DIURETICS Na + H2O excretion ( urinary excretion) 3 Types : o Loop Diuretics o Thiazides o K+ sparing agents Mechanisms of action : o Act on membrane

e transport protein o Osmotic effects o Inhibit enzyme (carbonic anhydrase) o Interfere with hormone receptors Main Indications: o HTN (thiazides is 1st line treatment in uncomplicated HTN) o Acute LVF (furosemide offloads pulmonary edema) o Chronic HF (loop diuretics in mild HF, spironolactone in moderate to severe HF) o Liver failure and Ascites (spironolactone control resultant edema/ascites).

A) Loop Diuretics o Act on thick ascending limbs of Loop of Henle o Block Na+/K+/2Cl- transporter that absorb salt [ion] in interstitium H2O reabsorption o Eg: Furosemide (lasix) o Adverse effects : postural hypotension, cause/exacerbate gout, ototoxicity, hypokalaemia B) Thiazides o Act on distal convoluted tubules o Block Na+/Cl- co-transporter that reabsorb NaCl, Ca2+ reabsorption o Long-term treatment o Eg : Hydrochlorothiazide (esidrex), indapamide (lozol) o Adverse effects : postural hypotension, cause/exacerbate gout, hyperglycaemia (insulin resistance), hypokalaemia C) K+ sparing Agents o Act on collecting ducts o Do not promote K+ secretion into urine. Therefore, tend to be used as adjunctive therapy with other diuretics that tend to lower blood K+ level (loop diuretics, thiazides) o Prescribed only if the patient has or at risk of hypokalaemia o Eg : ENaC blocker/Non-competitive aldosterone receptor antagonist Amiloride (fruco, frumil, moduret), Triamterene (dyrenium) Competitive aldosterone receptor antagonist Spironolactone (aldactone), Eplerone (inspra) Uses in chronic LF, chronic HF, ascites Not used in 1o HTN o Adverse effects : similar to sex steroids (eg gynaecomastia), hyperkalaemia/arrhythmia

ANTI-DEPRESSANTS Depression is due to NA and/or 5-HT Several types : o Monoamine Reuptake Inhibitors o MAO-A inhibitors o Others (Natural, ECT, Lithium)

A) Monoamine Reuptake Inhibitors o TCA block reuptake of NA and 5-HT Excreted as glucuronides in urine Effect by blocking: Monoamine reuptake Muscarinic Ach receptors Histamine receptors 5-HT receptors Side effects: Normal dose : H1 block (sedation), muscarinic block (anticholinergic effects- dry mouth, constipation, etc), -adrenergic block (postural hypotension), alcoholic effect. Overdose : excitement, delirium, convulsions, respiratory depression, coma. Eg : Amitriptyline (amyline), Imipramine (tofranil), Doxepin (sinequan, deptran) o SSRI block reuptake of 5-HT When given with MAO inhibitors, it can cause Serotonin Syndrome (tremor, hyperthermia, CVS collapse) Side effects: Mostly mild side effects (feel sick and anxious, nausea, anorexia, insomnia, loss of libido, etc) Eg : Fluoxetine (prozac), Fluvoxamine (faverin), Paroxetine (seroxat, aropax, extine), Citalopram (cipramil, ciprager, celica, seropram), Sertraline (lustral, zoloft, eleva) Fluoxetine and Paroxetine can inhibit hepatic metabolism of TCA. B) MAO Inhibitors o 2 types : Non-selective MAO inhibitors : Phenelzine (nardil), Tranylcypromine (parnate), Isocarboxazid (marplan) Selective MAO inhibitors : Moclobemide (manerix, aurorix, amira) o Drugs Interactions : With drugs Serotonin Syndrome when given with TCA/SSRI High fever when given with Pethidine With foods Contraindicated with cheese and yeast products (tyramine).

OPIATES 3 classes : o Natural : Morphine, Codeine o Semisynthetic : Heroin, Oxycodone o Synthetic : Pethidine, Fentanyl, Tramadol (zydol), Methadone, Dextropoxyphene, Tapentadol - Effects of drugs : o CNS Analgesia, euphoria, sedation (drowsiness, no amnesia), respiratory depression, cough suppression (codeine), pupillary constriction, truncal rigidity (fentanyl, sulfentanil), addiction, NnV. o PNS CVS : vasodilation, bradycardia, hypotension GIT : constipation, pyloric and ileocecal sphincters spasm, all intestinal secretions A) Morphine o Oral morphine not reliable 1st pass metabolism. o Main effect is binding to and activating the -opioid receptors o Enter brain but slowly. Enter placental barrier rapidly. o Use: Gold standard for acute, severe, agonising pain. o Common SE: addiction, tolerance, rapid psychological dependence, constipation o CI: acute respiratory depression, renal failure, ICP, biliary colic. o Treatment of morphine overdose : Naloxone o Brand names: cyclimorph, sevredol, oramorphs, MST continus B) Codeine o Methylmorphine, a pro-drug of morphine o Fluoxetine and paroxetine (SSRI), diphenhydramine (antihistamine) reduce or block the conversion of codeine to morphine. o Uses: analgesic (mildmoderate pain), antitussive, antidiarrheal, sedative, suppress premature labour contractions. o Common SE : drowsiness, constipation. o CI: acute respiratory depression without monitoring, acute or severe asthma, hypercarbia, suspect paralytic ileus. o Lower potency than morphine. Good oral bioavailability. C) Heroin o Diacetylmorphine/Diamorphine o 3x more potent than morphine o More lipid soluble and enter the brain easily. More euphorient. Less prominent sedative + emetic effect. o Use: analgesic (severe pain) D) Tapentadol o Dual mode of action as -opioid receptor agonist and norepinephrine reuptake inhibitor. o Use: Analgesic (moderatesevere acute pain) o Brand name : Palexia

E) Oxycodone o 2b-opioid agonist o Given through oral, IV, IM, SC injection, rectal, or intranasal. o Use: Relieve moderatesevere pain. o Common SE: constipation, fatigue, dizziness, nausea, headache, dry mouth, anxiety, sweating, etc. o CI: acute respiratory depression without monitoring, acute or severe asthma, hypercarbia o Brand name: oxycontin, oxynorm, targin F) Fentanyl o Strong -opioid receptors agonist o Fentanyl analogue: Sulfentanil, Remifentanil (ultiva) o SE: diarrhea, nausea, constipation, dry mouth, somnolence, confusion, sweating, etc o CI: hypersensitivity to opioids, cautions in elderly patients, renal impairment, hepatic impairment, head injury, ICP,impaired pulmonary/cardiovascular function, GI obstruction, prostatic hypertrophy, CNS depressant use, resp. depressant use, hypotension, biliary disease, seizure disorder, inflammatory bowel disease o Brand name: Abstral, Effentora, Instanyl, Durogesic Dtranc, Matrifen, Actiq, Fental, Sublimaze. G) Methadone o Main effect is binding to and activating the -opioid receptors o Uses: analgesic (moderatesevere pain) and a maintenance anti-addictive (eg morphine detox) and reductive preparation for use by patients with opioid dependency o Common SE: hypotension, incomplete or infrequent bowel movements, drowsiness, dizziness, malaise, NnV o CI: Significant respiratory depression, acute or severe asthma without monitoring, known or suspected paralytic ileus, hypersensitivity to Methadone o Brand name: Pinadone DTF, Phymet DTF