Drugs Affecting ANS Type Cholinergic Agonist Drugs Direct Acting: Acetylcholine Bethanechol Carbachol Pilocarpine Indirect Acting:

Physostigmine Neostigmine Organophosphorous compound Atropine Ipratropium Trimethaphan Vecuronium Tibocuararine Pancuronium Noradrenaline Adrenaline Oxymetazoline Xylometazoline Phenyephrine Dobutamine Salbutamol Dopamin Prazosin Terazosin Propanolol Atenolol Uses/ Functions - Decreases Heart rate and Blood Pressure - Increases GIT motility & secretion - Relaxation of sphincters - Increases respiratory secretion Inhibit cholinesterase enzyme Adverse Effect

Cholinergic Antagonist

Anti-muscarinic Atropine: use in bradycardia and organic phosphate poisoning Ganglion Blocker Neuromuscular blocker

Sympathomimetics

Facilitate/mimic actions of sympathetic nervous system

Anti-adrenergic (sympatholytic)

adrenergic blocker adrenergic blocker

Neuromuscular Blocking Agents Type Competitive, nondepolarising agents Drugs Curare Pancuronium Gallamine Mivacurirum Atracurirum Vecuronium Succinylcholine Suxamethonium Uses/ Functions - Compete with Ach for binding receptor Adverse effects - Muscarinic blocking - Histamine release - Apnea - Hypotension

Non-competitive, depolarising agents

Desensitize receptor for Ach

Bradycardia Hyperkalemia Hypotension Muscle pain Apnea Stroke Cerebral palsy Multiple sclerosis

Direct-acting muscle relaxant

Neostigmine Dantrolene Dantrium Botulinum toxin A

Treatment of Myasthenia Gravis Inhibit muscle release Treatment of Malignant Hyperthermia Inhibit release of Ach from presynaptic nerve Cosmetic use: removal of facial wrinkles

NSAIDs Type Non-selective COX inhibitor Drugs Aspirin Ibuprofen Piroxicam Uses/ functions Aspirin: - Anti-inflammatory (3-6 g/day) - Antipyretic, Analgesia (1 g/day) - Anti-platelet (75-325 mg/day) Analgesic Antipyretic Selectively inhibit COX-2 Adv over non-selective COX inhibitor: Low chance of bleeding, less gastric mucosal damage Inhibit COX-2 but still can inhibit COX-1 Adverse Effects - Peptic ulcer - Decrease renal blood flow - Allergic reaction (leukotrines) - Angioedema - Delay labors - Depletion of glutathione conjugation in children and alcoholic Enhanced CVS risk Salt & water retention Less anti-inflammatory action

Paracetamol

Selective COX-2 inhibitor

Celecoxib Itoricoxib Parecoxib Nimesulide Meloxicam Nabumetone

Refential COX-2 inhibitor

Anti-arrhytmic Drugs Type Class Ia Drugs Quinidine Procainamide Disopyramide Lidocaine Tocainide Flecanide Uses/ functions - Block Na channels with moderate potency - Block K channels - For supra-arrhythmia and ventricular arrhythmia - Block Na channels weakly - only for ventricular arrhythmia, after MI Block Na channels markedly Weakly block Ca channels For supra and ventricular arrhythmia Blocking norepinephrine and epinephrine Slows AV node conduction Inhibit K gates Used in atrial fibrillation and flutter use in bradycardia use in heart block slows AV conduction Adverse effects - Pro-arrhytmic - Visual disturbance - Abdominal pain - Dizziness - Seizure - Drowsiness - Blurred vision - Hallucination - Depression

Class Ib

Class Ic

Class II Class III Non-classified Non-classified

Esmolol Amiodarone Sotalol Digoxin Atropine Adenosine

Pro-arrhytmic Ventricular arrhythmia bradycardia

malaise facial flushing chest pain

Antihypertensive Drugs Type 1-adrenoceptors antagonist Drugs Selective: Prazosin Terazosin Doxazosin Non-selective: Phenoxybenzamine Phentolamine Selective 1: Atenolol Esmolol Acebutolol Metoprolol Non-selective: Timolol Propanolol Vasodilator: Carvedilol Labetolol Pindolol Nebivolol Partial agonist: Acebutolol Pindolol Enalapril Lisinopril Peridopril Uses/ functions - Block 1-adrenergic receptors - Reduces muscular tone of arterioles - Dilatation of veins Adverse effects - Postural hypotension - Nausea

Reflex tachycardia

-adrenergic antagonist

Reduces release of renin from juxtraglomerular cells, thus reducing output of Angiotensin II

Bradycardia

Reduces heart rate and contractility

Asthma Nightmare Bradycardia

Block -adrenergic receptors Release nitric oxide Dilates muscular vessels

Less bradycardia risk

ACE inhibitor

Inhibit ACE Reducing Angiotensin II, aldosterone Increases bradykinin Bring about vasodilatation Reduces total peripheral resistance Reduces sodium retention

Cough Mild hypotension

Type 2-adrenoceptor agonist

Drugs Clonidine Methyldopa

Uses/ Functions - Inhibition of noradrenaline release - Causes vasodilatation

Diuretics

Aldosterone antagonist: Spironolactone Eplerenone Thiazide

Inhibit action of aldosterone

Adverse Effects - Dry mouth - Sedation - Male sexual dysfunction - Tiredness - Depression - Postural hypotension - GIT disturbance - Hyperkalemia - Hyponatremia Hypokalemia hypocalcemia Cough Dizziness Hyperkalemia Flushing Headache Reflex tachycardia Reflex tachycardia except for amlodipine

Angiotensin receptor inhibitor Vasodilators

Irbesartan Telmisartan Valsartan K channels opener: Minoxidil CCB: Amlodipine Nifedipine Diltiazem cGMP activator: Hydralazine Nitrovasodilator: Sodium nitroprusside

Activation of ATP-regulated potassium channels in arterioles Inhibit calcium entry Decrease total peripheral resistance inhibit angiotensin receptor bring about vasodilatation reduce total peripheral resistance Bring about vasodilation

Tachycardia Vomiting Nausea Headache Dizziness Abdominal pain

Treatment of Myocardial Infarction Type Organic nitrates Drugs Nitroglycerine Isosorbide dinitrate Isosorbide mononitrate Dihydropiridines: Amlodipine Nifedipine Verapamil Diltiazem Aspirin Clopidogrel Heparin Warfarin Ranozaline Atenolol Metoprolol Propanolol Timolol Uses/ Functions - Causes vasodilatation - Decreases preload and afterload Vasodilatation Adverse Effects - Headache - Reflex tachycardia - hypotension - Oedema - Wheezing - Hypotension - Headache - Reflex tachycardia - Cause MI if use with beta blocker

Calcium channel blockers

Anti-thrombotic & lipid-lowering drugs

Vasodilatation Decrease myocardial activity Decreases heart rate Prevent thrombosis

Late Na channels blocker -blocker

Decrease intracellular Ca overload in myocardium Decrease heart rate Decrease myocardium contractility

Torsades de pointes Hypotension Cause serious MI if use with verapamil/ diltiazem

Lipid-lowering Intervention Type HMG-CoA inhibitor Fibrates Drugs reductase Atorvastatin Rosvastatin Simvastatin Gemfibrosil Fenofibrate Bezafibrate Nicotinic acid Uses/ functions - Decrease LDLC by 20-55% Adverse effects - Headache - Bowel upset - Muscle tenderness - Myalgia - Hepatitis - Gall stones - Rashes - Skin flushing - Itching - Vomiting - Liver dysfunction

Decrease TGL by 20-50%

Niacin

Decrease TGL by 20-50% Increase HDLC by 20-35%

Ezetimibe

Ezetimibe

Decrease LDLC by 15-20% Use with statin to reduce AE of statin

Treatment of Congestive Heart Failure Type Diurectics Drugs Frusemide Spironolactone Uses/ Functions Adverse effects - Decrease ECF volume - Decrease preload - Block effect of aldosterone from damaging heart, kidney and vessels - Decrease aldosterone effects - Vasodilatation - Decrease cardiac remodelling Venous dilatation

Vasodilators

-blocker

Cardiac glycosides Parental Inotropic drugs

ACE inhibitors: Enalapril Ramipril Lisinopril Nitrovasodilators: Nitroglycerine Isosorbide mononitrate Isosorbide dinitrate Direct vasodilators: Hydralazine Metoprolol Bisoprolol Carvedilol Digoxin Digitoxin & Dopaminergic agonist: Dopamine Dobutamine Phosphodiesterase: Milrinone Inamrinone

Arterial dilatation Decrease myocardium activity Decrease arrhtymia Decrease cardiac remodelling Inhibit Na/K pump SA & AV node inhibiton Inotropic effect Vasodilation For acute heart failure

Pharmacology of Asthma Type 2-adrenoceptor agonist (bronchodilators) Drugs Salbutamol (short acting) Salmeterol (long acting) Formeterol (long acting) Uses/ Functions Adverse effects - Salbutamol: - Tremor Increase mucus clearance and decrease mediator - tachycardia release - hyperkalemia - Salmeterol, formeterol: In nocturnal asthma - inhibiton of PDE enzyme - narrow margin of safety - prevent degradation of cAMP - nausea - inhibit cell surface of adenosine receptors - vomiting - bring about bronchodilation - tremor - increased mucociliary clearance - insomnia - tachycardia - relax bronchospasm - dry mouth - decreased mucus secretion - competitive antagonist at CysLT receptor - GIT disturbance - inhibit action of leukotrienes - Dry mouth - relaxes bronchial smooth muscle - headache - well tolerated especially for children - depress inflammatory response - dysphonia - inhibit leukotrines - oral thrush - cytokines and prostaglandins formation - systemic penetration inhibit degranulation of mast cell cough transient bronchospasm throat irritation high cost

Methylxanthine (bronchodilators)

Theophylline Thebromine Caffeine

Muscarinic antagonist (bronchodilator) CysLT receptor antagonist (bronchodilator) Glucocorticoids

Ipratropium Tiotropium Montelukast Zafirlukast

Mast cell stabilizers

Beclometasone Budesonide Prednisolone Cromoglycates Cromolyn Nedocromil Omalizumab

Anti-IgE

act by complexing IgE prevent binding of IgE to effector cells

10

Pharmacology of Cough Type Pharyngeal demulcents Drugs Lozenges Cough drops/syrups Glycerine Sodium iodide Potassium iodide Guifenesin Ammonium salts Syrup Ipecac Bromhexine Opioids: Codeine Pholcodeine Non-opiods: Noscapine Dextrometrophan Diphenhydramine Promethazine Chlorpheniramine Benadryl Uses/ functions - Sooth mucus membrane of throat - Reduce afferent impulses from pharyngeal mucosa - Increase bronchial secretion Adverse effects Disadvantages: short-acting inflamed/irritated

Expectorant

Mucolytics Antitussives

Induce thin copious bronchial secretion Reduce viscosity of bronchial secretion Act in CNS to raise threshold of cough centre

Constipation Sedation Addictive

Advantages: no constipation, sedation, no addictive

Antihistaminic

Relieve allergic rhinitis syndrome Relieve itching and swelling

Decongestants

Ephedrine Pseudoephedrine Oxymetzoline Zylometazoline

Vasoconstriction of nose vessels Reduction in oedema and secretion

Sedation Fatigue Dry mouth Fatigue Dizziness Sedation Nausea Headache

11

Haematinics Type Iron supplement Drugs Oral: Ferrous sulphate Ferrous gluconate Ferrous fumarate Parentral: Iron dextrane Iron sucrose Sodium ferric gluconate Cynocobalamine Hydroxycobalamine Folate Uses/ Functions - For iron-deficiency anaemia - Parenteral iron: For oral iron not tolerated Failure to absorb iron due to gastrectomy Chronic bleeding Adverse Effects - Epigastric - Nausea - Staining teeth

B12 supplement Folic acid supplement Erythropoietin

For B12-deficieny anaemia

Erythropoietin

For folic acid deficiency Folic acid deficiency in pregnant causes neural tube defects Essential for erythropoiesis -

Uses of folic acid in B12 deficiency may worsen the condition Never use alone in B12-defeciency

Increases blood viscosity Increase clot formation Hypertension

12

Immunosuppressant Drugs Type Calcineurin inhibitor Drugs Ciclosporin Uses/ Functions - Binds to cyclophilin - Inhibit IL2 production - Inhibit activation of mitogen activated protein kinases Adverse effects - Nephrotoxicity - Hypertension - Fluid retention - Tremor - Headache - Hyperlipidemia - Pleural and pericardial effusion - Cardiomyopathy children Bone marrow suppression Hair loss Vomiting Fever Hypotension GI ulceration Bleeding Diarrhoea Vomiting

Tacrolimus Antiproliferative agents Azathioprine

Binds to FK-binding protein-12 Inhibit IL2 production Metabolized to 6-mercaptopurne Inhibit T-cell DNA synthesis Supressing cell and antibody immune response

Mycophenolate Mofetil

IL2 receptor antibodies

Basiliximab Daclizumab Sirolimus

mTOR inhibitor

Corticosteroids

Cortisol Budesonide

Deprive guanine to lymphocytes by inhibit nucleotide converting enzymes Block IL2 receptor CD4 T-cells no longer can be activated to produce interleukin Binds to FK-binding Protein-12 Inhibits cytoplasmic kinase mTOR Retarding mitogenic protein & DNA synthesis Supress promotion of IL2 expression by calcineurin

13

Drugs affecting Blood Coagulation Type Fibrinolytics Drugs Streptokinase Urokinase Alteplase Injectable: Heparin LMW Heparin (enoxaparin, dalteparin, tinzaparin) Oral route: Warfarin Uses/ Functions - Cleaves plasminogens to plasmin - Plasmin lyses fibrin to fibrin degradation products - For MI and massive pulmonary embolism - Accelerates antithrombin III through IV and subcutaneous - LMWH: selectively inhibit factor Xa less frequency of bleeding lower risk of osteoporosis lower incidence of thrombocytopenia - inhibits Vitamin K reductase - Vitamin K dependant carboxylation of factor II, VII, IX, X cannot occur - 5 days of action onset - Aspirin use because other NSAIDs bind reversibly with platelet - Inhibit COX enzyme in platelets - Selectively inhibit Thromboxane A2 - Inhibit purinergic receptor - Inhibit activation of glycoprotein IIb/IIIa on surface of platelets - Inhibit glycoprotein IIb/IIIa receptors - Inhibit platelets aggregation Adverse effects - Systemic lytic state - Hemorrhage Bleeding Thrombocytopenia osteoporosis

Anti-coagulants

Anti-platelet

Aspirin (75-325mg/day) Clopidogrel Abciximab

Bleeding Teratogenic effect to pregnant mother If overdose: just use blood transfusion GI bleeding GI irritation Haemorrhage Abdominal discomfort Haemorrhage Nausea Vomiting Hypotension Nausea Vomiting Bleeding

Anti-fibrinolytic

-aminocaproic acid tranexaemic acid

Inhibit plasminogen activation Preventing fibrinolysis

14

Treatment for Neoplastic Diseases Type Alkylating agents Antimetabolites Drugs Cyclophosphamide Procarbazine Methotrexate 6-mercaptopurine 5-flurouracil Cystosine arabinoside Topotecan Irinotecan Epiphodophyllotoxins Etoposide Teniposide Vincristine Vinblastine Paclitaxel Doxorubicin Epirubicin Uses/ functions - Cell cycle non specific - Attach to DNA bases and interfere with DNA replication - S phase specific - Inhibit synthesis of DNA bases Adverse effects

Camptothecin analogs

S phase specific Interference with DNA cleavage

Anti-mitotic drug

Anthracycline antibiotics

M phase specific Binding tubulin Inhibit polymerization of microtubules Inhibit transcription Inhibit DNA replication

Cytoxicity

Cytotoxicity

15

Drug Treatment of Acid Peptic Disease Type H2 receptor blockers Drugs Cimetidine Ranitidine Famotidine Nizatidine Uses/ Functions - Decrease 60-70% acid secretion - Decrease basal and stimuli induced secretion - Decrease basal nocturnal secretions - Uses: Duodenal ulcer healing Gastric ulcer healing Prophylaxis of aspiration pneumonia GERD healing Stress ulcer healing Treat Zollinger-Ellison syndrome - Ionize and inhibit H-K-ATPase - Supress 80-90% acid secretion - Uses: Bleeding peptic ulcer Adverse effects - Headache - Dizziness - Bowel upset

Proton pump inhibitor

Omeprazole Lansoprazole Pantoprazole (IV) Rabeprazole (IV)

Prostaglandin analogue

Misoprostol

Antacids

Systemic antacids: Sodium bicarbonate Sodium citrate Non-systemic antacids: Magnesium hydroxide Aluminium hydroxide Magnesium trisilicate Magaldrate

increase mucus secretion increase bicarbonate decreased acid and gastrin increase mucosal blood flow prevents NSAID-induced peptic ulcer Uses: Gastritis Systemic acidosis Alkalize urine Non ulcer dyspepsia Episodes of gastritis

- Nausea - Loose stools - Headache - Abdominal pain - Muscle pain - rashes Disadvantages: - Abdominal cramps - Diarrhoea - Uterine bleeding - 4 times/day dose - Systemic alkalosis

Poorly absorbed insoluble

16

Type Sodium Alginate Sulcralfate

Drugs Sodium Alginate Sulcralfate

Eradication of H. pilori

Omeprazole Lansoprazole Amoxicilin Tinidazole Clarithromycin

Uses/ Functions Adverse Effects - forms thick frothy layer floating on gastric contents preventing acid contact with oesophageal mucosa - sticky gel consistency at pH<4 - constipation - coats ulcer base, - 4 times/day dose - precipitate dietary protein - increase mucus, HCO3 secretion - uses: peptic ulcer stress ulcer gastritis stomatitis - Indirect inhibiton of H. pilori by altering acid environment - Direct inhibiton of H. pilori - Triple drug therapy provides faster ulcer healing and lower relapse rates

17

Treatment of Vomiting Type D2 blockers Drugs Metaclopramide Domperidone Uses/ Functions Adverse effects - Increases Lower Oesophageal Sphincter Metaclopramide: - Relax pyloric sphincter - Diarrohea - Increase peristaltic activity - Sedation - Uses: - Acute muscle dystonia All vomiting except labyrinthine cause - Parkinsonism like symptoms Pregnancy vomiting - Galactorrhoea in long use Dyspepsia Domperidone: GERD - Not crossing BBB, so less Parkinsonism like Duodenal intubation symptoms (adv) Gastric stasis - Still have other adverse effects like metaclopramide Prior emergency surgery - Antagonism of the serotonin receptor in CTZ - Headache - Uses: - Abdominal discomfort All vomiting except labyrinthine cause - Constipation Anticancer drug induced vomiting Post anaesthetic Disease induced vomiting Malignancy associated Radiation sickness Pregnancy vomiting - Inhibiting parasympathetic activities Hyoscine: - Causing relaxation of smooth muscle of GIT - Sedation - Uses: - Dryness of mouth Vomiting due to motion sickness, disease of Dicyclomine: inner ear and ototoxic drugs - Dryness of mouth - Hyoscine: - Constipation Prophylaxis of motion sickness - Blurring vision

5-HT3 blockers

Ondasetron Granisetron

Muscarinic blocker

Hyoscine Dicyclomine Prochlorperazine

18

Type H1 blockers

CB1 agonist Corticosteroids

Drugs Promethazine Diphenhydramine Dimenhydrinate Cyclizine Meclizine Cinnarizine receptor Dronabinol Dexamethasone (IV)

Uses/ Functions - Anti-histamine

Adverse effects - Sedation - Psychomotor in coordination - Dryness of mouth - Constipation after long use

Benzodiazepines Pyridoxine

Uses: Cancer chemotherapy-induced vomiting Uses: Anticancer drug vomiting Uses: Anti-emetic effect uses: anti-emetic effect

Psychological effect Sympathomimetic effects

Amnesia sedation

19

Drugs affecting Intestinal Motility Type Bulk-forming agents Drugs Bran Uses/ functions Bran: - Lignin in bran retains water - Increases luminal volume - Increases peristaltic activity Isphagula: - Undergo fermentation by bacterial flora - Forming short chain of fatty acids - Have pro-kinetic action - Increases bacterial mass that contributes increased stool volume - Lower surface tension of stool - Allows mixing of aqueous and fatty substances - Enhances mucosal secretion - Lubricates hard faecal matter - Easy passage of had faecal mass Adverse effects Limitations: - 2,3 days for effect - Unpalatable (unpleasant taste)

Ispaghula

to 1-3 days Abdominal cramps (AE)

Stool softeners & Docusate sodium emollients Liquid paraffin

Stimulant purgatives

Bisacodyl Sodium picosulfate

Saline laxatives

Magnesium sulphate Magnesium hydroxide Magnesium citrate Sodium phosphate Polyethene glycol

- 1-3 days - Bland to taste - Deficiency of fat soluble vitamins Activated by colonic flora Limitations: Interfere with reabsorption of water intestines - Abdominal cramps Increase intestinal secretions - Electrolyte imbalance Stimulate myentric plexus, increases peristaltic - Colonic atony activity Produce soft, semifluid stools in 6-8 hours Retain water in lumen - Cramps Increase peristalsis - Electrolyte imbalance Complete emptying of bowel Watery stools Action in 1-3 hours Uses: Pre-surgical, pre-endoscopic, pre-radiographic colonic cleansing 20

Type Saline laxatives

Drugs Lactulose

5-HT4 agonists

Mosapride Tegaserod

Enema

Tap water Normal saline Glycerin Treatment of Diarrhoea: 1. treatment of fluid depletion (rehydration) 2. correction of shock and acidosis 3. antimicrobial therapy anti-motility drugs Rehydration IV fluids ORS Anti-motility Loperamide - -receptor agonist drugs - increases segmental activity - decreases peristaltic activity Diphenoxylate - decrease secretion - increase anal sphincter tone Atropine - -receptor blocker - decrease peristalsis Racecadotril - Converted into thiorphan in intestine - Inhibits enkepalinase - Increase cAMP concentration - Decreases intestinal secretion

Uses/functions Adverse effects - Colonic bacteria breakdown lactulose into osmotic Limitations: active products - Flatulence - Uses: chronic constipation - Nausea - Enhance Ach secretion - flatulence - Increase cAMP mediated secretion - Uses: Chronic constipation Irritable bowel syndrome - bowel distension causes evacuation reflex - glycerine: lubricates hard faecal mass

abdominal cramps rashes crosses BBB have CNS adverse effects

Nausea Vomiting Drowsiness flatulence

21

Drugs for Diabetes Mellitus Type Sulfonyurea Drugs Glibenclamide Gliclazide Glipizide Glimepiride Repaglinide Nateglinide Sitaglipin Uses/functions - acts on cells - causes depolarization - increase insulin secretion - also decrease glucagon - short duration - only postprandial insulin secretion - preserve beta cell function longer - inhibit enzyme DPP-4 - inhibit degradation of GLP-1 - prolong actions of insulin release - Insulin sensitizers - Enhances insulin inhibition of gluconeogenesis - Increase glucose uptake in muscle Adverse effect - hypoglycaemia - weight gain

Meglitidines

DPP-4 inhibitor

Biguanides

Metformin

Thiazolidinediones Pioglitazone Rosiglitazone

-glucosidase inhibitor

Acarbose Miglitol

Insulin

Rapid acting: Insulin Lispro Insulin Aspart

Activates Peroxisome proliferator activator receptor on nucleus Activates insulin response genes Increase uptake of muscle glucose Decrease gluconeogenesis in liver by same mechanism Inhibit alpha-glucosidase enzyme Prevent dietary carbohydrates from converting to glucose Reduced postprandial hyperglycemia Duration: 3-5 hrs Best control of postprandial sugar Less hypoglycaemia risk

inflammation of nasal mucosa Urinary tract infection Diarrhoea Abdominal discomfort Nausea anorexia metallic taste lactic acidosis Hepatoxicity Weight gain Oedema Anaemia

Abdominal bloating Flatulence Diarrhoea

22

Type Insulin

Drugs Short acting: Regular insulin Intermediate acting: NPH (Isophane) insulin Lente insulin Slow acting: Insulin detemir Insulin glargine

Uses/functions Duration: 6-8 hrs Duration: 20-24 hrs

Adverse effects

Duration: 14 hrs 24 hrs

23

Antithyroid Drugs Types Anti-thyroid agents (Thioamodes group) Drugs Prophylthiouracil Methimazole Carbamizole Uses/Functions - to prevent hormone synthesis - inhibit thyroid peroxidase enzyme - prevent incorporation of iodine into tyrosyl residue - block iodine organification - inhibit coupling of iodotyrosyl groups Prophythiouracil: - inhibit peripheral deiodination of T4 -> T3 Uses: - to control disorder in anticipation of a spontaneous remission - immediately after radioactive iodine to control hypersecretion - control disorder in preparation for surgery - block iodide uptake by gland - Perchlorates competers Na-I-symporters - high concentration if iodide inhibits organification and hormone release - Uses: Preoperative operation before thyroid surgery Thyroid storm use along propranolol and thioamide agent Protect thyroid gland from radioactive agent Adverse Effects - maculopupular pruritic rash - urticarial rash - vasculitis - arthralgia - agranulocytosis

Ionic inhibitor Iodides

Thiocynates Perchlorates Iodides

Perchlorates causes aplastic anaemia hyperthyroidism Swelling of lips, eye lids Angioedema of larynx Joint pain Fever Petechial haemorrhage Iodism Acneiform rash Swollen salivary gland Ulceration of mucosa Rhinorrhea Metallic taste Drug fever

24

Type Radioactive iodine

Drugs I131

I123

Uses/Functions - Emits and particles - Orally administered (80-120 Ci/gm of tissue) - Trapped, incorporated into iodotyrosine - Deposited into colloid - rays ionizing effect leads follicular cell necrosis, disruption and fibrosis without damaging surrounding tissue - rays only - no ionizing effect - for diagnostic scanning

Adverse effects - Delayed hypothyroidism - Contraindicated in young and pregnant woman - Long latent period (3-6 months)

25

Adrenocorticoids Major effects of corticosteroids Glucocorticoids - immunological

Anti-inflammatory

Carbohydrate metabolism

Fat metabolism Protein metabolism

Cardiovascular

Central nervous system Anterior hypothalamus pituitary Mineralcorticoids - Kidney

Effects - Decrease production of T and B lymphocytes and macrophages - Decrease function of T and B lymphocytes - Reduced responsiveness to cytokines - Inhibition of complement system - Reduced production of acute inflammatory mediators - Decrease activity of macrophages and fibroblasts - Reducing numbers and activity of circulating immunocompetent cells, neutrophils and macrophages - Increase gluconeogenesis - Decrease cellular uptake and utilization of glucose - Increase storage of glycogen in liver - Redistribution of lipid from steroid-sensitive stores to steroid resistant stors - Increased catabolism - Decrease anabolism - Protein degradation - Increased sensitivity of vascular system to catecholamines - Reduced capillary permeability leading to raised blood glucose - High levels can cause mood changes or psychotic state and - Reduced endogenous secretion of endogenous glucocorticoids

Increased permeability of apical membrane of cells in distal renal tubule to sodium Stimulation of Na/K ATPase pump leading to reabsorption of Na and loss of K in urine Water retention, leading to increased BP

26

Type Glucocorticoids

Drugs Hydrocortisone (cortisol) Prednisolone Deflazacort Betamethasone Dexamethasone Beclometasone Triamcinolone

Mineralcorticoids

Fludrocortisone

Uses/Functions - Orally for adrenal replacement therapy - Intravenously in status asthmaticus and anaphylactic shock - Orally for allergy and inflammatory disease - Orally for allergy and inflammatory disease - Orally and intravenously - Supress inflammation and allergy - Reduce cerebral oedema - Used as aerosol for asthma - Used as cream and ointment in eczema (anti-inflammatory) - Used in severe asthma - Administered by intra-articular for rheumatoid arthritis - Administered orally with glucocorticoid - Replacement therapy

Adverse effects - Central obesity - Moon face - Hyperglycemia - Osteoporosis - Loss of skin structure - Easy bruising - Muscle weakness - Muscle wasting - Suppression of growth children - Cushings syndromes

in

27

Drugs acting on Kidney Type Loop Diuretics Drugs Frusemide Torasemide Uses/Functions - Inhibition of Na-K-2Cl symport - Decrease Na, K, Cl, H - Increase renal blood flow - Increase venous capacitance acute effect (IV) - Uses: Acute pulmonary oedema Chronic CHF Oedema due to nephrotic syndrome, chronic renal insufficiency Hepatic oedema Acute renal insufficiency Forced diuresis - Inhibit Na-Cl symport - Decrease Na, K, Cl, Mg, H - Increase Ca - Slowly decrease BP - Uses: Hypertension Oedema Renal calcium stone - Increase aldosterone level - Uses: Hypertension Oedema Hepatic cirrhosis Primary hyperaldosteronism - Inhibit renal epithelial Na channels - Uses: Hypertension Oedema Adverse effects - Fluid and electrolyte imbalance - Alkalosis - Ototoxicity - Dyslipidaemia - Hyperglycaemia - Hyperuricemia - Skin rash - Photosensitivity - Diarrhoea

Thiazide diuretics

Hydrochlorothiazide Polythiazide Chlorthalidone Indapamide

Potassium sparing Spironolactone diuretics Eplerenone (Aldosterone antagonist)

Triamterene Amiloride

- Electrolyte imbalance - Uricemia - Glycemia - Dyslipidaemia - Sexual dysfunction - Diarrhoea - Hypersensitivity - Photosensitivity Toxicities: Hyperkalemia Peptic ulcer Sexual characteristic altered Drowsiness Skin rashes Toxicities: Hyperkalemia Diarrhoea Megaloblastic anaemia in cirrhosis Photosensitivity 28

Type

Drugs

Osmotic diuretics

Mannitol

Carbonic Anhydrase Inhibitor

Acetazolamide Dorzolamide

Uses/Functions Potassium sparing diuretics always use with frusemide and thiazides to decrease K loss. Hypokalemia can lead to arrhythmia - Only by intravenous - Increase osmolarity of plasma and tubular fluid - Increase plasma volume - Increase GFR - Uses: Acute renal failure Cerebral oedema Glaucoma - Decrease Na, K, Cl, HCO3 - Uses: Glaucoma Altitude sickness

Adverse effects

Contraindication: Oedema Cerebral haemorrhage

Toxicities: - Allergic - Bone marrow depression - Drowsiness

29

Oral contraceptives Type Oestrogen Drugs Natural oestrogen: 17-estradiol Estrone Estriol Equilin Synthetic oestrogen: Ethinyl estradiol Mestranol Diethylstilbestrol (DES) Dienestrol Uses/ functions Actions: - Development and maturation of female internal and external genitalia - Growth of breasts - Bone growth - Closure of epiphyses - Growth of myometrium and development of endothelium lining - Distribution of subcutaneous fat - Pubic and axillary hair - Ovarian follicular development - Regulation of menstrual cycle Uses: - Hypogonadism - Menstrual abnormalities - Menopausal therapy - Oral contraception - Androgen-dependant prostatic tumour by DES - Bind competitively to oestrogen receptor - Uses: Clomiphene treat infertility in cases of anovulation in women with intact hypothalamic-pituitary axis Fulvestrant treat women with progressive breast cancer after tamoxifen + - Suppress secretion of gonadotrophin of - Follicular secretion, follicular maturation, oestrogen surge, LH surge, and ovulation do not take place - Taken for 21 days with a 7 days of break to induce withdrawal bleed - If taken delay greater than 12 hours, effect may be lost Adverse effects - Nausea - Headaches - Cholestasis - Increased risk of endometrial cancer - Postmenopausal bleeding -

Anti-oestrogen

Clomiphene Fulvestrant Tamoxifen Toremifene

Ovarian enlargement Hot flashes Nausea Vomiting

Combined oral Ethinylestradiol contraceptives analogue progesterone

Nausea Vomiting Headache Weight gain Breast tenderness Impaired liver function Impaired glucose tolerance 30

Type Progesterone-only (minipill)

Drugs Low-dose progesterone

Uses/ functions of Causes thickening of cervical mucus preventing penetration Causes suppression of gonadotrophin secretion Taken orally Taken daily Causes thickening of mucus Causes suppression of gonadotrophin secretion Medroxyprogesterone administered intramuscularly Etonogestrel-releasing implant placed subdermally

Adverse effects sperm Menstrual irregularities Nausea Vomiting Headache Weight gain Breast tenderness

Depotprogesterone

Medroxyprogesterone acetate Etonogestrelreleasing implant Levonorgestrel -

Post-coital pill

Progesterone agonists

Progesterone Medroxyprogesterone Dydrogesterone Hydroxyprogesterone Norethisterone

Progesterone antagonist

Mifepristone

High doses of a progesterone Prevent implantation of fertilized Induced contraction of smooth muscle Accelerate movement of fertilized egg into unprepared uterine endometrium mimics endogenous progesterone taken orally/transdermal patches/subcutaneous implants uses: premenstrual symptoms severe dysmenorrhoea menorrhagia endometriosis contraception hormone replacement therapy Bind to progesterone receptors but did not bring about any effect Sensitize uterus to prostaglandin, for termination of pregnancy Taken orally

Menstrual irregularities Nausea Vomiting Headache dizziness Menstrual irregularities Nausea Vomiting Headache Weight gain Breast tenderness

Vaginal bleeding Faintness Nausea Vomiting

31

Pharmacology of Parkinsons Disease Type Drugs Levodopa Uses/ Functions - Precursor of dopamine - Decarboxylated to dopamine - Bradykinesia and rigidity quickly respond to levodopa - Reduction in tremor - Less effective in eliminating postural instability and shuffling gait - Directly act at striatal dopamine receptors - Use in fairly advanced Parkinson disease Adverse effects - Anorexia - Nausea - Vomiting - Hypertension - Tachycardia - Arrhythmia - Anxiety - Confusion - Delusions - Hallucination - Brownish discolouration of saliva, urine

Dopamine receptor agonist

Pergolide Bromocriptine

Monoaminooxidase inhibitor Antiviral

Selegiline

Amantidine

Irreversible inhibitor of MAO-B Retards breakdown of dopamine Enhances and prolong dopamine effect Use as initial therapy for mild PD

Muscarinic antagonist

Benztropine Trihexiphenidyl Diphenhydramine Biperidin

Use in early PD Drug of choice in drug-induced Parkinsonism: Reserpine Anti-psychotic drugs

Lethargy Dizziness Sleep disturbances Nausea Vomiting Dry mouth Anorexia Urinary retention Drowsiness Mental confusion Restlessness Dryness of mouth Blurred vision Urinary retention Constipation

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Type COMT Inhibitors

Drugs Tolcapone Entacapone

Uses/ Functions - Increases duration of effect of levodopa - Should be taken with carbidopa/ levodopa - Can reduce dose, thus reduce AE

Adverse effects

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Sedatives and Hypnotics Type Drugs Benzodiazepines Ultra-short acting (<6hrs) : Triazolam Midazolam Short acting (10-12hrs) : Lorazepam Oxazepam Temazepam Intermediate acting (1218hrs): Alprazolam Nitrazepam Longer acting (12-24hrs): Diazepam Flurazepam Clonazepam Chlordiazepoxide Uses/ functions - Increases frequency of openings of GABAergic channels - Advantages over barbiturates: Lower neuronal depression Wider margin of safety Do not effect REM sleeps Little effect on cardiovascular and respiratory system Flumazenil used for overdosage of BZD - Treating anxiety states: Alprazolam Lorazepam Oxazepam Diazepam Chlordiazepoxide - Treating insomnia: i. Transient insomnia Triazolam temazepam ii. Short term insomnia Temazepam Flurazepam iii. Chronic insomnia Flurazepam Nitrazepam - Pre-anaesthetic and induction of anaesthesia: Diazepam Lorazepam Midazolam - Skeletal muscle relaxation Diazepam Adverse effects - Sedation - CNS depression - Irritability - Excitement - Rage - Ataxia - Confusion - Tolerance and dependence on prolonged use and withdrawal symptoms on stoppage

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Type Drugs Benzodiazepines

NonZolpidem benzodiazepines Zaleplon hypnotics Zopiclone

blocker

Propanolol

Anti-histamine Anti-depressant Anti-psychotic (neuroleptics) Anxiolytic

Promethazine

Uses/functions - Anticonvulsant: Diazepam Lorazepam Clonazepam (absent seizure) - Alcohol withdrawal Diazepam Oxazepam chlordiazepoxide - Act on BZ1 receptor - Minimal muscle relaxing effect - Minimal anti convulsant effect - Increase slow wave sleep, no effect on REM - Zolpidem and Zaleplon for transient insomnia - Zopiclone for short term insomnia - Uses: Palpitation Tremor GIT upset Hypertension Helps in decrease anxiety - Used in children - Depressed patients improvement of mood - Improve sleep - Promote sleep in resistant insomnia Used for General Anxiety Disorder Partial agonist at 5-HT1A receptor Inhibit serotonin release Induction of anaesthesia Anticonvulsant Epilepsy

Adverse effects

Buspirone

Barbiturates

Thiopental Methohexital Phenobarbital

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Opiods Analgesic Type agonist Drugs Morphine Uses/ functions - Tranquillity - Euphoria - Decrease fear, anxiety, restlessness - Depress cough - Uses: Cancer pain Fracture pain Post-operative pain Biliary colic MI Left ventricular failure Balanced anaesthesia - Better oral efficacy - Less respiratory depression - Less constipation - Abuse potential unclear - Uses: Musculoskeletal pain Post-operative pain - Uses: Labor pain - High lipid solubility - Quick onset of action by IV route - Short acting - Less respiratory depression by epidural route - Better CV stability - Uses: Labor pain, During surgery, Postoperative pain, cancer pain Adverse effects - Constipation - Physical and psychological tolerance - Nausea - Vomiting - Increase biliary tract pressure - Urinary retention - Hypotension - Pruritus - Drowsiness - Mental clouding - Respiratory depression

Tramodol

Pethidine Fentanyl Sufentanyl

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Type agonist

Drugs Methadone

Uses/ functions - Uses: As analgesic Treating heroin opioid addicts - Better oral bioavailability - Mild withdrawal reactions

Adverse effects

Opioid antagonist

Naloxone Naltrexone

Morphine congener

Codeine

partial Buprenophrine agonist

agonist

Pentazocine

Intravenous For opioid poisoning Oral Prevent relapse of heroin abuse and alcohol abuse Depress cough centre Uses: Dry cough Musculoskeletal pain Highly lipid soluble Longer duration Uses: Post-operative pain Cancer pain Treating heroin addicts Ceiling effects for analgesia

Constipation Drowsiness

Nalbuphine

Ceiling effects for analgesia

Produce dysphoria Increase BP and heart rate due to sympathetic stimulation Produce dysphoria

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Pharmacodynamics Pharmacodynamics: study of effects of drugs on body and their mode of actions Drug: chemical substances used for treatment, cure, prevention or diagnosis in human/animal Receptor: specific macromolecular protein which is capable to bind with specific physiological ligand or drug Affinity: ability of a ligand molecule to bind to receptor Efficacy (intrinsic factor): ability of ligand to induce functional change in receptor and trigger response Agonist: has affinity and efficacy Antagonist: Has affinity, lack efficacy Prevent binding of ligand to receptor, prevent physiological action No action from antagonist itself Reversible antagonism: increasing concentration of agonist will overcome antagonism completely (Atropine overcome by Neostigmine) Irreversible antagonism: increasing concentration of agonist will not overcome antagonism

Receptor regulation: Continued receptor stimulation causes decreased availability of receptors, causes desensitization of receptors thus bring about less effectiveness of agonist Continued presence of receptor also causes increased availability of receptors and increased transducer mechanism, causes increase sensitization of receptor, increasing action of agonist and causes withdrawal reaction when drug stop taken.

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Functional/ Physiological antagonism: Endogenous ligands act at its own receptors which bring about opposite effect E.g adrenaline produce broncodilatation, histamine brings about broncoconstriction

Pharmacological/ receptor antagonism: Drug act as antagonist at receptor

Drug dosage: Def: appropriate amount of drug needed to produce certain degree of response in patient Dosage = amount + dosage form + frequency + duration Regulated dose: dose adjusted by repeat measurement of affected body function E.g antihypertensive, anti-diabetic Target level dose: response to drug not easily measureable. Response expected with certain range of plasma concentration E.g: anti-depressant, anti-epileptic, lithium Titrated dose: maximal dose achieved by titrating with acceptable level of adverse effect E.g: anti-cancer drug, corticosteroids

Drug potency: Amount of drug needed to produce response Higher potency doesnt confer superiority

Drug efficacy: Maximal response of a drug can elicit

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Drug A is more potent that Drug B Drug C shows lowest potency and lowest efficacy Drug A and B have same efficacy Drug A and B have same efficacy Drug A is more potent than B Drug C and D have same efficacy Drug D is more potent than C C and D is have less efficacy than A and B

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Safety Margin of a drug: Dose of drug need to be increased to obtain maximum beneficial effects until the dosage that gives toxic effect Therapeutic/Safety range is bound by dose that which minimal therapeutic effect and dose that produce maximal acceptable toxic effect Wider the safety margin, safer the drug

Therapeutic Index: TD50/ED50 TD50: dose that produce toxic effect in 50% of human ED50: dose that produce desired effect in 50% of population

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Treatment of Malaria Type 4-aminoquinolines Drugs Chloroquine Amodiaquine Uses/Functions - Treatment of P. vivax, ovale and malariae - Does not produce radical cure - Interferes with parasite haem detoxification - Dosage: tablets of 100mg or 150mg - Amodiaquinie: ACT for chloroquine resistrant Falciparum Adverse effects - Nausea - Vomiting - Skin rashes - Itching - Headache - Visual disturbance - Prolonged administration may cause irreversible retinopathy as in treatment of rheumatoid arthritis cinchonism hypoglycaemia hypotension large doses can cause hypotension, cardiac arrhythmia and AV block

Quinoline methanol Cinchona alkaloid

Mefloquine Quinine Quinidine

Biguanide Diaminopyrimidines 8-Aminoquinoline

Proguanil Pyrimethamine Primaquine

Effective blood schizonticide Act on mature trophozoite stage Also kills sexual stages of P.vivax, malariae,and ovale but not mature gametocytes of falciparum Preparation: i) tablets of quinine hydrochloride, quinine dihydrochloride, quinine sulphate and quinine bisulfate ii) injections of quinine hydrochloride, quinine dihydrochlorie, and quinine sulphate Prophylaxis of malaria with choloroquine Inhibit dihydrofolate reducatase of Plasmodium Used with sulfadoxine effective against intrahepatic forms of all types of malaria parasite used to provide radical cure of P. vivax and P. ovale preparations: tablets of 5 mg, 7.5 mg, 15 mg primaquine diphosphate

Megaloblastic anaemia Folate deficiency haemolytic anaemia in G6PD deficiency patient abdominal pain leucocytosis leukopenia agranulocytosis GI symptoms

Sulfonamides, Sulfones

Sulfadoxine Dapsone

Produce sequential block in folate and inhibits synthesis of purines and pyrimidines 42

Types Tetracyclines Sesquiterpine lactones

Drugs Tetracycline Doxycycline Artesunate Artemether Arteether

Amino alcohols

Halofantrine Lumifantrine

Naphthoquinone

Atovaquone

Uses/functions - Short term prophylaxis in areas with multiresistant strains of Plasmodia - Attack from young rings to schizont - Active against all Plasmodium species - Also kills falciparum gametocytes - Inhibit essential calcium adenosine triphosphate - Artemether preparations: i) Capsule of 40mg arthemether ii) Tablet of 50 mg iii) 80mg injection iv) 20mg of arthemether with 120mg lumefantrine - Artesunate preparation: i) Artesunic acid + sodium bicarbonate = sodium artesunate right before injection ii) Also by oral(50mg/200mg), rectal(100mg/400mg) or IM - Artheether i) IM injection of 150mg of artemotil in 2ml of injectable solution Halofantrine - Blood schizonticide - Active against Falciparum Lumifantrine - Long acting erythrocytic schizonticide - Inhibit heme polymerization and inhibition of protein and nucleic acid synthesis - Used only in combination with artemether - Inhibit electron transport to reduce membrane potential of mitochondria - Admin with proguanil - Treatment and prophylaxis of Falciparum

Adverse effects

GI disturbance Dizziness Tinnitus Reticulocytopenia Neutropenia ECG abnormalities

GI disturbance Headache Rash

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Beta lactam antibiotics & cell wall inhibitor antibiotics Types Natural penicillin Drug Penicillin G Uses/functions - B-lactamase sensitive - For gram positive cocci: streptococcus pyogenes, s. pneumonia, s. viridans, s. faecalis - For gram positive bacilli: c. tetani, c. perfringes, c. diptherie, B. anthrasis, Listeria monocytogenes - Prophylactic: rheumatic fever, bacterial endocarditis Adverse effects - Allergy - Superinfections by Candida - Diarrhoea - Haemolysis - Nephritis - Neurotoxicity - Jarisch-Herxheimer reaction

Acid resistant penicillin

Penicillinase resistant penicillin

Aminopenicillin

Procain penicillin Benzathin penicillin Phenoxy methyl - Acid stable penicillin - For minor infections - Effective against anaerobic organisms - Prophylaxis of rheumatic carditis Methicillin - Used in infections by penicillinase-producing Oxacillin staphylococci Cloxacillin - Used in skin and soft tissue infection Dicloxacillin Nafcillin Flucloxacillin Ampicillin Ampicillin Becampicillin - Broad spectrum: effective against Gram Talampicillin positive bacilli and gram negative bacilli Amoxicillin - Uses: bite wound infection, enterococci endocarditis, intra-abdominal/ skin/soft tissue infections, meningitis

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Types Carboxypenicillin Ureidopenicillin

Drugs Carbenicillin Indanyl carbenicillin Mezlocillin Ticarcillin Piperacillin

Uses/ functions

Adverse effects

First generation cephalosporins

Cephazolin Cephalexin Cephadroxyl

Second generation cephalosporins

Cefotixin Cefaclor Cefuroxime axetil Cefuroxime

Effective against Pseudomonas aeruginosa Effective against gram negative bacilli except Klebsiella Uses: intra-abdominal/skin/soft tissue infection, nosocomial pneumonia Effective against gram positive cocci e.g Proteus mirabilis, E. coli, Klebsiella pneumonia Uses: skin infection of staphylococci or streptococci UTI due to E. coli Cephazolin used to prevent invection of staphylococci and aerobic enteric bacilli during surgery Active against S. aureus, S. pyrogens, S. pneumonae, Haemophilus influenza, Enterobacter aerogenes, Neisseria species, Proteus mirabilis, E. coli, Klebsiella pneumonie, Serratia marcescens Uses: Cefotixin: diverticulitis, pelvic inflammatory disease, prevention of infections during surgical procedure Cefuroxime(oral): Respiratory tract, skin infections and UTI Cefuroxime(parenteral): community acquired pneumonia, pneumonia due to H. influenza or Pneumococci

Haemolytic anaemia Thrombocytopenia Interstitial nephritis Abnormal liver function test

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Types Third generation cephalosporins

Drugs Cefixime Cefotaxime Ceftriaxone

Fourth generation cephalosporins

Cefipime Cefpirome

Monobactams

Aztreonam

Carbapenems

Imipenem Meropenem Ertapenem

Uses/functions - Gram negative action - Can cross BBB - Activity against pseudomonas Uses: - Cefixime gonorrhoea, otitis media - Cefotaxime and Ceftriaxone septicaemia, pneumonia, gonorrhoea, intra-abdominal infections, osteomyelitis, otitis media, skin infections, soft tissue infections, UTI - Ceftazidime Pseudomonas aeruginosa infections - Activity against both gram positive and negative bacteria - Used to treat infections due to multi drug resistant organisms in hospital - Active against Gram negative rods e.g Klebsiella, Pseudomonas and Serratia - Used in penicillin allergic patients, renal insufficiency and patient that cant tolerate amino glycosides - Drug of choice for initial empirical therapy in severe infections - Uses: - Infections due to multidrug resistant gram negatives bacilli, drug of choice for ennterobacter, intra-abdominal infections, pelvic, skin, soft tissue, bone, joint, urinary, respiratory and nosocomial infections - Imipenem combined with cilastatin - Meropenem and ertapenem have less renal and CNS toxicity

Adverse effects - Opportunistic infection with resistant bacteria or candida albicans or C. difficile diarrhoea - Cholethiasis (ceftriaxone)

Occasional GI upset

GI upset Allergic reactions CNS effect convulsion)

(confusion,

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Type Cell wall synthesis inhibitor

Drugs Vancomycin

Teicoplanin Daptomycin Bacitracin

Uses/ functions Adverse effects - Inhibit gram positive bacterial cell wall - Redmans syndrome synthesis - Used for MRSA and infections due to IV catheters, pseudomembranous colitis (used with metronidazole) - Same as vancomycin Topical antibiotic Combined with neomycin, polymyxin B and corticosteroids Demonstrates synergistic activity against enterococci, MRSA when combined with cephalosporins, aminoglycosides and others

Fosfomycin

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Macrolides and protein synthesis inhibitor Type Macrolides Drugs Erythromycin Uses/functions - Effective against Gram positive bacteria and spirochaetes - Not effective against Gram negative except for Neisseria gonorrhoeae and H. influenza Adverse effects - GI upset - Rashes - Fever - Transient hearing disturbance - Cholestatic jaundice - Epigastric pain - Thrombophlebitis - Opportunistic infection of GI/ vagina

Azithromycin

Clarithromycin

Ketolides Telithromycin Lincosamides Clindamycin -

Effective against Gram postitive Bacteria More effective against H. influenza More active against Legionella Excellent action against Toxoplasma gondii Twice more affective against H. influenza compared to erythromycin Effective against Mycobacterium avium-intercellulare Useful in leprosy and against H. pylori Macrolides are drug of choice for M. pneumonae infections, Legionnaires pneumonia, Chlamydial infection, Diphtheria, Pertussis, Alternative drugs in tetanus, streptococcal tonsillitis, pharyngitis, pneumonia, mild staphylococcal infection Prophylactic drug in rheumatic fever after surgery of valvular lesion to prevent endocarditis Have increased activity against erythromycin resistant gram positive cocci such as S. pneumonia Effective against H. influenza, C. pneumonia, M. catarrhalis, Bordetella pertussis, and Legionella pneumophila Effective against Gram-positive cocci Inhibit protein synthesis Used in infection by Bacteroides organisms and Staphylococcal infection of bones and joints

GI disturbance Pseudomembranous colitis

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Type Oxazolidinones

Drugs Linezolid

Streptogramins Quinupristin Dalfopristin -

Uses/functions Active against wide variety of Gram-postive bactria Used in treatment of MRSA, penicillin-resistant Streptococcus pneumonia and vancomycin-resistant enterococci To treat pneumonia, septicaemia, skin and soft tissue infections Inhibit bacterial protein synthesis by binding to a site on 50s ribosomal subunit individually exhibit bacteriostatic activity combined together as IV injection, they are active against Gram-positive bacteria effective against MRSA and vancomycin-resistant Enterococcal faecium

Adverse effects - Thrombocytopenia - Diarrhoea - Nausea - Rash - dizziness

infusion site inflammation pain arthralgia myalgia nausea vomiting diarrhoea

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Fluoroquinolones and Aminoglycosides Type Quinolone Drugs Nalidixic acid 1st Generation: Norfloxacin (oral) 2nd Generation: Ciprofloxacin (oral, topical, IV) Ofloxacin Pefloxacin 3rd Generation: Levofloxacin Lemofloxacin Gatifloxacin Moxifloxacin 4th Generation Trovafloxacin Streptomycin Tobramycin Kanamycin Neomycin Soframycin Gentamicin Amikacin Netilmicin Uses/ Functions - Inhibit bacterial DNA gyrase - Prevent supercoiling of DNA - Inhibit topoisomerase IV in gram positive bacteria - Bactericidal in nature - 1st and 2nd generation highly effective against gram negative organisms - 3rd generation effective against streptococci and anaerobes - 4th generation effective against gram positive and anaerobes - Uses: UTI, gonorrhoea, Thyphoid, septicemias, meningitis Nalidixic acid for chronic UTI and diarrhoea bind to 30S ribosomal subunit inhibit protein synthesis bactericidal active against aerobic gram negative bacilli, staphylococci, mycobacteria combined with penicillin G/ampicillin/vancomycin for enterococci uses: gentamicin for enterococci septicaemia streptomycin for tuberculosis neomycin and framycetin for ear and eye infection Adverse effects - GI upset - Allergic reaction - Dizziness - Headache - Confusion - arthropathy

Aminoglycosides

Ototoxicity Tinnitus Headache Dizziness Nausea Nephrotoxicity Neuromuscular block

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Broad spectrum antibioticss Types Chloramphenicol Drugs Chloramphenicol Uses/functions - Binds to 50s subunit respectively - Inhibit transpeptidation - Block binding of aminoacyl moiety of tRNA to mRNA complex - Inhibited by hepatic glucoronosyltransferase - Uses: Bacteriostatic Bactericidal for H. influenza, N. meningitides, Bacteroides Treatment of pneumococcal and meningococcal meningitis in beta-lactam-sensitive person Used in infections where tetracycline is contraindicated Used in combination with metronidazole for treatment of abscess Brucellosis where tetracycline is contraindicated Short acting (6-12 hrs): - Bind to 30S Tetracycline - Blocks Chlortetracycline - Impaired by food and multivalent cations Oxytetracycline - Uses: Against gram positive and negative M. pneumoniae (tetracycline) Intermediate acting Chlamydia (12-16hrs): Granuloma inguinale Demeclocycline Rickettsia Long acting (16Vibrio cholera 24hrs): Acne Doxycycline GI ulcers by H. pylori Minocycline Amoebiasis Lyme disease Adverse effects - GI disturbances - Candidiasis - Anaemia - Leukopenia - Thrombocytopenia - Gray baby syndrome

Tetracycline

GI disturbances Candidiasis Tooth enamel dysplasia Irregularities in bone growth Hepatic toxicity Fanconis syndrome Photosensitivity (Demeclocycline) Vestibular toxicity

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Types Cotrimoxazole

Drugs Cotrimoxazole

Uses/functions - Bacteriostatic - Produce sequential blocks - Uses: Lower UTI Respiratory tract infections Bacterial diarrhoeas Typhoid fever P. carinii infections Meliodosis Chancroid

Adverse effects - Skin rashes - GI disturbances - Exfoliative dermatitis - Nausea - Vomiting - Megaloblastic anaemia

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Anti-Tubercular Drug

Type

Drugs Pyrazinamide

Ethambutol

Rifampicin

Uses/ functions - Weak bactericidal - Active in acidic - Lethal to intracellular Uses: Multiagents short-term therapy of uncomplicated pulmonary tuberculosis - Bacteriostatic - Inhibit cell wall synthesis - Supresses growth of INH & streptomycin-resistant tubercle bacilli - Bactericidal to M. tuberculosis - Effective against all subpopulation of mycobacteria - Active against extra&intracellular organisms Bactericidal Effective against intra & extracellular bacilli Active in acidic and alkaline media Bactericidal Effective only against extracellular bacilli Only as IM injection

Isoniazid

Streptomycin

Adverse effects - Liver damage - Hyperuricemia - Gout - Rashes - Arthralgia - Optic neuritis - Red-green colour blindness - C/I: children <6 y.old - Hepatitis - Body secretion become reddish orange - Leprosy - Hepatic injury - Peripheral neuritis - Urinary retention - Insomnia - VIII cranial nerve damage - Problem with hearing and balance - Nephrotoxicity

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