-Table-of-Summary-of-Drugs.docx.pdf

Anti-angina Agents (credit to: yin yian) Drug Class Drug Name Indications Pharmaco MOA/ Side/ Contraindications -kinetics Pharmacodynamics...

Anti-angina Agents (credit to: yin yian) Drug Class Drug Name Indications Pharmaco MOA/ Side/ Contraindications -kinetics Pharmacodynamics Adverse effect Organic Nitrates Nitroglycerin/ GTN-sublingua Nitrate converted to NO by enzymetic Headache, Glyceryl l/ process, activates GC, increased cGMP postural trinitrate (GTN) spray level, Decrease Ca2+, relaxation hypotension Onset : 2 mins (vasodilation) , facial Isosorbide Duration: 25 flushing, mononitrate mins Venodilation- Decreased preload & tachycardia (ISM) Arterial Vasodilation- Decreased ISM- Oral afterload, Decrease cardiac work, Onset: 30 mins decrease O2 demand Duration: 12 Coronary vasodilation- hours Increased myocardial perfusion, increase O2 supply Beta blocker Propranolol Stable angina -Decrease HR Atenolol pectoralis -Decrease cardiac contractility, Metoprolol Hypertension decrease O2 demand + Nitrate for -Decrease HR, diastolic filling time angina increase, increase coronary perfusion, + CVS drugs to increase O2 supply prevent MI Ca2+ channel Nifedipine Nifedipine- Nifedipine- blocks Ca2+ channel in blocker Verapamil variant angina vascular cells, peripheral vasodilation, Diltiazem (elderly) increased coronary flow, increase O2 supply Verapamil- Verapamil-block Ca2+ channels cardiac stable & muscle, decrease cardiac contractility, unstable angina decrease O2 demand Inotropic Agents (CHF) Drug Class Drug Name Indications Pharmaco MOA/ Side/ Adverse Contraindications -kinetics Pharmacodynamics effect Cardiac Glycoside Digoxin CHF (+ve inotrope) +ve inotrope: Inhibition of GIT: abd pain, Ventricular Digitalis NA K ATPase pump, anorexia ,nausea, dysrhythmias, MI, Atrial fibrillation (-ve increase intracellular Na, diarrhea hypokalemia, chronotropic) Na Ca pump stops CNS: headache, hypomagnesemia, pumping out Ca, increase hallucination, hypercalcemia intracellular Ca, increase confusion contractility Vision change -ve chronotropic: Indirect Decrease vagal stimulation on AV intracellular K- node, increase refractory facilitate Dig period, decrease effect, toxicity ventricular rate, Eg: Furosemide, bradycardia excretion of K in ascending loop of Henle Beta adrenergic Dobutamine CHF Selective Beta 1 agonist- Tachycardia, agonist synthetic catecholamine: increase SBP strong inotropic effect (OD), increase myocardial O2 Peripheral vasodilation demand, secondary to metabolite: arrhythmia 3-O-methyldobutamine (antagonist of alpha-adrenoreceptor)  Phosphodiesterase Inamrinone Inamrinone (less used)- I.V Inhibit PDE3, increase Hypotension, inhinitor Milirinone dangerous arrhythmia intracellular CAMP headache, - increase Ca, contraction arrhythmia Milirinone(preferred) X of cardiac m. increase heart O2 demand -decrease Ca, relaxation of vascular smooth m. Calcium sensitizer Levosimedan Benefit I.V Increase myocardial Headache, -X increase heart O2 needs sensitivity to Ca, enhance hypotension -Vasodilation affinity of Troponin C to Ca -Not cause arrhythmia during systole, Increase -Reduce death in contractility decompensated HF Anti-HPT (credit to: Gee) Drug class Names Indication Pharmacokinetic MOA/ Side/adverse effect Contraindication (ADME) Pharmacodynamics Beta Blocker Non-selective β As 1st line HPT tx when -Orally active cardiac β1 Bradycardia -heart blocks (-olol) Propanolol others disease coexists. -Take several receptors,↓HR↓CO Hypotension -bradycardia Carteolol e.g. heart failure, weeks to develop kidney β1 receptors, Rebound HPT -CHF Nadolol previous MI, high risk full effects renin release, -COPD (withdraw) Penbutolol angina pectoris, -Propanolol: angiotensin II, ↓TPR -DM (severe Pindolol migraine, headache. extensive and aldolsterone, ↓salt Bronchospasm peripheral vascular Timolol For HPT with asthma highly variable 1st and water Bronchoconstriction disease) (penbutalol, pindolol pass effect. retention, ↓blood Insomnia =ISA- partial β2 Onset: 30min volume, ↓CO Depression Selective β1 agonist-some degree of Duration: 6-12 hrs Nightmares Metoprolol bronchodilation Constipation Atenolol Hypoglycemia Acebutolol Sexual dysfunction ↓exs tolerance  NO CNS side effect (Atenolol,Metoprolol= hydrophilic) **Labetalol (both α HPT crisis in pregnancy i.v./infusion NOT cause reflex Same as and β blocker) Onset 5-10 mins, Additional α1 tachycardia non-selective β HPT+ CHF lasts 3-6 hrs blocking, vasodilate, blocker **Carvedilol ↓BP Diuretics Thiazides 1st choice in mild HPT, -orally active reabsorption of Na+ Hypokalemia -Hypotension Hydrochlorothiazide long term for essential -A,E rates vary by Na+Cl- Hyperuricemia -Allergy to sulphur Bendrofluazide HPT considerably co-tansporter, (70%) medications ↓Ca+ content -all thiazides= ↓renal tubular Hyperglycemia -Gout ligands for organic reabsorption, Loop Diuretics Act promptly acid secretory sys, ↓ salt and water (10%) -Renal failure Furosemide ↑Ca+ content (Urine), compete with uric retention. Hypomagnesemia -Lithium therapy ↓renal vascular R, ↑ acid for ↑Na+ and water -Hypokalemia renal BF, for poor renal elimination excretion,↓ECFv, Caution: pt takes digoxin at -May worsen function ↓CO/renal BF same time/ those diabetes For additional benefit in predisposed to cardiac Potassium-sparing cardiac remodeling in aldolsterone arrythymias (LVF, IHD,CHF) Spironolactone HF receptors of distal tubule. Centrally Clonidine For HPT complicated by ↓sympathetic Sedation Acting Drugs renal disease outflow from Depression For HPT pregnant pt/ vasomotor center in Rebound HPT /HPT α-Methyldopa renal insufficiency, the brain, ↓HR, ↓CO, crisis (clonidine) asthma,HF ↓BP Vasodilators Hydralazine For moderate to severe Direct vasodilation Reflex tachycardia HPT, often combine β arteries/arterioles, Edema blocker and diuretics ↓PR, reflex Headache tachycardia; BP↓, Nausea  Alone to control renin release, Sweating pregnancy-induced HPT sodium retention, Arrhythmia eclampsia edema. Precipitation of angina Lupus-like syndrome (if high dose)- myalgia, arthralgia, skin rash, fever Indirect vasodilator For moderate to severe α1 receptor in Postural Prazosin (selective α1 HPT in combination with periphery, hypotension antagonist) other anti-HPT drugs. vasoconstriction, (1st dose phenomenon) allow vasodilation, Nasal congestion ↓TPR without ↑CO Failure of ejaculation Adrenergic neuron **rarely used today release of Na from Postural blocker adrenergic neuron hypotension Guanethidine Nasal congestion Failure of ejaculation Ganglion blocker Short-acting, used i.v. Blockade of both Trimethaphan during surgery/ sympathetic and emergency (HPT crisis) parasympathetic nervous **now withdrawn system Ca channel blocker Arteriodilators Oral L-type Ca channel, ↓ Pronounced -heart block (-dipine,others) Ca2+ entry to vasodilation induce reflex -sick sinus syndrome Dihydropyridines All grades of essential vascular smooth tachycardia (slow conducting (DHP) HPT muscle, relax, effect) Headache Nifedipine For moderate to severe i.v. vasodilation, ↓PR, -renal/ hepatic Nicardipine (combine β blocker) Onset 5-10 mins ↓BP, ↓workload Peripheral edema dysfunction Alternative for pt Last for 15-30 Hypotension - pregnancy Non-DHP contraindicate to mins Bradycardia /lactation Verapamil, Diltiazem thiazide/β blocker Skin flush/ rash Nausea Dizziness Fatigue KATP channel opener For HPT crisis/ i.v. Converted to Hirsutism quick-acting minoxidil sulphate, Minoxidil open K+ channel, hyperpolarization, arterioles relax,↓TPR, ↓BP Diazoxide Non- diuretic thiazide Same as above Hyperglycemia Hyperuriceamia Edema  Nitrovasodilator Venodilators+ Cont. infusion React with –SH Cyanide poisoning Na Nitroprusside arteriodilator Immediate onset group, release NO, (dyspnea, vomit, LOS, For ICU HPT crisis but lasts only vasodilation, ↓TPR dilated pupils, ataxia, Post-op heart surgery 2-5mins dizziness, headache, shallow breathing) Suppress iodine uptake (hypothyroidism) ACE inhibitor Captopril -HPT with All ACE inhibitor ACE, formation Ang Postural -pregnant women (-prils) Enapril CHF,T1DM,when not completely II: hypotension (d/t fetotoxic) Benazepril thiazide & β blocker are absorbed orally. vasoconstriction, Renal insufficiency -Angioneurotic contraindicated Ramipril,Fosinopril TPR and afterload↓, edema Reflex tachycardia -HPT w renal require only release of -renal artery dysfunction 1/day. Taken on aldosterone,↓CO Hyperkalemia stenosis empty stomach (no salt/ water Peptic ulcer except retention) Chest pain Captopril (require degration of Arrhythmia M:hydrolysis by bradykinin Angioedema hepatic enzymes) (vasodilator) Persistent dry cough Through renal Fetotoxic elimination except Fosinopril. T1/2=2-12hrs Angiotensin Losartan -as substitute for ACE All orally active, Block Ang II Teratogenic -pregnant women II receptor Irbesartan inhibitor which pt has dosage only 1/day. receptor (Gq Skin rash, dry blockers Candersartan severe Losartan-extensive coupled): Alopecia (ARBs) cough/angioedema first pass hepatic Vasodilatation, TPR Syncope (-sartan) metabolism and afterload↓, include conversion release of Postural to active aldosterone,↓CO hypotension  metabolites (no salt/ water Dry mouth (others inactive retention) Tooth pain metabolites) Eliminate through urine, feces NO S/E as ACE inhiitor: Angioedema Persistent dry cough Dopamine 1 Fenoldopam Safely used all HPT i.v. -Glaucoma receptor crisis, benefit for renal Onset 2-5 mins agonist insufficiency Lasts 30 mins CNS stimulant (credit to: Elene) Name of drugs Site of Action Mechanism of Action Side Effect Analeptic drugs -Brainstem -Increase respiratory activities and -Respiratory stimulants (Doxapram, Amphinazole) -Spinal vasomotor centres (reflex stimulation) -Convulsion agents (Strychnine, Picrotoxin, Leptazol) Psychostimulants -Dopamine i. Stimulates release dopamine -If overdose, the stimulation will last (Physhomotor stimulants) neurons ii. Blocks reuptake sites of dopamine till 5 – 20/30 hours then followed by -Amphetamine, Caffeine, Nocotine, Cocaine, Ecstasy pills iii. Inhibits monoamine oxidase (MAO) depression, anxiety and hunger which then cause increase of dopamine -It also may cause death d/t burst of activity in brain blood vessels in brain, muscle damage, heart + renal failure, dehydration + violence Psychostimulants -Block dopamine reuptake sites thus Withdrawal syndrome (Physhomotor stimulants) allowing dopamine to remain active in -Fatigue, troubled sleep, irritability, -Amphetamine, Caffeine, Nocotine, Cocaine, Ecstasy pills the synapse longer intense hunger, depression, suicidal Psychostimulants (Physhomotor stimulants) -Amphetamine, (Methylxanthenes -Caffeine, Theophylline), Nocotine, Cocaine, Ecstasy pills Physchodysleptic agents (Psychotomimetic agents) -Effects over thoughts, perception and -Lysergic acid Diethylamide, LSD mood -Mescaline -Psilocybin Name of drugs (CNS Depressant) Site of Action Mechanism of Action Side Effect Anxiolytic and Hypnotic drugs GABA receptors - it induced the inhibition effects of -Muscle relaxant -Barbiturate (Pentorbarbitone) GABA’A’ receptors -Amnesia effects -Benzodiazepine (Short acting ~ Triazolam, Lorazepam -Induction with alcohol Long acting ~ Diazepam, Chlordiazepoxide) -5 HT Agonist (Buspirone) Anxiolytic and Hypnotic drugs -Buspirone at -Headache -Barbiturate (Pentorbarbitone) dopamine -Nausea -Benzodiazepine (Short acting ~ Triazolam, Lorazepam neurons -No sedation and incoordination Long acting ~ Diazepam, Chlordiazepoxide) -Gepirone at 5-HT -5 HT Agonist (Buspirone, Ipsapirone, Gepirone) receptor in cerebral Opoids -Brain -Inhibits the neurotransmitter release -Constipation -Morphine -Spinal cord -Inhibits the Ca uptake into the -Respiratory depression -Diamorphine presynaptic neurons -Sedative -Codein -Enhance the release of potassium -Reduce GIT motility -Pethidine -Nausea and vomiting -Fentanyl (China White) and Sufentanyl -Histamine release -Etorphine Withdrawal syndrome -Pentazocine -Flu-like syndrome -Buprenorphine -Yawn -Naloxone -Running nose -Methadone -Hypertension -Diarrhea -Muscle spasm -Fever -Anxiety  Antipsychotic drugs (neuroleptic drugs, antiSchizhoprenia -Dopamine -Antagonisme at the dopamine receptor Mainly for typical or major tranquilizers) receptors D2 -PseudoParkinsonism (Tremor, -Typical (Chlorpozamine, Haloperidol) -Serotonin -Antagonisme at monoamine receptors dystonia, muscle spasm d/t direct -Atypical (Sulpiride, Clozapine) receptors inhibition at nigrostriatal receptors) -Tardive dyskinesia (Involuntarily movement inhibition also known as Rabbit syndrome d/t proliferation of dopamine receptors at corpus striatum) For both typical and atypical -Antiemesis -Endocrine effects (gynaecomastia, reduce growth hormone secretion) -Effects from monoamine receptors inhibition (dry M.U.S.C.A.R.I.N.E) -Cardiovascular effect (Vasodilatation, hypotension) -Idiosyncratic effects and hypersensitivity (Jaundice, Leukopenia+agranulocytosis) -Skin reaction (Urticaria) Drug Mechanism of action Side effects Pharmacokinetics Phenobarbitone - Inhibits high frequency, repetitive firing of - worsen absence & atonic seizures long plasma half- life, >60h neurons only at high concentrations (PB, Luminal®) - toxicity - sedation, cognitive - enhancement of inhibitory effects of impairment, behavioral changes, -the oldest AED GABA-mediated neurons induction of liver enzymes (risk of drug interactions, eg.with phenytoin) - ↑ duration of opening of Cl- channel ,depression Primidone - metabolized to phenobarbitone and - Should be started slowly to avoid - longer half-life phenylethylmalonamide ( PEMA), both active sedation and GI problems (Mysolin®) metabolites -absorbed completely, low plasma protein binding Benzodiazepines - bind to BAGA inhibitory receptors to ↓ firing - toxicity : rate sedation, ataxia, behavior disorder, (Clonazepam, withdrawal syndrome Klonopin ®) - ↑frequency of opening of Cl- channel Phenytoin - block voltage-gated sodium channel once - hypersensitivity reactions :skin -Half- life 24 h they are activated (use-dependent block) rashes, lupus - Saturation kinetics, unpredictable (PHT, Dilantin®) plasma levels - selectively binding to the channel in the - agranulocytosis , megaloblastic - plasma monitoring often required - oral, occasional inactive state & slowing the recovery rate anemia, hirsutism - prevent reopening of inactivation gate - ↓number of functional channels in repetitive - gingival hypertrophy (gum will grow firing Action Potential (inhibit high frequency over the teeth) repetitive firing) - worsen absence seizures -ataxia, vertigo, fetal malformation Carbamazepine - similar to phenytoin -bone marrow depression Half -life 12-18h (CBZ, Tegretol®) - block voltage-gated sodium channel once (leukopenia, neutropenia, they are activated (use-dependent block) thrombocytopenia, aplastic anemia) - prevent reopening of inactivation gate - sedation, ataxia, blurred vision, - ↓number of functional channels in repetitive water retention, hypersensitivity firing Action Potential (inhibit high frequency reactions, liver failure ( rare) repetitive firing) -Strong induction of liver enzymes, so -inhibits high frequency of repetitive firing risk of drug interactions Valproic Acid - use-dependent blockade of Na+ channels - teratogenic (spina bifida) Half -life 12-15 h -liver toxicity (VPA, Depakote®) - inhibitor of GABA transaminase, ↑ GABA level in the brain, ↑ inhibitory GABA action -generally less than with other drugs - nausea, hair loss, weight gain, fetal malformations Ethosuximide - block T-type Ca2+ channel - Gastric distress ( nausea, anorexia) Long plasma half-life -60h -mood changes, headache (Zarontin®) - inhibiting repetitive 3Hz/second spike wave -exacerbate tonic-clonic seizure discharges in thalamic neurons Drug Mechanism of action Side effects Pharmacokinetics Tiagabine - GABA reuptake inhibitor (block re-uptake of - dizziness, tremor, nervous, cognitive -Plasma half life -7h presynaptic GABA) slowing, psychosis, depression, light -Liver metabolism (TGB, Gabitril®) headedness, sedation Topiramate - block glutamate receptors (AMPA subtype) - CNS side effect : dizziness, fatigue, -Plasma half-life -20h confusion, nervous, cognitive slowing -excreted unchanged (TPM, Topamax®) -teratogenic ( Fetal malformations)  - block voltage-dependent of sodium -sedation -fewer pharmacokinetic interactions channels than phenytoin - potentiate GABA inhibitory effect (acting at a site different from PB & BZ) ** as phenytoin Felbamate -block glutamate receptor (NMDA subtype) - severe hepatitis, aplastic anemia (only -Plasma half-life -20h for refractory cases) -Excreted unchanged (Felbatol®) -Third line drug, used only for refectory periods because of severe side effects - fewer acute side effects - used mainly for severe epilepsy ( Lennox-Gastaut syndrome) Gabapentin - block L-type calcium channel dizziness, nystagmus, tremor, ataxia, Plasma half-life 6-9h - ↑ GABA levels fatigue (GBP, Neurontin®) - adjunct in partial & generalized tonic-clonic -fewer side feects, mainly sedation seizures Zonisamide -block T-type calcium channels - drowsiness, dizziness, irritation, - Plasma half-life -70h -? inhibit CABA reuptake cognitive impairment, somnolence, (ZNS, Zonegran®) Hyalurnic Acid (HA) agitation/irritation -segation (slight), appetite suppression, weight loss Vigabatrin - irreversible inhibitor of GABA transaminase - CNS side effect : drowsiness, dizziness, - short plasma half-life but enzyme - ↑ inhibitory effect of GABA confusion, psychosis, visual defects, inhibition is long lasting (VGB, Sabril®) sedation, behavioural and mood changes ( occasionally psychosis) - visual field deficits **(contraindicated if pre-existing mental illness is present) Lamotrigine - suppress sustained rapid firing of neurons - sedation, ataxia, diplopia -Plasma half-life 24-36h and produce a voltage -dizziness, rashes (LTG, Lamictal®) -inhibit glutamate rekease - use-dependent inactivation of sodium channels - add-on therapy with valproic acid for partial & generalized tonic-clonic seizures Anaesthesia (Credit To: Aen) ANAESTHESIA ‘ without sensation ‘ TYPE GENERAL ANAESTHETICS ( GA ) LOCAL ANAESTHETICS ( LA ) Concept Reversible loss of consciousness A transient loss of sensation in a defined region Put person to sleep without producing a loss of consciousness Work centrally on brain - CNS Type Inhaled Ester-linked Procaine indication Infiltration anesthetics Intravenous Nerve block Balanced agents Pharmacokinetic Rapidly metabolized by esterase enzyme (liver dysfunction) Adverse effect Acute toxicity Allergy ( ester > amide )  vasodilatation Amide-linked Lidocaine indication Infiltration Nerve block Topical Anti-arrhytmatic agent Pharmacokinetic Quickly absorbed + dealkylated in liver Adverse effect Toxicity : >> procaine ventricular fibrillation cardiac arrest CNS effects MOA Act on CNS : Act on defined region : By modifying electrical activity of By blockade of impulse conduction neuron – alteration function of ion along nerve axons from site of pain stimulus to CNS channel Conduction block : Synaptic block : Properties Smooth + rapid induction of Lipid solubility anesthesia Ph influence Rapid recovery after cessation Vasodilatation Minimum adverse effects Wide margin of safety Adequate skeletal muscle relaxation Method of - Surface anesthesia administration Infiltration anesthesia Nerve block IV regional anesthesia Pharmacokinetic Inhaled Anesthetics : Systemic absorption Metabolism: Amount that reaches brain -Ester-linked LA Partial Pressure of anesthetics – -Amide-linked LA thermodynamics of anesthetics Solubility of gas into blood  Cardiac Output Toxicity HHC : Depress other excitable tissue Hepatotoxicity (brain/heart/smooth muscle/NMJ) Nephrotoxicity Systemic toxicity Malignant hyperthermia Direct neurotoxicity GA DRUG Onset of Duration Type Drug Advantage Side effect Indication Contraindication act of act Inhalational Older agent Ether Slow Post op nausea Analgesic onset/ Vomiting Muscle relaxant recovery Highly explosive Obsolete ( Irritant to resp tract preference for something newer except when modern facilities unavailable) Chloroform Cyclopropane Nitrous oxide Rapid 1-3 mins Bone marrow For surgery & Pregnancy 15-30 secs depression; dentistry megaloblastic (anaesthetic + anaemia analgesic effects) HHC Halothane Methoxyflura ne Enflurane Rapid less metabolism seizure induction/ than halothane recovery less risk of toxicity than less accumulation halothane in fat  Isoflurane = 2 -DM metabolism ) dexamethasone stimulate protein Desoxycorticostero cortisol-receptor weeks) -Osteoporosis catabolism/ lipolysis, ne Infection -Renal disease complex leukemia (↑blood Triamcinolone Diabetes -Immuno-compr level leukocytes) IV/IM- Causing gene Na+,water omise dexamethasone activation retention -Mental health Hydrocortisone mRNA production Muscle weakness problem Prednisone Protein synthesis -Pregnant  Aerosol- -CHF/systemic Beclomethasane HPT Mineralocortic Hydrocortisone, Addison disease, D:>90% plasma Aldosterone binds to Salt and water oids (Regulate fludrocortisones diagnose Cushing protein bound. receptor causes retention salt retention) syndrome, M:by liver gene-transcription congenital adrenal enzymes, translation. hyperplasia, relieve conjugated w inflammation, treat glucoronic acid/ Aldosterone-induced allergy sulfate protein increase cell Accelerate lung E: excrete by permeability to Na+ maturation kidney Na+ influx Sex Corticoids Testosterone Hypogonadism/ A: IM/ transdermal, Testosterone Anaemia -Men with (Androgenic propionate testicular buccal tablets, Increase bone density Osteoporosis breast or effect) dysfunction, senile topical gels Increase muscle Hirsutism (F) prostate osteoporosis, severe E: kidney, urine strength and volume Gynaecomastia(M) carcinoma burns,endometriosis Sports -Children Improve hair growth , fibrocystic breast Performance -Heart and renal disease and sebum (abuse)-↑muscle pt production strength, Penile growth endurance, lean Stimulation of stem body mass cell growth in bone marrow Oral Contraceptive Pill ( Credit to: Lim) Drug class Names Indication Pharmaco-k MOA/Pharmocodynamic Side effect Contraindication inetic Combined Oral Etrogen-Ethinyl Prevention for Absorbed The hormones in the COC Estrogen-related(Breast Pregnancy, Contraceptive Estradiol fertilization orally make your body think that it is discomfort, increase risk neoplasm, DM, (COC) pregnant, as a result ovaries of breast&cervial cancer, liver disease, Progestin-noret stop releasing eggs. The lining headache, nausea, gall bladder hindrone, of the womb will not develop vomit, gall bladder disease, CVS norgestrel enough for an egg to grow. The disease, weight gain, disease fluid in the neck of womb chloasma, pruritus become thicker, which make vulvae) the sperm difficult to swim into womb Progestin related (Hirsutisme, mood swing, depression, cholestasis jaundice) CVS effect for age above 35 and smoker (Thrombophlebitis, stroke, MI) Progestin-only Norethindrone Women that Same as COC Irregular menstrual Same as above Pill (Mini Pill) intolerant to cycles estrogen, smoker Emergency Levonorgestrel( Prevention of Delay ovulation and prevent Same as COC side effect Same as above Hormonal high dose pregnancy implantation Contraception progestin only), following Preven(Combina unprotected tion of Ethinyl intercourse Estradiol &Levonorges)  Non-contracep Same as above For women Same as COC side effect Same as COC side effect Same as above tive uses of with OCP heavy/irregula r menstrual, endometriosis, protect ovarian&endo metrial cancer Drug class Names Indication Pharmacokinetic MOA/ Side effect Contraindication Pharmacodynamics Iodine ONLY if iodine deficiency is the cause Hormone Levothyroxine 1st line drug of Replacement (Synthetic T4) choice for Therapy hypothyroidism Liothyronine Acute emergency in (Synthetic T3) myxedema coma Liotrix (Combination of synthetic T3 and T4) Armour Thyroid (Natural T3 and T4) Hypothyroidism (Credit to : Wei Qing) Hyperthyroidism- Graves’ disease (Credit to Wei Qing, Seak tin) Drug class Names Indication Pharmacokinetic MOA/Pharmacodynamics Side effect Contraindication Thionamides Propylthiouracil Effective in long - Oral Inhibit hormone synthesis - Agranulocytosis, Pregnant woman (PTU) term tx of - 6-8 weeks before through irreversible binding thrombocytopenia, and breastfeeding hyperthyroidism maximum effect of the to TPO : SLE-like syndrome (crosses placenta drug achieved - inhibit the iodination - Skin rash, urticaria and enters breast - Crosses placenta process - Arthralgia milk ) - Enters breast milk (PTU - inhibit the coupling - Fewer -PTU lesser less) reactions - Relapse **Additional effect of PTU : - Cholestatic jaundice Metimazole Half-life (t1/2): inhibit the deiodination of (MMI) (MMI) PTU: 2 hours T4 to T3 in peripheral MMI : 8-12 hours tissues Ionic Inhibitor Perchlorate Inhibit the uptake of iodine - Aplastic anemia (CIO4-) into thyroid gland by - Gastric ulcer inhibits the Na+ / I- transport protein 131 Radioactive I - Tx of choice for Half-life (t1/2): Selectively taken up by the - Children Iodine (RAI) Grave’s Disease 8 days abnormal thyroid gland, - Pregnant patients Therapy and multinodular emit both χ-rays and β (teratogenic) toxic function -radiation, then irradiates - Test for thyroid and destroy the thyroid function cells without damaging the adjacent cells Iodide Salts KI, -only used for - Given orally in high - Block thyroid hormone -iodisme (swollen (Non-radioacti SSKI (potassium emergency mx of doses release (via –ve feedback salivary & lacrimal ve: 127I) iodide), thyroid storm meachanism) glands) Lugol’s solution, -presurgery for - Decreases the size and -skin rashes Iodoral (tablet subtotal vascularity of the thyroid form of Lugol’s thyroidectomy gland solution) (lugol’s solution) Beta-blockers - Presurgery tx Symptomatic effect on - Thyroid storm palpitation and tremor but do not alter the rate of T3 and T4 synthesis  MOA Advantages / Side effect Examples Disadvantages Sulfonylureas Binds SUR I Disadvantages : Hypoglycemia 1st gen: (Insulin on KAPT Requires Weight gain (NOT Tolbutamide releaser) channel functionin suitable for 2nd gen: causes g β-cells obese patient) Glipizide channel to be Allergies closed effective Depolarizati No on causes specific calcium effect on channel to plasma opened, lipids increase Strongly calcium bound to influx plasma Stimulate albumin β-cells to secrete insulin Biguanides (Liver) ↓ Advantages: Hepatotoxicity Metformin (Insulin gluconeogen ↓free GI disturbance Sensitizers) esis fatty acid, Lactic acidosis ( (Muscles) ↑ LDL and NOT suitable for Insulin Triglyceri patient with sensitivity des renal, liver or and causes ↑ No weight glucose gain  uptake and Less risk heart failure and utilization of pregnant patient) (Adipose hypoglyca tissue) ↑ emia glucose uptake, ↓ lipolysis Disadvantages: ↑ HDL Glitazones (Liver) Advantages: Fluid retention Troglitazone (Insulin ↓gluconeoge ↓Triglyceri CHF Rosiglitazone Sensitizers) nesis des Hepatotoxicity (Adipose Restore (Troglitazone) tissue) β-cells activate function peroxisome proliferator- activated receptor ɣ, forming a complex PPAR ɣRXR promoting transcription of insulin-sensi tive genes Acarbose (Intestine) Disadvantages: Abdominal - -competitive discomfort  inhibitor of Only to (bloating, α-glucosidas be taken flatulence, e causes along diarrhea) slows down with the Heaptotoxicity of 1st bite of disaccharide a meal ( s and hence polysacchari need to des to take 3x monosaccha per day rides 🡪risk of -↓ glucose overdosa absorption ge) from gut Anti-diabetic (Credit to Hui Shan) CELL CYCLE SPECIFIC AGENTS (CCS) - Effective for high growth fraction malignancies Drug name Indications Mechanism of action Toxicities Folic Acid Analog Methotrexate - Acute lymphocytic leukemia -Inhibitor of dihydrofolate reductase - Bone marrow - Burkitt lymphoma in (enzyme that catalyzes conversion of folic suppression (rescued children acid to tetrahydrofolate) with leucovorin ie. Folic - Breast cancer acid)  - Bladder cancer -Tetrahydrofolate is a necessary cofactor in - Nephrotoxicity - Head and neck carcinomas thymidylate synthesis; thymidylate - Low-dose MTX (effective for essential for DNA synthesis and repair. inflammatory diseases) such as -Thus, it inhibits dTMP synthesis and purine severe psoriasis, rheumatoid synthesis arthritis & Crohn disease. Pyrimidine Analog 5-Fluorouracil - Treatment of slowly growing -Inhibits dTMP synthesis - Myelosuppression solid tumors such as colorectal, (strong) breast, ovarian, pancreatic, and gastric carcinomas - When applied topically, effective in the tx of superficial basal cell carcinomas Cytarabine - Tx in acute nonlymphocytic -Inhibits DNA polymerase (myelogenous) leukemia (AML). -Incorporated into nuclear DNA and can terminate chain elongation -Inhibits RNA function Purine Analog 6-Mercaptopurine 6-MP : -Inhibit the de novo purine ring (6-MP) - Maintenance of remission in biosynthesis. Thus, inhibits purine 6-Thioguanine acute lymphoblastic leukemia synthesis (6-TG) - Crohn disease -Incorporated into nucleic acids (DNA and RNA) thus results in non-functional RNA and DNA. B) PLANT ALKALOIDS- generally antimitotic (M-phase) + disturbs mitochondrial function. Vinca Alkaloids Vinblastine -Tx for leukaemia, Hodgkin’s, -Blocks mitosis in metaphase. - Vincristine has NO general - Derived from Vincristine lymphoma. -Binds to tubulin and blocks tubulin to toxicities (ONLY Periwinkle or polymerize to form microtubule thus neuromuscular effects ). Kemunting Cina. inhibits function of microtubules - Thus, it prevents chromosomal segregation and cell proliferation Podophyllotoxins Etoposide -Tx in lung cancer -Inhibits topoisemarase II - General toxicities (refer -In combination -Disturbs mitochondria functions. lecture notes)  with bleomycin and cisplatin -Inhibit RNA synthesis - Haemotoxic for testicular carcinoma. Camptothecins Topotecan -Tx in metastatic ovarian -Inhibit topoisomerase I (essential for - Myelosuppression - From Happy Tree cancer DNA replication) - Bone marrow suppression (Xi Shu) -Tx of small cell lung cancer Taxanes Paclitaxel -Tx in lung, ovarian and -Active in metaphase of cell cycle - Neutropenia - mitotic spindle poison breast cancer -Promote polymerization - Leukopenia from Yew tree. and stabilization of tubulin -Leading to accumulation of microtubule -The overly stable microtubules formed are nonfunctional, and chromosome desegregation does not occur -Results in death of cell C.) ANTIBIOTICS Bleomycin -Testicular cancers -Also can act on non-dividing cells (G0) - Fever -Hodgkin lymphoma -Attack the phosphodiester bonds of DNA, - Allergy resulting in strand breakage (DNA - Pulmonary fibrosis fragmentation) and chromosomal aberrations - NO myelosuppression CELL CYCLE NON-SPECIFIC AGENTS - Effective for BOTH low-growth (solid tumors) and high growth fraction malignancies  Drug Name Indications Mechanism of action Toxicities A.) ALKYLATING AGENTS - Wide variety of - intra-inter -General toxicities - Possess an alkyl haematologic and crosslinking DNA group to form solid tumours. chains : covalent bond with N7 guanine. cells. N1, N3 adenosine. - Carbonium ions N3 cytosine. production (reactive intermediate). - disturbances at replication and transcription processes - DNA chain disruption. Nitrogen Mustards Cyclophosphamide - Myelosuppression - Hemorrhagic cystitis - Alopecia - Amenorrhea Ethylenimines Theotepa Alkyl Sulfonates Busulfan - chronic granulocytic - Myelosuppression leukemia - Pulmonary fibrosis (aged patients) Nitrosoureas Carmustine - Brain tumors - Exert cytotoxic - Delayed effects by an hematopoietic alkylation that depression inhibits replication, - Renal toxicity  RNA and protein - Pulmonary fibrosis synthesis. - Inhibit several key enzymatic processes by carbamoylation of amino acids in proteins in the targeted cells. B.) ANTIBIOTICS - DNA direct acting Doxorubucin (Adriamycin®) - Breast carcinoma - Inhibits - Cardiotoxic (high - Lung carcinoma topoisomerase II dose) - Acute lymphocytic activity. leukemia - Lymphomas Dactinomycin - DNA intercalation - Inhibit RNA polymerase activity & transcription Mitomycin - Metabolic activated - Nephrotoxicity + to alkylating agent pulmonary fibrosis PLATINUM COORDINATION C.) CISPLATIN - Cisplatin : - Similar to Alkylating - Nausea and vomit COMPLEXES - Water soluble IV Tx metastatic agent, reactive - Tinnitus (ototoxicity) + - Carboplatin is developed testicular carcinoma Diamine-platinum. nephrotoxic. due to cisplatin’s severe toxicity.  (with VBL and Intra-DNA cross - Carboplatin is less bleomycin) linking (N7 / O6 toxic, ONLY tx ovarian carcinoma guanine). myelotoxic. (with Inhibits both cyclophosphamide) polymerases for DNA Bladder carcinoma replication and RNA synthesis. - Carboplatin : DNA rupture. used when patients cannot be vigorously hydrated Antimicrobial Agents (Credit to: Sin Jor) Drug class Names Indication Phamacokinetic MOA/ Pharmacodynamics Side effects Contraindication Cell Wall B-lactams *Bacterial meningitis * Given ⮚ Hypersensitivity - From ⮚ (BACTERICIDAL) inhibit the Synthesis Antibiotics * Bone and joint orally,intramuscular mild skin rash to Inhibitors infections and intravenous.( last step in peptidoglycan synthesis anaphylactic shock and *Skin and soft tissue intrathecal not death Penicillins infections. advisable) ⮚ Binds at the serine residue of (PCNs) *Bronchitis * Lipid insoluble : ⮚ Superinfection the PBP (transpeptidase) that (Candidiasis, diarrhea) * Pneumonia unable to enter cross-links the peptidoglycan *Urinary tract infections mammalian cell and strands. * Syphilis  cross BBB ( unless ⮚ Mimicking the meninges is inflamed) * Eliminated mainly D-alanyl-D-alanine residues through renal that would normally bind to this active site ⮚ The weakness in the cell wall causes the cell to lyse (OSMOTIC LYSIS) Cephalosporins *Most given parentally, * Similar to Penicillins : interfere * Allergic rxn less severe ⮚ Avoid in ⮚ Surgical prophylaxis intramuscularly or bacterial peptidoglycan than PCN but there may combination ⮚ Skin and soft tissue intravenously ( maybe synthesis after binding to be some cross-reactivity with other infections (due to orally also ) Beta -lactamase with PCN-allergic pt ototoxic drugs Strep. & S. aureus * Excretion through infections) kidney. ⮚ Urinary tract infection (E. coli) ⮚ Cephs is 1st-line treatment of Klebsiella infections (synergy with aminoglycoside) Glycopeptides Binds to amino acid side chain - Vancomycin of NAM molecules, interfering with peptidoglycan synthesis Protein Aminoglycosides * Highly polar. ⮚ ototoxicity due to Avoid in ⮚ Irreversibly bind to the 30s Synthesis Gentamicin * Usually given irreversible damage on 8th combination ⮚ superficial infections Inhibitors intramuscularly or subunit (16S ribosomal RNA) with other ⮚ Synergism with other intravenously. ( not so that it changes the shape ototoxic drugs cranial auditory nerve from GIT) of 30S subunit. * ½ life = 2-3 hrs -Hearing loss (cochlear ATB ⮚ Induce misreading of the * Cross placenta ut do toxicity) -with β-lactam not cross BBB mRNA and therefore -Vertigo, loss of balance (synergism)in tx of production of faulty proteins (vestibular toxicity) bacterial corneal ulcer ⮚ Nephrotoxicity  -Acute tubular necrosis Tetracycline Tx of chlamydial disease * Given orally and ⮚ Teeth and bone ⮚ Not ⮚ Bind 30S subunit reversibly parenterally. recommende * Absorption improved hence, - Yellow discoloration of ⮚ Inhibit aminoacyl transferase , d for young in absence of food, teeth decreased absorption blocking the binding of tRNA - Retardation of bone in presence of milk to the acceptor site (A site) growth children, on the mRNA-ribosome ⮚ Photosensitivity rxns pregnant & complex (severe sunburn) nursing ⮚ Prevents continuation of mothers protein synthesis ⮚ Superinfection ⮚ Avoid in (candidiasis, combination pseudomembranous colitis with other ⮚ Nephrotoxicity nephrotoxic drugs and in renal disease Macrolide ⮚ tx of superficial ocular * Administered orally, ⮚ Bind reversibly to the 50S ⮚ P450 inhibitors- can infections involving can also be subunit affect bioavailability of conjunctiva & cornea parenterally. ⮚ Block the translocation of the other drugs. Antibiotics * Do not cross BBB. Erythromycin ⮚ Alternative to TC ribosome to the next codon * ½ life = 90 min (Ak-mycin®) against Chlamydial * Partly inactivated in ⮚ GIT side effect trachomatis infection liver. in adult * Majority eliminated in bile. Nucleic Fluoroquinolones *Given orally, well ⮚ Inhibit DNA enzyme in ⮚ Ciprofloxacin is a CYP450 ⮚ Not ⮚ Urinary tract infections Acid absorbed. susceptible microorganisms inhibitor and may cause recommende Synthesis : even when caused by * Most fail to cross BBB multidrug- resistant interfering with replication. life-threatening d for < 18 yr Inhibitor bacteria ⮚ BACTERICIDAL interaction with other (damage drugs growing cartilage)  ⮚ Caution to ⮚ Bacterial diarrhea take with (Shigella, Salmonella, E. coli) renal or CNS disorder, ⮚ Infections of soft seizures or tissues, those taking musculoskeletal and Theophyline intra- abdominal infections ⮚ Respiratory tract infections (TB, URTI, LRTI) ⮚ Gonococcal infection ⮚ Ciloxan® ophthalmic solution and ointment. ⮚ Tx of infections in corneal ulcer and conjunctivitis ⮚ Joint symptoms –joint swelling, tendonitis, tendon rupture Inhibitors Sulfonamide *-Readily absorbed in * Compete with PABA for ⮚ Hypersensitivity rxn ⮚ Combined with of Folate GIT. dihydropteroate synthtase. -Rashes, pruritis, erythema, Synthesis trimethoprim ( * Pass into * Inhibit growth of bacteria, not co-trimoxazole) for exfoliative dermatitis, inflammatory exudates kill ( BACTERIOSTATIC ) Pneumocystis carinii. drug-induced fever. and cross both * PABA = precursor in the placental and BBB. synthesis of folic acid in ⮚ Hematological disorder * For infected burns *Metabolised mainly in bacteria -Acute hemolytic anemia *For some sexually liver. * Folate required for synthesis (G-6PD), aplastic anemia transmitted of precursor of DNA and RNA Agranulocytosis, infections.( eg: thrombocytopenia,  trachoma, chlamydia, granulocytopenia (due to chancroid ) bone marrow suppresion) Trimethoprim * Given orally *Folate antagonists. * Nausea * Fully absorbed from *Inhibit dihydrofolate reductase * Vomiting. GIT, reached high , reduced amount of * Blood disorder concentrations in lungs tetrahydrofolate that is * Skin rashes and kidneys., fairly high essential for DNA synthesis. in CSF. * Eliminated by kidney with decreased urinary pH. Drug Class Names Indication Pharmacokinetics MOA/Pharmacodynamics Side effect Contraindication COX ASA Antipyretic acetylsalicylic acid is inflammation effect GIT irritation ( Abnormal inhibitors Analgesic metabolished when COX-1 ( helps to build asymptomatic due renal function Adult: 650 mg two acetyl group is up prostaglandin to to analgesic effect) h/o of peptic Anti-inflammatory being removed, only produce the mucus Salicylism ( ulcer Anti-platelet (reduce left salicylic acid in that protect the GIT tinnitus, vertigo, bleeding risk of heart attack, body that lead to the ototoxicity, diathesis use in CVS disorder, COX-1 & 2. nausea, vomiting ) MI) easy to be distributed Respiratory d/t weak acid alkalosis hard to be eliminated Children (younger than 12 yrs old)  Reye’s syndrome d/t ASA is zero-order Indomethacin More potent Easy to be distributed inflammation effect Can cross placenta anti-inflam. than and absorbed due to COX-1 ( helps to build and affect baby ASA (Rheumatoid, lipid soluble up prostaglandin to when pregnancy Gout) produce the mucus Analgesic that protect the GIT Limited antipyretic than ASA