Pharmacy Drugs Flashcards

Question

Thiazide Diuretics

Answer 1

Examples Bendroflumethiazide Indapamide Indications Hypertension Oedema secondary to congestive cardiac failure, liver disease or nephrotic syndrome Contraindications Hypokalaemia, Hyponatraemia, Hypercalcaemia Mechanism of Action Thiazide diuretics inhibit the Na+/Cl- co-transporter in the luminal membrane in the distal tubule of the kidney. This blocks the reabsorption of Na+ and therefore water. Result is lower blood volume and pressure. Adverse Drug Reactions Hypokalaemia, hyperuricaemia, Impaired glucose tolerance Hyponatraemia, hypermagnesemia, Hypercalcaemia, Metabolic alkalosis Cholesterol and triglyceride levels increase

Answer 2

Examples o Infliximab (Monoclonal Antibody) o Adalimumab Mechanism of Action o Blocks the effects of TNF-α o Decreased inflammation, decreased Angiogenesis, decreased joint destruction ``` Adverse Drug Reactions o Increased infections o Tiredness, dizziness o Itching o GI disturbances ```

Answer 3

Levonorgestrel Emergency Contraception ‘Morning after pill’ – Up to 72hrs after sex Very high oral doses of progesterone (1.5mg) alone, or a Progestogen with an oestrogen to prevent implantation of fertilised egg o 75% effective o Indications – Emergency Contraception after unprotected sex o Contraindications – Oestrogen contraindications, need to ask about cycle and when they had sex to determine if the woman is already pregnant. If this is the case it would be illegal to prescribe (abortion).

Answer 4

``` Examples Olanzapine Risperidone Quetiapine Clozapine ``` Route of Administration Oral ``` Mechanism of Action Higher affinity for 5-HT2A receptors than Dopamine D2 Receptors Sedation – Within hours Tranquilisation – Within hours Antipsychotic – Several days or weeks ``` Adverse Drug Reactions Vary between drugs Olanzapine – Significant weight gain, suppressed “full” signals Risperidone – Increased prolactin Sedation Extrapyramidal side effects at high doses ``` Toxicity CNS depression Cardiac toxicity Risk of sudden death with high dose Prolonged QT interval -> Torsades de points Risk of sudden death with large dose ``` Therapeutic Notes Atypical antipsychotics have less extrapyramidal side effects, so are therefore more acceptable to patients First line treatment in schizophrenia

Answer 5

Route of Administration - Oral Indications o Prevention and treatment of MI / Ischaemic stroke, Analgesic o Anti-inflammatory agent Contraindications - Children under 12 years who are at risk of Reye’s Syndrome, Breastfeeding, Haemophilia, peptic ulcers, known hypersensitivity Mechanism of Action - COX-1 Enzyme inhibitor, Prevents the formation of Thromboxane A2 from Arachidonic Acid in platelets. Thromboxane A2 stimulates phospholipase C, increasing calcium levels and causing platelet aggregation Adverse Drug Reactions - Bronchospasm, GI haemorrhage Drug-Drug Interactions - Displaces Warfarin from plasma proteins (PKs) Increases Anti-Coagulant effect of Warfarin at a different site (PDs) Therapeutic Notes Aspirin at 150mg daily after MI has been shown to decrease mortality

Answer 6

Examples - Metformin Indications- Type II diabetes – Endogenous insulin presence required Contraindications o Compromised HRH function o In respiratory disease Mechanism of Action o Unknown o Increases insulin receptor sensitivity, enhancing skeletal and adipose glucose uptake o Inhibits hepatic gluconeogenesis o Reduces hyperglycemia, but does not induce hypoglycemia o Tends to be give 2-3 times a day prior to meals to provide acute negative feedback on top of a basal endogenous insulin signal Adverse Drug Reactions o GI disturbances – ameliorated by slow dose titration o Lactic Acidosis

Answer 7

Examples Senna Route of Administration Oral Indications Constipation and bowel evacuation prior to medical/surgical procedures Contraindications Intestinal obstruction Mechanism of Action Increase gastrointestinal peristalsis and water and electrolyte secretion by the mucosa. Possibly by excitation of sensory enteric nerves. Adverse Drug Reactions Colonic atony (thus constipation) Hypokalaemia (Changing electrolyte balance in the gut) Therapeutic Notes Anthraquinone group is the most frequently used. Senna can be bought O.T.C. (Senokot) Abuse can be detected via Melanosis Coli (pigmentation of bowel wall)

Answer 8

``` Antirheumatic Drugs (DMARDs) (DRUGS SLOW DOWN DISEASE PROGRESSION, DON’T JUST TREAT INFLAMMATION) ``` Examples - Sulfasalazine Indications o Rheumatoid arthritis o Inflammatory bowel conditions Contraindication o Renal impairment o Hypersensitivity Mechanism of Action o Sulfasalazine is broken down in the gut to the active component 5-aminosalicylate (5-ASA) and sulfapyridine, which acts as a vehicle to transport the drug to the colon. o Inhibition of T-cell proliferation and IL-2 production. Reduced Neutrophil chemotaxis and degranulation. Adverse Drug Reactions o Mostly due to sulfapyridine (10-45% of patients) o Myelosuppression o Hepatitis o Rash o GI disturbances (Nausea, vomiting, abdominal pain) Therapeutic Notes o Few ADRs/DDIs seen in Pregnancy o Treating Rheumatoid Arthritis o Only 30-40% 5-ASA is absorbed o Molecular mechanism does not involve COX inhibition o Inhibit T-cell proliferation and IL-2 Production, reduced neutrophil chemotaxis and degranulation o Treating Inflammatory Bowel Disease o 5-ASA reaches the colon in large quantities, but acts via an unknown mechanism (again not COX inhibition)

Answer 9

Examples - Alteplase Reteplase Route of Administration - Intravenous Indications Myocardial infarction, pulmonary embolism Contraindications Recent haemorrhage, trauma, surgery, aortic dissection, coma, history of cerebrovascular disease Mechanism of Action t-PAs are tissue-type plasminogen activators, Plasminogen -> Plasmin Adverse Drug Reactions Nausea, vomiting, bleeding/haemorrhage

Answer 10

Examples o Ipratropium bromide o Tiotropium bromide Indications o Adjuncts to β2 agonists in asthma treatment o COPD Route of Administration o Inhaled Mechanism of Action o Bind to and antagonise M3 cholinergic receptors on bronchial smooth muscle. This blocks the constricting effect of Ach and also inhibits mucus secretion. Adverse Drug Reactions o Not well absorbed through the lungs, avoiding major systemic ADRs o Dry mouth

Answer 11

The POP consists of low-dose Progestogen (a Progesterone analogue). This causes thickening of cervical mucus, preventing sperm penetration. It also has an adverse effect on the endometrium, affecting implantation. Contraception is less reliable than the COCP. It also causes suppression of gonadotrophin secretion, and occasionally ovulation, but the latter effect does not occur in the majority of women. During treatment with the POP ovulation still takes place and menstruation is normal. Route of Administration Oral - Daily, at the same time, starting at day 1 of menstrual cycle. If delay in taking the pill is greater than 3 hours, contraceptive effect may be lost Indications Contraception – More suitable for heavy smokers and patients with hypertension or heart disease, diabetes mellitus, or other contraindications for oestrogen therapy Contraindications Pregnancy, arterial disease, liver disease or breast or genital tract carcinoma Adverse Effects Menstrual irregularities, nausea, vomiting and headache, weight fain, breast tenderness

Answer 12

Name Medroxyprogesterone (synthetic Progesterone) Ethinyloestradiol (synthetic oestrogen) Route of Administration Oral - One a day for 21 days, then break, placebo or iron pill for 7 days Indications Contraception and Menstrual Symptoms Contraindications Pregnancy, breast feeding, heart disease, hypertension, hyperlipidaemia or any prothrombotic coagulation abnormality, diabetes, migraine, breast or genital tract carcinoma, liver disease ``` Mechanism of action Progesterone o Cervical mucus plug o Negative feedback to hypothalamus / pituitary Oestrogen o No LH surge ``` Adverse Effects Venous thromboembolism, Hypertension, decreased glucose tolerance, headaches, mood swings, acne, flushing, nausea, vomiting, headache

Answer 13

``` Examples Atenolol Bisoprolol Propranolol Sotalol ``` ``` Indications Angina Post myocardial infarction Hypertension Arrhythmias ``` Contraindications Non-selective β-blockers (e.g. Propranolol) must not be given to asthmatic patients. Bradycardia, hypotension, AV block, Congestive Cardiac Failure Mechanism of Action Antagonise β-adrenoreceptors. β1-receptors are found in the heart, when they are activated they cause increased Chronotropy and Inotropy. Inhibit renin release Adverse Drug Reactions Bronchospasm, fatigue and insomnia, dizziness, cold extremities, hypotension, bradycardia and decreased glucose tolerance in diabetic patients Drug-Drug Interactions Prevents Salbutamol working (β2-adrenoagonist) Verapamil – Both have –‘ve inotropic action

Answer 14

Examples Codeine (opiate analgesic) Loperamide - Imodium (opiate analogue) Route of Administration Indications Contraindications Inflammatory Bowel Disease – Toxic Megacolon ``` Mechanism of Action Act on opioid receptors in the bowel Reduce motility (increase time for fluid reabsorption) Increase anal tone and reduce sensory defecation reflex ``` Adverse Drug Reactions Nausea, vomiting, abdominal cramps, constipation drowsiness Therapeutic Notes Imodium is 40 times more potent than Morphine as an antidiarrhoeal agent, and penetrates the CNS poorly

Answer 15

Examples Lactulose Movicol (Movicol) Route of Administration Lactulose – Oral Magnesium and Sodium Salts – Rectal Movicol – Orally with fluid (powder) Indications Constipation Lactulose - Liver failure (reduced production of ammonia) Contraindications Intestinal obstruction Mechanism of Action Increase water content of the bowel via osmosis Lactulose – Disaccharide (galactose/fructose) that cannot be hydrolysed by digestive enzymes. The fermentation of lactulose by colonic bacteria gives acetic and lactic acid. This has an osmotic effect ``` Adverse Drug Reactions Flatulence Cramps Abdominal discomfort Caution required to prevent intestinal obstruction ``` Therapeutic Notes Magnesium and Sodium act quickly and are quite severe, so should be reserved for ‘resistant’ constipation if urgent relief is required Lactulose takes 48 hours to work Movicol takes 2-4 days to get relief

Answer 16

``` o AV node blocker o Decreased Automaticity o Increased AVN refractory period o t½ = a few seconds o Given as rapid IV bolus to diagnose and treat supraventricular tachycardias ``` Can be useful in distinguishing SVT with aberrant conduction from VT

Answer 17

``` Inhalational (Volatile) Agents o Nitrous Oxide (N2O) o Isoflurane o Desflurane o Sevoflurane ``` Intravenous Agents o Propofol o Ketamine

Answer 18

Examples Entacapone Route of Administration Oral Indications Adjunct to L-DOPA therapy to reduce end-dose ADRs Contraindications Phaeochromocytoma Mechanism of Action Inhibits the enzyme COMT, which degrades dopamine Adverse Drug Reactions Nausea and Vomiting Abdominal pain Diarrhoea

Answer 19

Inhibits tubular Na/K-ATPase Drug-Drug interaction with Thiazide Diuretics. Hypokalaemia leads to increased digoxin binding and toxicity. Atrial fibrillation or heart failure, Not used as a diuretic, as it has minimalm diuretic effects.

Answer 20

Examples Haloperidol Chlorpromazine Route of Administration Oral Depot (every 2/3/4 weeks) ``` Mechanism of Action Dopamine D2 Receptor Antagonist Sedation – Within hours Tranquilisation – Within hours Antipsychotic – Several days or weeks ``` Adverse Drug Reactions Extrapyramidal effects – Hours or days Neuroleptic malignant syndrome – Severe rigidity, hyperthermia, autonomic instability, cognitive changes (delirium). Associated with elevated plasma creatine phosphokinase (CPK). Extremely rare, but very serious ADR of all antipsychotics. Weight gain Endocrine changes (e.g. prolactinaemia) Pigmentation ``` Toxicity CNS depression Cardiac toxicity Risk of sudden death with high dose Prolonged QT interval  Torsades de points Risk of sudden death with large dose ``` Therapeutic Notes Haloperidol is safe in emergencies

Answer 21

Examples Ranitidine Route of Administration Oral Indications Peptic ulcer disease and GORD Mechanism of Action Competitively antagonist H2 receptors, blocking the amplifying action of Histamine on Parietal cells ``` Adverse Drug Reactions Dizziness Fatigue Gynaecomastia Rash ``` Drug-Drug Interactions Cimetidine is a CYP450 enzyme inhibitor Avoid use with patients being treated with Warfarin, Phenytoin etc. Therapeutic Notes Given at night when acid buffering by food is at its lowest

Answer 22

Examples Ispaghula Husk Route of Administration Oral Indications Constipation, particularly when hard stools are present ``` Contraindications Dysphagia Intestinal obstruction (Adhesions, ulceration) Colonic atony Faecal impaction ``` Mechanism of Action Increases the volume of the non-absorbable solid residue in the gut, distending the colon and stimulating peristaltic movement. Adverse Drug Reactions Flatulence Abdominal distension GI obstruction Therapeutic Notes A normal fluid intake is essential Clinical effects may take several days to develop

Answer 23

Examples Hyoscine Route of Administration Oral or patch Indications Motion sickness Mechanism of Action Direct antagonist of muscarinic cholinergic receptors (M1) Adverse Drug Reactions Systemic anti-cholinergic effects, bradycardia

Answer 24

``` Examples o Ibuprofen o Naproxen o Diclofenac o Celecoxib o Aspirin ``` Indications o Musculoskeletal and joint disease o Analgesia for mild to moderate pain o Symptomatic relief in fever Contraindications o Gastrointestinal ulceration or bleeding o Previous hypersensitivity to any NSAID o Caution in asthma and when renal function is impaired Mechanism of Action o Inhibit Cyclooxygenase enzyme, preventing Prostaglandin synthesis ``` Adverse Drug Reactions o GI – Ulceration o Renal – Reversible drop in GFR o Skin reactions (15% for some NSAIDs) o Asthmatic bronchospasm (10% incidence) o Allergic response o Prolongation of bleeding time (platelet inhibition) ``` Drug-Drug Interactions o Warfarin (protein binding reaction) o Methotrexate (protein binding reaction) o Sulphonylureas (protein binding reaction) o ACE inhibitors – Attenuate action Therapeutic Notes o Aspirin is associated with risk of the post-viral Reye’s Syndrome in children o Paracetamol overdose produces the toxic metabolite NAPQI via Phase I metabolism o Paracetamol has virtually no anti-inflammatory action, it is used to treat mild to moderate pain and fever

Answer 25

Examples - Abciximab Route of Administration - Intravenous Indications o Prevention of ischaemic cardiac complications in patients undergoing Percutaneous Coronary Intervention (PCI) o Short term prevention of MI in unstable angina patients Contraindications Active bleeding Mechanism of Action o Monoclonal Antibody to Glycoprotein IIb/IIIa Receptors o Prevents platelet aggregation Adverse Drug Reactions o Haemorrhage, nausea, vomiting, hypotension Drug-Drug Interactions o Works synergistically with Warfarin to decrease Coagulability

Answer 26

Class 1 anti arrhythmic Route of Administration Oral (well absorbed) Intravenous ``` Indications Supraventricular tachyarrhythmias (Atrial arrhythmias) ``` Contraindications Heart failure, history of MI Mechanism of Action Blocks fast, inward Na+ ion channels (Phase 0) Adverse Drug Reactions Dizziness, visual disturbances, arrhythmias Drug-Drug Interactions Metabolised by CYP2D6 and eliminated renally. Inducers/inhibitors

Answer 27

Route of Administration Oral (only 1% reaches the brain due to peripheral metabolism) Indications Parkinsonism (excluding drug-induced extrapyramidal symptoms) Contraindications Closed angle glaucoma Mechanism of Action L-DOPA is the immediate precursor of Dopamine and is able to penetrate the blood brain barrier to replenish the dopamine lost in the Neostriatum. ``` Adverse Drug Reactions Nausea and vomiting Psychiatric side effects (Schizophrenia-like symptoms) Cardiovascular effects (hypotension) Dyskinesia ``` Drug-Drug Interactions L-DOPA is given in combination with a peripheral DOPA decarboxylase inhibitor (Sinemet, Madopar), reducing necessary dose, side effects and increase the amount of L-DOPA reaching the brain Vitamin B6 increases peripheral breakdown of L-DOPA Therapeutic Notes Extensive peripheral metabolism of L-DOPA means that large doses have to be given to produce therapeutic effects. These large doses are more likely to bring about adverse effects. Absorbed in competition with amino acids (note – high protein meals) 90% inactivated in intestinal wall by MAO and DOPA decarboxylase 9% converted to dopamine in peripheral tissues 1% crosses BBB to enter the CNS (competes with amino acids) ``` Advantages Highly efficacious Low side effects Disadvantages Precursor, needing enzyme conversion# Long term loss of efficacy and development of involuntary movements ```

Answer 28

Examples Procyclidine Route of Administration Oral Mechanism of Action Antagonists at the muscarinic receptors that mediate striatal cholinergic excitation Main action in treatment of Parkinson’s disease is to reduce excessive striatal cholinergic activity Adverse Drug Reactions CNS effects – Mild memory loss, acute confusional states Dry mouth and blurred vision (less common) Therapeutic Notes Termination of anticholinergic treatment should be gradual, as parkinsonism can worsen when these drugs are withdrawn

Answer 29

Examples Candesartan Losartan Indications Hypertension Contraindications Pregnancy, breastfeeding Caution in renal artery stenosis and aortic stenosis Mechanism of Action Bind to and antagonise the receptor for Angiotensin II – Angiotensin 1 Receptor (AT1 R). Inhibits vasoconstriction and aldosterone stimulation by angiotensin II. Adverse Drug Reactions Renal failure Hyperkalaemia

Answer 30

Class 1 anti arrhythmic Route of Administration Intravenous Indications Ventricular arrhythmias following MI Contraindications AV block Heart failure Mechanism of Action Blocks fast, inward Na+ ion channels (Phase 0) Adverse Drug Reactions Hypotension, bradycardia (negative inotrope) Nystagmus Seizures

Answer 31

Examples Verapamil Properties Impedes calcium transport across myocardial and vascular smooth muscle cell membrane Class IV anti-arrhythmic agent (prolongs action potential/effective refractory period) Peripheral vasodilation and a reduction in cardiac preload and myocardial contractility Adverse Effects Constipation (can potentialte constipation that is already present) Risk of bradycardia Reduced myocardial contractility (-‘ve inotrope) so can worsen heart failure

Answer 32

Examples Amlodipine Properties Good oral absorption Protein bound > 90% Metabolised by the liver ``` Adverse effects Sympathetic nervous system activation – tachycardia and palpitations Flushing, sweating, throbbing headache Oedema Swollen ankles with amlodipine Gingival hyperplasia (rare) Gynaecomastia (rare) ```

Answer 33

Route of Administration - Oral Indications Prophylaxis and Treatment of DVT, PE, AF, Prosthetic Heart Valves Contraindications Cerebral thrombosis, peripheral arterial occlusion, peptic ulcers, hypertension, pregnancy Mechanism of Action Blocks Vitamin K’s reduction to its active form, which is require for its action as a cofactor in the synthesis of factors II, VII, IX & X Adverse EffectsBleeding/Bruising, Haemorrhage, Teratogenic Drug-Drug Interactions CYP450 Inducers PCBRAS oPhenytoin, Carbamazepine, Barbiturates Rifampicin, Alcohol (chronic), St. John’s Wort CYP450 Inhibitors GO-DEVICES o Grapefruit Juice, Omeprazole, Disulfiram, Erythromycin, Volporate, Isoniazid, Cimetidine & Ciprofloxcain, Ethanol (acutely), Sulphonamides o Highly protein bound, can be displaced, raising plasma conc. Therapeutic Notes o Use INR to monitor, measure of the Extrinsic coagulation pathway o Reverse effects with Vitamin K IV (affects Warfarin use for 6 weeks), or Fresh Frozen Plasma, Prothrombin Complex Concentration

Answer 34

``` Examples Salbutamol - SABA Terbutaline - SABA Formoterol - LABA Salmeterol - LABA ``` Mechanism of Action - β2 agonists act on the β2 receptors found on bronchial smooth muscle. The receptors are coupled to Gs Proteins, which cause an increase in cAMP and consequent decrease in intracellular [Ca2+]. This reduces the binding of Ca2+ by light myosin, causing smooth muscle dilation. Additionally, the decrease in intracellular Ca2+ will also increase Ca2+ activated K+ currents, thus hyperpolarising muscle cells further and augmenting bronchodilation. Adverse Drug Reactions o Inhaled high doses can cause skeletal muscle tremor (β2 activity) o Even though β2 agonists are very selective, they can still antagonise cardiac β1 receptors enough to induce tachycardia and dysrhythmia Drug-Drug Interactions o β-blockers such as Propranolol, which bind to both β1 and β2 receptors

Answer 35

Examples - Cyclophosphamide Indications - Immunosuppression/Cancer chemotherapy Contraindications - Pregnancy Mechanism of Action o Pro-drug, that is activated by CYP450s. o Alkylating agent, which creates cross-links in DNA so that it cannot replicate. Therefore it selectively acts on cells with a higher mitotic rate. Adverse Drug Reactions o Induction of bladder cancer (urine concentration of acrolein metabolite) o Lymphoma and Leukaemia o Infertility & Teratogenesis Drug-Drug Interactions - Pro-drug is activated by CYP450s (inducers/inhibitors)

Answer 36

Route of Administration Oral, rectal Indications All forms of epilepsy, except absence seizures Contraindications AV conduction problems Mechanism of Action Prolongs VGSC inactivation state ``` Adverse Drug Reactions CNS – Dizziness, drowsiness, ataxia, motor disturbances, numbness, tingling GI disturbances – Vomiting CVS – Variations in BP Hyponatraemia Rashes Rarely myelosuppression – neutropenia ``` Drug-Drug Interactions CYP450 Enzyme Inducer Many drug interactions, e.g. Warfarin, OCP Protein bound Another protein binding drug can raise Carbamazepine conc. Antidepressants (SSRIs, MAOIs, TCAs and TCA) interfere with Carbamazepine’s action Therapeutic Notes Well absorbed, 75% protein bound Linear Pharmacokinetics Initial t½ is ~30hrs, but is a strong inducer of CYP450s and therefore affects its own Phase I metabolism. In repeated use t½ falls to ~15hrs Drug monitoring required to adjust dosing due to falling t½

Answer 37

Examples Aliskiren Indications Hypertension Contraindications Pregnancy Caution in patients at risk of hyperkalaemia, Na+ and volume depleted patients, severe renal impairment and renal stenosis Mechanism of Action Antagonises Renin, preventing the conversion of Angiotensinogen -> Angiotensin I. Reduces plasma renin activity by 50-80% Adverse Drug Reactions Angio-oedema, hyperkalaemia, hypotension, GI disturbances Drug-Drug Interactions Furosemide Therapeutic Notes t½ of ~40 hours, supporting once daily doses Mainly eliminated as an unchanged compound in faeces (78%) Not metabolised via CYP450

Answer 38

Route of Administration Oral, intravenous Indications All forms of epilepsy, except absence seizures Mechanism of Action Prolongs VGSC inactivation state Stops the spread of excitation from focus Adverse Drug Reactions CNS effects – dizziness, ataxia, headache, Nystagmus, nervousness Gingival Hyperplasia (20%) Rashes – Hypersensitivity (Stevens-Johnson Syndrome 2-5%) Drug-Drug Interactions CYP450 Inducer Many drug interactions, e.g. Warfarin, OCP Cimetidine -> Phenytoin Increase Well absorbed, 90% Protein Bound Competitive binding, e.g. with Valproate, NSAIDs Can exacerbate non-linear PKs Therapeutic Notes Phenytoin displays Non-Linear Pharmacokinetics at Therapeutic concentrations (linear at sub-therapeutic levels). This means close monitoring of free plasma levels is required.

Answer 39

Route of Administration Oral, intravenous Indications All forms of epilepsy Contraindications Acute liver disease/hepatic dysfunction Mechanism of Action Weak inhibition of GABA inactivation enzymes -> Increased GABA A Weak stimulus of GABA synthesising enzymes -> Increased GABA A Weak VGSC blocker and Weak Ca2+ channel blocker -> Redcued Discharge Adverse Drug Reactions Generally less severe than with other AEDs CNS sedation – Ataxia, tremor Weight gain Hepatic Dysfunction – Transaminases increased in 40% of patients Rarely hepatic failure Drug-Drug Interactions Adjust therapy with other AEDs Care needed with adjunct therapy, as both Valproate and adjunct PKs are affected. E.g. displaces Lamotrigine and Phenytoin, raising their free plasma concentrations Antidepressants (SSRIs, MAOIs, TCAs and TCA) inhibit Valproate Antipsychotics antagonise Valproate, by lowering convulsive threshold Aspirin displaces Valproate from plasma proteins, raising its free conc. ``` Therapeutic Notes 100% absorbed, 90% protein bound Linear Pharmacokinetics, t½ = 15hrs Close monitoring of free plasma concentration is required Monitor for hepatic disorders ```

Answer 40

Examples o Bezafibrate Route of Administration - Oral Indications - Hyperlipidaemia which does not respond to dietary control Contraindications - Pregnancy, breast feeding, gall bladder disease, severe renal or hepatic impairment, Hypoalbuminaemia Mechanism of Action o Peroxisome Proliferator-Activated Receptor-α (PPAR-α) agonist o LDL lowering (variable amount) o HDL increases of 15-25% in hypertriglyceridemia o Decreases Triglycerides 25-50% ``` Adverse Drug Reactions o Gastrointestinal disturbances o Dermatitis, pruritus, rash o Impotence o Headache, dizziness, blurred vision ``` Drug-Drug Interactions - Increased chance of myalgia and myopathies when taken with statins Fibrates can be used in conjunction with statins, but typically are only used as first line choices in hypertriglyceridemias.

Answer 41

Intercalating o Doxorubicin - intercalatye between base pairsin DNA o Oaunorubicin - Inhibits topoismoerase 2 Cytotoxic Alkylating Agents o cyclophoshamide - Corss link DNA o cisplatin - cross link DNA Antimetabolites o Methotrexate - Antifolate (myelosuppreion common) o Azathioprine - 5asa o 5 fluro uracil - irreversibly inhibits Thymidylaate synthatse Microtbuble Inhibnitors o Taxanes - promote and stabalise tubulin polymer into microptubule o Vinca Alkaloids - inhibit polymerisation of tubulin Bleomycin - Forms free radical causing DNA scission

Answer 42

``` Examples o Morphine o Diamorphine o Codeine o Tramadol ``` Indications o Pain releief ``` Contraindication o Acute respiratory depression o Acute alcoholism o At risk of paralytic ileus o Head injuries (prior to neurological assessment) ``` Mechanism of Action o Bind to endogenous opioid receptors o Open K+ channels – hyperpolarise cells and reduce excitability o Close voltage gated Ca2+ channels, inhibit release of Substance P neurotransmitter ``` Adverse Drug Reactions o Respiratory Depression o Miosis (Important overdose sign) o Euphoria o Confusion o Psychosis o Coma o Tolerance and dependence o GI disturbances (nausea, vomiting, constipation) o Rarely anaphylactic responses ```

Answer 43

Examples o Colestyramine Route of Administration - Oral Indications - Elevated cholesterol resulting from a high LDL concentration Contraindications - Biliary obstruction Mechanism of Action o Bile acids are produced from cholesterol. The bile acid sequestrants will bind to bile acids in the intestine. This prevents their reabsorption and further conversion of hepatic cholesterol into bile acids. Lower levels of hepatic cholesterol leads to increased LDL receptor expression and lowered plasma cholesterol concentration. Adverse Drug Reactions o GI disturbances – Nausea, vomiting, constipation, abdominal pain, flatulence, heart burn o Very few systemic side effects as they are not absorbe

Answer 44

Route of Administration - Oral Indications o Used in conjunction with Warfarin in prophylaxis against thrombosis due to prosthetic mechanical heart valves Mechanism of Action o Inhibits Phosphodiesterase enzyme o Phosphodiesterase increases cAMP, which increases Ca2+, which causes platelet aggregation Adverse Drug Reactions Hypotension, nausea, diarrhoea, headache Drug-Drug Interactions o Works synergistically with Warfarin to decrease Coagulability

Answer 45

Examples Bromocriptine Ropinirole Apomorphine Route of Administration Oral Apopmorphine is always given subcutaneously Indications Used in combination with L-DOPA in an attempt to reduce it’s late adverse effects, or when it does not control symptoms Mechanism of Action Agonists for Dopamine D2 Receptors ``` Adverse Drug Reactions Similar to that of L-DOPA, but more common and more severe Nausea Hypotension Psychiatric symptoms ``` Therapeutic Notes Bromocriptine is most used

Answer 46

Examples o Atorvastatin - long half life o Simvastatin - Short half life Route of Administration - Oral Indications Hyperlipidaemia which has not responded to changes in diet and exercise Secondary prevention in patients with serum cholesterol greater than 5.5mmol/L (value varies depending on local policy) Contraindications - Pregnancy, breastfeeding, liver disease Mechanism of Action o HMG-CoA Reductase inhibitor. Prevents cholesterol synthesis in the liver. Lower liver cholesterol concentration stimulates the production of LDL receptors, increasing the rate of LDL removal from plasma Adverse Drug Reactions - Serious ADRs tend to be limited, even at the highest does of statin given. o Increased transaminase levels - rapidly reversible, no evidence of chronic liver disease o Myopathy - Diffuse muscle pain, primarily seen when used in combination with cyclosporine and occasionally erythromycin & niacin. Can test levels of creatinine kinase if symptomatic to confirm the presence of myopathy o GI Disturbances o Arthralgia o Headaches Drug-Drug Interactions o CYP450 inducers/inhibitors. o Inhibitors significantly increase the risk of myopathies as the drugs spends more time in the plasma and therefore is more likely to interact with muscle tissue

Answer 47

``` Antirheumatic Drugs (DMARDs) (DRUGS SLOW DOWN DISEASE PROGRESSION, DOESN'T JUST TREAT INFLAMMATION) ``` Indications - Immunosuppression and Cancer chemotherapy Contraindications - Pregnancy Route of Administration - Orally, intravenously, intramuscularly, intrathecally Mechanism of Action o Antifolate o Competitively antagonises Dihydrofolate Reductase (DHFR), preventing the regeneration of intermediates (tetrahydrofolate) essential for the synthesis of purines and thymidine, thus inhibiting DNA synthesis. ``` Adverse Drug Reactions o Mucositis o Myelosuppression o Hepatitis, cirrhosis o Increased infection risk o Teratogenesis ``` Drug-Drug Interactions o Adverse DDIs with drugs affecting renal blood flow and renal elimination, e.g. NSAIDs Therapeutic Notes o Essential to carry out clinical monitoring o Baseline chest X-ray, FBC, LFT, U+E + Creatinine o Monthly FBC, LFT, U+E + Creatinine o Oral bioavailability is dose dependent, so usually given IV o Plasma protein binding ~50% - NSAIDs displace, raising plasma concentration 90% renal elimination – glomerular active and tubular secretion o Intracellular/hepatic metabolism to polyglutamates. These polyglutamates accumulate in cells and also bind very strongly to DHFR. Polyglutamates can be retained in cells for weeks to months o Weekly, not daily dosing

Answer 48

Naloxone Opioid receptor antagonist. Reverses the adverse agonistic effects. Rapidly reverses respiratory depression.

Answer 49

Examples Administered as Lithium Carbonate Indications Mood stabiliser (Antimanic and Antidepressant activity) Prophylaxis of Mania and Depression in bipolar disorder Augmentation of antidepressants in unipolar depression ``` Contraindications Renal impairment (renal excretion) ``` Mechanism of Action (Theories) Electrolytes and channels – May compete with Mg2+ and Ca2+ channels Neurotransmitters – Lithium increase 5HT. Chronic Lithium may reduce 5HT receptor sites Second messenger systems – Lithium attenuates the effects of neurotransmitters on their receptors, without altering receptor density ``` Adverse Drug Reactions Memory problems (learning new information) – 52% Thirst – 42% Polyuria – 38% Tremor (very fine) – 34% Drowsiness – 24% Weight gain – 18% Hair loss Rashes ``` ``` Toxic Effects Vomiting Diarrhoea Coarse tremor (progression from fine tremor) Dysarthria (difficulty speaking) Cognitive impairment Restlessness Agitation ``` Drug-Drug Reactions NSAIDs will raise Lithium plasma concentration Therapeutic Notes Good evidence for reducing suicides Drug monitoring for toxic levels in case of toxic effect Toxicity is treated with supportive measures, anticonvulsants, increased fluid intake/IV fluids, Haemodialysis may be necessary

Answer 50

Mechanism of Action o Gastric and pancreatic lipase inhibitor, reducing the conversion of up to 30% of dietary fat to fatty acids and glycerol Adverse Drug Reactions o Broad GI disturbances o (Soft fatty stools, flatus, faecal discharge/incontinence)

Answer 51

Examples Venlafaxine Indications Depression Contraindications Hypertensive patients, as Venlafaxine raises blood pressure ``` Mechanism of Action Inhibit the reuptake of both serotonin and noradrenaline, thus potentiating neurotransmitter activity in the CNS Dose dependent Low dose blocks Serotonin High dose blocks Noradrenaline ``` Adverse Drug Reactions Common – Anorexia, nausea, diarrhoea (normally settles in 2-3 weeks) Rare – Precipitation of mania, tremor, extrapyramidal syndromes (Similar to SSRIs, but occur with less frequency) Sleep disturbances Hypertension Dry mouth Hyponatraemia Drug-Drug Interactions MAOIs – Used in combination can cause potentially fatal serotonergic syndrome of hyperthermia and cardiovascular collapse Therapeutic Notes Second line treatment for depression Similar to TCAs, but adverse effects are reduced as Venlafaxine has little affinity for histamine or α-adrenoreceptors Relatively short t½ – may be a withdrawal syndrome on discontinuation

Answer 52

Examples Ispaghula Route of Administration Oral Indications Particularly useful for patients with IBS and those with ileostomy Contraindications Intestinal obstruction Mechanism of Action A relatively small amount of faecal fluid (10-20ml) influences composition. Bulk forming antidiarrhoeals absorb this fluid.

Answer 53

Used to increase HDL levels and is also found to decrease the risk of cardiovascular events. Inhibits lipoprotein-a synthesis Side effects include o Skin flushing and itching o Dry skin o Skin rashes -Eczema exacerbations or Acanthosis nigricans (thickened brown, leathery patches of skin)

Answer 54

Examples Diltiazem Properties Impedes Calcium transport across the myocardial and vascular smooth muscle cell membrane Prolongs the action potential/effective refractory period Peripheral vasodilation and reduction in cardiac preload and myocardial contractility Verapimil-lite – does not work quite to the same extent as the others Adverse Effects Risk of bradycardia Negative inotropic effect (less than Verapamil) can worsen heart failure

Answer 55

Route of Administration- Oral Indications o Secondary prevention of cardiovascular/cerebrovascular events Mechanism of Action o ADP Antagonists o Inhibits ADP-ADP receptor interaction, which aids platelet aggregation Adverse Drug Reactions o Haemorrhage o GI disturbances – Discomfort, nausea, vomiting Drug-Drug Interactions o Works synergistically with Warfarin to decrease Coagulability Therapeutic Notes If patient is allergic to Aspirin, Clopidogrel can be used instead

Answer 56

Examples Cyclizine Route of Administration Oral, IV or IM Indications Acute nausea and vomiting Contraindications Myocardial ischaemia Mechanism of Action Antagonises H1 receptors Adverse Drug Reactions Can cause QT prolongation Crosses the BBB – Sedative effect

Answer 57

Examples Domperidone Metoclopramide Route of Administration Oral Rectal (extensive 1st pass metabolism) Indications Acute nausea/vomiting Especially induced by L-DOPA or dopamine agonists Mechanism of Action Acts on the Postrema on the floor of the 4th ventricle Acts on the stomach to increase the rate of gastric emptying Adverse Drug Reactions Stimulates prolactin release Metoclopramide – extra-pyramidal reactions (dystonia) occur in 1%, therefore is avoided in Parkinson’s disease

Answer 58

Examples Fluoxetine (Prozac) Citalopram Sertraline Route of Administration Oral (almost completely absorbed from gut) Indications Depression Mechanism of Action Act with a high specificity for potent inhibition of serotonin reuptake into nerve terminals from the synaptic cleft Only minimal effects on noradrenaline uptake Adverse Drug Reactions Common – Anorexia, nausea, diarrhoea (normally settles in 2-3 weeks) Rare – Precipitation of mania, tremor, extrapyramidal syndromes Drug-Drug Interactions MAOIs – Used in combination can cause potentially fatal serotonergic syndrome of hyperthermia and cardiovascular collapse Therapeutic Notes First line treatment for depression Citalopram is the most selective reuptake inhibitor Paroxetine is the most potent reuptake inhibitor Long elimination t½ (once daily dosage), metabolised in the liver Relatively safe in overdose if taken on their own

Answer 59

Examples o Ramipril o Lisinopril Route of Administration - Oral Indications o Hypertension o Heart failure o Renal dysfunction Contraindications - Pregnancy, renovascular disease, aortic stenosis Mechanism of Action o ACE inhibitors cause inhibition of Angiotensin Converting Enzyme, consequently reducing Angiotensin II and Aldosterone levels. This causes vasodilation and consequent reduction in peripheral resistance and reduced sodium retention. o Reduce breakdown of the vasodilator Bradykinin Adverse Drug Reactions o Characteristic dry cough o Angio-oedema (rare, but more common in black population) o Renal Failure o Hyperkalaemia o Hypotension, dizziness and headache, diarrhoea and muscle cramps

Answer 60

Examples Imipramine Lofepramine Route of Administration Oral Indications Depression Mechanism of Action MAOIs block the action of monoamine oxidase, the enzyme that metabolises monoamines (noradrenaline and serotonin). There are two subtypes, MAOA and MAOB. Inhibition of MAOA gives the best antidepressant efficacy. Adverse Drug Reactions Hypertension CNS stimulation causing excitement and tremor Dry mouth, blurred vision Drug-Drug Interactions MAOIs reduce the metabolism of barbiturates, opioids and alcohol. Therapeutic Notes Response to treatment with MAOIs may be delayed for ~3 weeks.

Answer 61

Examples Imipramine Lofepramine Route of Administration Oral Indications Depression Amitriptyline – Chronic, neurological pain Clomipramine – Good evidence for OCD treatment ``` Contraindications Recent MI or arrhythmias (especially heart block) Manic phase Severe liver disease Epilepsy (TCAs lower seizure threshold) ``` Mechanism of Action Block serotonin and noradrenaline reuptake. Also have affinity for H1, muscarinic and α1 and α2 receptors. Adverse Drug Reactions Noradrenergic uptake block in the heart – Arrhythmias Muscarinic blocking effects – Dry mouth, constipation α-adrenergic blocking effects – Postural hypotension H1 blocking effects – Sedation Weight gain Constipation Therapeutic Notes Lipid soluble, long t½ (once/twice daily dose), metabolised by liver

Answer 62

``` Examples o Amiloride (Na+ channel blockers) o Spironolactone (Aldosterone Antagonist) ``` Route of Administration - Oral Indications o In conjunction with other diuretics in managing heart failure or hypertension. They are only mild diuretics. o Aldosterone antagonists used in the treatment of hyperaldosteronism o Primary – Conn’s Disease o Secondary – Result of heart failure, liver disease or nephrotic syndrome Contraindications - Renal failure Mechanism of Action o Na+ channel blockers o Block Na+ reabsorption by principal cells o Aldosterone Antagonist o Competitive antagonist at aldosterone receptors. This reduces the secretion of Na+ Site of Action Late distal tubule and collecting duct Adverse Drug Reactions o GI disturbances o Hyperkalaemia (in patients in renal failure) o Hyponatraemia o Spironolactone – Gynaecomastia, menstrual disorders, erectile dysfunction due to androgenic cross-reactivity (interacts with oestrogen synthesis) Drug-Drug Interactions o Interaction with ACE inhibitors, increasing risk of hyperkalaemia

Answer 63

Examples Omeprazole Lansoprazole Esomeprazole Route of Administration Oral Indications Short term treatment of peptic ulcers Severe GORD Confirmed oesophagitis Eradication of H. Pylori (part of triple therapy) Zollinger-Ellison Syndrome (Gastrin secreting pancreatic tumour) Mechanism of Action Irreversibly inhibit Na/K-ATPase that is responsible for proton secretion from parietal cells. Adverse Drug Reactions GI upset, nausea Headaches Risk of gastric atrophy with long-term treatment Drug-Drug Interactions Omeprazole is a CYP450 enzyme inhibitor Avoid use with patients being treated with Warfarin, Phenytoin etc. Therapeutic Notes PPI action is delayed as not all pumps are active all of the time. Maximum efficacy is after 2-3 days. Restoration of stomach acid requires de novo synthesis, so after treatment stops it will take a few days for acid to return to normal