Drugs Flashcards

Question

Atypical antipsychotics ``` I: 4 M A: 6 W: 3 I: 3 E: 4 ```

Answer 1

Indications (4): - Urgent psychomotor agitation causing dangerous or violent behaviour - Schizophrenia - when the first generation extrapyramidal (or other) SE are problematic - Bipolar disorder - in acute episodes of mania or hypomania - N/V Mechanism: - Block post-synaptic dopamine D2 receptors - 3 main dopaminergic pathways in CNS: mesolimbic (midbrain and limbic system/ frontal system), nigrostriatal pathway (substantia nigra with corpus striatum of the basal ganglia), tuberohypophyseal pathway (hypothalamus with the pituitary) - Antipsychotic effect probably comes from action in mesolimbic system Features differentiating second generation - Improved efficacy in treatement resistant schizophrenia, and against negative symptoms - Lower risk of extrapyramidal symptoms - Mechanisms for these differencce include a higher affinity to other receptors (particularly 5-HT2A), and looser binding to D2 receptors Adverse effects (6): - Sedation - EPSEs (not as common as in 1st gen) - Metabolic disturbance - weight gain, DM, lipid changes - QT- interval elongation (--> arrhythmias) - Risperidone - effects tuberohypophyseal, effecting prolactin secretion --> breast symptoms, and sexual dysfunction - Clozapine - 1% of patients get deficiency of neutrophils, and rarely MI Warnings (3): - Caution in CVD - Do not use clozapine in those with severe heart disease or Hx of neutropenia Interactions (3): - Sedation increased when other sedating drugs used - Dopamine blocking anti-emetics - Drugs that prolong the QT interval (e.g.amiodarone and macrolides) Examples (4): Quetiapine, olanzapine, risperidone, clozapine

Answer 2

Indication (1): - Inflammatory skin conditions, such as eczema Mechanism (3 classes of action): - Immunosuppressive - Metabolic - Mineralocorticoid Topically most effect is local, but can get systemic effects with potent or prolonged use . Adverse effects (8): - Skin thinning - Striae - Telangiectasia - Contact Dermatitis - Derioral dermatitis - Exacerbate acne - Rebound worsening (on withdrawl) - Adrenal suppression Warnings (2 C/Is): - Infection (C/I) - Facial lesions (C/I) Interactions (1) : - If using several topical agents, space out to allow absorption ``` Example drugs (2): Hydrocortisone, betamethasone ```

Answer 3

Indications (3) - Atropine - first line in severe symptomatic bradycardia to increase HR - IBS - for there antispasmodic effect - Palliative - reduce copious respiratory secretions Mechanism: - Bind to mus receptor, where competitively inhibits acetylcholine --> decreases PSNS - Increase heart rate and conduction - Reduce smooth muscle tone and the peristaltic contraction; including in gut and urinary tract - Reduce secretions from glands in the respiratory tract and gut - In eye cause relaxation of pupillary constrictor and cilary muscles --> causing pupillary dilation and preventing accommodation Adverse effects (6): - PSNS: tachycardia, dry mouth, constipation - Reducing detrusor muscle activity can cause urinary retention in patients with BPH - Blurred vision - Some antimuscarinics (inc atropine) have central effects --> drowsiness and confusion Warnings (1 C/I, 1 caution): - Arrhythmia (C/I) unless bradycardia - Angle-closure glaucoma (caution) Interactions (1) - Adverse effects more pronounced when with other drugs with antimus efffects e.g tricyclics Examples (3) Atropine - bradycardia Hyoscine butylbromide - IBS, palliative Glycopyrronium

Answer 4

Indications (3): - Primary prevention of CVS events - Secondary prevention alongside lifestyle changes - Treating hyperlipidaemia Mechanism: - Reduce serum cholesterol levels by inhibiting HMG CoA reductase - reduces production by liver and increases LDLs - They indirectly reduce triglyceride and increase HDL levels - These effects slow and sometimes reverse atherosclerosis Adverse effects (4) - Headaches - GI - Muscle issues (aches, myopathy, rhabdomyolysis) - Raised ALT --> drug induced hepatitis Warnings (4): - Hepatic impairment - Renal impairment - Breastfeeding - Pregnancy (cholesterol needed in fetal development) Interactions (2): - Metabolism is reduced by cytochrome P450 inhibitors (amiodarone, diltiazem, itraconazole, macrolides and protease inhibitors) - Metabolism is also reduced by Amlodipine. ``` Example drugs (4): Simvastatin, atorvastatin, pravastatin, rosuvastatin ```

Answer 5

Indications (2): - Preventing leg cramp - First line treatment for Plasmodium falciparum malaria Mechanism: - Lower excitability of the motor end plate in response to acetylcholine --> fewer muscle contractions - Rapid killing of schizont stage P. falciparum parasites in the blood Adverse effects (8): - Tinnitus - Deafness - Blindness - GI upset - Hypersensitivity reactions - Longer QT interval - Potentially fatal in overdose - Hypoglycemia, which can also occour in malaria so more problematic Warnings (3): - Hearing or visual loss - First trimester of pregnancy (teratogenic) - G6PD deficiency (haemolysis) Interactions (2): - Other drugs that prolong the QT interval or cause arrhythmias (amidarone, antipsychotics, quinolones, macrolides - SSRIs

Answer 6

Indication (2): - Ulcerative colitis - mesalazine - RA - sulfasalazine = DMARD Mechanism: Ulcerative Collitis: - Aminosalicylates therapeutic effect achieved by releasing 5-aminosalicylic acid (5-ASA) - Precise MOA of 5-ASA unknown but it has both anti-inflammatory and immunosuppressive effects - Appears to act topically rather than systemically - 5-ASA preps are designed to delay delivery of active ingredient until reaching colon - Sulfasalazine - 5-ASA bound to sulfapyridine** which is catabolised by bacterial enzymes in the gut). Rheumatoid Arthritis - Sulfapyridine (bound to Sulfasalazine) has therapeutic effect (MOA unknown), but Mesalazine has not therapeutic effect in RA. Adverse effects (4 both, 2 sulfasalazine): Both: - GI upset (i.e. nausea, dyspepsia) - headache - Rare but serious blood abnormalities (i.e. leucopenia, thrombocytopenia) - Renal impairment. Sulfasalazine only: - Reversible decrease in the number of sperm (oligospermia) - serious hypersensity reaction (incl pyrexia, rash and liver abnormalities). Warnings (1) - Aspirin allergies (all are salicylates) Interactions (2): - Drugs that alter gut pH = Mesalazine tablets with a pH-sensitive coating (.e. Asacol MR)= PPI >> increase gastric pH >> tablet coating broken down prematurely - Lactulose lowers stool pH and may prevent 5-ASA release in the colon ``` Example drugs (2): Mesalazine, sulfasalazine ```

Answer 7

Indication (2): - Iron deficiency anaemia - Prophylaxis of iron deficiency anaemia Mechanism: - Replenishes iron stores, which are stored as ferratin in the liver, bone marrow, spleen and skeletal muscle. Adverse effects (3): - GI upset - nausea, epigastric pain, constipation, diarrhoea - Black poo - Rarely hypersensitivity reactions if given IV (eg anaphylaxis) Warnings (2): - May exacerbate bowel Sx in pts with intestinal disease (eg IBD, diverticular disease) - Caution giving IV iron in atopic pts Interactions (1): - Oral iron can reduce absorption of drugs such as levothyroxine and bisphosphonates, so therefore they should be taken >2 hrs before iron ``` Example drugs (2): Ferrous fumarate, ferrous sulfate ```

Answer 8

Indications (4): - Prevent clot extension and recurrence in deep vein thrombosis and pulmonary embolism (collectively, venous thromboembolism [VTE]) - Prevent embolic complications (e.g. stroke) in atrial fibrillation. - Prevent embolic complications (e.g. stroke) after heart valve replacement (short term after tissue valve replacement, lifelong for mechanical valve replacement) - Warfarin is not used to prevent arterial thrombosis (e.g. myocardial infarction, thrombotic stroke) - as this is driven by platelet aggregation, it is prevented by antiplatelet agents, such as aspirin and clopidogrel. Mechanism: - Warfarin inhibits hepatic production of vitamin K-dependent coagulation factors and cofactors - Vitamin K must be in its reduced form for synthesis of coagulation factors. It is then oxidised during the synthetic process. - An enzyme called vitamin K epoxide reductase reactivates oxidised vitamin K - Warfarin inhibits vitamin K epoxide reductase, preventing reactivation of vitamin K and coagulation factor synthesis ``` Adverse effects (1): - Bleeding ``` Warnings (3): - Risk of haemorrhage - Liver disease - Pregnancy (fetal abnormalities in first trimester, risk of bleeding towards term) Interactions (5): - Low therapeutic index - Small changes in hepatic warfarin metabolism by cytochrome P450 enzymes can cause clinically significant changes in anticoagulation. - Cytochrome P450 inhibitors (e.g. fluconazole, macrolides, protease inhibitors) decrease warfarin metabolism and increase bleeding risk. - Cytochrome P450 inducers (e.g. phenytoin, carbamazepine, rifampicin) increase warfarin metabolism and risk of clots. - Antibiotics can increase anticoagulation in patients on warfarin by killing gut flora which synthesise vitamin K.

Answer 9

Indication (2): 1) Mild-moderate Alzheimer's disease 2) Mild-moderate dementia in Parkinsons disease (rivastigmine) Mechanism (7): - Acetylcholine is an important Neurotransmitter in CNS, essential for learning and memory - Key in Alzheimer's/ dementia in Parkinsons (where Acetylcholine declines) - increases ACh availability - Improves cognitive function and reduces rate of decline Adverse effects (5) - Asthma - COPD - Peptic ulcers/bleeding - Neuroleptic malignant syndrome (NMS) - EPSEs Warnings (2C/Is, 4 cautions): - Sick Sinus Syndrome (C/I) - Heart block (C/I) - Asthma (caution) - COPD (caution) - Peptic Ulcers (caution) - Parkinsons (caution) Interactions (4): - NSAIDs - Corticosteroids - Antipsychotics (increased risk of NMS) - Beta- blockers (and other rate-limiting medications > bradycardia / heart block) ``` Example drugs (2): Donepezil, rivastigmine ```

Answer 10

Indication (4): - Mod-severe depression (1st line) - Also in mild depression if psych treatments fail - Pain disorder - OCD Mechanism: - SSRIs preferentially inhibiting neurone reuptake of serotonin (5-HT) from the synaptic cleft >> increasing its availability for neurotransmission - SSRIs differ from tricyclic-antidepressants as they do not inhibit NA uptake and cause less blockade of other receptors - Efficacy of both drug classes v depression is similar, but SSRIs have few adverse effects so preferred Adverse effects (10): - GI upset - Appetite and weight disturbance - Hypersensitivity reactions - Hyponatraemia - Suicidal thoughts/behaviours may increase - Lower seizure threshold - Prolong the QT interval (i.e. citalopram) and can predispose to arrhythmias - Increased risk of bleeding - At high doses, or in combo w/ other antidepressants, can cause 'serotonin syndrome' - autonomic hyperactivity, altered mental state and neuromuscular exciting - Sudden withdrawal of SSRIs --> GI upset, neurological symptoms, 'flu-like symptoms and sleep disturbance Warnings (4): - Epilepsy (caution) - PUD (caution) - Young (caution) - Hepatic impairment (caution) Interactions (4): - Don't co-prescribe MAO-Is as both increase synaptic serotonin (>> serotonin syndrome) - Gastro-protection should be given when SSRIs given with aspirin/NSAIDs - Bleeding risk also increased when anticoagulants co-prescribed - SSRIs should not be combined w/ other drugs that prolong QT interval (i.e. antipsychotics) ``` Example drugs (4): Citalopram, fluoxetine, sertraline, escitalopram. ```

Answer 11

Indication (4): Tx of infections: - Antibiotic-associated colitis (C diff) - Oral infections or aspiration pneumonia (Gm -ve anaerobes) - Surgical and gynae infections (Gm -ve anaerobes) - Protazoal infection (eg giardiasis, trichomonal vaginal infection, amoebic dysentery) Mechanism - Enters anaerobic bacteria by passive diffusion, where it is reduced, generating a nitro free radical, which binds to DNA, causing widespread damage, DNA degradation and cell death - Only anaerobes and protazoa can reduces metronidazole this way, so it doesn't work on aerobic bacteria Adverse effects (3): - GI upset - Hypersensitivity reactions - Peripheral and optic neuropathy, seizures and encephalopathy in high doses or prolonged courses Warnings (2): - Metabolised by CP450, so reduce dose in severe liver disease - Do not drink alcohol while taking, as this drug inhibits acetaldehyde dehydrogenase Interactions (2): - It is a CP450 inhibitor (so any drug metabolised by CP450 will be have raised concentrations in serum) - Increased risk of toxicity when taken with lithium

Answer 12

Indication (2): - Epilepsy prophylaxis - 1st mono / adjunct therapy in generalised tonic-clonic seizures, absence seizures - Bipolar disorder as mood stabiliser (but not in mania / hypomania) Mechanism: - Reduces neuronal excitability and electrical conductance inhibits seizure activity - Binds to active neurone Na channels, prolonging Na influx (preventing triggering) - May also bind to post-synaptic AMPA receptor Adverse effects (9) - Headache - Drowsiness - Irritability - Blurred vision - Dizziness - GI Upset - Skin rash - Steven Johnson syndrome - Neuroleptic malignant syndrome Warnings (3) - Hypersensitivity to other anti-epilpetic drugs - Hepatic Impairment (dose reduction) - Pregnancy > use with caution + closely monitor but safe Interactions (6) - Metabolised by Glucuronidation (CORPS-V): ↑Glucuronidation Inducers = ↓ Reduce Lamotrigine concentration: 1) C - Carbamazepine 2) O - Oestrogens 3) R - Rifampicin 4) P - Phenytoin 5) S - Simeprevir and other Protease Inhibitors ↓ Glucuronidation Inducers = ↑ Increases Lamotrigine concentration: 6) V - Valproate

Answer 13

Indications (2): - Treating gram + infection e.g. endocarditis if severe and/or penicillins cannot be used due to resistance - Treating antibiotic associated colitis caused by C. diff Mechanism: - Specific to gram + aerobic or anaerobic bacteria - Inhibits growth and cross linking of peptidoglycan chains, preventing synthesis of the cell wall of gram + bacteria - Resistance is increasing, partly due to modification of cell wall to prevent vanc binding Adverse effects (5): - Thrombophlebitis (pain and inflammation of the vein at infusion site - 'Red man syndrome' (erythema, hypotension, bronchospasm) or other anaphylactoid reactions, especially if infused too quickly - True allergies can also occour (immidiate or delayed) - Nephroxocity, ototoxicity - Blood disorders Warnings (1): - Careful monitoring of plasma concentrations to avoid toxicity (esp in renal failure) Interactions (3): - Higher risk of oto and nephro toxicity when prescribed with aminoglycosides, loop diuretics or ciclosporin

Answer 14

Indication (3): - Prevent gout - Prevent uric acid and calcium oxalate renal stones. - To prevent hyperuricaemia and tumour lysis syndrome associated w/ chemotherapy Mechanism - Xanthine oxidate metabolises xanthine (produced from purines) to uric acid - Allopurinol is a xanthine oxidase inhibitor, therefore it lowers plasma uric acid conc and reduces precipitation of uric acid in joints/kidneys Adverse effects (3): - Most common side effect is a skin rash (mild up to severe - Drug hypersensitivity is a rare, life-threatening side effect that can incl pyrexia, eosinophilia, lymphadenopathy - Starting allopurinol can trigger/worsen an acute attack of gout Warnings (2C/I, 1 caution): - Acute attacks of gout (C/I) - Recurrent skin rashes or more severe hypersensitivity (C/I) - Severe renal/hepatic impairment (caution) Interactions (3): - Cytotoxic drug mercaptopurine - and its pro-drug azathioprine - require xanthine oxidate for metabolism - Co-prescription: w/ amoxicillin, increases the risk of skin rash - ACEI/thiazides, increases risk of hypersensitivity reactions.

Answer 15

Indications (4): - Acute Coronary Syndrome, where rapid inhibition of platelet aggregation can stop thrombosis - To prevent occlusion of coronary artery stents - Long term secondary prevention of thrombosis in cardiovascular, cerebrovascular and peripheral arterial disease - Reduce risk of thrombus/stroke in atrial fibrillation if warfarin and NOAC is contraindicated Mechanism: - Prevents platelet aggregation and by irreversibly binding to ADP receptors on the surface of platelets - Pathway is independent of COX pathway, so synergistic with aspirin Adverse effects (3): - Bleeding - GI upset (Dyspepsia, abdo pain, diarrhoea) - Thrombocytopenia Warnings (1 C/I, 2 cautions): - Active bleeding (C/I) - Might need to stop 7 days before elective surgery - Caution if renal and hepatic impairment, particularly if this is causing additional risk of increased bleeding. Interactions (3): - Pro-drug, needs hepatic cytochrome P450 metabolism. Efficacy reduced by P450 inhibitors - Other antiplatelets increase risk of bleeding - Other anticoagulants increase risk of bleeding

Answer 16

Indication (2): - Status epilepticus (after failure of benzodiazepines) - Reduce generalised or focal seizures Mechanism: - Incompletely understood. Reduces neuronal excitability and electrical conductance, inhibiting seizure activity Adverse effects (5): - Long term = Appearance changes skin coursening, acne hirsutism, gum hypertrophy. - Dose-related neurological effects = cerebellar toxicity (nystagmus, ataxia and discoordination) - Haematological disorders and oesteomalacia (induces folic acid and vitamin D metabolism) - Hypersensitivity reactions and anaphylaxis - Phenytonin toxcity can cause cardiovascular collpase and respiritory depression Warnings (2): - Reduce doses in hepatic imparement becuase has low therapeutic index and metabolised by Zero-order kinetics - Teratogenic (fetal hydantoin syndrome) - women planning pregancy must see specialist and take high dose folic acid before conception Interactions (4): - P450 inducer, so reduces efficacy of warfarin, oestrogen and progesterone amongst others. - Cytochrome p450 inhibitors (SICKFACES.COM) increases effect and side effects. - Complex interactions with other epileptic drugs. - Efficacy reduced by drugs that lower the seizure threshold (e.g. SSRIs, Ticyclics, antipsychotics and tramadol)

Answer 17

Indications (1): - Prophylaxis and treatment of nausea particularly in general anaesthesia and chemotherapy Mechanism: - Serotonin not involved in vestibular communication. So will have no effect on motion sickness Adverse effects (2): - Constipation/diarrhoea - Headaches Warnings (1): - Small risk that 5-HT antagonists may prolong the QT interval, avoid in those with long QT interval Interactions (1): - Avoid in those using other drugs that prolong the QT interval; antipsychotics, quinine, SSRIs Examples (2): Ondansetron, granisetron

Answer 18

Indication (2): - Peptic ulcer disease - for treatment of gastric and duodenal ulcers, and NSAID associated ulcers, - GORD and Dyspepsia symptom relief Mechanism: - Histamine H2 Receptor blockers reduce gastric acid secretion. - Acid is normally produced by the proton pump of the gastric parietal cell, which secretes H+ into the the stomach lumen in exchange for drawing K+ into the cell. - Proton pump is regulated by histamine, released by local cells, and binds to the H2 receptors on the parietal cell. This activates the proton pump by a second-messenger system. - The proton pumps can be triggered by other mechanisms, so it can't completly stop gastric acid production, unlike PPIs, which can. Adverse effects (3): - Diarrhoea - Headache - Dizziness Warnings (2): - Renal impairment - reduce dose - Like PPIs, they can disguise symptoms of gastric cancer Interactions (0) ``` Example drugs (1): Ranitidine ```

Answer 19

Indications (4): - Alendronic acid for those at risk of osteoporotic fractures - Pamidronate and zoledronic acid for severe hypercalcaemia of malignancy - Pamidronate and zoledronic acid - myeloma, and breast cancer with bone metastases, decrease fractures, cord compression and need for readiotherapy or surgery - First line in active Paget's disease (to reduce bone turnover) Mechanism: - Reduce bone turnover by inhibiting osteoclasts - Bisphosphonates have similar structure to naturally occuring pyrophosphate so are incorporated into bone - As bone resorbed, bisphosphonates accumulate in the osteoclasts and inhibit activity and promote apoptosis --> reducing bone loss and improving bone mass Adverse effects (4): - Oesophagitis - Hypophosphataemia - Osteonecrosis of jaw (rare, more likely if IV, good dental care decreases this) - Atypical femoral fracture (in long term treatment) Warnings (4C/I): - Severe renal impairment (C/I) - Hypocalcaemia (C/I) - Upper GI issue (C/I) - Dental disease, smoking (C/I) Interactions (1): - Binds ca, so reduced absorption if taken with ca salts (i.e. milk), as well as antacids and iron salts Examples (3): Alendronic acid - osteoporosis Disodium pamidronate Zoledronic acid - hypercalcaemia and bone mets

Answer 20

Indication (1): - Diarrhoea (IBS or gastroenteritis) Mechanism: - Loperamide is an opioid like pethidine, but does not penetrate CNS so no analgesic effects - Agonist of opioid μ-receptors in the GI tract - Increases non-propulsive contractions of the gut smooth muscle - Reduces propulsive contractions (peristaltic) - Slows transit time and increases anal sphincter tone. - Slower time --> more water absorbed --> harder stool Other opioids have similar effects (but also are analgesics) Adverse effects (3): - Constipation - Cramping - Flatulence Warnings (2C/I, 1 caution): - Acute UC (C/I) - C. diff (C/I) - Acute bloody diarrhoea (dysentry) = bacterial infection - esp. E. Coli as can cause haemolytic-uraemic syndrome (HUS) Interactions (0) ``` Example drugs (2): Loperamide, codeine phosphate ```

Answer 21

Indications (4): - Acute coronary syndrome, acute ischaemic stroke - inhibit platelet aggregation can prevent of limit arterial thrombosis - Long-term secondary prevention of thrombotic arterial events in patients with cardio and cerebro vascular and peripheral arterial disease - Reduce intracardiac thrombus and stroke in a. fib (if warfarin and NOACs CI) - Mild to moderate pain Mechanism: - Irreversibly inhibits COX --> reducing thromboxane and arachidonic acid which are pro-aggregatory factors --> decreased platelet aggregation ---> decrease risk of arterial occlusion - Antiplatelet effect occurs at low doses - Antiplatelet effect lasts the life time of the platelet - so wears off as new platelets are made Adverse effects (8): - GI irritation, can become ulceration and haemorrhage - Hypersensitivity --> bronchospasm - High dose --> tinnitus - OD: hyperventilation, hearing changes, metabolic acidosis and confusion, convulsions, cardiovascular collapse, respiratory arrest. Warnings (3C/I, 1 caution) - Reye's syndrome risk in under 16s (C/I) - Hypersensitivity (C/I) - third trimester as could prematurely close ductus arteriosus (C/I) - Peptic ulceration (prescribe protection), or gout (caution) Interactions (1): - Synergistic with other antiplatelets, can be therapeutically beneficial, but increases bleeding risk

Answer 22

Indications (3): - Allergies - Itch relief (pruritus) and hives (urticaria) - Adjunctive treatment in anaphylaxis (after adrenaline) Mechanism: - H1 receptor antagonist - histamine released from storage granules in mast cells when Ag binds to IgE. Mainly via H1 receptors - Histamine induces Type I hypersensitivity; increased cap permeability causing oedema, vasodilation causing erythema, and itch due to sensory nerve stimulation - Antihistamines block histamine effect by blocking H1 Adverse effects (2): - First generation (chlorphenamine) - cause sedation, as histamine maintains wakefulness - Second generation (loratadine, cetirizine and fexofenadine) - can't cross BBB so don't cause sedation Warnings (1 C/I): - Severe liver disease (C/I) Interactions (0) Examples (3): First generation: chlorphenamine Second generation: loratadine, cetirizine and fexofenadine

Answer 23

Indications (1): - Reduce urinary frequency, urgency, and urge incontinence in overactive bladder (first line pharmacological tx) Mechanism: - Bind to mus receptor - competitively inhibits acetylcholine --> decreases PSNS - Reduced detrusor contraction --> bladder relaxation --> increased capacity - Antimuscarinics for overactive bladder selective for the M3 receptor which is the main subtype in the bladder Adverse effects (5): - Dry mouth - Tachycardia - Constipation - Blurred vision - Urinary retention can occur if bladder outflow obstruction Warnings (3C/I, 2 cautions): - UTI (C/I) - Arrhythmia (C/I) - Urinary retention risk (C/I) - Elderly and dementia (caution) - Angle-closure glaucoma (caution) Interactions (1) - Adverse effects more pronounced when with other drugs with antimus efffects e.g tricyclics Examples (3): Oxybutynin, tolterodine, solifenacin

Answer 24

Indications (1): - Local fungal infections Mechanism: 3 types: - Ergosterol found in fungal cell membranes - Polyene antifungals- bind to ergosterol in fungal cell membranes, creating polar pore which allows intracellular ions to leak out of the cell - kills or slows growth of funghi - Imidazole and Triazole antifungals :- inhibit ergosterol synthesis, impairing cell membrane synthesis, cell growth and and replicaiton. Adverse effects (8) - Local irritation - Oral: GI upset, headache, hepatitis, hypersensitivity - Rare: severe hepatic toxicity, prolonged QT interval predisposing to arrhythmias Warnings (3): - F - liver disease (caution) - Moderate renal impairment - dose reduction - Teratogenic Interactions (4): - None with nystatin or clotriamazole. - Fluconazole inhibits cP450 causing increase in plasma concentrations when prescribed with drugs that are metabolised by P450 enzymes (i.e. carbamazepine, warfarin, simvastatin) - Reduces affect of clopidogrel as it is a prodrug that gets activated in liver metabolism. - Increases risk of serious arrhythmias if prescribed with drugs that prolong the long QT (amiodarone, antipsychotics, macrolides, SSRIs etc) Examples: Topical: - Nystatin - mouth thrush candidiasis - Lotrimazole - skin and genital fungus inc. athlete's foot, ring worm and thrush Oral: - Fluconazole, one of dose for vaginal candidiasis

Answer 25

Indication (1): - Prevention and treatment of chest pain in stable angina Mechanism: - Causes arterial and venous vasodilation - Converted to nitric oxide, increasing cGMP and thus reducing intracellular Ca2+ in vascular smooth muscle cells, causing them to relax - reduces cardiac preload and L ventricular filling, reducing cardiac work and oxygen demand, thus relieving angina - Also activates K+-ATP channels, leading to hyperpolarisation of cell membrane, resulting in inactivation of voltage-gated Ca2+ channels, leading to further vasodilation Adverse effects (8) - Flushing - Dizziness - Headache - Nausea, vomiting - Hypotension - Rarely; GI, skin, mucosal laceration. Warnings (3C/I): - Poor L ventricle function (C/I) - Hypotension (C/I) - Pulmonary oedema (C/I) Interactions (1): - Phosphodiesterase inhibitors (eg sildenafil) significantly enhance nicorandil's hypotensive effects

Answer 26

Indications: - Treating type 2 DM as a single agent where metformin is contraindicated or not tolerated Mechanism: - Insulin sensitiser - Activate PPARγ - Induce genes which enhance insulin action in muscle, adipose tissue and liver, increase glucose uptake and utilisation and reduce hepatic gluconeogenesis - Do not stimulate pancreatic insulin secretion so no risk of hypoglycaemia Cause weight gain leading to insulin resistance. Adverse effects (7): - Anaemia - Minor neuro symptoms (dizziness, headache, vision) - Oedema and cardiac failure (with insulin) - Weight gain - Small increased risk of bladder cancer and bone fracture in women. - Severe liver toxicity Warnings (2C/I, 4 cautions: - Heart failure (C/I) - Bladder cancer (C/I) - CVS disease (caution) - RFs for bladder cancer (caution) - Hepatic impairment (caution) - Elderly (caution) Interactions (1): - Combinations of diabetic drugs can increase risk of hypoglycemia and cardiac failure Example drugs: Pioglitazone

Answer 27

Indication (4 classes of disease, 2 examples of each): - Treat allergy or inflammatory diseases (anaphylaxis, asthma) - Suppression of autoimmune diseases (inflammatory diseases) - Cancer chemotherapy (Myeloma/lymphoma/breast cancer) - Hormone replacement in adrenal insufficency or hypopituitarism Mechanism: - They bind to cytosolic glucocorticoid receptors, which translocate to the nucleus and regulate gene expression - Upregulate anti-inflammatory genes - Downregulate pro-inflammatory genes - Metabolic changes, like gluconeogenesis, and increase catabolism, increasing circulating amino and fatty acids - Mineralocorticoid effects, stimulating Na+ and water retention, and K+ excretion Adverse effects (5): - Immunosuppression, increasing risk of infection - Metabolic effects can cause diabetes and osteoporosis - Increased catabolism causes proxymal muscle weakness, skin thinning, bruising and gastritis - Behavioural changes, including insomnia, psychosis, and suicidal ideas - Hypertension, hypokalaemia, and oedema, from mineralocorticoid actions Warnings (2 cautions): - Infection (caution) - Children (caution) Interactions (4): - Increased risk of Peptic ulcers and GI bleeding when used with NSAIDs - Enhance hypokalemia in patients taking B2 agonists, theophylline, loop or thiazide diuretics - Efficacy may be reduced by p450 inducers - Will reduce immune response to vaccines ``` Example drugs (3) Prednisolone, ydrocortisone, dexamethasone ```

Answer 28

Indications (5) - First line for seizures and status epilepticcus - First line management of alcohol withdrawal - Sedation for interventional procedures - Short term for anxiety - Short term for insomnia Mechanism: - Target of benzos is the γ-aminobutyric acid type A (GABAA) receptor - GABAA receptor is a chloride channel that opens in response to GABA binding - the main inhibitory NT in the brain. - Opening the channel allows Cl to flow into cell making cell more resistant to depolarisation - Benzodiazepines facilitate and enhance binding of GABA to the GABAA receptor --> depressing synaptic transmission - ETOH acts on GABAA, and in excessive use the patient becomes tolerant, so abrupt cessation provokes the excitatory state of alcohol withdrawal - so give a benzo and remove in controlled way Adverse effects (5): - Drowsiness - Sedation - Coma - Little cardioresp depression in benzo od (compared to opioid), but loss of airway reflexes --> obstruction --> death - More than a few weeks use can cause dependance - with withdrawal reaction when removed Warnings (1C/I, 2 cautions): - Respiratory impairment/neuromuscular dysfunction (C/I) - Give lower dose in elderly - Liver failure (caution) Interactions (2): - Additive to other sedating drugs (inc. alcohol and opioids) - Most depend on cP450 for elimination - so cP450 inhibitors (e.g. amiodarone, diltiazem, macrolides, fluconazole) increase their effect Examples (5): Diazepam, temazepam, lorazepam, midazolam, chlordiazepoxide

Answer 29

Indication (3) - For early Parkinson's, when dopamine agonists (ropinirole) may be preferred over levodopa - In later Parkinson's disease levadopa is intergral, while dopamine is an option for add-on therapy. - Levodopa and dopamine agonists are options for secondary parkinsonism, although first try to identify primary cause. Mechanism: - In parkinsons there's a deficiency of dopamine in the nigrostriatal pathway between the substantia nigra in the midbrain to the corpus striatum in the basal ganglia - It's not possible to give dopamine itself, because it doesn't cross the blood-brain barrier - L-dopa is a precursor of dopamine, which can enter the brain by a membrane transporter - Ropinirole and pramipexol are relatively selective agonists for the D2 receptor, which predominates in the striatum. Adverse effects (6): - Nausea - Drowsiness - Confusion - Hallucinations - Hypotension - Major issue is the wearing off effect, where the patients symptoms worsen towards the end of dosage interval Warnings (3 cautions) - Elderly (caution) - Cognitive/psychiatric disorder (caution) - CVS disease (caution) Interactions (3): - Levadopa is always given with a peripheral dopa-decarboxylase inhibitor, in order to reduce its conversion to dopamine outside the brain - Dopaminergic agents should not be combined with antipsychotics, metaclopromide ``` Example drugs (3): Levadopa (as co-careldopa or co-beneldopa), ropinirole, pramipexol ```

Answer 30

Indications (5): - Ischaemic heart disease: first line option to improve symptoms and prognosis associated with angina and acute coronary syndrome - CHF - A. Fib - decreases ventricular rate, and in paroxysmal a fib, to maintain sinus rhythm - Supraventricular tachycardia (SVT) - restore sinus rhythm - Hypertension - used when Ca channel blockers, ACE inhibitors, and thiazide diuretics are insufficient Mechanism: - β1 adrenoreceptors are located mainly in the heart - β2 adrenoreceptors are located mostly in smooth muscle of blood vessels and airways - Via β1 -receptor, β-blockers reduce force and speed of contraction - Relieves Myocardial ischaemia by decreasing work and oxygen demand, and increasing myocardial perfusion - Improve prognosis in heart failure by protecting the heart from effects of chronic sympathetic stimulation - Slow the ventricular rate in a. fib. by prolonging refractory period of the AV node. - SVT often has 're-entry' circuits that takes in the AV node; β blockers break this circuit thus restoring sinus rhythm - In HTN, β blockers work in a few ways, including decreasing renin secretion. Adverse effects (6): - Fatigue - Cold extremities - Headache - Nausea - Sleep disturbance and nightmares - Impotence in men Warnings (3C/I, 3 cautions) - Heart block (C/I) - In asthma β-blockers cause life threatening bronchospasm (C/I) - Haemodynamic instability (C/I) - Usuallly safe in COPD but prudent to choose a β-blocker that is β1 selective (caution) - In HF start at low dose and increase slowly, as can impair cardiac function at first (caution) - Decrease dose in hepatic failure (caution) Interactions (1): - Do not use with non-dihydropyridine ca channel blockers (e.g. verapamil, diltiazem) - cause heart failure, bradycardia and even asystole Examples Bisoprolol, atenolol, ropanolol, metoprolol

Answer 31

Indications (1): - Treating type 2 diabetes. Used as a single agent to control blood glucose if metformin is contraindicated or not tolerated Mechanism: - Stimulate pancreatic insulin secretion - Block ATP dependent K+ channels in the pancreas beta cell membrane - Depolarisation and opening of voltage gated Ca2+ channels - Higher intracellular Ca2+ leads to more insulin secretion - Residual pancreatic function required - Anabolic hormone release -> weight gain -> insulin resistance -> :( Adverse effects (3): - GI - Hypoglycaemia - Rare hypersensitivity reactions (hepatic toxicity, drug hypersensitivty syndrome, haematological abnormalites). Warnings (2): - Metabilised in the liver, metabolites excreted in the urine, half life 10-12 hrs so dose reduction in patients with liver or renal impairment - Increased risk of hypoglycemia if liver impairment, malnutrition, adrenal or pituitary insufficiency and in the elderly Interactions (2): - Other diabetic drugs (hypoglycemia more likely) - Efficacy reduced with drugs that elevate blood glucose (prednisolone, thiazide and loop diuretics) ``` Example drugs (1): Gliclazide ```

Answer 32

Indications (2): - Oral Cephalosporins are 2nd and 3rd line for urinary and respiratory tract infections - IV cephalosporins and carbapenems are broad spectrum so can be used for most indications, but are reserved for tricky infections (very severe, complicated) Mechanism - - Have a Beta-Lactam ring, so inhibit cross-linking peptidoglycans in cell wall - The cell then swells, lyses, and dies - Broad spectrum - More resistant to Beta-Lactamases than penicillins are Adverse effects (4): - GI upset (nausea and diarrhoea) - Antibiotic associated colitis (C.diff) Can cause colonic perforation - Hypersensitivity, both immediate and delayed, likely to occur if allergic to penicillin - Risk of CNS toxicity, and can cause seizures, particularly with renal impairment Warnings (1 C/I, 3 cautions): - Penicillin allergy (C/I) - Epilepsy (caution) - C diff risk (caution) - Reduce dose in renal impairment (caution) Interactions (3): - Enhance anticoagulant effect of warfarin, by killing normal gut flora, which synthesise vitamin K - Cephalosporins may increase nephrotoxicity of aminoglycosides - Carbapenems reduce plasma concentration and efficacy of valproate Example drugs: Cefalexin, cefotaxime, meropenem, ertapenem

Answer 33

Indication (1): - Open-angle glaucoma and ocular hypertension (few side effects than topical β-blockers Mechanism: - Analogues of prostaglandin F2α reduce intraocular pressure by increasing outflow of aqueous humour via the uveoscleral pathway Adverse effects (5): - Blurred vision - Conjunctival reddening - Ocular irritation - Pain - May cause permanent change in eye colour by increasing melanin Warnings (1): - Caution if lens is absent (aphakia) or artificial (pseudophakia) and patients at risk of iritis, uveitis and macular oedema Example drugs: Latanoprost, bimatoprost

Answer 34

Indication (2): - Secondary prevention of stroke (combine with aspirin) - To induce tachycardia during a myocardial perfusion scan in the diagnosis of ischemic heart disease. Mechanism: - Antiplatelet, causing increase in intra-platelet cAMP, which inhibits platelet aggregation - Vasodilation, by blocking cellular uptake of adenosine, which prolongs its effect on blood vessels, causing vasodilation Adverse effects (6): - Headache - Flushing - Dizziness - GI symptoms - Increased risk of bleeding - Thrombocytopenia (rare, normally just affects function, not number) Warnings (2): - Because it causes vasodilation and tachycardia, it can cause problems in (IHD, aortic stenosis, HF) - The effect is used in a myocardial perfusion scan to see if tachycardia causes ischaemia Interactions (2): - Dipryidamole inhibits uptake up adenosine, which could cause cardiac arrest - There's increase risk of bleeding if combined with other antiplatelets, or with anticoagulants

Answer 35

Indications (3): - Respiratory and skin/soft tissue infections, where penicillins are contraindicated by allergy - Severe pneumonia, in addition to penicillin, to cover atypical orgamisms (eg leigionella, mycoplasma pneumoniae) - Eradication of H. pylori (for example, causing peptic ulcer disease) in combination with PPI and either amoxicillin or metronidazole Mechanism: - Inhibit bacterial protein synthesis (50S subunit on ribosome, blocking translocation) - Has a bacteriostatic effect (stopping bacterial growth, but not killing it) - Broad spectrum - Erythromycin - mostly gram +ve & some -ve - Synthetic macrolides (eg clarithromycin/azithromycin) increased activity vs gram -ve (eg haemophilus influenzae) Adverse effects (6): - Allergic reactions - Nausea, vomiting, abdo pain & diarrhoea - Antibiotic-associated colitis - Liver abnormalities - Prolonged QT interval (predisposing to arrhythmias) - Ototoxicity at high doses Warnings (2C/I, 1 caution) - Macrolide hypersensitivity (C/I) - Severe hepatic impairment (C/I) - Reduce dose in severe renal impairment (caution) Interactions (2): - Erythromycin and clarithromycin are both CP450 inhibitors, therefore they interact with any drug metabolised by CP450 (notably warfarin & statins). - Caution in pts taking drugs that cause arrhytmias or prolong QT interval (amioderone, antipsychotics, quinines, quinolone abx, SSRI)

Answer 36

Indication (1): First line abx for uncomplicated lower UTI Mechanism: - Reduced in bacterial cells by nitrofuran reductase to an active metabolite which damages bacterial DNA and causes cell death - Active vs gram+ (eg staphylococcus saprophyticus) and gram- (e.coli) organisms which commonly cause UTIs - Klebsiella and proteus species have intrinsic resistance to nitrofurantoin Adverse effects (5) - GI upset (nausea and diarrhoea) - Hypersensitivity reactions - Turns urine brown - Rarely can cause chronic pulmonary reactions (eg fibrosis), hepatitis and peripheral neuropathy from prolonged administration - Haemolytic anaemia in neonates Warnings (2C/I, 1 caution) - Pregnancy (C/I) - Renal impairment (C/I) - Caution in long term use for UTI prophylaxis, as this increases risks of adverse effects

Answer 37

Indication (2): - ER positive positive breast cancer (early / locally advanced) - adjuvant treatment post-surgery to reduce risk or recurrance - Advanced ER positive positive breast cancer (if HER2 negative and pre-menopausal) to slow progression - Note: Not used in HER2 positive cases as other treatments availible. - Note: Aromatase inhibitors used if post-menopausal (if contraindicated > Tamoxifen) Mechanism: - 2/3 breast cancers are ER positive - Oestrogen promotes growth of these cancers - Tamoxifen = Selective Estrogen Receptor Modulator (SERM) > prevents oestrogen binding - Aromatase inhibitors interfere with Androgen > Oestrogen conversion outside the ovary (thus reducing ER stimulation) - Note: Aromatase inhibitors have almost no effect on ovarian Oestrogen production (ineffective in Pre-menopause) ``` Adverse effects (5 both, T2): Tamoxifen / Aromatase Inhibitors induce symptoms of Menopause: - Vaginal dryness - Hot flushes - Osteoporosis - Agranulacytosis (rare) - Liver failure (rare) ``` Tamoxifen Only: - Increased VTE risk - Increased endometerial cancer risk Warnings (3C/I): - Pregnancy - miscarriage risk (Tamoxifen C/I) - Breast Feeding (Tamoxifen C/I) - Pre-menopausal (Aromatase C/I) Interactions (3): - Tamoxifen = ↓CYP450 inhibitor (CRAP GPs BS) > ↑ bleeding Warfarin - Fluoxetine (inhibit Tamoxifen activation) - Paroxetine (inhibit Tamoxifen activation) ``` Example drugs (3): Tamoxifen, anastrozol, letrozole ```

Answer 38

Indications (3): - Streptococcal infection (+ macrolide if severe), endocarditis and skin and soft tissue infections (added to flucloxacillin if severe) - Clostridial infection (e.g. tetanus) - Meningococcal infection (e.g. meningitis, septicaemia) Mechanism: - β-lactam ring tragets enzymes responsible for cross-linking of peptidoglycans in bacterial cell walls, resulting in cells swelling, lysis and death - Bacteria can become resistant by various mechanisms, including β-lactamase Warnings (2) - Renal impairment - Penicillin allergy Interactions (1): - Reduces renal excretion of methotrexate increasing risks of toxicity ``` Example drugs (2): Benzylpenicillin, phenoxymethylpenicillin ```

Answer 39

Indication (2): - Alternative first line for hypertension where a calcium channel blocker would be unsuitable e.g. due to oedema, or symptoms of heart failure - Add on treatment for hypertension, in patients where the BP isn't controlled by a CCB and ACE inhibitor or ARB Mechanism: - Inhibit the Na+/Cl- Co-transporter in the DCT. Prevents the reabsorption of sodium and water - Inital fall in extracellular fluid, but after awhile the RAAS system reverses this, at least in part - Long term antihypertensive effect is probably mediated by vasodilation Adverse effects (6): - Hyponatraemia, although rarely problematic - Hypokalaemia - Cardiac arrythmias (from hypokalaemia) - May increase plasma glucose (and unmask diabetes) - May increase LDL- Cholesterol and Triglycerides - Impotence in men Warnings (2 C/I, 1 caution): - Hypokalaemia (C/I) - Hyponatraemia (C/I) - May cause gout, due to reduction in uric acid excretion Interactions (2): - Effectiveness reduced by NSAIDs - Avoid other drugs that lower potassium, like loop diuretics ``` Example drugs (3): Bendroflumethiazide, indapamide, chlortalidone ```

Answer 40

Indications (2): - Constipation and faecal impaction (particularly in patients who cannot increase their dietary fibre intake) - Mild chronic diarrhoea associated with IBS or diverticular disease Mechanism: - Contains a hydrophilic substance which is not absorbed or broken down in the gut - This attracts water into the stool (like dietary fibre), and increases its mass (so these laxatives won't work without adequate fluid intake) - Increased stool bulk stimulates peristalsis, helping to relieve constipation & help with diarrhoea Adverse effects (3) - Mild abdo distension - Flatulence - Rarely - can cause faecal impactation and GI obstruction Warnings (1C/I): - Do not use in pts with intestinal obstruction, faecal impactation, ileus (failure of peristalsis), or recent abdo surgery (at risk of paralytic ileus from anaesthetic) ``` Example drugs (3): Ispaghula husk, methylcellulose, sterculia ```

Answer 41

Indication (3): - Paracetamol poisoning antidote - Contrast nephropathy - help prevent renal injury due to radiographic contrast material - To reduce the viscosity of respiratory secretions (acting as a mucolytic). Mechanism: - Paracetamol poisoning antidote. At therapeutic doses Paracetamol is metabolised mainly be conjugation w/ glucuronic acid and sulfate with a small amount converted to N-acetyl-p-benzoquinone (NAPQI) which is hepatotoxic - Normally, this is detoxified by conjugation w/ gluthione but in paracetamol glutathione is overwhelmed >> free NAPQI causes liver damage - Acetylcysteine replenishes the body's supply of glutathione Adverse effects (3): - In large doses, via IV, can cause "anaphylactoid reaction" - similar to anaphylaxis (nause, tachycardia, rash, wheeze) but involves IgE-independent histamine release - Therefore once reaction has settled (by stopping acetylcysteine + antihistamines + bronchodilator), it is safe to restart acetylcysteine albeit at lower dose - When administered as mucolytic, acetylcysteine can cause bronchospasm - therefore bronchodilator (i.e. salbutamol) should be given immediately beforehand

Answer 42

Indication (3): - Acute Ischaemic Stroke - Alteplase increases the chance of living independently if given within 4.5 hours of the onset of stroke - Acute ST elevation Myocardial Infarction - Alteplase and streptokinase can reduce mortality when given within 12 hours of symptoms, when given antiplatelets and anticoagulants. Primary PCI has generally superseded fibrinolytics in this context - Massive PE with Heamodynamic Instability - Fibrinolytic drugs reduce clot size, and pulmonary arterial pressures, but no evidence that they improve mortality Mechanism: - Catalyse the conversion of plasminogen to plasmin, which dissolves fibrinous clots, and re-canalise occluded vessels. This allows reperfusion. ``` Adverse effects (4 normal, 4 requiring treatment cessation): - Nausea - Vomiting - Brusing around injection site - Hypotension Treatment should be stopped if - Serious bleeding - Allergic reaction - Cardiogenic shock - Cardiac arrest ``` Warnings (1 current medical condition, 1 precaution in stoke, 1 past drug history precaution): Predisposition to bleeding - Recent haemorrhage - Recent trauma - Bleeding disorders - Severe hypertension - Peptic ulcers In acute stoke intercranial haemorrhage must be excluded with CT scan before treatment Previous streptokinase is a contraindication to repeated streptokinase, due to production of anti-steptokinase antibodies. Interactions (3): Increased risk of haemorrhage in patients taking - Anticoagulants - Antiplatelets - Ace inhibitors also increase anaphylactoid reactions. ``` Example drugs (2) Alteplase, streptokinase ```

Answer 43

Indication (6): - Focal epilepsies - Neuropathic Pain - Second-line option in diabetic neuropathy (after duloxetine) - First line in other painful neuropathies - Migraine prophylaxis (Gabapentin) - Generalised Anxiety Disorder (Pregabalin) Mechanism: - Binds with Voltage-Sensitive Calcium Channels, where it prevents inflow of calcium channels - This inhibits neurotransmitter release, which reduces neuronal excitability - Gabapentin is closely related to GABA, the major inhibitory neurotransmitter. It's mechanism however seems unrelated to GABA Adverse effects (3): - Drowsiness - Dizziness - Ataxia Warnings (1): - Renally eliminated, so doses should be reduced in renal impairment Interactions (1): - Sedative effects are enhanced when combined with other sedating drugs, such as benzodiazepines ``` Example drugs (2): Gabapentin, pregabalin ```

Answer 44

Indication (3): - Short acting (glyceryl trinitrate (GTN)) - acute angina and chest pain associated with acute coronary syndrome (ACS) - Long acting (isosorbide mononitrate) - prophylaxis of angina where a beta-blocker and/or calcium channel blocker are insufficient - IV - tx of pulmonary oedema in combination with forusemide and oxygen Mechanism: - Converted to nitric oxide, which increases cGMP thus reducing intracellular Ca2+ in vascular smooth muscle cells, causing vasodilation - This reduces preload and L ventricle filling, reducing cardiac work and oxygen demand, thus relieving angina and cardiac failure ``` Adverse effects (1): - Vasodilatory effects (flushing, headaches, light headedness, hypotension) ``` Warnings (3C/I) - Aortic stenosis (C/I) - Haemodynamic instability (C/I) - Hypotension (C/I) Interactions (2): - Don't use with phosphodiesterase inhibitors (eg sildenafil) as they enhance and prolong the hypotensive effect of nitrates - Caution with antihypertensive medications (ACE/ARB/beta-blocker/CCB/thiazide-like dieuretic) ``` Example drugs (2): Isosorbide mononitrate, glyceryl trinitrate (GTN) ```

Answer 45

Indication (2) - Mild-to-moderate pain, as an alternative or addition to paracetamol (paracetamol has less adverse effects, and a similar analgesic effect) - Regular treatment for inflammatory pain, particularly of the MSK system (eg RA, severe OA, acute gout) Mechanism - Inhibits COX, which normally catalyses the conversion of arachidonic acid to prostaglandins (PG) - COX-1 acts to stimulate production of PGs that do things like preserve integrity of GI mucosa and maintain renal perfusion (by dilating afferent arteriole in glomerulus) - COX-2 acts to stimulate production of PGs that cause inflammation and pain - Aspirin also inhibits the production of thromboxanes, which help form blood clots. Giving it it's antiplatelet effect Adverse effects (5) - GI toxicity - Renal impairment - Increased risk of MI and stroke - Hypersensitivity reactions (eg bronchospasm, angioedema) - Fluid retention Warnings (4C/I, 4 cautions) - Severe renal impairment (C/I) - Heart failure (C/I) - Liver failure (C/I) - Known NSAID hypersensitivity (C/I) - Reduce dose in PUD, GI bleeding, CVS disease, renal impairment (caution) Interactions (4): Increased risk of: - GI ulceration - aspirin, corticosteroids - GI bleeding - antcoagulants, SSRIs, venlafaxine - Renal impairment - ACE-i/ARB, diuretics Warfarin - increased bleeding risk - Antihypertensives and diuretics have reduced efficacy ``` Example drugs (3) Naproxen, ibuprofen, etoricoxib ``` Extras (3) - Oral NSAIDs should be taken with food to minimise GI upset - Consider GI protection (PPI - lansoprazole) in pts at risk of GI complications - Selective COX-2 only inhibitors have decreased risk of GI problems but increased risk of CV events

Answer 46

Indications (2): - Mod-severe depression where 1st line SSRIs are ineffective - Neuropathic pain (unlicensed) Mechanism: - Symptom relief appears to be due to tricyclic antidepressants inhibiting neuronal reuptake of serotonin (5-HT) and NA from the synaptic cleft >> increasing their availability for transmission - Tricyclic antidepressants also block loads of other receptors incl: muscarinic, histamine (H1), A-adrenergic (A1 + A2) and dopamine (D2) receptors - accounts for extensive adverse effects... Adverse effects (4 receptors, OD, withdrawal): - Anti-muscarinic: dry mouth, constipation, urinary retention and blurred vision - H1 + A1: sedation and hypotension - Dopamine: breast changes, sexual dysfunction and, rarely, extrapyramidal symptoms (tremor and dyskinesia) - Other/combined receptor blockade - cardiac adverse changes (incl arrhythmias and ECG changes - incl prolonged QT and QRS durations); convulsion, hallucinations and mania - OD: tricyclics are v dangerous, causing severe hypotension, arrhythmias, convulsions, coma and respiratory failure (can be fatal) - Sudden withdrawal: GI upset, neurological, 'flu-like symptoms and sleep disturbance. Warnings (6 cautions): - Elderly (caution) - Epileptics (caution) - CVD (caution) - Constipation (caution) - Prostatic hypertrophy (caution) - Raised intraocular pressure (caution) Interactions: - Tricyclic antidepressants shouldn't be given w/ monoamine oxidase inhibitors as both drug classes increase serotonin and NA levels at synapse (>> hypertension +/- hyperthermia +/- serotonin syndrome) - Tricyclic antidepressants can augment antimuscarinic, sedative or hypotensive adverse effects of other drugs Example drugs: Amitriptyline, lofepramine.

Answer 47

Indication (2): - Acute Herpesvirus infections - Suppression of recurrant herpesvirus infections Mechanism: - Herpesvirus family are double stranded DNA viruses Adverse effects (5): - Dizziness - GI disturbance - Rash - Phlebitis (if given IV) - AKI (in high doses > crystal induced AKI - hydrate to reduce risk Warnings (3 cautions): - Pregnancy (caution - often benfit outweighs risk) - Breastfeeding (caution - often benefit outweighs risk) - Severe Renal Impairment > Toxicity (renally excreted)

Answer 48

Indications (2): - Bipolar - acute management of manic episodes, prophylaxis - Epilepsy: first choice for absence seizures and an option for focal seizures Adverse effects (5): - GI upset, diarrhoea - Tremors - Fatigue - Weight gain - Thinning hair Interactions (2): - CYP450 inhibitor (SICKFACES.COM) > ↑Warfarin ↑ bleeding + other epilepsy drugs - Aspirin = displaces it from binding sites = increased adverse effects

Answer 49

Indication (3): - Peptic Ulcer disease (including NSAID associated) - Dyspepsia and GORD symptom releif - H.pylori (with combination antibiotics) Mechanism: - Reduce acid secretion by irreversibly inhibiting H+/K+ATPase in gastric parietal cells Adverse effects (3): - Gastrointestinal disturbances and headache - Increased C.diff infection risk - Prolonged treatment can cause hypomagnesaemia (can lead to tetany and ventricular arrhythmia) Warnings (2) - May disguise symptoms of gastric cancer - inquire about red flags - Can increase risk of fracture in elderly and osteoporosis Interactions (2) - Reduce antiplatelet effect of clopidogrel (particularly omeprazole) by decreasing it's activation by cytochrome P450 enzymes - Lansoprazole and pantoprazole appear to have less effect ``` Example drugs (3): Lansoprazole, omeprazole, pantoprazole ```

Answer 50

Indication (2): - Benign prostatic hyperplasia - 1st line med option to improve symptoms - Resistant hypertension add-on treatment, when other medicine is insufficient Mechanism: - Most drugs in this class (incl doxazosin, tamsulosin and alfuzosin) are highly selective for A1 adrenoceptors - mainly found in smooth muscles (blood vessels and urinary tract - especially bladder neck and prostate). Stimulation induces contraction and vv - A-blockers therefore cause vasodilation (>>decrease in BP) and reduced resistance to bladder outflow Adverse effects (3): - Postural hypotension - Dizziness - Syncope Warnings (1C/I): - Existing postural hypotension (C/I) Interactions (2): - Caution when introducing A-blockers to other antihypertensive drugs - may be prudent to omit one of these when 1st dose of A-blocker is taken - Particularly with regards to B-blockers which inhibit the reflex tachycardia which forms part of compensatory mech to vasodilation ``` Example drugs (3): Doxazosin, tamsulosin, alfuzosin ```

Answer 51

Indication: - First line for control of blood glucose in T2DM Mechanism - Lowers blood glucose by increasing sensitivity to insulin - Suppresses hepatic glucose production, increases glucose uptake and utilisation by skeletal muscle, and suppresses intestinal glucose absorption - Does not stimulate pancreatic insulin secretion, thus it does not cause hypoglycaemia - Reduces weight gain and can induce weight loss, thus preventing worsening of insulin resistance Adverse effects (3): - GI upset (n&v, taste disturbance, anorexia, diarrhoea) - These effects may contribute to weight loss - Rarely lactic acidosis (precipitated by illness that causes metformin accumulation (eg renal impairment)) Warnings (3 C/I, 3 caution): - Severe renal impairment (C/I) - AKI (C/I) - Sepsis, shock, dehydration, severe tissue hypoxia (C/I) - Hepatic impairment (caution) - Alcohol intoxication, may precipitate lactic acidosis (caution) - Chronic alcohol overuse (caution) Interactions (3): - Withold before and 48 hrs after injection of IV contrast, when increased risk of renal impairment - Other drugs with potential to impair renal function (eg ACE-i, NSAIDs, diuretics) should also be used with caution - Prednisolone, thiazide and loop diuretics elevate blood glucose, hence reducing efficacy of metformin

Answer 52

Indications (1): - Asthma Adverse effects (4): - Headache (common / mild) - Abdominal pain (common / mild) - Increased rate of upper respiritory tract infections (URTI) vHyperactivity / reduced ability to concentrate (rare) - ?EGPA (Eosinophilic granulomatosis with polyangiitis [aka Churg-Strauss]) - poor evidence Warnings (2): - Only prescribe if not controlled with ICS - Pregnancy = caution - no evidence but safe to continue if already taking ``` Example drugs (1) Montelukast ```

Answer 53

Indications (5): - Osteoporosis - CKD to treat secondary hyperparathyroidism and renal osteodystrophy - Calcium (as calcium gluconate) with hyperkalaemia - Hypocalcaemia that is symptomatic (paraesthesia, tetany, seizures) - Vit D in deficiency - rickets, osteomalacia Mechanisms: - Ca needed for normal function of muscle, nerve, bone and clotting - Ca homeostasis controlled by PTH and vit D, which increase serum Ca levels and bone mineralisation, and calcitonin which reduces serum Ca levels - In osteoporosis there is Ca deficiency - administering Ca and vit D may reduce the rate of bone loss - if this means less fractures is unclear - CKD reduced phosphate excretion and reduced vit D activation causes hyperphosphataemia and hypocalcaemia ---> hyperparathyroidism which causes range of bone problems (osteodystrophy) - treatment may includ oral Ca supplements to bind phosphate in gut, and alfa calcidol to provide vit d that is not dependent on renal activation. - In hyperkalaemia Ca raises the myocardial threshold potential reducing risk of arrhythmias Adverse effects (2): - Dyspepsia - Constipation Warnings (1): - Don't give Ca and Vit D in hypercalcaemia Interactions (2): - Reduces absorption of other drugs, Fe, bisphosphonates, tetracyclines, levothyroxine - IV; don't let it mix with sodium bicarb as can precipitate Examples (4): Calcium carbonate, calcium gluconate, cholecalciferol, alfacalcidol

Answer 54

Indication (1): - Treatment and prevention of hypokalaemia Mechanism - Normally tops up depleted potassium - Thiazide and loop diuretics excrete potassium, so potassium spacing are preferred - Redistributive hypokalaemia is where there is normal total potassium but low serum potassium (i.e. it's in the cells) Adverse effects (8): - Unpalatable - N/V - Diarrhoea - Flatulence - GI obstruction - Ulceration - Bleeding - HyperK --> arrhythmia Warnings (2 cautions): - Renal impairment (caution) - Severe renal impairment (caution) Interactions (1): - Caution when used with potassium elevating drugs (e.g. IV potassium chloride, aldosterone antagonists, potassium sparing diuretics, ACEI, ARBs ``` Example drugs (2): Potassium chloride, potassium bicarbonate ```

Answer 55

Indication: - Skin and soft tissue infections - e.g. cellulitis (in combination with benzylpenicillin) - Osteomyelitis and septic arthritis - Endocarditis Mechanism: - β-lactam ring inhibits enzymes responsible for cross-linking peptidoglycans, which weakens cell walls leading to swelling, lysis and death - Altered acyl side chain protectes the β-lactam ring, making it effective agains β-lactamase producing staphylococci (but not MRSA, obvs which reduces penicillin binding affinity) Adverse effects (4) - Anaphylaxis - Minor gastrointestinal upset - Liver toxicity (Cholestasis and hepatitis - rare) - CNS toxicity with high dose and severe renal impairment Warnings (2C/I, 1 caution) - Penicillin allergy (C/I) - Hepatotoxicity (C/I) - Reduce dose in those with severe renal impairment (caution) Interactions (1): - Reduces renal excretion of methotrexate (increasing toxicity) Example drugs: Flucloxacillin

Answer 56

Indications (2): - Reduce absorption of certain poisons (incl some drugs) from gut - single dose - To increase elimination of certain poisons - multiple doses Mechanism - Molecules are aDsorbed* onto the surface of the charcoal as it travels through the gut, reducing their aBsoprtion into the gut - However, the affinity of charcoal for the poison (its efficacy) is dependent on the poison: weakly ionic and hydrophobic substances (i.e. benzos, methotrexate) are well adsorbed by the charcoal, whereas as strongly ionic and hydrophillic substances (i.e. strong acids/bases, alcohols, lithium and iron) are not - Multiple doses are used where the poison diffuses readily into the gut - The multiple doses maintains a steep poison conc gradient (high in blood circulation, low in GI lumen) so ensure higher adsorption to the charcoal Adverse effects (3): - Black stool and vomiting - Aspiration of activated charcoal: pneumonitis, bronchospasm and airway obstruction - It can also precipitate intestinal obstruction Warnings (1C/I, 2 cautions): - Reduced LOC (C/I) without airway protection - Persistent vomiting (caution) - Reduce in increased risk of intestinal obstruction (caution) Interactions: -Prevents absorption of many drugs taken therapeutically as well as those taken in overdose

Answer 57

Indications (3): - Epilepsy - 1st choice for focal seizures, with and without secondary generalisation, and for primary generalised seizures - Trigeminal neuralgia - 1st choice to control pain, reduce frequency and severity of attacks - Bipolar disorder - prophylaxis in patients resistant/intolerant of other medications Mechanism: - Not fully understood - Inhibits neuronal sodium channels, reducing neuronal excitability. (same MOA as Phenytoin) - This reduces electrical 'kindling, in the temporal lobe and limbic system Adverse effects (6): - GI upset, nausea and vomiting - Neuro effects, dizziness and ataxia - 10% will get a hypersensitivity effect, often a maculopapular rash - Rare effect (1/5000) is Antiepileptic hypersensitivity syndrome, usually within 2 months. Presents with severe skin reaction, fever, lyphadenopathy and systemic illness - Mortality of 10% - Can cause oedema and hyponatremia, due to diuretic effect Warnings (2C/I, 3 cautions): - Pregnancy - can cause problems (take folic acid) - Prior antiepileptic hypersensitivity syndrome (C/I) - Hepatic disease (caution) - Renal disease (caution) - Cardiac disease (caution) ``` Interactions (5): - Carbamazepine induces Cytochrome P450 enzymes, meaning that you need to give more of drugs that are metabolised by this, like: - Warfarin - Oestrogen - Progestogen - Other antiepileptics Efficacy reduced by drugs which lower seizure threshold - SSRIs - Tricyclics - Antipsychotics - Tramadol ```

Answer 58

Indication (2): - VTE - low molecular weight heparin (LMWH) is 1st line for VTE prophylaxis, initial tx for DVT and PE - Acute coronary syndrome (ACS) - LMWH or fondaparinux are part of 1st line therapy to improve revascularisation and prevent thrombus progression Mechanism: - Unfractionated heparin (UFH) - inhibits thrombin and factor Xa - LMWH - Inhibits factor Xa preferentially over thrombin - Fondaparinux - inhibits factor Xa only Adverse effects (3): - Bleeding - Injection site reactions (as with all injections) - Rarely heparin-induced thrombocytopenia, caused by a low platelet count and thrombosis. It is an immune reaction and is more likely to happen with UFH Warnings (3): - Use with caution in pts with increased risk of bleeding - Invasive procedures (Avoid around time of proceedure) - Renal Impairment - Lower dose of fondaparinux or LMWH - or use UFH instead Interactions (1): - Antithrombotic drugs (increased bleeding risk = avoid unless good reason (eg using LMWH while initiating warfarin tx, or combining LMWH with antiplatelet drugs (aspirin/clopidogrel) in ACS tx ``` Example drugs (4): Enoxaparin (LMWH), dalteparin (LMWH), fondaparinux, unfractionated heparin ``` Extras - LMWH and fondaparinux have more predictable effects than UFH, and thus do not usually require laboratory monitoring, whereas UFH requires aPTT test. - Protamine sulfate can reverse anticoagulation from UFH. Less effective for LMWH. Ineffective for fondaparinux - The trade name for dalteparin is "Fragmin", which is what is used on the wards at George's

Answer 59

Indication (2): - Seizure Prophylaxis (focal, myoclonic, generalised) - Established convulsive status epilepticus if has not responded to benzodiazepines (selected cases) Mechanism: - Synaptic vesicle protein 2A (SV2A) are present in synapse NT vesicles - Vesicle exocytosis releases \NTs into the synaptic cleft - ?? Mechanism - alters vesicle exocytosis > modulating neuronal exciticity Adverse effects (6): - Drowsiness (10%) - Headache - Dizziness - Weakness - Mood Disturbance / Psychiatric disturbance (rare - withdraw drug) - severe Hypersensitivity reaction (rare) Warnings (2 cautions) - Renal Impairment (caution) - Pregnancy (caution) Interactions (1): - Few, unlike other epileptic medications (which is it's main advantage

Answer 60

Indication (2): - Asthma (step 2) - COPD - where severe airway obstruction or recurrent exacerbations. Normally with LABA or Long acting antimuscarinic bronchodilator Mechanism: - They pass through the plasma membrane, and interact with receptors in the cytoplasm. They move to the nucleus to modify gene transcription - Pro-inflammatory Interlukins and other mediators are downregulated - Anti-inflammatory proteins are upregulated - Reduces mucosal inflammation - Widens the airways - Reduces mucus secretion. Adverse effects (3): - Oral candiditis (thrush) - Hoarse voice - Some evidence of increased risk of pneumonia in COPD Warnings (1): - High dose inhaled corticosteroids should be used with caution in COPD patients with a history of pneumonia, and ``` Example drugs (3): Beclometasone, budesonide, fluticasone ```

Answer 61

Indication (2): - Asthma - To controls symptoms and prevents exacerbation, at steps 3 and 4 - COPD - To control symptoms and prevent exacerbation, in patients who have severe airflow obstruction or recurrent exacerbations Mechanism: - Corticosteroids suppress inflammation - Long acting B2 agonists stimulate bronchodilation ``` Adverse effects (Steroids= 6, LABAs = 3) Inhaled corticosteroids can cause - Oral thrush - Hoarse voice - Might cause pneumonia in COPD - Adrenal suppression (at high doses for long time) - Growth retardation (high doses for long time in kids) - Osteoporosis ``` LABAs can cause - Tremor - Tachycardia - Arrhythmia - Muscle Cramps Warnings (Steroids= 2, LABAs = 1): Inhaled corticosteroids should be used in caution with - COPD patients with history of pneumonia - Children (Growth suppression) LABAs should be used in cation with - Cardiovascular disease, where tachycardia may cause angina or arrhythmia. Interactions (0) ``` Example drugs (2): Seretide, symbicort ```

Answer 62

Indication (5): - Severe infection, particularly those caused by Gram -ve aerobes (incl P. Aeruginosa) - Severe sepsis - Pyelonephritis + complicated UTI - Biliary and other intra-abdominal sepsis - Endocarditis Mechanism: - Spectrum of action incl: Gram -ve aerobic bacteria, staph and mycobacteria - Aminoglycosides bind irreversibly to bacterial ribosomes (30S subunit) >> inhibit protein synthesis and are bactericidal - Aminoglycosides enter bacterial cell via an oxygen-dependent transport system - Bacterial resistance: Innate - strep and anaerobes don't have this transport system; Acquired - other bacteria have reduced cell membrane permeability or have enzymes that modify aminoglycosides to prevent them reaching ribosomes - Penicillins weaken bacterial cell walls so can enhance aminoglycoside take up Adverse effects (3): - Nephrotoxicity and ototoxicity due to aminoglycoside accumulation in renal tubular epithelial cells and cochlear/vestibular cells respectively - Nephrotoxicity presents as decreased urine output and increased serum creatinine/urea; potentially reversible - Ototoxicity is often not noticed until after resolution of the acute infection when patient complains of hearing loss, tinnitus and/or vertigo; potentially irreversible Warnings (2): - Aminoglycosides are renally excreted - monitoring plasma drug conc is essential to prevent nephrotoxicity/ototoxicity, especially in neonates/the elderly and in the renally impaired - Aminoglycosides can impair neuromuscular transmission so shouldn't be given to patients w/ myasthenia gravis until absolutely necessary Interactions (2): - Ototoxicity is more likely if co-prescribed w/ loop diuretics (i.e. furosemide) or vancomycin - Nephrotoxicity is more likely id co-prescribed w/ ciclosporin, platinum chemotherapy, cephalosporins or vancomycin Example drugs: Gentamicin, amikacin

Answer 63

Indication (4): - Severe acute pain - Chronic pain - Breathlessness (end of life care) - With O2, Furosemide + nirates for Breathlessness and anxiety (acute pulmonary oedema) Mechanism: - CNS: activation of opioid µ-receptors > reduction in neuronal excitibility and pain transmission - Medulla: Reduce respiritory drive and breathlessness. Reduce sympathetic activity (in MI = reduce heart rate and O2 demands) Adverse effects (6): - Respiratory and neurological depression - Nausea and vomiting - Pupil constriction - Constipation - Itching - Heavy use = tolerance, dependance and withdrawal Warnings (3): - Doses should be reduced in the elderly, hepatic and renal failure. - Avoid in respiritory failure - Avoid in biliary colic Interactions (1): - Other sedating agents (antipsychotics, benzodiazepines and tricyclic antidepressants) ``` Example drugs (2): Morphine, oxycodone ```

Answer 64

Indications (4): - Urgent psychomotor agitation causing dangerous or violent behaviour - Schizophrenia - when the second generation metabolic SE are problematic - Bipolar disorder - in acute episodes of mania or hypomania - Nausea and vomiting Mechanism: - Block post-synaptic dopamine D2 receptors - 3 main dopaminergic pathways in the cns; mesolimbic (midbrain and limbic system/ frontal system), nigrostriatal pathway (substantia nigra with corpus striatum of the basal ganglia), tuberohypophyseal pathway (hypothalamus with the pituitary) - Antipsychotic effect probably comes from action in mesolimbic system - D2 also in CTZ - explaining the anti nausea/vomiting effects Adverse effects (8): - Sedation - Extrapyramidal effects (from blocking nigrostriatal pathway); acute dystonic (Parkinsonian movements), akathisia (inner restlessness), neuroleptic malignant syndrome (rare but life-threatening SE, rigidity, confusion, autonomic dysregulation and pyrexia) - Tardive dyskinesia (tardive = late, occurs months post therapy), (pointless involuntary movement) - Drowsiness - Hypotension - QT- interval elongation (--> arrhythmias) - Erectile dysfunction - Hyperprolactinaemia symptoms due to tuberohypophyseal D2 blockade (e.g. menstrual disturbance, galactorrhoea, breast pain) Warnings (2C/I, 1 caution): - Dementia (C/I) - Parkinson's (C/I) - Elderly patients need lower dose (caution) Interactions (1): - Drugs that prolong the QT interval (e.g.amiodarone and macrolides) Examples (3): Haloperidol, chlorpromazine, prochlorperazine

Answer 65

Indication (1): - Mild-to-moderate pain, secondary to simple analgesics Mechanism: - Paracetamol poorly understood ?COX inhibition - Codeine and dihydrocodeine are weak opiods and are metabolised by Cytochrome p450 to mophine, and are agonists of opioid µ-receptors Adverse effects (3, 3 OD): - Nausea - Constipation - Drowsiness - OD - hepatotoxicity, neuro/resp depression Warnings (4): - Severe respiratory disease (caution) - Elderly (caution) - Hepatic impairment (caution) - Renal impairment (caution) Interactions (1): - Other sedating drugs (anipsychotics, benzodiazepines or tricyclic antibiotics ``` Example drugs (2): Co-codamol, co-dydramol ```

Answer 66

Indications (5): - Severe infections, broad specturm of potential pathogens (including p. aeruginosa) - Where antibiotic resistance is likely - Immunocompromise - Commonly prescribed for LRI UTIs - Intra-abdominal sepsis of skin/soft tissue infections Mechanism: - Inhibit enzymes responsible for cross-linking peptidoglycans in bacterial cell wall - β-lactam ring has been modified to be more effective, particularly against p.aeruginosa - Combination with tazobactam inhibits β-lactamase producing bacteria (S.aureus/ Gram-negative anaerobes) Warnings (1 C/I, 2 cautions): - Penicillin allergy (C/I) - Risk of C diff (caution) - Reduced dosage with moderate/severe renal impairment (caution) Contraindicated with Penicillin allergy; Caution with people ar tisk of C.diff; Reduce doseage in patients with moderate/severe renal impairment Interactions (2): - Reduces excretion of Methotrexate (increasing toxicity) - Enhances anticoagulant effect of warfarin (killing bacteria involved in vit K metabolism) ``` Example drugs (1): IV Pipercillin in combination with Tazobactam aka. Tazocin ```

Answer 67

Indications (2): - COPD - short-acting antimuscarinics are used to relive breathlessness, long acting antimuscarinics are used to prevent breathlessness and exacerbations. - Asthma - short-acting antimuscarinics are used as adjuvant tx in acute exacerbations. Long acting antimuscarinics are (added to corticosteroids, and Long acting B2 agonists,) at step 4 of the asthma scale Mechanism: - Binds to muscarinic receptor, competitively inhibits acetylcholine - therefore blocks the parasympathetic - So increase heart rate and conduction; reduce smooth muscle tone - including in resp tract; reduces secretions from glands in respiratory and GI. - In the eye cause relaxation of the pupillary constrictor and ciliary muscles --> pupillary dilation and stops accommodation. Adverse effects (2): - When anti-mus brochodilators taken by inhalation there is relatively little systemic absorption so uncommon to have side effects - Dry mouth may happen Warnings (2): - In angle-closure glaucoma can cause raised intraocular pressure - Be cautious if risk of arrhythmias Examples (3): Ipratropium, tiotropium, glycopyrronium

Answer 68

Indications (4): - Hypertension 1st of 2nd line treatment - Chronic heart failure - 1st line treatment of all grades - to improve symptoms and prognosis - Ischaemic heart disease - reduce risk of subsequent CV events, incl MI and stroke - Diabetic nephropathy and CKD w/ proteinuria Mechanism: - ACEI block action of ACE to prevent conversion of angiotensin I to angiotensin II (stimulates vasoconstriction and aldosterone secretion) >> reduces peripheral vascular resistance (afterload) >> lowers BP - It particularly dilates the efferent glomerular arteriole >> reduces intraglomerular pressure >> slows progression of CKD - Stimulation of aldosterone release >> increased Na and water excretion >> reduced pre-load (beneficial in heart failure) Adverse effects (5): - Hypotension (especially after 1st dose) - Persistent dry cough (due to increased levels of bradykinin which is usually inactivated by ACE) and hyperkalaemia (low aldosterone >> K retention) - ACEI can also cause/renal failure - especially in patients w/ renal artery stenosis who rely on constriction of efferent arteriole to maintain glomerular filtration - If detected early, these adverse effects are usually reversible on stopping the ACEI - Rare but important side effects of ACEI are angioedema and other anaphylactoid reactions Warnings (1C/I, 2 cautions): - AKI (C/I) - RAS (caution) - Pregnancy and breastfeeding (caution) Interactions (3): - Due to risk of hyperkalaemia, ACEI should be avoided in patients taking other K-elevating drugs (i.e. K supplement or K sparing diuretics) except under specialist advice for advanced heart failure - In combo w/ other diuretics, ACEI may be associated w/ profound 1st dose hypotension - Combo of NSAID + ACEI increases risk of renal failure ``` Example drugs (3): Ramipril, lisinopril, perindopril ```

Answer 69

Indications (2): - Analgaesic = WHO pain ladder rung - Antipyretic = reduce fever and associated symptoms Mechanism - Poorly understood - Weak COX inhibitor, reducing PGE2 concentrations in the thermoregulatory region of the hypothalamus - Possibly Selective COX2 - hence does not effect gut mucosa Warnings (1C/I, 4 cautions) - Hepatotoxicity risk (C/I) - Alcoholism (increased NAPQI production = caution) - Malnutrition (caution) - Underweight (caution) - Severe hepatic impairment (caution) Interactions (1): - Cytochrome p450 inducers may increase rate of NAPQI production = increased risk in OD ``` Example drugs (4): Paracetamol is in Lemsip, Cocodamol, Calpol, Sudafed ```

Answer 70

Indications (4): - Pneumonia - UTI - Combination treatment for Hospital aquired infection of intra-abdominal sepsis (co-amoxiclav) - Combination treatment (co-amoxiclav) for H.pylori associated peptic ulcers Mechanism: - β-lactam ring inhibits enzymes responsible for cross-linking peptidoglycans, which weakens cell walls leading to swelling, lysis and death - Altered side chains make it more effective against gram-negative bacteria - Addition of Clavulanic acid (co-amoxiclav) increases activity to β-lactamase producing bacteria (S.aureus, gram-negative anaerobes) Adverse effects (2): - Anaphylaxis - GI upset such as antibiotic-associated colitis (due to overgrowth of C.diff) Warnings (1 C/I, 2 cautions): - Penicillin allergy (C/I) - Risk of C diff (caution) - Reduce dose in severe renal impairment (caution) Interactions (2): - Reduces renal excretion of methotrexate (increasing toxicity) - Kills off bacteria responsible for Vit.K metabolism = enhances warfarin effect ``` Example drugs (2): Amoxicillin, coamoxyclav ```

Answer 71

Indication (4): - Insulin replacement in people with T1DM and control of blood glucose in people with T2DM where oral hypoglycaemic tx is inadequate. - Diabetic emergencies (eg DKA or hyperglycaemic hyperosmolar syndrome). - Perioperative glycaemic control in some patients - Hyperkalaemia (alongside glucose + treatment to correct the underlying cause) Mechanism: - For DM - stimulates GLUT-4 transporters to go to cell membrane, allowing more glucose to get into cells - For hyperkalaemia - drives K+ into cells, reducing serum K+ (only works while insulin being given, the effect is reversed once insulin is discontinued) Adverse effects (2) - Hypoglycaemia - Lipohypertrophy Warnings (1): - Insulin clearance is reduced in patients with renal impairment, so more insulin in serum -> increased risk of hypoglycaemia Interactions (2): - Other hypoglycaemic agents will increase hypoglycaemia risk - Corticosteroids increase insulin requirements ``` Example drugs (4): Insulin aspart, insulin glargine, biphasic insulin, soluble insulin ``` Extra (5): - Rapid acting (immediate onset, short duration) -> insulin aspart (Novorapid) - Short acting (early onset, short duration) -> soluble insulin (Actrapid) - Intermediate acting (intermediate onset and duration) -> isophane insulin (Humulin) - Long acting (flat profile, regular administration) -> insulin glargine (Lantus) - Biphasic insulin = rapid + intermediate (eg Noromix)

Answer 72

Indication (2): - Dry or scaling skin disorders, with or without topical corticosteroids, in treatment of eczema - Can also be used in psoriasis Mechanism: - They replace water in dry skin - They reduce water loss, by reducing water evaporation from the skin surface Adverse effects (2): - Can cause greasiness of skin, but this is vital to therapeutic effect - They can exacerbate acne vulgaris and folliculitis, by blocking pores and hair follicles Interactions (1): - Space applications with other topical applications, to prevent drugs like topical corticosteroids from being blocked from the skin. ``` Example drugs (2): Aqueous cream, liquid paraffin ```

Answer 73

Indication (3): - Constipation and faecal impactation - Bowel prep prior to surgery or endoscopy - Hepatic encephalopathy Mechanism - Consists of osmotically active substances (sugars or alcohols) that are not digested or absorbed, therefore remaining in gut lumen - They hold water in stool, maintaining its volume and stimulating peristalsis - Lactulose also reduces ammonia absorption, which acidifies the stool, thus inhibiting proliferation of ammonia-producing bacteria (helpful in pts with liver failure, in whom ammonia has a major role in the pathogenesis of hepatic encephalopathy) Adverse effects (5): - Flatulence - Abdo cramps - Nausea - Diarrhoea - Phosphate enemas can cause local irritation and electrolyte disturbances Warnings (2) - Don't use in intestinal obstruction (risk of bowel perforation) - Phosphate enemas cause significant fluid shift, so caution in pts with heart failure, ascites, and electrolyte imbalances Interactions (1): - May increase the effect of warfarin ``` Example drugs (3): Lactulose, macrogol, phosphate enema ```

Answer 74

Indications (1): - Thiamine (vitamin B1) to treat and prevent Wernicke’s encephalopathy and Korsakoff’s psychosis - Folic acid (the synthetic form of folate or vitamin B9) - Used in megaloblastic anaemia due to folate deficiency, and in the first trimester of pregnancy to reduce the risk of neural tube defects - Hydroxocobalamin (a synthetic form of cobalamin or vitamin B12) is used in the treatment of megaloblastic anaemia and subacute combined degeneration of the cord due to vitamin B12 deficiency - Phytomenadione (the plant form of vitamin K). For all newborn babies to prevent vitamin K deficiency bleeding, and is used to reverse the anticoagulant effect of warfarin (prothrombincomplex concentrate should also be given in cases of major bleeding) Mechanism: - Organic substances used in metabolic processes - Folic acid is involved in normal cell division, initiating cell proliferation may be how it causes neural tube closure - Phytomenadione reverses Warfarin by providing a supply of vitamin K for vitamin K-dependent clotting factors by the liver ``` Adverse effects (1): - IV phytomenadione and high-dose thiamine may rarely cause anaphylaxis ``` Warnings (2): - In patients with co-existing B12 and folate deficiency, you should replace both vitamins simultaneously - replacing folate acid alone may speed up subacute combined degeneration of the cord due to B12 deficiency. - Phytomenadione is less effective in reversing warfarin in patients with severe liver disease, as clotting factors are synthesised in the liver. Interactions (1): - When attempting to restart warfarin after vitamin K has been given, it may result in erratic dosingrequirements. Example drugs Folic acid, thiamine, hydroxocobalamin, phytomenadione.

Answer 75

Indication (5): - Used when ACEI are not tolerated due to cough - same indications - Hypertension - 1st of 2nd line treatment - Chronic heart failure - 1st line treatment of all grades - to improve symptoms and prognosis - Ischaemic heart disease - reduce risk of subsequent CV events, incl MI and stroke - Diabetic nephropathy and CKD w/ proteinuria Mechanism - ARBs block the action of angiotensin II on the AT1 receptor >> vasodilation >> reduced peripheral vascular resistance (afterload) - It particularly dilates efferent glomerular arterioles >> reduced intraglomerular pressure >> slows progression of CKD - By blocking angiotensin stimulatory effect on release of Aldosterone - promotes Na and water excretion Adverse effects (3): - Hypotension (particularly after 1st dose) - Hyperkalaemia and renal failure (patients w/ renal artery stenosis are particularly at risk as they rely on constriction of efferent arterioles to maintain GFR) - Less likely to cause dry cough and angioedema as ACEI (no impact on bradykinin metabolism) Warnings (2C/I, 1 caution): - Renal artery stenosis (C/I) - AKI (C/I) - Breastfeeding/pregnancy (caution) Interactions (3): - Due to risk of hyperkalaemia, ARBs should be avoided in patients taking other K-elevating drugs (i.e. K supplement or K sparing diuretics) except under specialist advice for advanced heart failure - In combo w/ other diuretics, ARBs may be associated w/ profound 1st dose hypotension - Combo of NSAID + ARBs increases risk of renal failure ``` Example drugs (3): Losartan, candesartan, irbesartan ```

Answer 76

Indication (1): - Dry eye conditions such as keratoconjunctivitis sicca or Sjögren’s syndrome Mechanism: - Sooth, lubricate and protect the eye from abrasive damage - Usually made of electolyte solution with a viscosity agent (which enables it to stay in the eye for longer) Oinments are highly viscous, longer lasting but blur vision Example drugs: Hypromellose, carbomers, liquid and white soft paraffin

Answer 77

Indications (2): - Constipation - Suppositories for faecal impactation Mechanism: - Increases water and electrolyte secretion from colonic mucosa, thereby increasing volume of colonic content and stimulating peristalsis. - Metabolism of Senna in particular in intestines produces metabolites that further stimulate peristalsis. Adverse effects (2): - Abdo pain & diarrhoea - Melanosis coli (reversible pigmentation of intestinal wall) can occur in prolonged use Warnings (1 C/I, 1 caution): - Intestinal obstruction --> perforation (C/I) - Haemorrhoids or anal fissures (caution) ``` Example drugs (4) Senna, bisacodyl, glycerol suppositories, docusate sodium ```

Answer 78

Indication (1): - Mild to moderate pain Mechanism: - Metabolised to form small amounts of morphine or dihydromorphine = agonists of opioid µ-receptors in CNS - Tramadol also effects serotonergic and adrenergic pathway (like SNRIs) Adverse effects (6): - Nausea - Constipation - Dizziness - Drowsiness - OD = neurological and respiritory depression - Never give IV = causes anaphylaxis like reaction Warnings (1C/I, 2 cautions): - Epilepsy (C/I) - Significant respiratory disease (caution) - Reduce dose in renal and hepatic impairment and for elderly (caution) Interactions (2): - Avoid using with other sedating drugs (antipsychotics, benzodiazipines and tricyclic antidepressants - Tramadol should be avoided with drugs that lower seizure threshold SSRIs, tricyclics. ``` Example drugs (3): Tramadol, codeine, dihydrocodeine ```

Answer 79

Indications: - Childhood schedule - Influenza vaccine annually for at risk groups - Pneumacoccal vaccine once for at risk groups Mechanism: - Introduce an antigen to lead to adaptive immune response (usually memory B cells) - May be inactivated, live but attenuated, a specific peptide or protein component or a detoxified exotoxin Adverse effects (3): - Local reactions and mild systemic effects - Severe hypersensitivity - MMR can cause measles like or mumps like illness Warnings (3): - Anaphylactic reaction to past dose or one of its constituents - Significant immunosuppression - Pregnancy Interactions (1): - Immunosuppressive drugs

Answer 80

Indications (1): - Short term treatment of debilitating or distressing insomnia. Mechanism: - Similar to benzodiazepines - They target GABAa receptors (these are chloride channels which open when GABA binds to them) - This allows Chlorine to flow into the cell making it more resistant to depolarisation - They also increase binding of GABA to GABAa receptors with widespread inhibitory effects (e.g. reduced anxiety, sleepiness and sedation) Adverse effects (5, OD): - Daytime sleepiness - Rebound insomnia when they are stopped - CNS effects (headache, confusion, nightmares, amnesia) - Dependance - Withdrawal symptoms (muscle pain, anxiety and headaches) - In overdose: drowsiness, coma, resp. depression - Zopiclone - taste distubances - Zolpidem - GI Warnings (4 cautions): - Elderly (caution) - Obstructive sleep apnoea (caution) - Resp. muscle weakness (caution) - Resp. depression (caution) Interactions (5): - Enhance the sedative effects of alcohol, antihistamines and benzodiazepines - Enhance the hypotensive effect of antihypertensive medications - P450 inhibitors (e.g. macrolides) can enhance sedation, whereas P450 inducers (e.g. phenytoin, rifampicin) can impair sedation ``` Example drugs (2): Zopiclone, zolpidem ```

Answer 81

Indication - First line local anaesthetic for many procedures (eg urinary catheterisation, suturing) - Uncommonly used as an antiarrhythmic in VT and VF Mechanism: - Enters the cell then blocks votage-gated sodium channels on the cell membrane - Prevents action potentials in the area supplied by the blocked nerve fibers - In heart, reduces duration of action potential, slows conduction velocity and increases refractory period, helping with VT and VF Adverse effects (6) - Initial stinging during administration - Drowsiness, restlessness, tremor, fits - OD causes hypotension and arrythmias Warnings (1): - Reduce dose in pts with a reduced cardiac output Interactions (1): - Co-adminstration with a vasoconstrictor (eg adrenaline) produces a desirable reaction that may prolong the anaesthetic effect (as less blood flow to the nerve to carry the lidocaine away, so it works for longer).

Answer 82

Indication (1): - Opioid toxicity associated with respiratory &/or neurological depression Mechanism: - Competitively antagonises opioid receptors (particularly the mu-receptor) - Displaces the exogenous opioid (eg morphine) from the receptor, thus reversing its effect Adverse effects (6): - An opioid withdrawal reaction may be precipitated in people who are addicted - Present with pain (if opioid was being taken for analgesia), restlessness, nausea & vomiting, dilated pupils, cold and dry skin with piloerection ("cold-turkey") Warnings (2): - Opioid dependence (caution) - Lower doses used in palliative care setting, to reduce risk of complete reversal of analgesia 400-1200 micrograms IV. Administered under direct supervision, increments of 200-400 mcg every 2-3 minutes until desired effect achieved.

Answer 83

Indication (2): - Highly effective and reversible hormonal contraception - Hormone replacement therapy for early or distressing menopausal symptoms Mechanism: - Contraception: Oestrogen and progesterone provide negative feedback, suppressing LH/FSH and prevent ovulation and also effect cervix and endometrium. - HRT: provides replacement for naturally falling Oestrogen/progesterone Adverse effects (4): - Irregular bleeding - Mood changes - Combined Pill (but not progesterone only) = increased VTE, CVD and CVA risk (careful in those with high baseline risk (worse for HRT as higher baseline risk) - Increased risk of Breast and cervical cancer Warnings (1C/I, 1 caution): - Breast cancer (C/I) - Avoid in those at increased risk for VTE and CVD (caution) Interactions (1): - Cytochrome p450 inducers (CRAP GPs) ``` Example drugs (2) Combined ethinylestradiol products, desogestrel ```

Answer 84

Oxygen Indications (3): - Hypoxaemia - Increasing reabsorption of pleural gas in pneumothorax - Reduce recovery time in carbon monoxide poisoning Mechanism: - Increases oxygen delivery to tissue by saturating blood - Accelerates nitrogen diffusion out of the body by reducing % nitrogen in alveolar air (pneumothorax gas is mostly nitrogen) - High pO2 competes with carbon monoxide for haemoglobin binding = reducing half-life} ``` Adverse effects (1): - Headaches ``` Warnings (2): - Chronic type 2 respiratory failure = risk of hypoxic drive (e.g. COPD) - Never allow near heat source or naked flames (e.g. smoking) Interactions: None