inhibition of Na ~ Ca exchange pump + 1 Cat in SER + * Contractility ii) Vagomimetic effect 4 Conduction from atrium to ventricle This is useful in AF.= 2 drugs in digitalis group Digoxin Digitoxin [withdrawn] Contraindicated in renal Failure Contraindicated in liver Failure Adverse Effects of Digitalis 2. GIT side effects — Nausea , vomiting (m/e) 2. Cardiac side effect -Arrhythmia 1) M/C Arrhythmia — Ventricular Bigeming it) Most specific - Non-Paroxysmnal Atrial tachycardia with AV block Gynecomastia Other drugs that cause gynecomastia [DISCO Drugs| DI — Digoxin S ~ Spironolactone C ~ Cimetidine 0 — Oestrogen 4. Xanthopsia — yellow vision Drug interactions in Digoxin VK amg” Increases Digoxin toxicity 1 ca Quinidine Verapamil Drugs increasing risk of digoxin toxicity Avniodarone Thiazide Management Of Digitalis Toxicity = Drug of choice in ventricular arrhythmias occurring due to digitalis is Lignocaine. + If antiarrhythmic drugs are not able to control then last drug of choice is DIGIBIND. It is an antibody against digitalis. Chronic CHF = Also known as compensated CHF > Major airs in CHE is to 4.4 Fluids - done by diuretics > Loop Diuretics 2.1 Work ~ by causing vasodilation -» Vasodilator 5.4 LVH (mainly responsible for mortality) 'B Types OF Vasodilators Are Venodilators ‘Arterial Dilators Mixed Dilators 1 Preload T After load {Both preload and after load Nitrates Hydralazine ‘ACE inhibitor, Angiotensin receptor blocker, Sodium nitroprusside LV (Left Ventricular Hypertrophy) + it is mainly due to aldosterone. + Drugs 4 LVH 12. B blockers 3. Angiotensin Receptor blockers 2. ACE inhibitors 4, Aldosterone Antagonists z Bu Gnd Ret GongMETOPROLOL, CARVEDILOL ° 6, Stimulation ———> Renin (Release From IG cells of kidney) —______, Angiotensinogen Angiotensin | Pi BenazePRIL | © ce | CaptoPRIL Angiotensin ti TelmiSARTAN | Q> Spironolactone |O Aldosterone New Drugs in CHE > BNP (Brain Natriuretic peptide) ~ Causes NatriuresisBNP ~ Causes Vasedilation BNP J NEP [Neutral Endopeptidase] Degradation +2. Nesritide > increases BNP ~ Not given orally (It is a peptide) 2. Sacubitril > NEP inhibitor ~ can be given orally 3. Omapatrilat > Inhibits both ACE and NEP Hypertension 4 types of drugs are used 1. Diureties 1. Vasodilators (i. Sympathetic blockers. IV. RAAS inhibitors |. Diuretics > Thiazide - Drug of choice I. Vasodilators: ~Act by different mechanisms 4 Release NO like sodium nitroprusside, hydralazine no + Guanyiy! eyelase 4 + cGMP (Powerful vasodilator) ~ Nitroprusside can cause eyanide poisoning on long term use > Hydralazine can cause SLE. Potassium channel openers M = Minoxidil D = Diazoxide H = Hydralazine Minoxidil — Causes hair growth so it is contra indicated in young fernales — It is used in alopecia. Diazoxide = It decreases insulin so causes hyperglycemia thus is contraindicated in diabetics. = It is used in insulinonna, @, Calcium channel blockers ~ Veraparnil ~ Diltiazern ~ Drugs whose name ends with Dipin ~ only blocks Ca channels in blood vessel only therefore also called peripheral Ca channel blockers = NimoDIPINE is indicated in subarachnoid hemorrhage I. Sympathetic Blockers 2. a receptor stimulants = Clonidine = Methyl-dopa > Clonidine can cause rebound HTN so should not be suddenly stopped. > Methyl-dopa is a prodrug. It causes hemolytic anemia 2. cand blockers = & Blockers — preferred in BPH IV. RAAS Inhibitors A. B-blockers B. ACE inhibitors C. Angiotensin receptor blockers (ARB) D. Aldosterone Antagonists E. Renin inhibitors Block Ca channels in heart as well as in blood vessels ACE Inhibitors - Properties C ~ Cough A= Angioedema P — Prodrugs except CAPTOPRIL and LISINOPRIL T ~ Taste alteration © = Orthostatic hypotension |, C/1 P ~ Pregnancy R — Renal arterial stenosis = Increased L — Lowers the risk of Diabetic nephropathy thus good drug for diabetie patients. Side effect of ACE inhibitors, not seen by ARBs F De Gat ibaAngiotensin Receptor Blockers (ARB) 440 > They have all properties of ACE inhibitors except they are not prodrugs and do not cause cough & angioedema. > Telmisartan 1 PPAR - y stimulation ~ So can be used in patients with insulin resistance. Renin inhibitors > Enal KIREN Alls KIREN > Remi KIREN According to INC ~ & Guidelines a HTN2 140/90 Grade stage | - 140 -159/ 40-99 Grade Stage Il -» 160/100 6. Goal BP < 40/40 inall Except Im Elderly > > 60 years without DM de CKD then BP can be < 150/40 wm of Hg ‘According to INC ~ ¢ First line deugs A= ACE inhibitors and ARBS c-cce D ~ Diuretics For special conditions HTN ~ thiazides Pregnancy -> Methyldopa (Routine HTN) > Hydralazine (Emergency HTN) > According to Harrison and standard textbooks Labetalol is given whether it is routine or emergency HTN. HIN Emergency: = Nitroprusside = Nicardipine ~ Doc According to ASH (American Society of HTN) HTN 2 130/80 mum of Hg Stage | - 130 -134/ 80-84 mm of Hg. Stage Il - 2 240/40 mm of Hg. ASH recommended the T/¢ only for stage ll HTN. ¥ Angina Pectoris Classical Variant / Prinzmetal Classical Angina > Main cause is atherosclerosis or obstruction of the coronary artery ~ We need to increase the blood flow which is done by decreasing the work. Variant Angina (Vasospastic Angina) > Main cause is vasospasm ive. Coronary vessel spasin ~ This can only be treated by vasodilation of coronary arteriesDrugs Used in Angina 1) Nitrates i) CCB (Ca channel blockers) iif) B — blockers i) K channel openers Nitrates GTN/NTG [Doc For acute angina given by sublingual route Isosorbide dinitrate (IDN) Isosorbide mono nitrate (IMN) - Minimur FPM PETN (Penta Erythritol tetra nitrate ) - (Longest acting) Amyl nitrite - (Shortest acting) All nitrates have high first pass metabolism so they have poor oral bioavailability. pegbegus “These drugs should be given with nitrate free period to avoid tolerance. Minimum 6-8 hrs. should be nitrate Free Nitrate -» NO -» t cGMP > Vasodilation mainly in vein Thus nitrates mainly decrease preload in classical angina But in variant angina only one answer is possible. ie. dilation of coronary artery. Mostly itis endothelium independent. sige PDE camp | ————> Degraded 4 tVD>1BP So, nitrates should never be combined with sildenafil ii) Ca Channel Blockers ~ Verapamil = Diltiazem -s Dipins are not used because they can cause tachycardia, They are peripheral Ca channel blockers. They cause refiex tachycardia. So they are not used in Angina. iit) B- Blockers ~ JHR = Contraindicated in variant angina. iv) K —Channel Opener (kco) = Nicorandil » Potassium channel opener + NO Release New Drugs in Angina 2. Wvabradine 1, = Funny current blocker VA ~ 4 Visual Acuity — Side effect BRADI - Bradycardiac agent 2. Rho Kinase Inhibitors ~ Fasudil = Netarsudil + For Glaucoma. Metabolic Modulating Drug 4 Trimetazidine ~ inhibits the Fatty acid oxidation thus heart starts utilizing glucose, thus less O2.will be sufficient and less blood will be sufficient for the heart. Thus, itis used in angina.Arrhythmias 442 5 classes of anti-arrhythmic drugs: (Vaughan William's Classification) ee ener Class | — Na* channel blockers Ser iamahet Class It ~ B blockers : Class it~ K° channel blockers Class IV ~ Ca’ channel blockers Class V - Others Class + Drugs Class | drugs are further classified into la —K° blocker tb ~ Ke opener le — No effect on k Class 1a - Quinidine ~ Procainarnide Class lb - Lignocaine = Phenytoin |, + Used only for ventricular arrhythmias ~ Tocainide Class te ~ Encainide ~ Fleeainide ~ Propafenone Class tt Drugs > They are mainly 8 blockers > They are used mainly for tachyarrhythmia. Class Ill Drugs — &’ channel blockers B ~ Bretyliam (= buctilide D ~ Dofetilide A — Aminodarone ~ Longest acting, t,,> 3 weeks S ~ Sotalol ~ Amminodarone — has all 4 mechanisms means it is mot only K° blocker but itis also Na’ blocker, B blocker and Ca blocker Adverse Effect of Amiodarone The = Hyper or Hypothyroidisnn Periphery of — ~ Peripheral neuropathy My ~ Myocardial depression Lung & ~ Lung fibrosis Cornea is ~ corneal deposits Photosensitive — Photosensitivity ~ Cause QT prolongation Lignocaine is DOC for digitalis induced ventricular arrhythmias as well as for most MI ventricular arrhythmias Class 1V Drugs > Cat” channel blockers = Verapamil ~ Diltiazem > Used for tachyarrhythmia whether they are atrial or ventricular > Ca channel blocker + B blockers should never be given together b/c they both block the heart and can cause Severe Bradycardia & AV Block. EBPrepLadderClass V Drugs: (Miscellaneous drug) > Adenosine > Atropine > Magnesium Adenosine > Shortest acting > T2/2 < 10 see > Used for Paroxysmal supraventricular tachycardia Atropine > Drug of choice for AV block and Bradycardia ‘Magnesium -» Drug of choice for Torsade's de pointes (TDP) or prolonged QT interval [Bystpidersa] 1. Statins + Inhibit HMG CoA reductase. So it decreases the formation of cholesterol in the liver which leads to up regulation of LDL receptors, so more cholesterol taken up From the blood. = Name should end with ‘Vastatin’ like Atorvastatin Rosuvastatin - Longest acting Simvastatin = Statins have maximum LDL cholesterol lowering capacity. = Given at night because HMG CoA reductase is maximum active at night but Atorvastatin and Rosuvastatin are long acting drugs, thus can be given any time of the day, > Statins can cause myopathy and risk of myopathy increases when 1. Statins combine with microsomal enzyme inhibitors like erythromycin ji. Statins combined with fibrates Pleiotropie Effects of Statin > Plaque stabilizing effect > Anti~inflanmatory effect “+ Decrease oxidative stress 2. Fibrates > Act by stimulating PPAR - «> 1 Lipoprotein lipase = Their major action is to lower TG (Triglycerides) 5. Bile Acid Binding Agents (BABA) > Cholestyramine + These are not absorbed. They go out themselves via GIT so are safe in children and pregnancy, > S/E increase TGs so they are contraindicated in hypertriglyceridernia. 4. Niacin (Vitamin 83) > Maximum HDL cholesterol increasing property = It can also decrease Lipoprotein-a > Not commonly used because of: ‘) Compliance limiting side effects = Flushing, Pruvitus i) t Uric acid — can result.in gout it) Contraindicated in DM because it increases insulin resistance. 5. PCSK - 4 Inhibitors “+ Monoclonal antibody against a substance called PCSK ~ ¢ FD oink Get Gary> This substance binds to LDL receptors and help in LDL degradation aaa = ALIROCUMAB = EVOLOCUMAB ~> They decrease LDL to a very high potential, more than statins but they are injectable drugs so drug of choice still revnain statins 6 Toreitrapib t ceTP © (cholesterol ester triglyceride protein) + HDL |. Histamine > Acts on 4 Receptors Hi, H2, HB, H4 > Ha - Mainly for acid secretion +H ~ Presynaptic receptor + H4 — Present on WBCs = So drugs commonly used are H1. Blockers Anti Histaminies f° Generation Ww Generation Can cross blood brain barrier Cannot cross blood brain barrier Has additional Ach inhibiting property| Absent Eg, Promethazine > £g. Terfenadine, Astemizole 2” Generation Anti-Histaminies > Eg, Promethazine > It can cause sedation and anti-cholinergic side effects > Can be used for common cold, motion sickness, akathisia 2. 2" Generation Anti Histaminies Terfenadine Cisapride Astemizole Astimizole | Cause QT prolongation Cetivizine Terfenadine Levocetirizine Loratadine 5 — HT receptors (serotonin) ee alll eer SHT, SHT: SHT, sur, ax B/D “> SHT4a Receptor Agonist Buspirone — For Anxiety = Antismoking drug “> SHT 18/2D Receptor agonist ~ Triptans Sumatriptan Naratriptan> Drug OF Choice For Acute Severe Migraine > CGRP is the major culprit in migraine > New drugs are formed which are monoclonal antibodies against CGRP (Calcitonin gene related peptide) which are used in prophylaxis of migraine. Eg Erenumab, Galcanezumab, Fremanezumab 3. SHT, Receptor Antagonist > 5 HT sxc antagonist are used as anti-psychoties like: clozapine 4. SHT, Receptor Antagonist + Drugs used are Ondansetron: Drug of choice for chemotherapy induced vowiting Granisetron 5. SHT, Receptor Agonist Cisapride Prokinetic drugs used for GERD Mosapride } 3. Prostaglandins (PG) + These are formed from phospholipids in the membrane Phospholipids PLP-AL 4 ° Avachidoni acid NSAIDS: cox“ N, L0x PG Leukotriene NSAIDs Aspirin = Can cause hyperuricemia so avoided in Gout. = increases the risk of Reye's syndrome = It has antiplatelet action. Its low dose is used in MI and stroke patients = Aspirin has no antidote, so in case of poisoning we have to alkalinize the urine. Paracetamol = has only antipyretic and analgesic activity. — It does not possess anti-inflammatory activity. Metabolite of PCM — Stimulates TRPV receptor (Vanilloid Receptor) — Analgesic action of it may be mediated by this receptor + PCM has antidote ie. N-Acetyleysteine ee, Acute Chronic + DOC - NSAIDS except Aspirin, POM Colchicine = It inhibit the migration of granulocyte into the joints so they will not be able to cause inflammation. — Most effective drug for acute gout is colehicine > Side effect - Myopathy and diarrhoea, so not drug of choice for acute gout. Chronic Gout > Need to decrease urie acid F De Gbint Re Cy4 Formation OF Uric Acid t Excretion of Uric Acid Xanthine Drugs used are called uricesurie agents like: = Probenecid Xanthine oxidase ~ Sulfinpyrazone ~ Lesinurad Uric acid SO Allopurinol -» DOC Febuxostat > Im birds urie acid is converted by uriease to Allantoin. + Uricase is absent in humans. If we take uricase from outside we can decrease uric acid by its metabolise ~ Drug: Rasburicase and pegloticase (New drug) Rheumatoid Arthritis > Pain and inflammation of joints ~ For acute treatment we use: - NSAIDS = Steroids +> It is only symptomatic treatment. It cannot slow down the joint destruction DMARDs (Disease modifying antirheumatic drugs) ~> AS they are very slow acting so they are also called SAARDs (slow acting anti rheumatic drugs) Classification Conventional DMARDS Biologicals = Chloroquine ‘Anakinra Sarilumab ~ Penicillamine Adalimmurnab = Azathioprine Certrolizumab = Gold salts Etanercept = Leflunomide Infliximal = lmmunosuppressant Golinmumab ~ Methotrexate (DOC) Abatacept Sherawat ~ sulfasalazine Methotrexate Drug of choice = Acts by increasing adenosine which possesses anti-inflanunatory activity > Contraindicated in Pregnancy (Drug of choice in pregnancy - CHOLORQUINE) Sulfasalazine: It is a prodrug & can be used in ankylosing spondylitis. Biological DMARDS > Basically act as antagonist of IL — I, IL ~ 6, TNE - « IL = 4. ~ Anakinra IL ~ 6 ~Saritumab TNA = & Antagonist -> A — Adalimumab + C ~ Certrolizumab > E ~ Etanercept. > Inhibitor — tnfliximal Goli — Golinwwnab= They are also used in Crohn's disease, psoriasis ete. 447 — They increase the risk of infections so are contraindicated in TB or Hepatitis~B virus infections Co-Stimulation Inhibitors Abatacept-It inhibits the activation of T-cells. CD80/86 + CD28 interaction is stopped by this drug, Anti-Mierobials = Cidal — Which kill bacteria = Static — which inhibit growth of bacteria Cidal Drugs BE — B - Lactam v A. P¥ancomycin F — Fluoroquinolone A ~ Aminoglycosides Classification Based On Action of Drugs 1) Inhibition of Cell Wall ~ Synthesis Firnaly — Fosforayein Bind to - B - Lactam Bact - Bacitracin Cell — Cycloserine Vall ~ Vancomycin B = Lactam Drugs ) Penicillin i) Cephalosporins Ut) Carbapenem IV) Monobactam 1) Penicillin a) PrG > initially used + Limitation — Not effective orally ~ Narrow spectrum ~ Resistance can develop to this drug Oral Penic Vv - Pav © = Oxacillin D ~ Dicloxacillin K = Cloxaeillin A Ampicillin / Amoxycillin. Extended Spectrum Penicillins = Effective against gram + ve and ~ ve bacteria A= Ampicillin / Amoxycillin Ci — Carbenicill Ty — Ticareillin M = Meslocillin effective against pseudomonas also A= Aslocillin P - PiperacilB ~ Lactamase inhibitors = Clavulanic acid ~ Sulbactam ~ Tazobactam Penicillinase Resistant Penicillins © ~ Cloxaeillin © = Oxaciliin N ~ Nafeillin D ~ Dieloxacillin ° M ~ Methicillin Uses OF Penicillins > Pencillin G is used for L- Listeria A ~ Actinomycosis S ~ Syphilis T ~ Tetanus M = Meningococcus AN = Anthrax For Syphilis: ro Beraathine PnG 2 IM 2.4 mU single injection Early latent Late Latent Benzathin PnG cS IM 2.4 mU 3 injection weekly given > In case of neurosyphilis - PmG or aquous penicilin given iv/im 6 times a day for 10-14 days. ‘Meningococcal infections > Drug of choice For empirical t/t ~ Ceftriaxone + For definitive t/t — Png > Prophylaxis - Rifampicin ~ Ceftriaxone (most effective but given by LM. route, therefore not commonly preferred) ~ Ciprofloxacin ~ DOC for mass chemoprophylaxis b/e ean be given orally. Gonococeal Infections ~ For gonococcal urethritis: DOC is Ceftriaxone + For non gonococcal urethriti DOC is Azithromycin > IF both gonococcal & non gonococcal urethritis — Azithromycin (Single dose is enough) ) Cephalosporins ~ Cephalosporins secreted in bile can go out through the faeces and are safe in renal failure. Eg ~ Ceftriaxone - Cefoperazone EBpPreptadderAntimicrobial safe in renal failure: Cef = That end with ONE in The — ~ Tigecyeline R = Rifampicin E Erythromycin N = Natfeillin A = Ampicillin L ~ Lincosamide (Clindamycin) Disease - Doxycycline Cephalosporin Active against Pseudomonas = Cefoperazone = Cefepime ~ Cefpirome ~ Ceftazidime most effective against pseudomonas WW) Carbapenem Imipenem = Effective against gram sve, -ve & anaerobes = it is broken down by enzyme in kidney called as Dehydropeptidase = Cilastatin inhibits this enzyme. = So impipenem is always given in combination with cilastatin. Side effect + Seizures so it is contraindicated in epileptic patients. Meropenem Ertapenem Doripenem Farupenem -+ All these are given without cilastatin and they have lesser risk of seizures than Imipencrn. IV) Monobactam Aztreonam > 2 inwportant properties 1) It does not show cross allergy ii) It is only for gram —ve bacteria Vancomycin = Drug that inhibits cell wall synthesis > Given by iv route = It is nephrotoxic and ototoxic = Causes release of histamine which lead to “Red man syndrome” > DOC for MRSA = DOC for Pseudomembranous colitis (only condition where it is given orally) For Staph Aureus -» Pn@ Penicillinase producing staph.aureus + CONDOM group of drugs (methicillin) MRSA. -> Vancomycin VRSA > Daptomycin Extended spectrum - Lactamase (ESBL) = It can break most of the anti-maicrobials but not carbapenems > Piperacilin + Tazobactam can also be effective against this enzyme producing bacteriaNew Delhi Metallo B Lactamase (NDM) > These enzymes can even break carbapenems. > Not inhibited by B — Lactamase inhibitors > COLISTIN is drug of choice for bacteria producing NDM. fi) Based on inhibition of Protein Synthesis 4a. Tetracyeline 6. Macrolides ¢ Aminoglycosides 4a. Tetracyelins Limitations /Contraindications K — Kidney failure (Except Doxycycline) 4 = Anti-anabolic actions P ~ Phototoxie | = Inhibit ADH release L ~ Liver failure D ~ Dentition and bone problem (C/I in growing children child & pregnancy) E ~ If given after expiry date can cause renal tubular acidosis V = Vestibular dysfunction Ss - SIADH R = Doe for Rickettsia | ~ Dee for inguinale granuloma L-Lav S| Manel Poumens N k= cholera A ~ Ameobiasis, ~ Bacteria develop resistance to tetracycline by forming Efflux pumps Tigecycline > Resistant to efflux pump > Like tetracycline, it has same mechanism of action. > Bacteriostatic ~ Broad spectrum > But it is not effective against pseudomonas. — It is secreted in bile so is safe in renal failure 6) macrolides > The drugs ending with “thromycin’ like Erythromycin Azithromyein Clarithromycin Chancroid . “CLAP” Corynebacterium L = Legionella A ~ Atypical pneumonia P - Pertussis= Azithronaycin: DOC for gonococeal + non gonococeal urethritis 1) Aminoglycosides > Drugs: Streptomycin Gentamicin > These drugs are only protein synthesis inhibitors which are bactericidal. > They are nephrotoxic, ototoxic and cause neuro-muscular blockade as side effect. stiaptonagain — First line drug in TB DOC for plague —+ For prophylaxis of plague - Doxycycline iit) Classification Based on Metabolism Inhibition Pteridine + PABA + glutamate (i) Sulfonamides FA synthase Ea Gi) Trimethoprinn, FH, o—}— diirrase Pyrimethamine FH, > | AND ii are static but combination of these two is cidal. Sulphonamides > Dapsane > They can cause allergy. So they can cause rashes on skin. Side Effect = aplastic wnswaia B ~ Bilirubin displacement so C/I in pregnancy & newborn babies C — Crystalluria = Rash A — Acetylation metabolisin 5 = Causes SLE H = Causes hemolysis in patients with G-6-PD deficiency. Cotrimoxazole + Trimethoprins + sulfamethoxazole $s > But when it reaches the blood, ratio becomes 1:20 which is optimal to kill the bacteria > Drug of choice for 3 bacteria: F~ Preimioagets Ni — Noeardia B - Burkholderia iv) Drugs Affecting DNA Gyrase a. Fluoroquinolones + The name ends with “floxacin” Norfloxacin Ofloxacin Ciprofoxacin Levofloxacin > They are cidalBioavailability > Levofloxacin - 100% bioavailability = Norfloxacin - Very low bioavailability Contraindications > Pregnancy & children > Cause seizures so avoided in epileptic patients Renal failure except Peftoxacin Moxifoxacin ‘Trovafloxacin Respiratory Fluoroquinolone 0 Ofloxacin M = moxiffoxacin G = Gatifloxacin Levo ~ levofioxacin > These can be used to kill any bacterial causing respiratory tract infection. Q. Which drug is NOT effective for which bacteria? MRSA - All B lactams not effective (except 5* generation Cephalosporins that have 'ROL! in end of their names) Pseudormonas ~ Vancomycin not effective Anaerobic Bacteria - Aminoglycoside not effective Mycoplasma — Cell wall synthesis inhibitors not effective Typhoid — Aminoglycosides not effective “Treatment of Specific Conditions TUBERCULOSIS: 8 Bling Sh a ine Essential “——____——> supplementary = tsoniazid S ~ Streptomycin = Rifampicin = Pyrazinamide ~ Ethambutol Cidal/Static | Cintra’ Extra ‘Hapatotoxic | Safe in Pregnancy Cellular) Bacteria cidal Both ‘Sate cidal ‘Both ‘Safe Cidal Intracellular Avoided Static Both Safe Cidal Extracellular Contraindicated> Best drug for fast growing, intermittently growing & slow growing bacteria Fast growing bacteria H = Isoniazid Intermittent — In caseous necrosis also R - Rifampicin known as spurters Slow growing — Intracellular Z — Pyrazinarnide| F Line Drugs 1) INH = Side effect - Causes peripheral neuropathy and hepatoxicity. i) Rifampicin — Always given empty stomach It causes enzyme induction leading drug interactions. = Also effective against leprosy > Also effective against pseudomonas and MRSA. iit) Pyrazinamide - It causes hyperuricemia so can cause gout. iv) ethambutol -» Causes red- green colour blindness (Optic neuritis) Vv) Streptomycin — Not effective orally, need to be given by injections. = Side Effects = Nephrotoxicity ~ Ototoxicity ~ Neuro-museular blockade 2% Line Drugs = Cyeloserine > PAS (p- aminosalieylic acid) > Ethionamide Side Effects Cycloserine - Neuropsychiatric Effects PAS = Hypothyroidisom Ethionamide - — Hypothyroidisen = Hepatotoxicity Other 2% Line Drugs Fluoroquinolone Injectable 0 = Offoxacin ~ Capreoraycin M ~ Moxitfoxacin = kanamycin G ~ Gatifloxacin ~ Armileacin Levofloxacin Clofazimine -» This drug was previously used for leprosy, but now used in TB also. Linezolide + This drug was approved for MRSA, but now it is also used in TB. New Drugs for TB |. Bedaguiline fi. Delaminid “+ Both of these drugs cause QT prolongation.Treatment of TB -+ According to the latest guideline in 2028, drug sensitive tuberculosis is divided into gay Category | Category New Patients Old Patients Phases of Treatment Category Intensive Phase Continuation Phase Tall 2 HRZE 4 HRE MDR = TB When bacteria is resistant to both (HécR) Intensive Phase Continuation Phase 6 months 48 months 6 drugs 4 drags Drugs are chosen after drugs sensitivity test. XDR ~ TB + Bacteria resistant to (HécR) and at least one Ruoroquinolone and one injectable drug Treatment of XDR - TB Inventive Phase Continuation Phase © months 28 months Minirnurn 7 drugs are used Minimum © drugs are used| ‘Treatment of Leprosy ‘Multibacillary leprosy (MB) Paucibacillary leprosy (PB) © months 8 months AS per latest guidelines treatment is same for both but duration is different: Drug Dose Rifampicin 600 mg/once month Clofazimine 300 mg / once month Clofazimine 50 mg / OD for 28 days Dapsone 100 mag / OD for 28 days > This treatment will be continued for 12 months in MB and 6 months in PB. > In case of drug resistant leprosy Ofloxacin Minocycline Clarithromycin ANTI RETROVIRAL DRUGS HIV > 4 types of drugs are used in HIV 2. Fusion inhibitors 2 Reverse transcriptase inhibitors 3. Integrase inhibitors 4 Protease inhibitors 1. Fusion inhibitors — 2. Types of Fusion inhibitors ') Drug that bind to GP-43 : Enfuvirtide. ii) Drug that bind to CCR-5: Maraviroc iil) Recently Developed Monoclonal antibody against CD, cells: ibalizumab2. Reverse Transcriptase inhibitors en <_< NNRTI ee ‘Nucleoside Nucleotide ~ Bfavirera ~Zidovudine =Tenofovir ~ Nevirapine -Larnivudine ~ Delavirdine -Stavudine -Zaleitabine ~Emtricitabine ~Abacavir Drugs Effective Against both HBV& HIV L - Lamivudine E - Emtricitabine T -Tenofovir ‘Abacavir +» This drug can cause MI in some patients who have HLA-B 5702, thus contraindicated in these patients. 3. Integrase Inhibitors Raltegravir ~ Elvitegravir ~ Dolutegravir + Now these drugs are promoted as First line drug for the treatment of HIV. 4. Protease Inhibitors - Ritonavir ~ Lopinavir = indinavir = Saquinavir “+ They are prone to drug interactions because they are metabolized by CYPSA4. ++ These can cause lipodystrophy syndrome. Insulin Resistance Hyperlipidemia Weight gain “Treatment Of HIV According to NACO guidelines + Use of multiple drugs that act on different viral targets is known as HAART (Highly active antiretroviral therapy). = Treatment should be done in all patients irrespective of their CD, count and symptoms. > Minimum 3 drugs should be used from mininnuna 2 groups. > Mainly we use 2NRTI +2 NNRTI/ integrase Inhibitors. Preferred First Line Therapy Tenofovir + Lamivudine + Emtricitabine F Pe tint Ra CyMALARIA Stages OF Malaria i. Erythrocytic stage — Responsible for symptoms ii. Exo-erythrocytic stage - Responsible for relapse of malaria fii. Gametocyte stage - Responsible for transmission i. Pre-erythrocytic stage — cause of malaria Drugs Used For These Stages Gametocytic stage: + Primaquine ~ kills Gametes of All 4 Species. “> So it is used for preventing the transmission of the bacteria Pre-erythrocytic stage: > Primaquine ~ Used for causal prophylaxis ji. Exo-erythrocytic stage: + Radical cure of malaria Primaguine ~ given for 2 weeks Tafenoquine — Single Dose Erythrocytic stage: > These drugs are used to treat malaria Fast Acting Drugs Slow Acting Drugs M = Mefloquine ~ Proguanil - Artemisinin ~ Pyrimethamine = Chloroquine ~ Sulfadoxine - — Halofantrine = Doxycycline Atovaquone = Res-@ (Quinine) ‘Treatment OF Malaria DOC for P. vivax malaria - Chloroquine fi DOC for P. falciparum malaria ACT (Artemisinin based combination therapy) << ke —_ 5 Artesunate Artemether Sulfadoxine / Pyrimethamine Lumefantrine ~All over india this is the Drug of choice in North —Eastern ACT of choice states because here parasite is resistant to sulfadoxine/ Pyrimethamine Prophylaxis For Malaria <6 weeks 6 weeks = Doxyegeline (Daily) = Mefloquine (weekly) ANTIFUNGAL 1 ‘Amphotericin — B (AMB) ~ Binds to estradiol and creates pores in the membrane. > Intracellular contents leak out causing fungus to di. lt is not effective orally thus given by injection. Due to this its use is limited to serious Fungal infections only EBPreptadder+ Side Effects 457 = Nephrotoxic- cause renal tubular acidosis with hypokaleria. (This is most common dose dependent side effect.) ~ Causes infusion related reactions. (Most common side effect) Liposomal Amphotericin—B is less nephrotoxic than conventional Amphotericin-B 2. 5-Flueytosine — It inhibits DNA polymerase. 3 Azoles ‘Triazoles Two types aa tmidazoles Drugs Ketoconazole Fluconazole > DOC for Cryptococcus & candida infections Itraconazole Voriconazole > DOC for Aspergillosis Posaconazole These are fungi static drugs “These drugs inhibit conversion of lanosterol L-24 demethylase a—eeeororwee ergosterol Terbinafine Group -+ These drugs inhibit an enzyme ie. squalene epoxidase so squalene deposits in cells that kill the fungus. > tis also a cidal drug, > DOL for dermatophytosis Griseofulvin > It inhibits mitotic spindle formation in fungus. > itis static drug. <> It has high affinity for keratin thus used for dermatophytosis but because of lot of relapses andl risk of disulficava like reactions, now a days, it is not commonly used. Echinocandins + Caspofungin — acts on cell wall of fungus > Acts by inhibiting B-2,3 glycan i. component of fungal cell wall > Used for candida and aspergilosis Drug Of Choice For Various Conditions > Kala Azar — Liposomal Amphotericin-B > Trypanosomiasi African trypanosomiasis South-American trypanosomiasis (Chage's disease) Early stage- Suramin ~ Benzimidazole Late stage - Melarsopro! ANTI HELMINTHIC 2 types of worms 1. Platyhelminthes (1. NematodesPlatyhelminthes + Eg. Tapeworms, flukes > Drugs of choice ~ Praziquantel > Except i. Dog Tapeworm (Echinococcus) - Albendazole is DOC fi. Liver Fluke (Fasciola hepatica) - Triclabendazole is DOC Nematodes > Drug of choice is ALBENDAZOLE > Except i Filarial worm — Diethylcarbamazine fi, Strongyloides ~ ivermectin Onchocerca - Ivermectin ANTIVIRAL DRUGS Influenza Virus > 2 types of drugs are used. Inhibit the uncoating of the virus = Amantadine like drugs Neuraminidase inhibitor ~ Oseltamivir — orally used ~ Zanamivir ~ inhalational route = Peramivir ~ These are drug of choice for HIN, HSN, swine flu and bird Flu respectively Hepatitis 8 -» Drug of choice ~ Tenofovir / Entecavir. Hepatitis C > 3 types of oral drugs 4 Protease inhibitors 1. NSSA inhibitors I, NSSB inhibitors Protease Inhibitors Boceprevir Telaprevir Grazoprevir Paritaprevir NSSA inhibitor: Ledipasvir Daclatasvir NSSB inhibitor: Dasabuvir Beclabuvir Sofosbuvir Drug of choice for Hepatitis ~ ¢ is combination of these drugs for different genotypes. Endocrine System Anterior Pituitary Gland ~ Seeretes following hormones which are regulated by hypothalaenic hormones.Anterior Pituitary Hormones Hypothalamus Hormones - GHRH, GHIH TSH - TRH Ww. ACTH - CRH Mv Gn = GnRH Prolactin -PIH GHIH: (Growth Hormone inhibiting Hormone) Also known as somatostatin. Uses — It is used for }) Secretory diarrhoea ji) Oesophageal varices ii) Malignancy of endocrine pancreas iv) Acromegaly + Somatostatin is very short acting. Drug similar is Octreotide (Long acting) GnRh (Gonadotropin Releasing Hormone) If given in pulsatile manner = t Gn seeretion ~ 1 Estrogen = t Progesterone = Testosterone = If given in continuous manner =4Gn = 4 Estrogen ~ 4 Progesterone = VTestosterone GnRH Agonist Drugs ~ Leuprolide ~ Nafarelin = Goserelin ~ Buserelin + They are all injectables. > They all have flare up reaction as side effect: Gnrh Antagonist Drugs ~ Cetrorelix ~ Ganirelix ~ Abarelix ~ Degarelix > These are also injectables = Elagolix: Orally effective, used for endometriosis.Wl. PIH (Prolactin inhibiting Hormone) > Dopamine, Bromocriptine, Cabergoline ~ Stimulates dopamine receptors which will decrease prolactin + These ave DOC for Hyperprolactinemia |. Galactorrhoea Wt infertility + Cabergoline is mostly used because it is long acting, Posterior Pituitary Hormones Oxytocin + 2 important functions 1, Contracts the uterus 2. Milk ejection > In breast engorgement it is drug of choice. > It is drug of choice for induction the labour + It is also used for PPH (Postpartum hemorrhage) Vasopressin / ADH > Act through 2 receptors V, d V, V,- Vasoconstriction V,~ Decrease urine/ cause urine Retention ~ Release of vWF/ Factor Vill from endothelium Drug stimulating V, Receptors: Terlipressin — D.O.C for oesophageal varices Drug stimulating V, receptor: Desmopressin — D.O.C for Diabetes insipidus (nocturnal enuresis) In SIADH > Vasopressin inhibitors are used like |. Conivapton ‘i Tolvapton (recently approved for Autosomal Dominant Polycystic Kidney disease) [ee | Type | Type t! = insulin = Pramlintide Insulin > Short acting insulin ~ Regular > Intermediate acting - Lente insulin Long acting — ultra lente insulin Ultrashort acting insulin: Lispro Aspart Gilisine Ultra long acting insulin: Glargine+ All are given by subeutaneous route. + Mostly given over abdomen except periumblical arca. > Can be given on anterior / lateral thigh or arm DOC For > Type | DM > Type lt DM uncontrolled + Diabetic Keto-acidosis > Pregnancy Side effects: = Hypoalycacmia Oral Anti-Diabetic Drugs They act by 4. Release of insulin: Drugs whose names end with “ide” A. Sulfonylurea - €g Glipizide B. Meglitinides — eg Repaglinide, Nateglinide All these drugs can cause hypoglycaemia 2. Other Methods: The drugs that act by other mechanism do not cause hypoglycemia a. Metformin > Can cause megaloblastic anaemia and lactic acidosis = Risk of lactie acidosis increases in kidney and liver disease thus contraindicated in these patients. — It causes maximum decrease in HbAte > Do not cause hypoglycaemia. > Do not cause weight gain. > Drug of choice for type 1! DM. b. Glitazones = They act by stimulating PPAR- y receptor > Reverse insulin resistance = Eg. Pioglitazones (Increases risk of urinary bladder carcinoma) Rosiglitazones (Increases risk of Mt!) “Troglitazone (banned because it cause liver damage) 2. & ~ Glucosidase inhibitors > Acarbose ~ inhibit the absorption of carbohydrates = IF hypoglyeaeinia occurs in presence of acarbose then food will not work and treatment is glucose New Drugs 2. Incretins: Injectable > Glucagon like peptide (GLP) analogue: increases insulin and decreases gastric motility. = GLP —2%4 5 Degrade (DPP4 - Dipeptydy| peptidase-4) GLP analogues: Gut GuP 2 Exenatide Teduglutide Liraglutide + Used in short bowel syndrome > Used in DM. F Bo Giint Re Cy> Side effect: - Pancreatitis ~ Increase the risk of medullary carcinowna thyroid (MCT) 2. DPP-4 inhibitors - Sitagliptin ~ Vildagliptin ~ Alogliptin ~ Linagliptin > All are contraindicated in renal failure except Linagliptin. ~ Side effect - pancreatitis 3. SGLT- 2 Inhibitors > Inhibit the reabsorption of glucose in the proximal tubules ~ Causes glycosuria ~ Drugs = Canaglifiozin = Dapagliflozin = Empagliflozin = Ertuglifiozin > Most common adverse effect is UTI THYROID Hypothyroidism ~> T4 ~ available as L- thyroxine DOC for all the patients of hypothyroidism > TS - available as thyronine Used for severe hypothyroidism ie. myxedema comma Hyperthyroidism > Propylthiouracil (PTU) is drug of choice in pregnancy Iodine 332 - Given orally + 73/2 - 8 days + Cause~ permanent hypothyroidism + Contraindicated in young patients <35 yrs. and in pregnancy ADRENAL GLAND Glucocorticoids + Short Acting Cortisone ~ Hydrocortisone “+ Intermediate acting ~ Prednisone ~ Prednisolone ~ Long acting = Dexamethasone (maximum glucocorticoid activity) ~ Betamethasone ~ Paramethasone Mineralocorticoids + Aldosterone (maximum maineralocorticoid activity) ~ Fludrocortisone = DOCA (deonycorticosterone acetate)+ Glucocorticoid with max. mineralocorticoid activity ~ Hydrocortisone 463 + Mineralocorticoid with max glucocorticoid activity - Fludrocortisone + Glucocorticoid with zero mineralocorticoid activity - Triameinolone = Dexamethasone - Betamethasone ~ Paramnethasone + Mineralocorticoid with zero glucocorticoid activity - DOCA ‘Antenatal uses of glucocorticoids = Given for foetal lung maturity > Betamethasone ~ 12mg, 2 doses at 24 hr. interval “+ Dexamethasone ~ rng, 4 doses at 12. hr. interval Drugs that inhibit the formation of glucocorticoids. + Metyrapone & mitotane used for Cushing syndrome. +5 These drugs are used to inhibit the adrenal gland hormones. OSTEOPOROSIS 2. Calcium 2. Vit-D 3. Calcitonin 4. Thiazides- prevent the excretion of calcium in the urine 5. Bisphosphonates (DOC) - Alandronate ~ Risedronate ~ Zoledronate + Inhibit osteoclast and inhibit bone resorption Effect - Oesophageal ulcers important precautions are taken to prevent oesophageal ulcers 4. Person should not lie down for half an hour. 2. Should be taken empty stomach 3 Should be taken with full glass of water 6. SERM (Selective Estrogen Receptor Modulator) > Actions: act at bone, breast, blood, endometrium and liver. Bone - t formation of bone Blood - + HDL Breast - tt CA breast risk Liver ~ ¢ clotting factor leading to thromboembolism Endometrium - t risk of endometrial cancer 7. Raloxifene > Agonist action in bone, blood and liver = Antagonist in breast and endometrium - It is used in osteoporosis but major side effect is thromboembolism. 8. Tamoxifen > Agonist in bone, blood, liver & endometrium - So it has adverse effect of thromboembolism and endometrial carcinoma. $ Da Quint Cs CoyNew Drugs in Osteoporosis 2. PTH,.., analogues = Teriparatide ~ Abaloparatide “> Stimulate osteoblast 2 Strontium Ranelate = It is the only drug that has dual action ~ Stimulates — blast = Inhibits ~ clast 3 Denosumab -» Monoclonal antibody against RANK ligand so osteoclast will not be stimulated. ‘TESTOSTERONE “Testosterone |r « ~ reductase « © Finasteride Dutasteride DHT Flutamide 2 i 1 Androgen receptor <——___~ | _nilutamide Bicalutamide Prostate Growth Enzalutamide Abalutamnide ~ Androgen receptor blocking drugs are strong because they are not activated by DHT or testosterone, so these drugs are used in prostate cancer. > 5-a reductase inhibitor drugs are used in benign hyperplasia of prostate ~ Finasteride like drugs can also be used for androgenic alopecia ORAL CONTRACEPTIVE PILLS ~ Estrogen + progesterone combination is used 22 days + 7 days (for withdrawal bleeding) Adverse effect Mi Moderate Severe Nausea - Acne + Cholestasis - edema ~ Chloasma CVS — thromboembolisin ~ Recurrent headache = Weight = CNS ~ depression = Mastalgia gain = Ca- breast (when given in = Abnormal bleeding high dose) ~ Loss of withdrawal = Ca~ cervix, bleeding > OCPs decrease the risk of endometrial and ovarian cancer. Emergency Contraceptives OCPs - estrogen + progesterone Progesterone only pills — Levonorgesterol Mifepristone — 600 mg single dose All these drugs should be used with in 72 hrs. of unprotected sexual intercourse Ulipristal ~ 30 weg (can be used upto 120 hrs) eyo EBbPreptadderCNS PARKINSONISM ovsginaun Poungane o waren > Imbalance between dopaminergic and cholinergic activity ++ 2 types of drugs ave used dopaminergic and anticholinergic me Se™* Dopaminergic Drugs To t DA 4 types of drugs are used L - DOPA Most effective drug Drug Releasing Dopamine ‘Amantadine - this is the only drug that does not cause dyskinesia rather it is used to treat dyskinesia. Side effect: Livedo reticularis, ankle edema MAO & COMT Inhibitors a. Selegiline - MAO-B inhibitor b. Entacapone - COMT inhibitor Drugs Stirmulating The Receptors ~ Pramnipexole ~ Ropinirole > These are now drug of choice for Parkinsonism. Levedopa L-DOPA Bisod brain barrier, | -DOPA (in brain) CARBIODOPA ©+» DOPA Decarboxylase DA (can't across blood brain barrier) Peripheral side effects + Carbidopa / Benserazide: peripheral DOPA decarboxylase inhibitors > So peripheral side effects will decrease + More L-DOPA will enter the brain and efficacy will increase Side effects are more due to deposition of DOPA in the brain causing psychosis ie. abnormal behaviour and dyskinesia. These effects cannot be decreased by carbidepa ANTI-EPILEPTIC DRUGS We can treat epilepsy by Lt GABA I 4 Glutamate ltt, Ca channel blocking IV. Nat channel blocking |. By nereasing the GABA > To increase the GABA drugs used are4) Drug That Release GABA ~ Gabapentin, Pregabalin 6) By Inhibiting Metabolism = Vigabatrin > Causes visual field defects > It is used for infantile spas 6) Drug inhibiting Reuptake ~ Tiagabine “> These are GAT-I inhibitor 4) Drugs Acting On Receptors ~ Barbiturates ~Phenobarbital (do not have antidote) ~ Benzodiazepines - Diazepam = Lorazepam ~ Alprazolam > Antidote of benzodiazepines is Flumazenil 'N. By Decreasing Action of Glutamate Glutamate receptors AMPA "NMDA AMPA inhibitors drug NMDA inhibitor drug Peranapanel Felbarmate (Not commonly used b/c of bone marrow depression) Ml. Ca* Channel Blocker + T-Cet channel blocker ~ Ethosuximide ~ first line drug in absence seizures. (Cf valproate is not given in the options) IV. Na ~ Channel Blockers ~ Phenytoin = Carbamazepine ~ Topiramate (can cause renal stones) 0-4 craving of alcohol Uses \ O-obesity M-migraine prophylaxis B-Bipolar disorder Adverse Effect OF Phenytoin H- Hirsutism, hypertrophy of guns O- Osteomalacia ‘T Teratogenicity (Fetal Hydantoin Syndrome) M- Megaloblastic anaemia A= Arrhythmia (only in acute overdose) L- Lymphadenopathy I~ Insulin b-rtglucose K- Vit. k deficieney A~ Ataxia (only in acute overdose)Valproate > It has all the mechanism of action > Drug of choice for ~ General tonic clonic seizures ~ Absence seizures = Myoclonic seizures = Atonic seizures ~ LGS (Lennox-Gastaut Syndrome) — Side effects a) Hepatotoxicity It is caused by a metabolite of valproate. This metabolite is produced if given with carbamazepine like drugs thus more hepatotoxic. 6) Pancreatitis ) Polycystic ovarian disease Lamotrigine > Side effects = Steve Johnson syndrome / Toxic epidermal necrolysis New Drugs ~ Levetiracetam - Brivaracetam 3 These drugs bind to SV.A proteins Recently Approved Drug For Epilepsy ~ Cannabidiol act on CB,-receptor Stiripentol cause t GABA + LDH + These drugs are indicated in “Dravet syndrome” ANTI PSYCHOTIC DRUGS — Psychosis occurs due to excessive dopamine in the brain. = IF any drug acts by blocking D, receptor of dopamine, it is called typical antipsychotic drug. = IF drug acts by any other mechanism then it is called atypical antipsychotic drug Typical Antipsychotic Drug ~ Haloperidol ~ Chlorpromazine + If D2 receptors are blocked more than required then extrapyramidal symptoms are produced that include: ~ Acute muscular dystonia (earliest symptom) ~ Akathisia (most common) = Drug induced parkinsonisen = Malignant neuroleptic syndrome ~ Tardive dyskinesia (late symptom) F De Shinde GgEPS Brug Of Choice Dystonia Benzhexol | Akachisi Propranolol Parkinsonism Benzhexol MNS Dantrolene Tardive dyskinesia valbenazine ~ Da receptors decrease prolactin but when we block D, receptor it leads to hyperprolactinemia that lead to galactorrhea & infertility. Atypical Anti-Psychotic Drugs Clozapine Paliperidone Olanzapine Ziprasidone Quetiapine Lurasidone Asenapine operidone All these drugs cause Lipodystrophy Syndrome (Max with Clozapine) Clozapine can cause Agranulocytosis All antipsychotic drugs cause dry mouth but clozapine causes sialorrhea. Most common side effect of clozapine is sedation Risperidone: Maxinnum D2. receptor blocking property > Among the atypical drugs it has highest risk of causing extrapyramidal symptoms as well as hyperprolactinemia. BIPOLAR DISORDER > Drug of Choice (in general)~ Lithium > Drug of Choice (in pregnancy)-Atypieal antipsychotic drugs Lithium L - Leucocyte ~ tnerease = Tremors (most common) = Hypothyroidism ' e H ' u M ~ Mother's in pregnancy avoid it because it causes Ebstein anomaly in baby (Congenital tricuspid atresia) ANTIDEPRESSANT DRUGS Antidepressants, Typical Atypical (tSHT) (other)Typical Drugs > 2 main mechanism of action ) MAQ-A inhibitor Mocloberide ¢——— Reuptake inhibitors ——, Non Selective Selective Inhibits reuptake of both Inhibits reuptake of only SHT ST Tricyclic Serotonin and Antidepressant Norepinephrine (Tea) Reuptake inhibitors (SNRI) Imipramine Venlafaxine Clomipramnine Duloxetine Desipramine Milnacipran Amitryptyline Nortryptylinne = These drugs are not ~ These are drug of choice Used now a days for severe depression Fluoxetine Paroxeine Dapoxetine Sertraline Citalopram Escitalopram Fluvoxamine > These are drug of choice for mild to moderate depression and neurotic conditions like: -ocD Bulimia Phobia — Side effects = Nausea ~ Anxiety ~ Sexual side effects like anorgasmia = Delayed ejaculation Discontinuation Syndrome “+ When antidepressants are stopped they lead to discontinuation syndrome so they should be gradually stopped + Fluoxetine: very long acting drug with minimum chance of causing discontinuation syndrome F Be bint Re GayopioiDs + Morphine like drugs + act on wk , 8 receptors Action On u ~ Receptors S- Sedation A — Analgesia C- Constipation R ~ Respiratory depression U ~ Euphoria 'M ~ Miosis (PIN POINT PUPIL in opioid overdose) Kappa Receptors > Can cause Dysphoria > Opioids can be used for any severe pain but they are contra indicated in biliary colic. > Loperamide : Used for the treatment of diarrhoea because they decrease Gi motility ‘Types OF opioids 9) Stimulate all uk, 8 receptors + €4g, Morphine, Pethidine, Tramadol Partial Agonist — Partial agonist at y receptor ~ Buprenorphine - produces ceiling effect on respiratory depression. iii. Agonist-Antagonist > k agonist 1. antagonist ~ Pentazocine: results in dysphoria, hallucination and bad dreams iv. Opioid Antagonist ~ Naloxone ~ short acting, LV. > Naltrexone - long acting, orally used in cases of maintenance. + Naloxone is drug of choice in acute cases of opioid poisoning. 2. Cytotoxic Drugs > Non specific > These drugs will kill the cells > 4 important side effects 4) Bone marrow depression &) Alopecia ©) Diarrhoea 4) Hyperuricemia Different Groups OF Cytotoxic Drugs ) Alkylating Agents {f= tfosfamide Bus ~ BusulfanNot - Nitrosourea Present ~ procarbazine Take —- Temozolomide My - Melphalan Cyele ~ Cyclophospharaide i) Anti-Metabolites 3 types a. Folic acid inhibitors 6. Purine like drugs c. Pyrimidine like drugs Folic Acid inhibitors Methotrexate ~ Pemetrexed ~ Pralatrexate Purine Like Drugs 6-mercaptopurine thioguanine Cladribine Fludarabine Pyrimidine Like Drugs ~ 5-fluorouracil Capecitabine - Gercitabine ~ Cytavabine + All The Antimetabolites Are S-Phase Specific Special Side Effects OF Cytotoxic Drugs Cisplatin = Ototoxie ~ Nephrotoxie ~ Vomiting (Cisplatin is most emetogenic drug) Vinblastin = release of ADH + SIADH Bleornycin — pulmonary fibrosis, Aagellate pigmentation of the skin Busulfan ~ pulmonary fibrosis Doxorubicin = Cardiotoxie Daunorubicin Cardiotoxie @- mercaptopurine Hepatotoxic 6- thioguanine — Hepatotoxie Cyclophosphamide — Cystitis (Hemorrhagic) Vineristin i ~ peripheral neuropathy 4 Targeted Anti-Cancer Drugs i. Monoclonal antibodies fi, Small moleculesMonoclonal Antibodies Cetuximab used in colorectal cancer. Rituximab used in Non-Hodgkin's lymphoma Trastuzumab- Breast cancer - It is Cardiotoxio ~ Antibody against HER -2/NEU Antigen ii. Small Molecules & Proteasome inhibitors = Bortezonsib txazomib = Carfitxomib + These drugs ave used for treatment of multiple myeloma 6. Tyrosine ~ Kinase inhibitors > Allare given orally Drugs used in CML 1 = imatinib - DOC for CML N = Nilotinib D - Dasatinib Drugs used in GIST S~ sunitinib 1 = imatinib (DOC) R ~ Regorafenio Drugs used in Lung Cancer E - Erlotinib € ~ Ceritinib G - Geftinio + Erlotinib & gefitinib inhibit EGF Receptors. Drugs used in renal cell Carcinoma P - Pazopanib A~ Axitinib S ~ Sorafenib S ~ Sunitinib For HCC (Hepatocellular carcinoma) - Sorafenib (DOC) Drugs used for breast cancer- Lapatinib (Act against HER-1 and HER -2 receptors) Drugs affecting flow of blood Drugs affecting cells Drugs Affecting Flow OF Blood 2. Drug inhibiting the thromboxane — A2 ~ Aspirin 2. Drug inhibiting ADP receptors Irreversible inhibitorsClopidogrel Ticlopidine Prasugrel sy RECEPTOR Fast acting drug 1, tor > Contraindicated in stroke aur Reversible inhibitors esto = Ticagrelor PLATELET AGGREGATION = Cangrelor inn . Drug inhibiting GP Il-b/til-a Receptors: @ Jane @innive oP a ANTIPLATELET = Abciximab - Tirofiban - Eptifibatide Anti-Fibrin/ Anti-Coagulants oral Injectable 4 _— i. Vit. K antagonist Indirect lla inhibitors Direct tla inhibitors = Warfarin - Unfractionated heparin| | - Hirudin ii, Factor Xa inhibitor - LMWH ~ Lepirudin = Rivaroxaban ~ Fondaparinux ~ Bivalirudin ~ Apixaban ~ Argatroban - Edoxaban = Melagatran - Betrixaban iii. Factor lla inhibitor = _Dabigatran warfarin > Very slow acting, so only used for maintenance > Contraindicated in pregnancy as leads to foetal warfarin syndrome > Monitoring is done by PT/INR > Overdose can lead to bleeding. ‘Treatment OF Bleeding Due To Warfarin > Factor lla, Vila, Xa, Xa Fresh Frozen plasma IP bleeding has not started & there is tendency For bleeding due to warfarin then Rx of choice is Vitamin K. It is metabolized by microsomal enzymes So it is prone to drug interactions ~ Braymes inducers 4 warfarin action = Enzyme inhibitors- + warfarin action Indirect A inhibitors > Injectable > Heparin group of drugs > They stimulate anti-thrombin 3 Unfractionated Low Molecular Weight Heparin Heparin (LMWH) + + ta xaQ xa®Fast acting so can be used for acute conditions. It is anticoagulant of choice in pregnancy, Monitoring is done by aPTT. Protamine Sulphate is Antidote for heparin. Metabolized by non- microsomal enzymes so doesn't cause drug interactions. It can also lead to thrombocytopenia ie. called HIT (heparin induced thrombocytopenia). Treatment for HIT syndrome is divect thrombin inhibitors. Drugs Affecting Cells OF Blood Rec > Growth factor for RBC is erythropoietin ~ IF we give erythropoietin from outside in form of Darbepoetin it will increase the formation of RBC Darbepoetin Uses + Anemia due to chronie renal failure > Bone marrow suppression wee Growth factor for WBC are G-CSF & GM-CSF G-CSF Drug (Granulocyte Colony Stimulating Factor) Filgrastina Peg ~ Filgrastim GM-CSF Drug (Granulocyte Monocyte Colony Stimulating Factor) Sargramostia Molgramostim These drugs are used for anti-cancer drug induced neutropenia i. Platelet Major growth factor in platelet is 1L-2.2 Injectable Drug That increase Platelets Oprelvekin - Recombinant IL-11. Oral Drug That increase The Platelets Thrombopoietin receptor agonist Eltrombopag ~ ITP Avatrombopag d in liver dis Lusutronbopag f US4 i liver disease PEPTIC ULCER DISEASE PARIETAL 1. Drug inhibiting the M, receptor cent > Pirenzepine 2 Drug blocking the H, receptor > Cimetidine > Ranitidine 3 Prostaglandin > Misoprostol - it is chemically PGES but work like PGE > Most specific drug for NSAIDS induced peptic ulcer but it is not the drug of choice for any ulcer. DOC will be proton pump inhibitors. BPreptadder HISTAMINEProton purap inhibitors Omeprazole Esomeprazole Pantoprazole Lansoprazole Rabeprazole DOC for Peptic Ulcer Disease DOC for GERD (Gastro — oesophageal reflux disease) DOC for ZES (Zollinger — Ellison syndrome) They ave the strongest acid inhibiting drug. All PPI are prodrugs. They are enteric coated “They are irreversible inhibitors of the proton pup. So they work like hit & run drugs They inhibit CYP2C24. Due to inhibition of CYP2C24, Clopidogrel cannot be activated and thus cannot be given with PPI. Pantoprazole ~ Have minimums inhibiting Rabeprazole 3 effect on CYP2CL9 Method Of Decreasing Peptic Ulcers Inibit acid Antacids (Fastest pain relievers in peptic ulcers) Eg. Al(OH), Mg(OH). Uleer protective > Sucralfate: cannot be given with antacid because they require pH<4 to polymerize Colloidal bismuth subcitrate Anti H. pylori > Triple drug therapy PPI + 2 Anti-microbial drugs 4 Metronidazole Amoxicillin Any 2 out of Clarithromycin = CAP ~ Clarithromycin + Amoxicillin + PPI + commonly used combination in India ANTI ~ EMETIC DRUGS Anticholinergic Drugs Hyoscine used for motion sickness. H, Innibitors Promethazine - motion sickness Doxylamine — morning sickness in pregnancy SHT, Blockers Ondansetron Granisetron‘Tropisetron. Palonosetron (most potent) > These are drug of choice for chemotherapy induced vomiting. /. Neurokinin antagonist (NK,antagonist / Substance-P antagonist) Aprepitant Fosaprepitant Rolapitane Netupitant + These are drug of choice for delayed vomiting D, Antagonist Metoclopramide Domperidone Metoclopramide Domperidone Can cross blood brain barrier = Cant cross Additional action to block 5 HTS receptors | — It doesn't It can cause extra pyramidal symptoms = It will not cause like muscular dystocia It is more strong antiemetic + Drug of choice for levodopa induced vomiting than domperidone INFLAMMATORY BOWEL DISEASE Ulcerative Colitis > Drug of choice is S-ASA preparation Eg. Sulfasalazine, Mesalamine > IF these are not effective then steroids are used. Crohn's Disease > Drug of choice is steroids > TNF-a inhibitors are used in steroid resistant cases A> Adalimumab C= Certolizumab E- Etanercept IN-Inflicimab Goli-Golinumab > These TNF - ainhibitors are contraindicated in TB and Hepatitis B. Respiratory Systema Asthma» Type | hypersensitivity reaction Drugs 1. Bronchodilators -» 3 groups are used a B, agonist 6. M, blockers © PDE inhibitors 4. B, Agonist > DOC for acute attack asthma Salbutamol, Terbutaline + Short acting 8 — agonist (SABA) Salmetrol, Formoterol +> Long acting B — agonist (LABA) EBPreptadier> SABA. - Fast acting = Used for acute condition + LABA. - Used as prophylaxis - Formoterol used for acute attack also b/e itis Fast acting Adverse Effect OF B, Agonist T= Tremors (M/C) “r= Tachyeardia T= Tolerance (mainly due to LABA) TT wave changes in ECG (due to 4K°) Ms Blockers = Ipratropium = Tiotropium “y These are used in patients where we can'tusef,~agonist like i person ison p blocker therapy. PDE inhibitor = Theophylline © Given orally or iv, not given by inhalation. Leukotrienes Phospholipids [P-A@ Arachidonic acid coxr/ tox © Prostaglandins Leukotriene (LT) LT Receptor © (Bronchoconstriction) a. Drug Inhibiting PLP-A2 - Steroids + in acute condition role of steroids is to increase sensitivity for B,—agonist LOX inhibitors - Zileuton LT- Receptor inhibitor = Zafirlukast = Montelukast Mast Cell Stabilizers = Nedocromil ~ Cromoglycate = Ketotifen > Used to prevent asthma Monoclonal Antibody Against IgE = Omalizumab > Used to prevent asthmaImmuno Suppressant Drugs 2. Glucocorticoids 2. Drugs targetting the calcineurin pathway 4. Calcineurin inhibitors > Inhibit the formation of IL-2 = Cyclosporin = Tacrolinnus NFAT-PO4 (inactive) (Nuclear Factor of activate T-cell) = Side effect of Cyclosporin / Tacrolimus Calcineurin@}, Nephrotoxic Hepatotoxie Neurotoxie tk t glucose t lipia 1BP Note -» Cyclosporine causes hirsutism but Tacrolimus does not cause hirsutism 6. IL-2 receptor inhibitors = Daclizunab ~ Basilixima ‘m-Tor inhibitor ~ Sirolimus “> It inhibits the action of IL-2 Side effect - Causes BM suppression 3. Monoclonal antibody > 1L ~ 3 receptor antagonist — Anakinra > TNF ~ a inhibitors > IL = 6 Receptor antagonist ~ Savilumnab Co-stimulation inhibitors ~ Abatacept Dephosphorylated NFAT (active) | 2 | IL-2 Receptor @ mTOR © { Inamnunity . Osmotic Diuretic It can work anywhere in nephron + Eg. Mannitol Uses: cerebral edema ~ acute congestive glaucoma > Here, main beneficial effect is osmotic effect ++ Contraindication = Cerebral haemorrhage = Pulmonary edema ~ Acute renal failure 2. Carbonic Anhydrase inhibitors “> Works on proximal tubulesAcetazolamide = Dorzolamide - Brinzolamide Na‘ HCO, are not absorbed and are excreted in the urine Na+ - diuretic effect HCO, - urinary alkalosis Metabolic acidosis tt causes maximnurn hypokalemia ‘They cause paraesthesia. Uses G- Glaucorna (angle closure glaucorna) A~ Alkalinize urine M- Mountain sickness E~ Epilepsy (catamenial epilepsy) 3. Loop Diuretics And Thiazides + Loop diuretics inhibit Na-K-2Cl pump — Thiazides inhibit Na-Cl purmp Loop Diuretics ~ Furosemide, —Torsemide | High ceiling and high efficacy ~ Bumetanide, Thiezides > Work in distal tubules + Side effect Loop diuretics and Thiazides Nai 1 glucose a 4 lipids Mg" uric acid 4H Effects On Ca” Is Different > Loop loses Car so causes | Ca" — Thiazides causes + Ca” — Loop diuretics are used in hypercalcemia & Thiazides are used in osteoporosis & recurrent renal stones. + Thiazides are drug of choice for nephrogenic diabetes insipidus. Drugs Working in Collecting Duct <——— £ Sparring Diureties ———, Epithelial sodium Aldosterone receptor Channel blockers (ENae Blockers) inhibitors Amiloride Spironolactone ‘Triamterene Eplerenone Use: cirrhosis Spironolactone and its congeners are only diuretics that do not work from the luminal side of the nephron and work from the basolateral side and inhibit the receptor. F Do Ghind Ret CgAnaesthesia FO Local Muscle General Anaesthesia Relaxant Anaesthesia LOCAL ANAESTHETICS Ester Amide ~ Cocaine ~ Lignocaine (most commonly used LA) ~ Procaine ~ Bupivacaine (Cardiotoxie) ~ Chlorprocaine (Shortest acting) _- Prilocaine (Meth-Hb) ~ Tetracaine = Etidocaine = Benzocaine ~Dibucaine (Longest acting) > Cocaine - Only LA that causes Vasoconstriction > All other LA cause vasodilation Adrenaline ~ It is used with LA for 2 purposes 2. To make it long acting 2. To decrease the systemic toxicity SKELETAL MUSCLE RELAXANTS 2 Types 2. Centrally acting muscle relaxant 2. Peripheral acting MR 1. Centrally Acting Muscle Relaxant ~ Either they increase the activity of GABA or they put the brakes by stimulating a, receptors ~ Drug Stimulating GABA, Receptor = Diazepam. + Drug Stimulating GABA, Receptors > Baclofen > Drug Stimulating a, Receptor > Tezanidine Peripheral Acting Muscle Relaxant 2 types Directly acting muscle relaxant > Dantrolene- drug of choice for malignant hyperthermia 6. Drugs Acting At Neuromuscular Junction > Act on Nim receptor at neuromuscular junction > Two types: i. Depolarizing MR. ‘i. Non depolarizing MR / competitive MR Depolarizing MR - Succinylcholine Shortest acting MR C/ in werve and muscle injury because it can cause + K° Hyperthermia can occur. {t is strong MR that causes fasciculations which are responsible for post-operative muscle pain. To prevent this non-depolarizing MR are used. ‘Non — Depolarizing MR ~ _d-Tubocurarine->'t releases lot of histamine that leads to vasodilation & bronchoconstriction.- Atracurium 481 ~ Cis-atracurium |, 4 Histamine Release = Mivacuriunn Both Atracuriumn & Cis-atracurium undergo Hoffmann elimination thus used in liver & kidney damage. Cis-atracurium causes less release of histamine as compared to the Atracurium. Mivacuriurn is shortest acting non-depolarizing muscle relaxant. (Overall shortest acting is suceinyleholine) No Histarnine Release by MR Pancuroniurn Pipecuronium | Drug of choice in patients Vecuronium —# with bronchial asthma Rocuronium Reversal Agents > Neostigmine - Competitive inhibitor of MR. = Stimulates muscarinic receptors that lead to side effects. > Sugammadex = Faster acting = Causes allergy to many people so not commonly used. GENERAL ANAESTHESIA Iintravenous/Inducing agents |. Thiopentone it. Propofol iii, Etomidate iv. Ketamine i Thiopentone - Barbiturate - Short acting because of redistribution = Fast onset Propofol = Drug of choice for Day care surgery Other Drugs used for day care surgery Dr ~ Desflurane ‘Manmohan ~ Midazolam Singh ——_~ Sevoflurane ls = Isoflurane A ~ Alfentanit Prime ~ Propofol Minister ~ Mivacurium iii. Etomidate + Drug of choice for cardiovascular surgery. > Side effect - Adrenal suppression iv. Ketamine k - kids E — Emergence reaction 1 ~ Act at Thalamocortical junction + Dissociative Anaesthesia 7 Do Gobind Rat Garg— Analgesic (Injection of all the anesthetic agents is painful except ketamine) ~ Meals (Full stomach) = nereases BP / IOP / ICP N= NMDA blocker E — Excellent bronchodilator, preferred in asthmatic patients ~ Anesthetic agent of choice in a patient with shock as it tes BP > 1 IOP ~ So avoided in glaucoma patients > TICP — Avoided in Head Injury patients. 2. Inhalational / Maintenance Anaesthetic Agents ~ Ether = Chloroform = tnflannmable = Cyclopropane ~ Not used now ~ Trilene Modern inhalational Agents -NO = Sevoflurane ~ Halothane ~ Desflurane - Enflurane ~ Methoxyfturane = Isoflurane ~ Xenon No > Maximum MAC 204% Least Potent drug > Mainly used for its analgesic action Halothane ~ Sensitizes heart to adrenaline > Contraindicated in pheochromocytoma surgery. Enflurane > C/I in Seizures Isoflurane > Used in cardio and neurosurgery Sevoflurane -» Preferred in children. Desflurane > Most irritant to respiratory pathway Methoxyflurane ~ Lowest MAC, most potent. > Maximum blood gas partition co-efficient means it is slowest acting drug. > Has lot of fluoride so can lead to nephrotoxicity Xenon ~+ Ideal anaesthetic agent > Fastest acting because low blood gas partition co-efficient > High MAC > Required in 70% concentration > Safe to almost all the organs > Analgesic as well as MR. > Not easily available ~ It is very costly so not commonly usedPulmonary Hypertension 2. Endothelin Antagonists (DOC) ~ Bosentan = Ambresenton = Macisentan IF these are not effective then drugs used are Sildenafil, Tadafil 2. Prostaglandins — lloprost (Not given orally) 3. Selexipag (Prostacyclin Agonist) = PGI, Agonist ~ Given orally Anti-Obesity Drugs L = Lorcaserine (SHT) / Liraglutide (GLP-2 analogue) © = Orlistat (Intestinal lipase inhibitor) S - Sibutramine (Not used because of cardiac side effects) T = Topiramate Weight [Drugs Used For Smoking] + Nicotine = Vareniziline (DOC for smoking cessation) > Bupropion (Not commonly used B/C it increases the risk of seizures.) Erectile Dysfunction P ~ Phosphodiesterase inhibitor (PDE inhibitor) Sildenafil (DOC) Tadalafit PDE Inhibitor should not be given to the patients taking nitrates A ~ Alprostadil (intracavernosal injection) Experimented drugs not used clinically A ~ Alpha blocker (Phentolarine) P ~ Papaverine “Anti-Aleohol Drugs None — Naltrexone OF — - Ondansetron The — - Topiramate Above — Acamprosate Hyperkalemia = It causes cardiae changes like arrhythwaias. > Treatment of hyperkalemia in emergency ~ Glucose insulin infusion ~ Salbutarnol = 10% Calcium gluconate (Reverse the changes of ECG) ~ K’ Binding resins — used for long term treatment.