3 Clinical Pharmacology

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- Application of drugs in body re medicines
- Bridges gap between laboratory science and medical practice
- Safety of prescribed medicine, maximise drug effects, minimise side effects

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3 Clinical Pharmacology

  1. 1. Clinical Pharmacology
  2. 2. Clinical pharmacology • Clinical pharmacology connects the gap between medical practice and laboratory science. • The main objective is to promote the safety of prescription, maximise the drug effects and minimise the side effects. • It is important that there be association with pharmacists skilled in areas of drug information, medication safety and other aspects of pharmacy practice related to clinical pharmacology.
  3. 3. Clinical pharmacology • Clinical pharmacologists usually have a rigorous medical and scientific training which enables them to evaluate evidence and produce new data through well designed studies • Their responsibilities to patients include, but are not limited to, analyzing – Drug therapeutics, toxicology (including reproductive toxicology), cardiovascular risks, perioperative drug management (those used in operations), psychopharmacology, and Iatrogenic effects (adverse drug effects)
  4. 4. Clinical Pharmacology • Clinical Pharmacology is the subject of the application of drugs to the body in the medicinal sense • Drugs can function either by action through receptors, or by altering the functions of the target cell/tissue
  5. 5. Principles of drugs action
  6. 6. Receptors • One facet of drug action is receptors – Agonist: do have a stimulatory effect • They produce a response – Antagonist: do not have a stimulatory effect • They do not produce a response, or have an overall blocking action for a parallel stimulation • Types: – Agonist: have a central pore – G – Protein: usually linked by secondary messengers to physiological (cellular) processes – Nuclear receptors for steroid hormones: in cell nucleus and regulate protein translation and thus synthesis – Kinase – linked receptors: usually process intrinsic tyrosine activity (insulin, cytokines, growth factors)
  7. 7. Neurotransmitters • These are substances released from the end of nerve axons, at synapses, and bind to receptors. They activate the receptors, by changing their configuration, and trigger a response in the post- synaptic membrane. If it is an agonist, it may stimulate a muscle contraction or gland secretion. • After they have produced their effect, they are inactivated by: – Postsynaptic enzymic degradation – Reabsorption into the pre-synaptic bulb
  8. 8. Hormones • These are chemicals that are released into the bloodstream, then they act on tissues that have receptors for them (see videos): – Cells a long way away (steroids) – Cells locally – Themselves • Drug Hormone Actions: – Inhibiting hormone release: • Antithyroid drugs – Increasing hormone release: • Antidiabetic drugs – Interact with hormone receptors: • Activating: steroidal anti-inflammatory drugs (NSAI) • Blocking: oestrogen antagonists – Local hormones (released in pathological processes): • Histamine - antihistamine • 5-HT, kinins • Prostaglandins – aspirin (NSAI)
  9. 9. Synapse - video
  10. 10. Drug-receptor interactions • A drug that has a stimulatory effect is an agonist • A drug that blocks this activity, or has an inhibitory effect is an antagonist (a term used in relation to the agonist) • Antagonists can bind in two ways: – Competitive antagonists bind reversibly with receptors; tissue response can be normalised/increased by increasing the dose of agonist – Irreversible antagonists bind irreversibly with receptors; their effect cannot be reversed by increasing agonist dose – Others: – Calcium-channel blockers do not via receptors, but further along to prevent the action of an agonist – Chemical antagonists bind to the active drug, inactivating it e.g. Protamine abolishes effect of heparin – Physiological antagonists are two agents with opposite effects that tend to cancel each other out e.g. Prostacyclin and thromboxane- A2 on platelet aggregation
  11. 11. Neuromuscular junction
  12. 12. ANS
  13. 13. Cholinergic Agonists Distigmine, Pilocarpine (Pilogel, Side Effects Salagen), Pyridostigmine • Diaphoresis (sweating) (Mestinon) • Headache • Urinary Urgency Effects • Nausea Improves muscular contraction • Diarrhoea Uses • Hypotension • Atonic Bladder and Urinary • Salivation Retention • Flushing – Postpartum or postoperative • Abdominal Pain and Cramps • Muscular Weakness • Bronchial Spasms (panting) – Myasthenia Gravis • Heart Palpitations or Tachycardia • Ocular Eye Pressure • Tremors – Glaucoma Interactions with other conditions • Asthma, hyperthyroid, hypotension
  14. 14. NMJ blockers • Presynaptic exocytosis (block released of acetylcholine): – Botulinum toxin (Botox): blepharospasm, hemifacial spasm (can produce paralysis for about 12 weeks), wrinkles – Baclofen (Lioresal) inhibit calcium influx necessary for exocytosis – usually only NMJ blockers – Aminoglycoside antibiotics: inhibit calcium influx necessary for exocytosis – usually only NMJ blockers – Dantrolene (Dantrium) -Chronic spasticity
  15. 15. Competitive NMJ blockers • Block nicotinic receptors: used by anaesthetists to relax skeletal muscle during ECT; usually given IV and don’t pass BBB or placenta. The drug of choice depends upon the side-effects – Includes: • Histamine release • Vagal blockade • Ganglion blockade • Sympathomimetic • Curare (introd 1942; not longer used) • Gallamine – doesn’t block ganglia, or releases histamine, but causes tachycardia • Pancuronium – an aminosteroid and blocks muscarinic receptors, causing atropine-like tachycardia • Vecuronium and atracurium – commonly used without CVS effect (only stable when kept cold at low pH, so in body its breakdown does not depend upon renal/hepatic function, so good for patients with those problems
  16. 16. Depolarising NMJ blocking drugs • Suxamethonium (Anectine)– depolarises the post-synaptic membrane; initiates brief contractions, then the block occurs because: – Inactivation of the voltage sensitive Na channels – Transforms activated receptors to a ‘desensitised state’ and unresponsive to ACh. • Disadvantages: – Initial muscle RXN may cause damage - pain – Damage causes K release – Repeated doses may cause bradycardia in absence of atropine
  17. 17. Potentiating drugs of NMJ • Neuromuscular transmission can be increased by anticholinesterases • They block the break down of acetylcholine and thus maintain, or potentiate, the effects of nerve stimulation • Effective in conditions like myasthenia gravis; an autoimmune condition with antibodies competing for receptors – Neostigmine – Pyridostigmine (Mestinon) • Dosage needs to be accurate; overdose can cause xs Ach and a depolarising block of the NMJ
  18. 18. Acetylcholinesterase Inhibitors e.g. Donepezil (Aricept), Side Effects Rivastigmine (Excelon), Pyridostigmine (Mestinon), • As Cholinergic Agonists Neostigmine, Galantamine Uses Interactions with other • Cognitive Deficit conditions – Alzheimers • Constipation • Attention Deficit (impaired memory) – ADHD • Muscular weakness – Myasthenia Gravis
  19. 19. ANS
  20. 20. ANS
  21. 21. ANS
  22. 22. Drugs acting at cholinergic synapses • Muscarinic agonists • Nicotinic agonists (ganglion stimulants) – Carbechol – Nicotine – Pilocarpine (Salagen) – Carbechol (weak) – Bethanechol – Anticholinesterases (weak) • Anticholinesterases – Edrophonium • Ganglion blockers – Trimetaphan – Neostigmine – Xs nicotine (depolarising block) – Distigmine – Pyridostigmine • Muscarinic antagonists – (organophosphorus – Atropine compounds) – Hyoscine – Ipratropium – Tropicamide – Benzatropine – Others
  23. 23. Antimuscarinic Agents – muscarinic blockers Atropine (Atropine), Benzatropine, • Side Effects Biperiden, Dicycloverine – Blurred vision /Dicyclomine (Merbentyl), Homatropine, Hyoscine (Buscopan), – Confusion Oxybutynin (Cystrin, Ditropan), – Drowsiness Orphenadrine (Biorphen, Disipal), – Dizziness/Vertigo Procyclidine (Arpicolin, Kemadrin), Tolterodine (Detrusitol), – Constipation Trihexyphenidyl, Trospium – Dry Mouth Others : Ipratropium Bromide (Atrovent, – Palpitations - Tachycardia Combivent, Respontin), Oxitropium, Tiotropium (Spiriva), Baclofen – Restlessness (Baclospas, Balgifen, Lioresal), – Headache Carisprodol, Dantrolene, – Urinary Retention Methocarbamol Uses • GI Tract, Bladder spasms – Irritable Bowel, Abdominal Pain, Incontinence • Muscle Rigidity and Spasms – Parkinsons • Bronchodilators – Asthma
  24. 24. Drugs acting at cholinergic synapses
  25. 25. Adrenaline Effects Biological advantage Sensation High heart beat Sends more glucose & oxygen to Thumping heart the muscles High respiratory rate Increased oxygenation of the Panting blood; rapid removal of carbon dioxide Arteriole constriction Blood diverted from skin & Person turns pale digestive system to muscles Muscle tension Ready for immediate action Tense feeling; Shivering; Erect body hair Glycogen is converted to Glucose available for energy glucose production Fats are converted to Muscles contraction fatty acids
  26. 26. ANS- Adrenoceptors • Adrenoceptors: - two main types: α, β – α: 2 types: • α1 – vasoconstriction • α2 – – inhibition of insulin release in pancreas – induction of glucagon release from pancreas. – contraction of sphincters of the gastrointestinal tract – negative feedback in the neuronal synapses – platelet aggregation
  27. 27. ANS- Adrenoceptors – β:- 2 types: – β1 – • Increase cardiac output • raising heart rate (positive chronotropic effect) • increasing impulse conduction • increasing contraction thus increasing the volume expelled with each beat (positive inotropic effect; increased ejection fraction). • Renin release from juxtaglomerular cells • Lipolysis in adipose tissue
  28. 28. ANS- Adrenoceptors • β2 - – Smooth muscle relaxation, e.g. in bronchi – Lipolysis in adipose tissue – Anabolism in skeletal muscle – Relax non-pregnant uterus – Relaxes detrussor muscle of bladder wall – Dilate arteries to skeletal muscle – Glycogenolysis and gluconeogenesis – Contract sphincters of GI tract – Thickened secretions from salivary glands – Inhibit histamine-release from mast cells – Increase renin secretion from kidney – Promotes insulin release from pancreatic beta cells
  29. 29. Drugs acting on sympathetic system Sympathomimetics • Adrenergic neurone blockers • Indirectly acting – Reserpine – Ephedrine – Amphetamine – Guanethidine – Cocaine – Bethanidine • Directly acting • Adrenoceptor antagonists – α- agonists – α – Blockers – α1, α2 • Noradrenalin – α1, α2 • Adrenaline • Phenoxybenzamine – α2 • Phentolamine • Clonidine (Catapress) • α-methyl-noradrenalin – α1 – α1 • Prazosin (Hypovase) • Phenylephrine • Doxazosin (Cardura) • Metaraminol • Guanethidine • Prazosin • Terazosin • Tamsulosin (Flomax)
  30. 30. Drugs acting on sympathetic system Sympathomimetics Side Effects • Indirectly acting • Diaphoresis (sweating) • Headache – Ephedrine • Palpitations – Amphetamine • Fatigue – Cocaine, • Angina – Methamphetamine • Depression • Hypotension – Dex(tro)amphetamine • Hypertension – Methylphenidate (Ritalin) • Dry Mouth – Modafinil • Nausea and Vomiting – Uses • Poor Appetite – Obesity • Diarrhoea • Abdominal Cramps – Somnolence • Overdose – restless, irritable, insomnia, – ADHD dizziness, tremors, talkative, fever, anxiety, – Sleep Apnea panic, confusion, delirium, hallucinations, – Fatigue aggressiveness, psychosis, suicidal/homicidal thoughts, convulsions, – Recreational Drugs coma, cerebral haemorrhage • These drugs should not be used concurrently with MAOI’s
  31. 31. Adrenergic (alpha) blockers • Doxazosin (Cardura), Side Effects Guanethidine, Prazosin, • Postural Hypotension Terazosin, Tamsulosin (Flomax), Bethanidine, • Nausea and Vomiting Phenoxybenzamine, • Nasal Congestion Phentolamine • Fatigue • Uses • Headache – Hypertension • Poor Ejaculation – Prostatic Hypertrophy • Palpitations - Tachycardia – Relieves constriction of • Oedema Bladder and Prostrate sphincters
  32. 32. Adrenergic β agonists – β- agonists – β- blockers – β1, β2 – β1, β2 • Adrenaline • Propranolol (Inderal) • Isoprenaline • Timolol (Moducren) – β2 – β1 (cardioselective) • Salbutamol • Terbutaline • Metoprolol (Betaloc, – β1 Lopressor) • Noradrenalin • Atenolol (Atecor) • Dobutamine
  33. 33. Adrenergic β agonists Adrenaline, Isoprenaline, Side effects Salbutamol, Terbutaline, • Tachycardia Noradrenalin, • Arrhythmias Dobutamine, Xamoterol Uses • Hypertension • Congestive Heart failure • Angina • Bradycardia • Asthma • Anaphylaxis
  34. 34. Drugs acting on sympathetic system
  35. 35. Managing hypertension • Usually done with a combination of factors; – Blood pressure reduction – Diuretics – Cholesterol – Anxiety
  36. 36. Blood pressure Drug groups used to control blood pressure: • β Blockers • Diuretics • Calcium channel blockers • Angiotensin converting enzyme (ACE) inhibitors • Angiotensin II receptor blockers (ARBS) There is no reliable/consistent evidence indicating substantive differences between drugs classes in the effects on BP, but side effects profiles of each drug class differ.
  37. 37. Beta Blockers Atenolol (Antipressan, Beta Adalat, Side Effects Tenormin, Tenoret), Betaxolol, Bisoprolol, • Heart Palpitations – Bradycardia Celiprolol, Esmolol, Metoprolol (Betaloc, • Hypoglycaemia (reduced glycogenolysis) Lopresor), Nebivolol (Nebilet), Acebutolol, Carvedilol, Labetalol, Nadolol, Pindolol, • Bronchoconstriction Propranolol (Cardinol,Inderal), Sotalol • Insomnia (BetaCardone,Sotacor), Timolol (Betim, • Nightmares Prestim, Timoptol) • Depression, Fatigue Action - Cardiac Selective and Non Cardiac • Cold Extremities Selective. • Peripheral Vascular Disease • Beta blockers counteract the action of • Reynaud's Syndrome noradrenalin, and reduce the force and speed of the heart beat. Non Cardiac • Decreased Libido and Ejaculation Selective drugs also prevent dilation of Problems blood vessels in the head and extremities. Contraindications Uses • Bradycardia • Hypertension • Hypotension • Migraines • Metabolic acidosis • Hyperthyroidism • Peripheral arterial disease • Angina • Heart block/failure • Myocardial Infarction • Phaeochromocytosis • Bronchial asthma
  38. 38. Diuretics • Aldactide, aldactone, Centyl, Side effects dyazide, fruside, lasix, moduret, • Headaches natrilix, napamide, natrilix, • Dizziness Actions • Fatigue • Reduce volume in cardiovascular • Urinary tract obstruction system • Postural hypotension Uses • GIT disorders • Hypertension • Electrolyte disturbances • Polyuria • Muscle cramps • Tinnitus
  39. 39. Calcium channel blockers • Nifedipine (adalat), Diltiazem Side effects (adizem), amlid, amlist, amlode, • Ankle swelling amlotan, diltam-retard, dilzem, entrydil, exforge, myostin, nifed, • Headache nivadil, plendil, rustin, tildiem, triapin, tritace, verap, verisop, • Flushing zanidip, • Palpitation Actions • Presynaptic neurone blocker • Nausea/dyspepsia Uses • Abdominal pain • hypertension • Dizziness • Lethargy
  40. 40. ACE inhibitors • Accupro, accuretic, aceomel, Side effects bitrite, capoten, captor, carace, • Headache coversil-arginine, cozaar, enap, geroten, gopten, innovace, • Dizziness lisopress, lispril, loavel, odrik, • Rhinitis/cough pendrex, ramic, ramilo, ramitace, • Upper respiratory tract infection vascace, zesger, zestan, zestril, • Fatigue zofenil • Nausea Actions • Dyspepsia Inhibits conversion of angiotensin I • Myalgia to angiotensin II • Chest/abdominal pain Uses • Hypotension • Hypertension • Angioedema
  41. 41. Angiotensin II blockers • Aprovel, atacand, • Side effects benetor, beta-adalat, • Chest/back/abdominal diovan, isoptin, istin, pain micardis, omesar, • Arthralgia teveten, • Fatigue Actions • Dyspepsia • Causes vasodilatation, blocks vasopressin • Rhinitis/pharyngitis release • Dyspnoea Uses • Upper RTI/viral • Hypertension • Headache • Dizziness
  42. 42. Antihypertensive drugs
  43. 43. Angina Drugs • Short acting nitrates – Glyceryl trinitrate (Glytrin, Nitrolingual) • Long acting nitrates – Isosorbide (Elantan, Imdur, Isomel) • Calcium antagonists – Nifedipine (Adalat, Nifed) – Amiodipine (Amid, Amiotan)
  44. 44. Cardiac Arrhythmias • Anti-Arrhythmics Side Effects Sodium Channel Blockers: Disopyramide, • Potential exacerbation of arrhythmias Flecainide, Phenytoin (Epanutin), • Flecainide, Propafenone – Dizziness, Procainamide, Propafenone, blurred vision, headache, nausea, ventricular tachycardia Quinidine • Amiodarone – interstitial pulmonary Potassium Channel Blockers: fibrosis, tremors, ataxias, dizziness, • Amiodarone (Cordarone), Sotalol thyroid and liver disease, photosensitivity, (Beta Cardone, Sotacor) muscle weakness, neuropathy • (Also Beta Blockers, Calcium Channel • Disopyramide, Quinidine – dry mouth, Blockers, Inotropic Agents – see urinary retention, blurred vision, constipation sections) • Quinidine – may cause SA or AV node Uses block, ventricular tachycardia, nausea, • Arrhythmias e.g. atrial fibrillation or vomiting and diarrhoea, blurred vision, flutter, ventricular fibrillation, tinnitus, headache, disorientation, atrioventricular blocks, sinus psychosis arrhythmias, Palpitations – • Procainimide – erythema, ventricular Bradycardia, Tachycardia arrhythmias, depression, hallucination, psychosis • Impulse tramissions from other than the sinoatrial node – e.g. potassium imbalance in other cardiac cells
  45. 45. Heart failure • Inotropic agents • Diuretics – Digoxin – Bendroflumethiazide – Dobutamine (Centyl K) • β- Blockers – Bumetanide (Burinex) – Carvedilol (Eucardic) – Furosemide (Frumil) – Bisoprolol (Cardicor) • Aldosterone antagonist – Metoprolol (Betaloc) – Spironolactone (Aldactide) • ACE inhibitors – Captopril (Capoten) – Enalapril (Innovace)
  46. 46. Cholesterol reducing drugs (Statins) • Atorvastatin (Lipitor), Fluvastatin, Side Effects • Muscle Cramps Lovastatin, Pravastatin (Lipostat), • Abnormal Liver Function Tests Rosuvastatin (Crestor), • Steatosis (Fatty Liver) Simvastatin (Vytorin, Zocor) • Pancreatitis, Hepatitis, Jaundice Action • NAFLD (Non Alcoholic Fatty Liver Disease) • NASH (Non Alcoholic Steatotic Hepititis) • Reduce LDL and VLDL Cholesterol • Cirrhosis by inhibiting HMG-CoA enzyme • Muscle Wastage – Rhabdomylosis (raised serum used to produce cholesterol in creatine ->urine) • Acute Kidney Failure (peripheral oedema, the Liver, and so reduce release weight gain, poor appetite, into the Bloodstream. • weakness, nausea) Uses Precautions • Not to be used with concurrent Liver Disease or • Hyperlipidemia (High Cholesterol) the Oral contraceptive. Liver function tests must be performed before administration and Also repeated regularly during treatment. Creatine • Cholesterol absorption inhibition Phosphokinase (CPK) levels should be performed in anyone with kidney impairment, – Ezetimibe (Ezetrol)- used in hypothyroid disorder, inherited muscle combination with statins disorders, previous muscle toxicity in conjunction with statin use or alchohol abuse
  47. 47. Fibrates/Bile Sequestrants/Lipase Inhibitors • (Questran), Colestipol, Ezetimibe Ezetimibe inhibits cholesterol absorption (Vytorin, Zetia), Niacin (Advicor, from the gut. Again the Liver Niacor,Niaspan), Omega 3 Acid responds by increasing LDL uptake from the blood. Ethyl Esters (Omacor), Orlistat (Zenical) Niacin acts on adipose tissue and blocks formation of fatty acids to circulate in Bile Acid Sequestrants bind with bile the blood to the Liver for repackaging acids and salts from the into LDL. GallBladder in the SI and cause Uses their excretion. The Liver then • Hyperlipidemia (High Cholesterol) takes up more LDL from the blood Side Effects to compensate for lack of dietary • BAS – Nausea, Flatulence, input, and also causes increased Constipation, interferes with bile acid production to take more absorption of fat soluble vitamins A D cholesterol from the gut. E and K Fibrates cause an increase in • Fibrates – cholelithiasis, muscle lipoprotein lipase which breaks inflammation and pain and muscular down VLDL and promotes storage weakness of fatty acids in adipose and other • Niacin – skin flushing, burning and tissues. itching, nausea, abdominal pain, hyperuricemia, and gout
  48. 48. Lipid lowering drugs
  49. 49. Blood coagulation – DVT etc • Anticoagulants: • Anti-platelet: – Vitamin K antagonist – Aspirin • Warfarin (Warfant) – Angina, MI – Heparin – Clopidogrel (Plavix) if – DVT, CVA, MI aspirin C/I – Bemiparin (Zibor) – Tirofiban (Agrastat) – Enoxaparin (Clexane) – Eptifibatide (Integrillin) • Fibrinolytics: – Abciximab (Reopro) • Myocardial infarction – Dipyramidole (Persantin) – Prosthetic heart valves – Streptokinase – Alteplase (Actilyse) – Reteplase (Rapilysin)
  50. 50. Anticoagulants • Abciximab, Aspirin (Caprin, Disprin, Side Effects Nuseal, Anadin), Clopidogrel (Plavix), Dipyridamole (Persantin, Asasantin), • Prolong bleeding times: Eptifibatide, Ticlopidine, Tirofiban Haemorrhage, GI Bleeding, • Other : Warfarin (Marevan, Thrombocytopenic Purpura Coumadin) Actions • Warfarin – pain and • Prevent platelet aggregation and swelling, headaches, coagulation reactions - venous dizziness, weakness, thrombosis, pulmonary embolism and thrombo embolisms. unusual bruising, nose Uses bleeds, bleeding gums, • Angina heavy menstrual bleeding, • Myocardial Infarction brown or pink urine, red or • Prevention of cardiovascular black stools, coughing or occlusion – DVT/embolism vomiting blood • Transient Ischemic Attacks (TIA’s)
  51. 51. Drugs affecting blood coagulation
  52. 52. Agents used in anaemia • Fe preparation (increases Fe available) – Oral: • Ferrous sulphate • Ferrous gluconate • Ferrous fumarate – Parenteral • Iron dextran (ferric hydroxide) • Iron sucrose (ferric hydroxide) • Vitamins (important for normal blood production) – B12, B9 (folate) • Erythropoietin (produced by the peritubular capillary endothelial cells in the kidney; stimulates erythropoiesis in bone marrow - If renal failure)
  53. 53. Agents used in anaemia
  54. 54. Ocular pharmacology • Glaucoma β – Blockers (reduce aqueous humour production) • Betaxolol (Betoptic) • Cartelol (Teoptic) • Timolol (Nyogel) Prostaglandin analogues (increase uveoscleral outflow) • Latanoprost (Xalatan) • Bimatoprost (Ganfort) Carbonic anhydrase inhibitors (reduce aqueous humour production) • Acetazolomide • Dorzolamide • Brinzolamide Sympathomimetic (reduces production aqueous humour and outflow) • Adrenaline, guanethidine (Ganda) • Brimonidine (Alphagan) • Age related macular degeneration – Verteporfin (Visudyne)
  55. 55. Ocular pharmacology
  56. 56. COPD (asthma/bronchitis/emphysema/cystic fibrosis etc) • Bronchodilators – Side effects (brochodilators) • Tremor (COPD) (Relievers) • Tachycardia – β2 agonists • Headache • Salbutamol (Ventolin) • Hypokalaemia • Terbutaline (Bricanyl) • Steroids (Preventers) – Muscarinic blockers – Beclomethasone (Becotide) • Ipratropium (Atrovent) – Serotide (salmetrol and – Combinations fluticasone) • Salbutamol, Ipratropium Side effects (Combivent) • Hoarseness – Xanthines • Candidiasis of mouth • Aminophylline (Phyllocontin)
  57. 57. Hay fever (rhinitis) and Anaphylaxis Antihistamines: Side Effects Non-sedating - Acrivastine, Cetirizine • Fatigue (Benadryl, Piriteze), (Des)Loratidine • Drowsiness (Clarityn), Fexofenadine, Levocetirizine, • Sedation Mizolastine • Hypotension Sedating – Alimemazine, Azatadine, Brompheniramine, Chlorphenamine • Dry mouth and eyes (Piriton, Contac 400, Tixylix), Cinnarizine • Palpitations – Tachycardia (Cinaziere, Stugeron), Clemastine, • Vertigo Cyclizine, Diphenhydromine, • Hunger Diphenylpyraline, Hydroxyzine, Meclozine, • Urinary Retention Promethazine (Phenergan, Sominex, Night Nurse, Pamergan, Tixylix Night Time), Triprolidine Overdose • Sodium Chromoglycate (Intal) • Hallucinations – Mast cell stabiliser; reduces • Convulsions histamine release in allergic asthma • Ataxia Uses • Coma • Allergic Rhinitis • respiratory and cardiac collapse • Dry out mucous membranes • Motion Sickness • Insomnia
  58. 58. Asthma hay fever and Anaphylaxis
  59. 59. Drugs on GIT 1 Antacids • Helicobacter pylori eradication – NaHCO3 – CaCO3 – Triple therapy – Mg(OH)2 • Omeprazole (Losec) – Al(OH)3 • Clarythromycin (Klacid) Acid secretion reducers • Amoxicillin (Amoxil) – Proton pump inhibitors • Omeprazole (Losec) – Lanzoprazole (Zoton) • Amoxicillin (Amoxil) – Omeprazole (Losec) • Metronidazole (Flagyl) – H2 anatogonists – Cimetidine (Cedine) Side effects – Rantidine (Zantac) – Famotidine • Nausea – Nizatidine • Diarrhoea – Esomaprazole Mucosal strenghteners • Headache • Sucralfate (Antepsin) • Dizziness • Bismuth chelate • Muscle Pain • Misoprostal (Cytotec) • Uterine Contractions Uses • Reduces secretion of Gastric Acid • Peptic Ulcers • Duodenal Ulcers • Gastro-oesophogeal Reflux
  60. 60. Drugs on GIT 1 – peptic ulcer
  61. 61. Drugs on GIT 2 – motility and secretions • Crohn's disease, ulcerative colitis • Gallstone dissolvers • Anti-inflammatory – Bile acids – Corticosteroids • Ursodeoxycholic acid • Hydrocortisone • Antispasmodics (smooth M relaxants) • Prednisolone (Predenama) – Muscarinic agonists – Aminosalicylates • Alverine (Spasmonal) • Sulphasalazine • Mebeverine (Colofac) • Mesalazine (Asacolon, Mezavant) • Peppermint oil (Colpermin) • Laxatives – Bulk • Antimotility drugs (Poss with rehydration) • Bran – Morphine-like agents • Ispaghula (Fibrogel) • Morphine – Osmotic • Codeine • MgSO4 • Diphenoxylate, Atropine • Lactulose (Lomotil) – Stimulant • Loperaminde (Imodium) • Senna • Motility stimulants (DA agonists) • Bisacodyl (Dulcolax) – Metoclopramide • Co-Danthromer (Codalax) – Domperidone • Glycerol (suppositories) • Pancreatic supplements – Faecal softeners • Docusate – Pancreatin (Nutrizyme) • Arachis oil (enema)
  62. 62. Diarrhoea • Diphenoxylate (Lomotil), Kaolin, Side Effects Loperamide (Diocalm, Imodium, • Abdominal Distension and Diareze, Arret), Methylcellulose Cramps (Celevac) • Flatulence Actions • Bloating • Opioid drugs to decrease muscle • Constipation propulsion in the bowel by working on local opioid receptors • Fatigue in the bowel and slow the • Drowsiness intestines. Bulk forming agents • Dizziness absorb water and irritants in the • Itching bowel and produce larger and • Rashes firmer stools. • Dry Mouth Uses Precautions • Diarrhoea • Not to used in cases of colitis • Can affect absorption of other drugs
  63. 63. Constipation Also • Bisacodyl, Glycerol, Senna, Sodium • Bulk Picosulfate, Lactulose (Duphalac, – Bran Regulose), Magnesium Citrate, – Ispaghula (Fibrogel) • Osmotic Magnesium Hydroxide (Milk of – MgSO4 Magnesia, Maalox, Mucogel), – Lactulose Magnesium Sulphate, Polyethylene • Stimulant Glycol (Liquid Paraffin) (Glycolax) – Senna – Bisacodyl (Dulcolax) Actions – Co-Danthromer (Codalax) • Stimulants irritate the GI tract and – Glycerol (suppositories) • Faecal softeners increase peristalsis for directly – Docusate stimulate colon activity. Softening – Arachis oil (enema) agents emulsify the stool. Osmotic Side Effects laxatives cause water to stay in the • Flatulence • Belching intestines • Stomach and Abdominal Cramps Uses • Diarrhoea • Nausea • Constipation • Abdominal Distension • Osmotic laxatives can cause electrolyte imbalances
  64. 64. Irritable bowel disease/syndrome • Aminosalicylates : Balsalazide, Side Effects • Nausea and Vomiting Mesalazine (Asacol, Pentasa, • Malaise Salofalk), Olsalazine (Dipentum), • Poor Appetite Sulfasalazine (Salazopyrin, • Diarrhoea Sulazine, Ucine) • Headaches • Abdominal Pain Actions • Joint Pain • These drugs block production of • Tinnitis prostaglandins and other • Insomnia chemicals that promote • Fatigue • Fever inflammation in the bowel • Rash Uses • Sore Throat • Ulcerative Colitis • Haemmorhage • Erythema Nodosum • Crohn’s disease • Hypertension • Palpitations • Pancreatitis • Liver problems
  65. 65. Drugs on GIT 2 – motility and secretions
  66. 66. Drugs acting on kidney - Diuretics • Thiazides (distal tubule, inhibits • Carbonic anhydrase Na reabsorption) inhibitors (weak – rarely used) – Bendroflumethiazide – Acetazolamide (Centyl) – Indapamide (Natrillix) • Aldosterone • Loop agents (inhibit Na/K/Cl • Potassium sparing reabsorption in ascending loop of Henle, diuretics (act on distal nephron; so no water) reduces Na reabsorption, so spares K) – Furosemide (Lasix) – Spironolactone – Butemamide (Burinex) (Aldactone) – Amiloride – Triametarene
  67. 67. Drugs acting on kidney - Diuretics • Thiazides Side Effects – Bendoflumethiazide (Inderex, Inderetic, Prestim), Chlorthalidone, Cyclopenthiazide, • Thiazides/Loop Diuretics Hydrochlorothiazide (Acezide, Capozide, Co- Betaloc, Dyazide, Moduretic), Indapamide • Hyponatremia – lethargy, muscle (Natrilix, Coversyl Plus), Metolazone, Xipamide cramps, dizziness, hypotension, Action confusion, palpitations, fainting • Inhibit the Na+ transporters in the • Hypokalemia – diet (bananas, citrus proximal and distal tubules, which allows fruits, prunes) - Muscle weakness, more water to stay in the tubules. These fatigue, dizziness, confusion, cardiac diuretics loose efficiency with decreased arrhythmias, constipation kidney function. They cause loss of potassium and magnesium, and cause • Hyperuricemia – gout increased calcium reabsorption. • Hyperlipidemia – high cholesterol Uses - broad • Hyperglycemia – increased blood • Premenstrual Oedema (severe) sugar (danger for diabetics) • Oedema Precautions • Ascites • Can decrease effectiveness of • Congestive Heart Failure anticoagulants • Nephrotic Syndrome • Can’t be used with low potassium, cirrhosis, Addison’s or with Lithium
  68. 68. Drugs acting on kidney - Diuretics • Loop Diuretics Side effects – Bumetanide (Burinex), Furosemide/Frusemide (Co-Amilofruse, Lasix, Frusol, Frumil, Lasikal), • Hyponatremia – lethargy, muscle Torasemide cramps, dizziness, hypotension, Actions confusion, palpitations, fainting • Loop diuretics work in the Loop of Henle (which accounts for 25-30% of all NaCL • Hypokalemia – diet (bananas, reabsorption) again inhbiting the Na+ citrus fruits, prunes) - Muscle transporters. They cause loss of weakness, fatigue, dizziness, potassium and magnesium but leave confusion, cardiac arrhythmias, calcium levels unchanged. constipation Uses • Pulmonary Oedema • Hyperuricemia – gout • Hyperkalemia • Hyperlipidemia – high cholesterol • Hypercalcemia • Hyperglycemia – increased blood Broad uses sugar (danger for diabetics) • Premenstrual Oedema (severe) • Oedema • Ascites • Congestive Heart Failure • Nephrotic Syndrome
  69. 69. Drugs acting on kidney - Diuretics • Potassium Sparing Side effects – Amiloride (Amilamont, Amilospare, Burinex, Co-Amilofruse, Moduretic), • Peptic ulcers Spironolactone, Triamterene (Dytac, • Infertility – sperm and egg Dyazide, Frusene, Triamax, Kalspare) abnormalities Actions • Nausea • Potassium sparing diuretics work in the • Lethargy collecting tubule and inhibit Na+ reabsorption there as with other diuretics • Confusion but also prevent potassium excretion. • Leg Cramps They are not strong diuretics but are often • Increased Blood Urea Nitrogen used alongside others to prevent potassium loss. • Increased Uric Acid Uses • Hyperlipidemia • Premenstrual Oedema (severe) • Hyperkalemia – tiredness, confusion, • Oedema muscle weakness, irregular pulse, • Ascites muscular paralysis, cardiac • Congestive Heart Failure arrhythmias, cardiac arrest. • Nephrotic Syndrome
  70. 70. Drugs acting on kidney - Diuretics
  71. 71. Central transmitter substances Fast point to point signalling Slow, regulatory, signals • Acetylcholine (nicotinic effects) • Neuropeptides (over 40 of these) – Substance P • Amino acids – Met-enkephalin – Glutamate (excitatory) – Leu-enkephalin – Aspartate – Angiotensin – GABA (inhibitory) – Somatostatin – Glycine – LH releasing H – Calcitonin gene-related peptide (CGRP) – Others • Monoamines – Dopamine – Nor-adrenalin – Adrenalin – Serotonin (5HT) – Acetylcholine (ACh) excitatory/muscarinic. Loss of cholinergic pathways important in Alzheimer's • Donezepil • Rivastigmine • Nitric oxide
  72. 72. Central transmitter substances
  73. 73. Antiepileptic drugs
  74. 74. Antiepileptic drugs • Generalised (tonic-clonic) • Status epilepticus iv and partial seizures – Lorazepam (Ativan) – Carbamazepine (Tegretol) – Diazepam (Valium, Anxicalm) – Valproate (Epilim) – Phenytoin (Epanutin) – Phenytoin (Epanutin) • General anaesthetics – Lamotrigine (Lamictal, – Propofol (Diprivan) Lamoro) – Thiopental – Topiramate (Topamax) • Absences – Phenobarbital (also sedative) – Ethosuximide – ‘Add ons’ if epilepsy not controlled: – Valproate (Epilim) – Vigabatrin (Sabril) – Gabapentin (Neurontin, • Grand mal and absences Gabin) – Valproate (Epilim) – Tiagabine (Gabitril) – BDZ: Clonazepam (Rovotril)
  75. 75. Drugs for Parkinson’s Disease • Aetiology • COMT inhibitor – Mostly unknown – Entacapone (Comptess) – Toxin induced (via MPTP, Carbon monoxide, Manganese) • Dopaminergic drugs: – Drug induced – DA precursor • Neuroleptics • Levidopa (Madopar) • Dopamine antagonists • (+Carbidopa (Sinemet) or • Antimuscarinic drugs Benserazide) – Muscarinic antagonists – Releases DA • Benzatropine • Amantadine (Symmatrel) • Procyclidine (Kemadrin) – DA agonists/ergot derivatives • Orphenadrine • Bromocriptine (Parlodel) • MAO inhibitors • Carbergoline (Carbaser, – Selegiline (Eldepryl) Dostinex) • Pergolide (Celance) – Non-ergot derivatives • Ropinirole (Adartrel, Requip) • Pramipexole (Mirapexin)
  76. 76. Parkinson’s Drugs • Entacapone (COMT), Amantadine Side Effects (Symmetrel), Bromocriptine • Hallucinations (Visual, Auditory) (Parlodel), Cabergoline, Lisuride, • Dyskinesias (too much activation Pergolide, Pramipexole (Mirapex), of CNS) Ropinirole (Requip), Levodopa/Carbidopa (Sinemet) Also: COMT (catechol-O-methyl • Levodopa/COMT - Tachycardia, transferase) Inhibitor – inhibits hypotension, brown urine, enzyme that breaks down anxiety, depression, poor Dopamine and Levodopa appetite, nausea, vomiting Dopamine Receptor Agonists – • Dopamine Agonists – nausea, activate Dopamine receptors fatigue, sleepiness artificially instead of Dopamine. • Amantidine – restlessness, The mechanism of action of dizziness, agitation, confusion, Amantadine (an antiviral agent postural hypotension, urinary against Influenza A) is unknown. retention, peripheral oedema, Levodopa/Carbidopa - precursor of toxic psychosis (mania) Dopamine and Carbidopa is a drug that helps it to be absorbed.
  77. 77. Drugs for Parkinson’s Disease
  78. 78. Antipsychotic drugs (neuroleptics) Phenothiazines; with side chain: Others: • Propylamine • Butyrophenones – Chlorpromazine (Clonactil) – Haloperidol (Haldol, Serenace) • Very sedative • Atypical drugs • Moderate anticholinergic and extrapyramidal effects – Clozapine (Clozaril) • Piperidine – Risperidone (Risperdal, perdamel) – Thioridazine – Sulpiride (Dolmatil) • Moderately sedative • Very anticholinergic and fewer extrapyramidal effects • Piperazine – Fluphenazine (Modicate) – Trifluoperazine (Stelazine) • Less sedative • Less anticholinergic and more pronounced extrapyramidal effects
  79. 79. Neuroleptics (antipsychotics) Typical Neuroleptics – Side Effects • Phenothiazines – Chlorpromazine (Chloractil, Largactil), Flupentixol (Fluanxol), Fluphenazine, • Parkinsonian Effects – loss of balance, Methotrimeprazine, Pericyazine, Perphenazine, Pipotiazine, Prochlorperazine (Buccastem, Proziere, tremors, tardive dyskinesias Stemetil), Thioridazine, Trifluoperazine; Benperidol, • Blurred Vision Haloperidol (Haldol, Serenace), Pimozide, (Ami)Sulpride (Dolmatil, Sulptil), Zuclopenthixol • Dry Mouth Atypical Neuroleptics - • Aripipazole (Abilify), Carbamazepine (Tegretol, Teril, • Sedation Timonil), Clozapine (Clozaril), Olanzapine (Zyprexa), • Confusion, Constipation Quetiapine (Seroquel), Risperidone (Risperdal), Zotepine (Zoleptil) • Urinary Retention Actions • All these drugs block DA receptors (opposite of • Drowsiness antiparkinsonian drugs). Atypical neuroleptics also block • Postural Hypotension 5HT receptors Uses • Dizziness, Fainting • Delusions, hallucinations, disorganised or catatonic speech or behaviour : • Amenorrhea – Schizophrenia, Schizophreniform Disorder, • Infertility, Impotence Schizoaffective Disorder, Delusional Disorders, Psychotic Disorders e.g. Personality Disorders, • Significant Weight Gain Mania – Aggressive behaviours of Autism • Neuroleptic syndrome – muscle – Tourette’s syndrome (Pimozide) rigidity, fever, stupor, unstable blood – Anti-emetics pressure • Seizures
  80. 80. Antipsychotic drugs (neuroleptics)
  81. 81. Anxiolytics and hypnotics • Anxiolytics • Hypnotics – Benzodiazepines BDZ – BDZ (central depressants) (central depressants) • Temazepam (Tenox) • Diazepam (Valium) (seizures) • Lormetazepam • Lorazepam (Ativan)(seizures) (Noctamid) • Alprazolam (Xanax) • Nitrazepam (Mogadon) – Antidepressants • Amitriptyline – Others (depression/anxiety) • Zopiclone (Zimovane) • Buspirone (anxiolytic) • Chloral hydrate • Citalopram (Cipramil)(panic • Clomethiazole disorders) (Heminevrin) – β – Blockers • (Barbiturates) not used much because of dependence • Propranolol
  82. 82. Anxiolytics Side effects Benzodiazepines (BDZ) • Amnesia (anterograde and retrograde) • Alprazolam (Xanax) • Drowsiness • Chlordiazepoxide (Librium) • Lack of coordination • Clonazepam (Klonopin) • Libido/erection problems • Diazepam (Valium) • Disinhibition/euphoria • Lorazepam (Ativan) • Confusion Action • Blurred vision Herbal treatments • Acts on GABA : BDZ receptor Cl- channel complex; this increases the duration of • Certain herbs are reputed to have anxiolytic properties, including the following: chloride ion channel opening at the • Rhodiola rosea (Arctic Weed/Golden Root) GABAA receptor, thus increases the • Bacopa monnieri (Brahmi) efficacy of GABA . By increasing the available amount of GABA typically have • Hypericum perforatum (St. John's Wort) relaxing, anti-anxiety and anti-convulsive • Matricaria recutita (German Chamomile) effects • Mitragyna speciosa (Kratom) • Piper methysticum (Kava) Uses • Sceletium tortuosum (Kanna) • Panic/anxiety disorders • Scutellaria spp. (Skullcap) • Insomnia • Valeriana officinalis (Valerian) • Seizures • Cannabis sativa (Marijuana) • ‘muscle relaxant’
  83. 83. Anxiolytics and hypnotics
  84. 84. Antidepressants • Tricyclics – Amitriptyline(Elavil, Tryptizol, Laroxyl) Side effects – Clomipramine (Anafranil) • dry mouth – Dosulepin (Prothiaden, Dolthep) • dry nose – Lofepramine (Gamanil) • blurry vision • SSRI – Citalopram (Cipramil) • lowered gastrointestinal motility – Fluoxetine (Prozac) or constipation – Paroxetine (Seroxat) • urinary retention Actions • cognitive and/or memory • Block reuptake of Noradrenalin abd impairment serotonin (5HT) and antagonise many other receptors (causing side effects) • Increased body temperature Uses • Drowsiness • Depression • anxiety • Bipolar disorders • Anxiety • emotional blunting • Social phobia • Confusion
  85. 85. Antidepressants MAOI’s (monoamine oxidase Side effects inhibitors) • Sleep disturbances • Isocarboxazid (Marplan) • Moclobemide (Aurorix, Manerix) • Nausea • Phenelzine (Nardil) • Dizziness • Selegiline (Eldepryl, Emsam) • Sometimes headaches • Tranylcypromine (Parnate) • Rarely confusion Action • Blocks monoamine oxidase, which breaks down neurotransmitters (nor- adrenaline, dopamine, serotonin) after presynaptic uptake), thereby potentiating their effects Uses • Depression
  86. 86. Antidepressants
  87. 87. Lithium • Camcolit, Priadel Side Effects Actions • Nausea, Diarrhoea, Drowsiness, Frequent Urination (polyuria), • Largely unknown. Thought Frequent Thirst (polydypsia), to work by decreasing Weight Gain, Hand Tremors, Acne release of NE and DA while Toxic effects stabilising or even • Should have regular checks of increasing release of 5HT (in kidney function, urine analysis, serum urea and creatinine, animal studies). thyroid and heart function Uses • Vomiting, Diarrhoea, Ataxia, • Mania in bipolar disorders Tremors, Convulsions, Coma, Confusion, Hyper reflexes, • Prophylaxis of depression Seizures, Nerve Damage, • Cluster headaches Hypotension, Albuminuria, Cardiac Arrhythmias
  88. 88. Epileptics/anticonvulsants • Acetazolamide, Carbamazepine (Tegretol, Teril, Side Effects Timonil), Clonazepam (Rivotril), Clobazam, Diazepam (Rimapam, Tensium, Valclair, Valium), • Common are : Nausea and Vomiting, Gabapentin (Neurontin), Levetiracetam, Headache, Confusion, Hallucinations, Lamotrignine (Lamictal), Lorazepam (Ativan), Phenobarbital (Gardenal), Phenytoin (Epanutin), • Also Piracetam, Primidone (Mysoline), (Sodium) • Sedation, Ataxia Valproate (Convulex – valproic acid, Epilim, • Penytoin – megaloblastic anemia, Orlept), Tiagabine, Topiramate, Vigabatrin hyperglycemia Actions • Carbamazapine – stupor, comia, • Anticonvulsants – bind with sodium or chlorine channels to slow action potentials. respiratory depression, blurred vision, • Some antipsychotics also bind with sodium rashes, liver toxicity, hyponatremia – channels (Carbamazepine, Lamotrignine) needs frequent blood and liver function • Some anxiolytics (benzodiazepines – tests when on drug clonazepam, clorazepate, diazepam, lorazepam) • Phenobartital, Primidone – vertigo, and barbiturates (Phenobarbital) bind with psychosis, rashes, agitation, confusion chorine channels • Valproate – tremors, rashes, alopecia, • Some drugs increase GABA release – which then thrombocytopenia, inhibition of platelets, binds with chlorine channels (Gabapentin) or interfere with its breakdown (valproate) liver failure Uses • Lamotrignine – rashes, internal bleeding • Sedative, anticonvulsant and muscle relaxant • Levetiracetam – insomnia • Topiramate – somnolence, anxiety, weight loss
  89. 89. Epileptics
  90. 90. Opioid analgesics - narcotics Opioid analgesics Side effects – Strong • Morphine • Respiratory Depression – main • Diamorphine (Heroin) • Dihydrocodeine (DF118) cause of death in opioid overdose • Oxycodone (Oxycontin/OxyNorm) • Tramadol (Zydol) • Constipation – Moderate • Sedation • Codeine – Endogenous peptides • Menstrual Changes • Endorphins • Enkephalins • Nausea and Vomiting • Actions • Addiction - • Acts on morphine receptors (μЌδσ) • Uses – pain: • Withdrawal symptoms – tearing, – myocardial infarction runny nose, sweating, yawning, – sickle cell crisis flushing, palpitations, spasms and – pre- and postoperatively twitches, shaking fever, – trauma restlessness, irritability, insomnia – severe chronic pain, e.g., cancer – pain from kidney stones – severe back pain
  91. 91. Opioid analgesics
  92. 92. Drugs used in nausea and vertigo (antiemetics) • Dopamine antagonists Side effects – Prochlorperazine (Stemetil) • Nausea – Metoclopramide (Maloxon, Primperan, Migramax, Paramax) • Indigestion – Betahistine (Serc), Domperidone • Drowsiness (Motilium), • Sedation • 5HT3 (serotonin) antagonists – Ondansetron (Zofran, Emital) • Diarrhoea – Granisetron (Kytril) • Headaches • Antimuscarinic drugs • Breast Distension – Hyoscine (Kwells) • Muscle Spasms/Tremors • Antihistamines – Cinnarizine (Stugeron) • Restlessness – Promethazine (Phenergan) • Reduced Libido – Cyclizine (Valoid) • Constipation Uses • Nausea and Vomiting from: • Vertigo/Dizziness (Betahistine) • Gastroentiritis (Domperidone) • Chemotherapy
  93. 93. Drugs used in nausea and vertigo (antiemetics)
  94. 94. Non-steroidal anti-inflammatory drugs (NSAI’s) • Salicylic acid derivatives – Aspirin Side effects • Propionic acid derivatives • All NSAIDs (except for Aspirin) – Ibuprofen (Brufen, Ibugel) – Fenbufen (Lederfen) increase likelihood of cardiovascular – Naproxen (Naprosyn) events, including myocardial • Others infarctions, CVA’s and worsening of – Diclofenac (Cataflam, Voltarol) hypertension. – Indomethacin (Indocid) – Nambumatone (Relifex) • All increase GI irritation, ulceration, – Phenylbutazone haemorrhage, and perforation; can • Selective COX2 inhibitors – Etoricoxib (Arcoxia) also cause Kidney toxicity – Celecoxib (Celebrex) • Aspirin (high/toxic doses) - • Analgesic only respiratory paralysis, coma, oedema, – Paracetamol Action hyperkalaemia, anaphylactic shock in • Block prostaglandin synthesis, thus 15% of patients reducing inflammation • Mefenamic Acid and Meclofenamate Uses – severe diarrhoea, bowel • Inflammation inflammation, haemolytic anaemia • Fever • Acetaminophen – skin rash, allergic • pain reactions, long term - renal tubular necrosis, hypoglycaemia, hepatic necrosis
  95. 95. Non-steroidal anti-inflammatory (NSAI’s)
  96. 96. Corticosteroids • Hormones Side effects – Hydrocortisone [Cortisol, • Stomach upset Cortisone] (Hydrocortone) • Increased appetite • Synthetic • Diabetes mellitus – Prednisolone/prednisone • Immunosuppression • Osteoporosis – Methylprednisone (Depo – • Elevated liver enzymes mendrone) • Cushing’s disease – Betamethasone (Betnesol, Long term effects Betnelan) • hyperglycaemia, insulin resistance, – Dexamethasone diabetes mellitus, osteoporosis, – Triamcinolone (Adcortil) anxiety, depression, gastritis, colitis, Action hypertension, erectile dysfunction, • Prevents phospholipid release, hypogonadism, hypothyroidism, reducing prostaglandin synthesis amenorrhoea, retinopathy. Uses • Inflammation • Immunosuppressant
  97. 97. Corticosteroids
  98. 98. Hyperthyroidism/Thyrotoxicosis • Methimazole, Carbimazole Side effects (Neo Mercazole), • Headache, dizziness, Propylthiouracil nausea, rashes, itching, Actions hair loss, mouth ulcers • Inhibit formation of T3 • Reduced Immunity and T4 • Fever Uses • Lymphadenopathy • Hyperthyroid conditions: (swollen lymph nodes) • Palpitations, hypertension, insomnia, headaches, aversion to heat
  99. 99. Hypothyroidism • Levothyroxine (Eltroxin), Side effects • Anxiety Liothyronine • Agitation Actions • Diarrhoea • Is a synthetic form of T4 • Weight Loss • Sweating Uses • Flushing • Underactive thyroid, • Muscle cramps manifesting as: weight • Angina • Palpitations gain, fatigue, aversion • Overdose – hyperthyroid! -> in to cold, cold addition, insomnia, headaches, extremities, low irritability, aversion to heat, hypertension metabolism
  100. 100. Thyroid and Anti-thyroid drugs
  101. 101. Posterior pituitary drugs • Desmopressin (Desmotabs, Side effects Nocutil), Vasopressin (ADH), Bromocriptine (Parlodel) • Desmopressin – headache, Actions nausea, vomiting, • Desmopressin metabolities nosebleeds, stomach pain, replace Vasopressin and convulsions, thrombosis, encourage water conservation myocardial infarction and release of blood coagulation • Bromocriptine – confusion, factors. Bromocriptine inhibits secretion of prolactin from the dizziness, nausea, vomiting, pituitary gland. headache, constipation, Uses dyskinesias • Diabetes Insipidus (Type 1) – polyuria, and nocturnal enuresis • High Prolactin levels – infertility and impotence
  102. 102. Sex hormones and drugs Infertility • Side effects • Anti-oestrogen • Headache – Clomifene (Clomid) Action • Oedema • Selective Estrogen Receptor Modulator • Hypertension (SERM), increasing production of • Nausea and Vomiting gonadotropins by inhibiting negative feedback on the hypothalamus • Post menopausal Uterine • Gonadotrophins Bleeding – Choriogonadotropin alfa (Ovitrelle) Long term use – Follitropin alfa, Lutotropin Alfa (Pergoveris) • Thromboembolisms Actions • Myocardial infarction, • Causes ovulation • Breast/Uterine Cancer • Androgens • Raloxifene – hot flushes, leg – Testosterone (Andropatch) cramps, swollen ankles, leg pain • Actions swelling and ulcers • Stimulates leydig cells to synthesize testosterone Uses • Infertility in men
  103. 103. Sex hormones and drugs • Female sex hormones (HRT) Side effects – Oestradiol (Climera, Evorel) • Headache – Estradiol, Medroxyprogesterone • Upset stomach, stomach cramps or (Indivina) bloating – Medroxyprogesterone (for • Diarrhoea endometriosis) (Provera) • Appetite and weight changes – Levonogestrel (emergency • Changes in sex drive or performance contraception) (Levonelle) • Nervousness Actions • Brown or black patches on the skin • Replaces hormones • Acne Uses • Swelling of hands, feet, or lower legs • Osteoporosis due to fluid retention • Menopause symptoms • Changes in menstrual flow – hot flashes, vaginal dryness, • Breast tenderness, enlargement, or urinary stress incontinence, chilly discharge sensations, dizziness, fatigue, • Sudden difficulty wearing contact irritability, and sweating lenses
  104. 104. Sex hormones and drugs
  105. 105. Antidiabetic drugs • Insulin preparations(Type 1 im) • Type 2 • Short acting • Sulphonylureas – Insulin, rDNA – Glibenclamide (Daonil) Saccharomyces cerevisiae – Glicazide (Daimicron) (Actrapid) – Glimepiride (Amaryl) – Insulin aspart (Novomix) – Glipizide (Glibenese) • Intermediate acting • Glucosidase inhibitors – Huminil 1 – Acarbose (Glucobay) – Insuman basal • Biguanides • Long acting – Metformin (Glucophage) – Insulatard – Levimir • PPAR gamma antagonists – Lantus – Pioglitazone (Actos) – Rosiglitazone (Avandia)
  106. 106. Type 2 Antidiabetic drugs • Sulphonylureas – Glibenclamide (Daonil) Side effects – Glicazide (Daimicron) • Hypoglycaemia: fatigue, – Glimepiride (Amaryl) tremors, hunger, headache, – Glipizide (Glibenese) Actions palpitations, blurred vision, – Act on the pancreas and block ATP confusion, cold sweats, potassium channels which causes influx of convulsions, coma calcium and insulin release. Also reduce glucagon levels and stimulate binding of • Weight gain insulin to target tissues. • Glucosidase inhibitors • HyperInsulinemia – Acarbose (Glucobay) • Acarbose and Metformin – • Biguanides – Metformin (Glucophage) GI disturbances: flatulence, Actions diarrhoea, cramping. Rarely – Inhibits glucogenesis in the liver reducing lactic acidosis the output of glucose from the Liver and blood sugar levels
  107. 107. Anti-diabetic drugs
  108. 108. Antibacterial –Nucleic acid inhibition • Sulphonamides (UTI) Side effects – Nitrofurantoin (Furandantin, Macrobid) – Trimethoprim (pneumocystis carinii) • nephrotoxicity due to crystalluria, (Monotrim Suspension) • hypersensitivity reactions from Actions rash to angioedema. – Prevents DNA synthesis – Inhibits B5 (important in AA synthesis) • Serious blood reactions e.g. Uses granulocytopenia, • Respiratory Tract Infections thrombocytopenia, megaloblastic • GI Tract Infections anemia, leukopenia, haemolytic • Urinary Tract Infections • Genital Tract Infections anemia. – Sulphonamides (UTI) • Other side effects – nausea, – Strep pneumoniae vomiting, stomach pain. – Nocardia asteroide, – H influenzae, • Contraindicated in pregnant – E Coli, Shigella women and infants under 2 – Trimethoprim months – Listeria monocytogenes, H Influenzae, Legionella pneumonphillia, E Coli, Proteus mirabilis, Salmonella typhi, Shigella
  109. 109. Antibacterial –Nucleic acid inhibition • Quinolones Side effects – Ciprofloxacin (Ciproxin, Biofloxcin) • Diarrhoea/nausea, – Levofloxacin (Tanavic) vomiting, – Moxifloxacin (Avelox) • Headache/dizziness, Actions phototoxicity. – Prevents DNA synthesis – Inhibits B5 (important in AA • To be avoided in pregnancy synthesis) and breast feeding and in Uses children under 18. – Neisseria gonorrhoeae, Bacillus • Can cause articular cartilage anthracis, Enterobacteriaceae, E Coli, Psuedomonas, Klebsiella erosion, causing ruptured pneumoniae, Proteus mirabilis, tendons in adulthood. Serratia marcescens, Shigella, H Influenzae, Legionella pneumophillia (Legionnaires Disease), Mycoplasma pneumonia, Chlamydia pneumonia, Mycobacterium tuberculosis
  110. 110. Antibacterial –Nucleic acid inhibition • 5-Nitroimidazoles Side effects – Metronidazole (anaeobic infn.) • Dapsone – methemoglobinemia, (Flagyl, Metronide) peripheral neuropathy, erythema – Rifampicin (TB, Leprosy) (Rifadin) nodosum Actions • Ethambutol – optic nerve neuritis, – Prevents cell walls formation and inhibits decrease in vision, colour blindness, protein folate and RNA synthesis. worsens gout Uses • Isoniazid – hypersensitivity reactions, peripheral neuritis, paresthesias, – Mycobacterial infections: convulsions in patients prone to seizures, – TB mental abnormalities, optic nerve neuritis – Leprosy • Rifampicin – nausea and vomiting, fever, – Pneumocystis rash, jaundice. Caution in patients with – Neisseria Meningitidis, chronic liver disease, alcoholics and the – H Influenzae elderly – Lung Infections • Rifabutin – rash, neutropenia, liver function text abnormalities, anemia, – Genitourinary Tract Infections thrombocytopenia – Meningitis • Pyrazinamide – gout, nausea, hepatitis, hyperuricemia, rash, joint pain
  111. 111. Antibacterial – nucleic acid inhibition
  112. 112. Antibacterial – cell wall inhibition • Penicillins • Cephalosporins – Benzylpenicillin (Crystapen) • Orally active – Penicillin V (Calvepen) – Cefaclor (RTI, otitis media, • Broad spectrum soft tissue, UTI, – Amoxicillin (RTI, GU, gynae, nasopharyngeal) (Distaclor, gonorrhoea, peritonitis, bac endocardiitis, Keftid) septicaemia, wound infn)(Augmentin, – Cefuroxime (Zinacef) Amoxil) – Cephalexin (RTI, otitis media, – Ampicillin (septicaemia, endocarditis, soft tissue, GU, dental infn) osteomyelitis, meningitis, abdominal (Keflex) surgery)(Penbritin, Clonamp) – Ceftriaxone (RTI, Renal, UTI, • Penicillinase resistant septicaemia, meningitis, soft – Flucloxacillin (staph infn., tissue, gonorrhoea) (Rosephin) endocarditis) (Flucillin) • Vancomycin (staph enterocolitis) • Antipseudomonal (Vancocin Matrigel) – Piperacillin, Tazobactam (RTI, • Teicoplanin (staph inf prophylactic) intra-abdominal, septicaemia, (Targocid) neutropenia) (Tazocin)
  113. 113. Antibacterial – cell wall inhibition Side Effects • Diarrhoea • Nausea and Vomiting • Abdominal Pain • Swollen Tongue • Bruising • Jaundice • Rash • Itching • Fever • Sore Throat • Nephritis • Neurotoxicity - especially in Epileptic patients • Eosinophilia
  114. 114. Antibacterial – cell wall inhibition
  115. 115. Antibacterial – protein synthesis inhibition • Actions • Chloramphenicol (eye infn) (Chloromycetin) • Attack bacterial ribosomes, prevents protein • Macrolides synthesis – Clarythromycin (RTI, acute otitis media, H.Pylori, ST infn) • Tetracyclines (Klacid) – Doxycycline (RTI, sinusitis, UTI, STI, cholera, plague) – Erythromycin (Erythroped, Erythyrocin) (Vibramycin) – Azithromycin (RTI, otitis media, genital chlamidia infn) – Minocycline (acne) (Minosil) (Zithromax, Azromax) – Uses – Uses – Bacillus antracis – Staph aureus/pneumoniae/pyogenes – Brucella – Corynebacterium diphtheriae – Vibrio cholerae – Bordetella pertussis – Yersinia pestis – Capmyobacter jejuni – Clostridium perfingens – Treponema palladium • Aminoglycosides • Others – Amikacin (pseudomonal infn) (Amikin) – Dalfopristin, Quinpristin (Serious gram+ infn) (Synercid) – Tobramysin (chronic airways infn pseudomonas) (Cidomycin, Genticin) – Gentamicin • Uses – Enterococcus Gram +ve – Brucella – Klebsiella – Pseudomonas – Yersinia Pestis
  116. 116. Antibacterial – protein synthesis inhibition
  117. 117. Antifungal drugs Antifungal – Side effects • Polyenes – Nausea, vomiting, skin irritation, H/A – Amphotericin B (Aspergilliosis, candida, • Clotrimazole – skin burns cryptococcal meningitis, histoplamosis) (Albecet) • Fluconazole – abdominal distension, – Nystatin (Candida) (Mycostatin) diarrhoea, hepatitis • Imidazoles[Topical] • Flucytosine – neutropenia, – Clotrimazole (Candida) (Canestan) thrombocytopenia, bone marrow depression, alters liver function tests, severe – Ketoconazole (candida) (Nizoral) enterocolitis • Triazoles • Itraconazole – hypokalemia, hypertension, – Fluconazole (candida, meningitis) (Diflucan, oedema Byfluc, Diflazole) • Ketoconzole –abdominal pain, gynecomastia, – Itraconazole (Candida, histoplasmosis, decreased libido, impotence, menstrual cryptococcal infn) (Sporanox) problems, affects liver function tests, • Flucytosine (Candida, crytococcal) (Ancotil) jaundice • Terbinafine (histoplasmosis, cryptococcal [not • Miconazole – vaginal irritation meningitis], systemic fungal) (Lamasil, Fungafine) • Amphotericin –fever, bleeding symptoms, • Caspofungin (candida, aspergillus) (Cancidas) abdominal pain, muscle and joint pain • Nystatin – diarrhoea • Terbinafine – blurred vision, affects liver function tests, neutropenia, hepatotoxicity
  118. 118. Antiviral drugs • Penetration inhibitors • Side effects – Amantadine (flu prophylactic) • Acyclovir – headache, diarrhoea, nausea (Symmetrel) and vomiting, renal dysfunction (high • Nucleoside Reverse Transcriptase dose) Inhibitors (NTRI’s) • Famiclovir – headaches, nausea, – Stavudine (HIV) (Zerit) adenocarcinomas and testicular toxicity – Zidovudine (HIV) (Retrovir) • Ganciclovir/Valganciclovir – GI upset, – Tenofovir (HIV) (Viread) neutropenia, carcinogenic, embryotoxic • Non-Nucleoside Reverse Transcriptase • Indinavir – headache, GI upset, Inhibitors NNRI’s nephrolithiasis, hyperbilirubinemia – Nevirapine (HIV) (Viramune) • Lamivudine – headache and dizziness • Protease inhibitors • Oseltamivir – GI upset – Ritonavir (HIV) Kaletra) • Ribaviran – elevated bilirubin, transient anemia – Saquinavir (HIV) (Invarase) • Rimantidine – GI upset • Neuramanidase inhibitor • Valacyclovir – GI upset, thrombocytopenia – Zanamivir (flu) (Relenza) purpura • Herpes Simplex • Zanamivir – headache, sore throat, cough, – Aciclovir (Zovirax) wheezing – Famciclovir (recurrent genital herpes) (Famvir)
  119. 119. Antifungal and antiviral drugs
  120. 120. Drugs – parasites - helminths • Intestinal nematodes • Platyheminths • Roundworm – Piperazine, levamisole, mebendazole, • Trematodes • Hookworm – Schistosomiasis – Bephenium, Trichlorethylene, Thiabendazole • Praziquantel • Whipworm – Mebendazole, thiabendazole – Cestodes • Threadworm (common in children) • Praziquantel – Thiabendazole, • Niclosamide – Medendazole (GIT worms) • Side effects (Vermox) • Albendazole – headache, nausea, liver toxicity, agranulocytosis, pancytopenia • Tissue Nematodes • Dying parasites can cause inflammatory – Filaria (blood worms, if in lymphatics responses, headache, vomiting, fever, convulsions and mental changes. can cause obstruction and swelling) • Mebendazole – abdominal pain and diarrhoea • Diethylcarbamazine • Ivermectin - fever, headache, dizziness, somnolence and hypotension. • Praziquantel – drowsiness, dizziness, malaise, GI disturbance and poor appetite • Thiabendazole – dizziness, poor appetite, nausea, vomiting, erythema multiforme, Stevens-Johnson syndrome (fever, skin lesions, mucous membrane ulcers)
  121. 121. Drugs – parasites - helminths
  122. 122. Drugs parasites - protozoa • Malaria (Plasmodium) • Amoebic dysentery – Tissue schizonticide – Metronidazole (Flagyl) • Primaquine • Giardiasis – Blood schizonticide (If – Metronidazole (Flagyl) clinical attack) • Proguanil (Paludrine) • Trochonomiasis • Mefloquine (Larium) – Metronidazole (Flagyl) • Chloquine (Avloclor) • Pneumocytosis – Pentamidine (Pentacarinat) • Leishmanisasis – Stibogluconate (Pentostam) • Tripanosomiasis – Suramin (Germanin)
  123. 123. Drugs parasites - protozoa • Amoebiasis (Amoebic Dysentery) • Chloroquine – nausea, diarrhoea, (Metronidazole, Paromomycin, abdominal pain, headache, dizziness, Tinidazole) hearing disorders, mood changes (see Mefloquine), rash, blurred vision • Cryptosporidiosis (Paromomycin) • Doxyclycline – nausea, vomiting, • Malaria (Chloroquine, Doxycycline, diarrhoea, mouth ulcers, headache, rash, Mefloquine, Quinine, Quinidine, photosensitivity, blurred vision Primaquine, Proguanil, • Mefloquine – nausea, vomiting, headache, Pyrimethamine) dizziness, abdominal pain, depression, • Giardiasis (Metronidazole, Tinidazole) anxiety, panic attacks, hallucinations, delusions, hearing disorders • Pneumocystis Pneumonia • Primaquine – abdominal bloating, (Atovaquone, Pentamidine, diarrhoea, methemoglobinemia, Sulfonamides) granulocytopenia, agranulocytosis, • Toxoplasmosis (Atovaquone, hemolytic anemia Pyrimethamine, Sulfonamides) • Quinine – nausea, vomiting, diarrhoea, • Trichomoniasis (Metronidazole, headache, tinnitus, dizziness, rash, hearing loss, blurred vision Tinidazole) • Malarial Drugs – discoloration of mucous • Trypanosomiasis (Sleeping sickness) membranes and nail beds, angina, (Pentamidine, Primaquine) palpitations, arrhythmias
  124. 124. Drugs parasites - protozoa
  125. 125. Drugs used in cancer Inhibit DNA synthesis Side effects – Cytarabine (inhibits DNA • Nausea polymerase) • Antimetabolites • Vomiting – Methotrexate • heart arrhythmias • lymphocytic leukaemia, • Neutropenia choriocarcinoma, Burkitt's lymphoma, breast • Hair loss – Capecitabine (Xeloda) • colorectalcancer and breast cancer – Fluorouracil – Raltitrexed – Mercaptopurine – lymphocytic leukemia • Vinca alkaloids -antimicrotubule – Vinblastine – Hodgkin’s lymphoma, cancer of lung/breast/testicles, head and neck – Vincristine – Non-Hodgkin’s lymphoma, lymphoblastic leukaemia, • Taxanes – Paclitaxel
  126. 126. Drugs used in cancer Inactivate DNA • Alkylating agents are • Alkylating agents carcinogenic and can cause – Chlorambucil (Endoxana) treatment induced – multiple myeloma and lymphocytic leukemia neoplasms many years after – Ifosfamide (Mitozana) treatment – Estramustine - prostate cancer • Common: – Cyclophosphamide (Endoxana) • Vomiting – Burkitts lymphoma, breast cancer • Stomatitis – Melphalan (Alkaran) • poor appetite, diarrhoea – multiple myeloma and lymphocytic leukaemia • hair loss – Bulsulfan (Busulfex, Myleran) • bone marrow suppression – Granulocytic leukaemia
  127. 127. Drugs used in cancer • Antibiotics (cytotoxics) Side effects – Doxorubicin – Hodgkin’s lymphoma, lung, • Nausea breast, bladder, stomach, thyroid and uterine cancer, • Vomiting Kaposi’s sarcoma • heart arrhythmias – Actinomycin D (inhibits transcription) • Neutropenia – gestational trophoblastic neoplasia, Wilms' tumour and • Hair loss rhabdomyosarcoma • Steroid hormones – Glucocorticoids – Oestrogens – Anti-oestrogens – Androgens • Monoclonal antibodies – Rituximab (B-Cell lymphoma) (Mabthera)
  128. 128. Drugs used in cancer
  129. 129. Adverse drug reactions

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