ASPIRIN Mechanism of Action Description: Aspirin is an analgesic, anti-inflammatory and antipyretic. It inhibits cyclooxygenase, which is responsible for the synthesis of prostaglandin and thromboxane. It also inhibits platelet aggregation. Duration: 4-6 hr. Pharmacokinetics: Absorption: Rapidly absorbed from the GI tract (oral); less reliable (rectal); absorbed through the skin (topical). Peak plasma concentrations after 1-2 hr. Distribution: Widely distributed; crosses the placenta; enters breast milk. Protein-binding: 80-90%. Metabolism: Hepatic; converted to metabolites. Excretion: Via urine by glomerular filtration, active renal tubular secretion and passive tubular reabsorption (as unchanged drug); via haemodialysis; 15-20 minutes (elimination half-life, parent drug). MIMS Class Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) / Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics) ATROPINE Mechanism of Action Description: Atropine is an anticholinergic agent which competitively blocks the muscarinic receptors in peripheral tissues such as the heart, intestines, bronchial muscles, iris and secretory glands. Some central stimulation may occur. Atropine abolishes bradycardia and reduces heart block due to vagal activity. Smooth muscles in the bronchi and gut are relaxed while glandular secretions are reduced. It also has mydriatic and cycloplegic effect. Pharmacokinetics: Absorption: Readily absorbed from the GI tract; also absorbed from mucous membranes, eye, and through intact skin. Distribution: Distributes throughout the body and crosses the blood-brain barrier and placenta. Metabolism: Incomplete metabolism in the liver. Excretion: Excreted in urine as unchanged drug and metabolites. Half-life reported to be 4 hr. MIMS Class Mydriatic Drugs / Antispasmodics / Other Cardiovascular Drugs / Antidotes & Detoxifying Agents

CAPTOPRIL Mechanism of Action Description: Captopril competitively inhibits the conversion of angiotensin I (ATI) to angiotensin II (ATII), thus resulting in reduced ATII levels and aldosterone secretion. It also increases plasma renin activity and bradykinin levels. Reduction of ATII leads to decreased Na and water retention. This promotes vasodilation and BP reduction. Onset: 1-1.5 hr. Pharmacokinetics: Absorption: Rapidly absorbed from the GI tract (approx 60-75%). Reduced absorption w/ food. Time to peak plasma concentration: Approx 1 hr. Distribution: It crosses the placenta and enters breast milk (approx 1%). Plasma protein-binding: Approx 30% (mainly albumin). Excretion: Via urine (40-50% as unchanged drug, the rest as disulfide and other metabolites). Elimination half-life: 2-3 hr. MIMS Class ACE Inhibitors/Direct Renin Inhibitors

CLOPIDOGREL Mechanism of Action Description: Clopidogrel inhibits adenosine diphosphate (ADP) from binding to its receptor sites on the platelets and subsequent activation of glycoprotein GP IIb/IIIa complex thus preventing fibrinogen binding, platelet adhesion and aggregation. Pharmacokinetics: Absorption: Rapidly but incompletely absorbed from the GI tract (oral). Distribution: Protein-binding: Extensive. Metabolism: Hepatic: Extensive; converted to inactive carboxylic acid derivative and thiol derivative (active). Excretion: Via urine and faeces (as metabolites and unchanged drug). MIMS Class Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics) FUROSEMIDE Mechanism of Action Description: Furosemide inhibits reabsorption of Na and chloride mainly in the medullary portion of the ascending Loop of Henle. Excretion of potassium and ammonia is also increased while uric acid excretion is reduced. It increases plasma-renin levels and secondary hyperaldosteronism may result. Furosemide reduces BP in hypertensives as well as in normotensives. It also reduces pulmonary oedema before diuresis has set in. Pharmacokinetics: Absorption: Fairly rapidly absorbed from the GI tract (oral). Distribution: Crosses the placenta and enters breast milk. Protein-binding: 99%. Excretion: Via urine (as unchanged); 2 hr (elimination half-life), may be prolonged in neonates and renal and hepatic impairment. MIMS Class Diuretics DIPHENHYDRAMINE Mechanism of Action Description: Diphenhydramine blocks histamine H1-receptors on effector cells of the GI tract, blood vessels and respiratory tract. It also causes sedation and has some anticholinergic action. Pharmacokinetics: Absorption: Absorbed well from the GI tract (oral); peak plasma concentrations after 1-4 hr. Distribution: Widely distributed, CNS; crosses the placenta and enters breast milk. Protein-binding:Highly bound. Metabolism: Extensive first-pass metabolism. Excretion: Via urine (as metabolites, small amounts as unchanged drug); 1-4 hr (elimination half-life). MIMS Class Antihistamines & Antiallergics

HYDROCORTISONE Mechanism of Action Description: Hydrocortisone is a corticosteroid used for its anti-inflammatory and immunosuppressive effects. Its anti-inflammatory action is due to the suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability. It may also be used as replacement therapy in adrenocortical insufficiency. Pharmacokinetics: Absorption: Readily absorbed from the GI tract (oral); sodium phosphate and sodium succinate esters are rapidly absorbed but the free alcohol and its lipid soluble ester are slowly absorbed (IM); Acetate is slowly absorbed (intra-articular inj); absorbed from the skin (denuded areas). Distribution: Crosses the placenta. Protein-binding: >90%. Metabolism: Hepatic (metabolised to hydrogenated and degraded forms). Excretion: Via urine (as conjugates and glucuronide, with small portion as unchanged drug). MIMS Class Corticosteroid Hormones / Eye Corticosteroids / Topical Corticosteroids HYOSCINE Mechanism of Action Description: Hyoscine competitively blocks muscarinic receptors and has central and peripheral actions. It relaxes smooth muscle and reduces gastric and intestinal motility. Onset: Oral, IM: 0.5-1 hr; IV: 10 min. Duration: Oral, IM: 4-6 hr; IV: 2 hr. Pharmacokinetics: Absorption: Tertiary salts: Readily absorbed. Quaternary salts: Poorly absorbed. Distribution: Reversibly bound to plasma proteins. Metabolism: Hepatic. Excretion: Via urine (as metabolites); 4.8 hr (elimination half-life). MIMS Class Mydriatic Drugs / Muscle Relaxants / Antivertigo Drugs / Antispasmodics

METOCLOPRAMIDE Mechanism of Action Description: Metoclopramide enhances the motility of the upper GI tract and increases gastric emptying without affecting gastric, biliary or pancreatic secretions. It increases duodenal peristalsis which decreases intestinal transit time, and increases lower oesophageal sphincter tone. It is also a potent central dopamine-receptor antagonist and may also have serotonin-receptor (5-HT3) antagonist properties. Pharmacokinetics: Absorption: Rapidly and almost completely absorbed from the GI tract (oral); peak plasma concentrations after 1-2 hr. Distribution: Widely distributed; crosses the blood-brain barrier and placenta; enters breast milk. Metabolism: Extensively hepatic. Excretion: Via urine (as unchanged drug, sulfate or glucuronide conjugates and metabolites), faeces; 4-6 hr (terminal elimination half-life). MIMS Class Antiemetics / GIT Regulators, Antiflatulents & Anti-Inflammatories

KETOROLAC Mechanism of Action Description: Ketorolac inhibits prostaglandin synthesis by decreasing the activity of the cyclooxygenase enzyme. Onset: 30-60 min (oral); 10 min (IM). Duration: 6-8 hr (oral/IM). Pharmacokinetics: Absorption: Well absorbed (oral/IM); peak plasma concentrations after 30-60 min. Distribution: Protein-binding: 99%. Crosses the placenta; enters breast milk; poorly penetrates into CSF. Metabolism: Hepatic via glucuronic acid conjugation. Excretion: Via urine (90%, as unchanged drug and metabolites); via faeces (remaining dose). Terminal elimination half-life: 4-6 hr; 6-7 hr (elderly); 9-10 hr (renal impairment). MIMS Class Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) / Ophthalmic Decongestants, Anesthetics, Anti-Inflammatories

METOCLOPRAMIDE Mechanism of Action Description: Metoclopramide enhances the motility of the upper GI tract and increases gastric emptying without affecting gastric, biliary or pancreatic secretions. It increases duodenal peristalsis which decreases intestinal transit time, and increases lower oesophageal sphincter tone. It is also a potent central dopamine-receptor antagonist and may also have serotonin-receptor (5-HT3) antagonist properties. Pharmacokinetics: Absorption: Rapidly and almost completely absorbed from the GI tract (oral); peak plasma concentrations after 1-2 hr. Distribution: Widely distributed; crosses the blood-brain barrier and placenta; enters breast milk. Metabolism: Extensively hepatic. Excretion: Via urine (as unchanged drug, sulfate or glucuronide conjugates and metabolites), faeces; 4-6 hr (terminal elimination half-life). MIMS Class Antiemetics / GIT Regulators, Antiflatulents & Anti-Inflammatories NOREPINEPHRINE Mechanism of Action Description: Norepinephrine is a direct-acting sympathomimetic which stimulates β1- and α-adrenergic receptors. Its α-agonist effects cause vasoconstriction, thereby raising systolic and diastolic BP with reflex slowing of heart rate. Onset: Rapid. Duration: Short; stops within 1-2 min after discontinuing the infusion. Pharmacokinetics: Absorption: Oral: Destroyed in the GI tract; SC: Poorly absorbed. Distribution: Mainly localises in sympathetic nervous tissue; crosses the placenta but not the blood-brain barrier. Metabolism: Metabolised in the liver and in other tissues by the enzymes catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). Excretion: Via urine (mainly as metabolites). MIMS Class Vasoconstrictors

PARACETAMOL Mechanism of Action Description: Paracetamol exhibits analgesic action by peripheral blockage of pain impulse generation. It produces antipyresis by inhibiting the hypothalamic heat-regulating centre. Its weak anti-inflammatory activity is related to inhibition of prostaglandin synthesis in the CNS. Onset: Oral: <1 hr. IV: 5-10 min (analgesia); w/in 30 min (antipyretic). Duration: 4-6 hr (analgesia). IV: ≥6 hr (antipyretic). Pharmacokinetics: Absorption: Readily absorbed from the GI tract. Time to peak plasma concentration: Approx 10-60 min (oral). Distribution: Distributed into most body tissues; crosses the placenta and enters breast milk. Plasma protein binding: Approx 25%. Metabolism: Hepatic via glucuronic and sulfuric acid conjugation. N-acetyl-p-benzoquinoneimine (minor hydroxylated metabolite), is usually produced in very small amounts by CYP2E1 and CYP3A4 isoenzymes in the liver and kidneys. Excretion: Mainly via urine (as glucuronide and sulfate conjugates, <5% as unchanged drug). Elimination half-life: Approx 1-3 hr. MIMS Class Analgesics (Non-Opioid) & Antipyretics

RANITIDINE Mechanism of Action Description: Ranitidine competitively blocks histamine at H2-receptors of the gastric parietal cells which inhibits gastric acid secretion. It does not affect pepsin secretion, pentagastrin-stimulated intrinsic factor secretion or serum gastrin. Pharmacokinetics: Absorption: Readily absorbed from the GI tract. Bioavailability: Approx 50%. Time to peak plasma concentration: Approx 2-3 hr (oral); approx 15 min (IM). Distribution: Widely distributed; enters breast milk, crosses the placental barrier. Volume of distribution: Approx 1.4 L/kg. Plasma protein binding: Approx 15%. Metabolism: Hepatically metabolised. Small portion is converted to N-oxide (major metabolite, approx 4-6% of a dose), S-oxide and desmethylranitidine. Excretion: Via urine (oral: Approx 30%, IV: 70%) as unchanged drug and in the faeces. Elimination half-life: Approx 2-3 hr. MIMS Class Antacids, Antireflux Agents & Antiulcerants

SALBUTAMOL Mechanism of Action Description: Salbutamol is a direct-acting sympathomimetic with β-adrenergic activity and selective action on β2 receptors, producing bronchodilating effects. It also decreases uterine contractility. Onset: Inhalation: 5-15 min; oral: 30 min. Duration: Inhalation: 3-6 hr; oral: 8 hr; modified-release preparation: 12 hr. Pharmacokinetics: Absorption: Readily absorbed from the GI tract. Metabolism: Hepatic and in the gut wall. Excretion: Via the urine as metabolites and unchanged drug. Some excretion in the faeces. MIMS Class Drugs Acting on the Uterus / Antiasthmatic & COPD Preparations

TRAMADOL Mechanism of Action Description: Tramadol inhibits reuptake of norepinephrine, serotonin and enhances serotonin release. It alters perception and response to pain by binding to mu-opiate receptors in the CNS. Onset: Approx 1 hr. Duration: 9 hr. Pharmacokinetics: Absorption: Readily absorbed from the GI tract. Bioavailability: Approx 70-75% (oral); 100% (IM). Distribution: Widely distributed. Crosses the placenta and enters breast milk. Metabolism: Extensive hepatic first-pass metabolism. Converted to O-desmethyltramadol (active) via N- and O-demethylation by CYP3A4 and CYP2D6 isoenzymes and also via glucuronidation or sulfation. Excretion: Via urine (as metabolites). Elimination half-life: Approx 6 hr. MIMS Class Analgesics (Opioid) TRANEXAMIC ACID Mechanism of Action Description: Tranexamic acid is an antifibrinolytic agent that competitively inhibits breakdown of fibrin clots. It blocks binding of plasminogen and plasmin to fibrin, thereby preventing haemostatic plug dissolution. Pharmacokinetics: Absorption: Absorbed from the GI tract; peak plasma concentrations after 3 hr (oral). Bioavailability: 30-50%, unaffected by food intake. Distribution: Widely throughout the body. Protein-binding: Very low. Crosses the placenta and distributed into breast milk. Excretion: Urine (as unchanged drug); 2 hr (elimination half-life). MIMS Class Haemostatics IPRATROPIUM BROMIDE + SALBUTAMOL Mechanism of Action Description: Ipratropium bromide is an anticholinergic agent that inhibits vagally-mediated reflexes by antagonising the action of acetylcholine. It prevents the increases in intracellular concentration of cyclic guanosine monophosphate (cyclic GMP) which are brought about by interaction of acetylcholine with the muscarinic receptors on bronchial smooth muscle. Salbutamol is a direct-acting β2-adrenergic agent. It acts on the airway smooth muscle resulting in bronchodilation. Pharmacokinetics: Distribution: Ipratropium: Minimally bound to plasma proteins. Excretion: Ipratropium: Elimination half-life: About 2 hr (after IV or inhalational admin). Plasma half-life of salbutamol: About 4-6 hr. MIMS Class Antiasthmatic & COPD Preparations