Pharmacology Flashcards

Question

What is the therapeutic window?

Answer 1

The concentration range over which drugs exert a clinically useful effect, without exerting significant toxic effects = TD50 (toxic conc) / EC50 (min conc)

Answer 2

* Renal disease - reduced clearance of renally excreted drugs (digoxin, aminoglycosides) * Disturbances to electrolytes - predisposes to toxicity * Hepatic disease - reduced clearance of hepatic metabolised drugs * Reduced CYP450 activity * Longer half lives = toxicity * Cardiac disease = reduced organ perfusion = reduced renal/hepatic blood flow * Excessive response to hypotensive agents

Answer 3

* Grapefruit juice - inhibits CYP450 isoenzymes * Decrease clearance of simvastatin, amiodarone * Increase exposure to drug * Cranberry juice - inhibits CYP2C9 isoenzyme * Decrease clearance of warfarin = increased anticoagulant effect = increased risk of haemorrhage

Answer 4

Unwanted/harmful reaction which occurs after administration of a drug and is suspected to be due to the drug * On target ADR = exaggerated therapeutic effect mainly due to an increased dosing * Same receptor in different tissues * Off target = interaction of drugs with other receptor types not intended for therapeutic effect * Also metabolites that act as a toxin

Answer 5

* Polypharmacy * Multi-morbidity * Ignorant, inappropriate or reckless prescribing * Extremes of age * Altered renal and hepatic functions * Drugs with narrow therapeutic windows

Answer 6

* Anticonvulsants * Antibiotics * Anticoagulants * Antidepressants * Antiarrhythmias

Answer 7

* Body weight/size * Age Sex * Genetics * General condition of health * Dose/formulation/route of drug * Resistance to drugs * Drug interactions * Protein binding * GI absorption * Metabolism * Changes in pH/electrolytes

Answer 8

Induction of CYP450: Increased transcription, translation or slower degradation * Decreased half life and increased clearance * Dosing will have to be increased Inhibition of CYP450: * Increased half life and decreased clearance * If dose is not decreased, this leads to toxic concentrations

Answer 9

Co-administration with drugs that affect gut motility and absorption by the gut will interfere with absorption. Eg: increased rate of gastric emptying will increase the rate of uptake via the small bowel

Answer 10

Affected by competition of drugs at protein/lipid binding sites * If drug has non-linear kinetics or a small therapetuic window, this can lead to toxicity * WIth linear kinetics, this is avoided by increasing clearance

Answer 11

* Decreased protein binding - increases free unbound drug and accelerates its removal * Inhibition of tubular secretion - increased plasma levels of the drug * NSAIDs * Can be used for therapeutic benefit (penicillin) * Changes in urine flow/pH

Answer 12

Oestrogen: * Breast tenderness * Nausea/vomiting * Thromboembolism * Endometrial cancer Progesterone: * Depression * Acne * Weight gain * Irritability

Answer 13

* Progesterone suppresses ovulation by inhibiting LH/FSH via negative feedback on hypothalamus and reduced GnRH * Progesterone stops fertilisation by thickening cervical mucous and thinning the endometrium * Negative feedback from oestrogen also inhibits LH/FSH on the anterior pituitary

Answer 14

* Venous thromboembolism * Myocardial infarction * Hypertension * Stroke in focal migraines * Headaches

Answer 15

Metabolised by cytochrome P450 in the liver * Efficacy reduced by enzyme-inducing drugs * Phenytoin * St John's Wort * Rifampicin * Efficacy increased by enzyme-inhibiting drugs * Grapefruit juice

Answer 16

* Thicken cervical mucous * Thin endometrium * Cannot support implantation

Answer 17

* Focal migraines * Risk of DVT * Risk of heart disease * Sickle cell disease * Breastfeeding women

Answer 18

* Irregular menstruation * Heavy menstruation * Mood swings * Weight gain

Answer 19

Benefits: * Relieves symptoms * Reduces osteoporosis Risks: * Endometrial/ovarian/breast cancer due to unopposed oestrogens * Ischaemic heart disease * Stroke * Venous thromboembolism * Further bleeding every month

Answer 20

* Anti-oestrogen (block receptors) * Clomiphene = ovulation induction by increasing GnRH/LH/FSH by inhibiting oestrogen * Tamoxifen = ovulation induction/breast cancer treatment * Anti-progesterone (partial agonist to progesterone receptors which inhibit progesterone action) * Mifepristone = termination of pregnancy/induction of labour

Answer 21

* Damage occurs to endothelial wall (smoking etc) * LDLs invade endothelium and become oxidised * Inflammatory response to damage recruits macrophages * Macrophages ingest oxidised LDL * Become foam cells * Aggregation of platelets * Migration and proliferation of smooth muscle cells * Also become foam cells

Answer 22

* TC = 5 * LDL \< 3 * HDL \> 1.2

Answer 23

* Lifestyle - exercise, diet, reduce alcohol intake, smoking * Lipid lowering drugs * Statins * Fibrates * Nicotinic acids (niacin) * Cholesterol lipase inhibitor

Answer 24

Inhibits cholesterol synthesis in the liver by inhibiting HMG-CoA reductase in the pathway from acetyl CoA → cholesterol

Answer 25

* Extensive first pass uptake in the liver * Intestinal absorption varies between 30-85% * Some statins require activation * Some statins eliminated via CYP3A4 enzymes * Difference in half lives (simvastatin is 1-4 hours and atorvastatin is 20 hours) affects dosing times

Answer 26

* Chronic liver disease * Increased transaminase levels * Myopathy * Arthralgias * GI complaints * Headaches

Answer 27

* Affected by CYP enzymes * Inhibitors increase risk of myopathy due to increased statin levels * Graprefruit juice * Verapamil * Inducers decrease efficacy * Rifampicin * St John's Wort * OATP2 (organic anion transport polypeptide) inhibitors decrease efficacy

Answer 28

* PPARalpha agonist - increases production of lipoprotein lipase * Reduces triglyceride production * Increases fatty acid uptake and oxidation * Used in hypertriglyceridaemia / hyperlipidaemia * Not used in hepatic / renal / gallbladder disease * Side effects include GI complaints, gall stones and myositis

Answer 29

* Reduces VLDL and increases HDL * Inhibits synthesis of Lipoprotein A * Not used liver disease or peptic ulcers * Side effects include hepatotoxicity, flushing, hyperglycaemia, activation of peptic ulcers

Answer 30

* Selectively inhibits intestinal cholesterol absorption * Decreases delivery of cholesterol to liver * Increases expression of hepatic LDL receptors * Decreases cholesterol content of atherogenic particles * Used in statin intolerant patients or to reduce risk of statin ADRs * Side effects include headache, abdominal pain, diarrhoea

Answer 31

* Inability to produce insulin due to betal cell failure * Adequate insulin production with insulin resistance * High correlation with obesity/liver fat content

Answer 32

* Decreases insulin resistance and hepatic glucose production * Enhances skeletal and adipose glucose uptake * Inhibits hepatic gluconeogenesis * First agent of choice - does not induce hypoglycaemia * Contraindicated in renal, cardiac and hepatic disease * Increase T1/2 and decrease clearance * Side effects include GI disturbances, lactic acidosis, vitamin B12 deficiency

Answer 33

* Binds to PPAR-ŷ to upregulate insulin signalling genes * Increases insulin sensitivity in muscle and adipose * Reduction of gluconeogenesis * Side effects: * CVS concerns * Weight gain * Fluid retention * Bladder cancer * Contraindicated in heart failure

Answer 34

* Antagonises B-cell K+/ATP channel activity → depolarisation due to decreased K+ current → increases Ca2+ → increased release of insulin from vesicles * Indicated in renal, cardiac and hepatic disease, children or in combination with metformin when HbA1c levels \> 7% * Side effects include hypoglycaemia, GI disturbances, weight gain * Contraindicated in elderly (hypoglycaemia) and obese patients

Answer 35

* Inhibits breakdown of carbohydrates to glucose by blocking a-glucosidase * ADRs: * Flatulence * Loose stools * Diarrhoea

Answer 36

* DPP-4 inhibitors/GLP1 agonists (injection) * Increases GLP1 from intestinal L cells * Increases insulin secretion and biosynthesis * Increases glucose uptake * Used with another hypoglycaemic drug if risk of hypoglycaemia or intolerance to sulphonylurea

Answer 37

* Stimulates uptake of glucose into liver, muscle and adipose tissue * Decreases hepatic glucose output by decreasing gluconeogenesis * Inhibits glycogenolysis * Promotes uptake of fats

Answer 38

1. Lifestyle changes - diet, exercise, alcohol, smoking 2. Hypoglycaemic drugs - metformin * Add sulphonylurea if HbA1c \> 7% * Add TZD (PPAR-y agonist) if HbA1c \> 7.5% or continue onto insulin 3. Exogenous insulin if HbA1c \> 7.5%

Answer 39

* Short acting * Works within 30-60 minutes with 8-10 hour duration * Several times a day to cover meals * Rapid acting * Works within 5-15 minutes with 4-6 hour duration * Just before eating - better for children * Intermediate acting * Works within 1.5-3 hours with 16-24 hour duration * Used as basal insulin/overnight control * Long acting * Works within 2-6 hours with 18-36 hour duration * Basal insulin/overnight control (high half life)

Answer 40

* Hypoglycaemia * Hyperglycaemia * Lipodystrophy * Reproduction of adipocytes leads to scar tissue * Painful injections * Allergy

Answer 41

* Normal blood glucose of 3.5-6.5 mmol/L * Regular monitoring to determine inssulin dosing levels * Dietary control is needed * Glucose non-enzymatically glycosylates haemoglobin - HbA1c * \> 7% indicated vascular risk * Monitor renal, hepatic, cardiovascular and neurological funtion to detect microvascular disease

Answer 42

* Orlistat - gastric and pancreatic lipase inhibitor * Reduces fat conversaion to fatty acids and glycerol * Causes soft fatty stool and flatus * Sibutramine - noradrenaline and serotonin re-uptake inhibitor * Appetite suppression * Increased thermogenesis due to increased metabolism * Causes increased heart rate and BP - not ideal in obese diabetics

Answer 43

The process of identifying and responding to safety issues about marketed drugs. It helps to survery safety of drugs and develop strategies to minimise risk and optimise benefits

Answer 44

* Identify unrecognised drug safety hazards and quantify their frequencies * Elucidate those factors predisposing to toxicity * Obtain evidence of safety so that a new drug's uses may be widened

Answer 45

* Type A = exaggerated pharmacological response * Predictable * Common * Low mortality * Type B = no expected from known pharmacology * Unpredictable * Rare * Higher mortality

Answer 46

* Spontaneous reporting = presentation due to recognition of a possible ADR * Establishing possible causal relationship * Cohort studies = identify exposed (drug) patients and observe to determine rate of occurrence of ADRs * Compare to controls * Case-control strudies = select cases with ADR and compare exposure to risk factor/drug * Compare to controls without ADR/disease

Answer 47

Advantages: * Involves all doctors * Occurs as soon as drug is marketed * Detects common and rare reactions * Cheap Limitations: * Under-reporting * Delays in reporting * No control group * Misleading reports

Answer 48

Advantages: * Good for rare ADRs * Relatively low cost * Indicate degree of risk (odds ratio) Limitations: * Needs prior hypothesis * Many biases * Suitable database may not be available

Answer 49

* Failure of patient to report * ADR is too trivial * Ignorance of reporting protocols * Lack of time * Uncertainty of relationship of the drug to the presentation

Answer 50

1. Haemagglutinin fuses with viral envelope and vacuole's membrane 2. M2 ion channel allows protons to move through viral envelope and acidify the core which dissembles the virus and release vRNA into cytoplasm 3. vRNA forms a complex with viral proteins to transport into the cell's nucleus 4. RNA polymerase transcribes vRNA into mRNA 5. mRNA enters cytoplasm and is translated into viral proteins 6. Viral proteins and RNA assemble and bud off the plasma membrane by exocytosis

Answer 51

SIngle-stranded RNA virus * Influenza A * Multiple hosts * Higher mortality * Antigenic shift and drift causes constantly mutating virus * Influenza B * Only humans * Lower mortality * Influenza C * Mainly humans * Common cold-like symptoms

Answer 52

M2 ion channel inhibitors * No movement of protons into virus * No acidifcation or dissembling of viral coat so RNA cannot leave Influenza A only - high levels of signle-point mutation in M2 gene causes rapid resistance emergence

Answer 53

* CNS * Dizziness * Anziety * Insomnia * Hallucination * GI disturbance * Hypotension Rimantidine displays less ADRs than amantadine

Answer 54

Oseltamivir/zanamivir Prevents new viral particles from esacaping the host cell * Blocks neuraminidase action * So no cleavage of bond with sialic acid membrane glycoprotein residues Used on influenza A and B

Answer 55

* GI disturbance * Cough * Headache * Nose bleed * Respiratory depression * Allergy * Liver inflammation

Answer 56

* 75 mg : 100 mg showed no difference in outcome * Earlier treatment started the shorter the duration of symptoms * Oseltamivir could reduce mortality by up to 70% even when dosing as long as after 64 hours * Treatment for 6 weeks with 75 mg significantly reduced incidence of flu * Prophylaxis

Answer 57

* Quinolones = prevent bacterial DNA from unwinding and duplicating via topoisomerase ligase * Ciproflaxacin * Folic acid antagonists = inhibit dihydrofolate reductase to stop cofactor (folic acid) in nucleotide synthesis * Trimethoprim * Sulphonamides

Answer 58

* Aminoglycosides = binds to 30s subunit of ribosomes * Gentamicin * Macrolides = prevents peptidyltransferases from attaching tRNA to the next amino acid (binds to P side on 50s subunit) * Erythromicin * Tetracyclines = blocks attachment of amino-acyl-tRNA to A site on the 30s subunit * Doxycyclin

Answer 59

* Beta-lactams * Penicillin * Cephalosporin * Carbapenems * Glycopeptides = inhibit peptidoglycan synthesis * Vancomycin

Answer 60

* Hypersensitivity * GI disturbance * Renal/hepatic toxicity * C. difficile infections * CNS toxicity *

Answer 61

Ensures adequate but non-toxic dose of antibiotic is administered * Markers - FBC, creatine kinase, renal function, stool samples * Especially important in aminoglycosides (kidney and vestibulocochlear damage) and vancomycin and any IV antibiotics

Answer 62

* Time dependent killing = prolonged antibiotic presence at site of infection * Not high concentration * Fusion over long periods * Penicillins, cephalosporins, glycopeptides * Concentration dependent killing = high antibiotic conentrations at site of infection * Not for long periods of time due to risk of toxicity * Aminoglycosides, quinolones

Answer 63

* Disc sensitivity testing * E tests - find out minimum inhibitory concentration * Breakpoint predicts likely response

Answer 64

* Drug inactivating enzymes * B-lactamases * Aminoglycoside enzymes * Altered target = target enzyme has lower affinity for antibacterials * Altered uptake * Decrease permeability (b-lactams) * Increase efflux (tetracyclines)

Answer 65

* Chromosomal mutation * Random gene mutation for resistance * Non-resistant cells die off * Resistant cell replicates and creates a new resistant colony * Horizontal gene transfer * Conjugation - plasmid transferred through pilus * Transduction - gene transferred via a vector (bacteriophage) * Transformation - free DNA passes through cell wall

Answer 66

* Esnure adherence to full course of antibiotics * Appropriate antibiotic and dose * Follow clinical guidelines * Stewardship interventions * Persuasive - education/reminders/feedback * Restrictive - authorisation/stop orders * Structural - expert systems/quality monitoring

Answer 67

* Patient factors * Severity of illness * Age * Co-morbidity * Pathogen factors * Resistance patterns * Virulence (degree of pathogenicity) * Antibiotic sensitivity

Answer 68

* Multi-drug resistant = non-susceptibility to at least 1 agent in 3 antimicrobial categories * Extensively-drug resistant = non susceptibility to at least 1 agent in all but 2 or fewer antimicrobial categories * Pan-drug resistant = non-susceptibility to all agents in all antimicrobial categories

Answer 69

Inflammatory change and proliferation of synovium leading to dissolution of cartilage and bone * Over expression of pro-inflammatory factors (IL-1, IL-6, TNF-a) * Treated with regular exercise, DMARDS (methotrexate, sulfasalazine, rituximab) NSAIDs

Answer 70

* Morning stiffness \> 1 hour * Arthritis of \> 3 joints in 1 hand * Serum rheumatoid factor * X-ray changes/nodules

Answer 71

Autoimmune attack of various tissues in the body including: * Pericardium and pleura - inflammation * Mouth and nose - ulcers * Muscles - aches * Face - butterfly rash * Joints - arthritis Associated with defects in apoptosis Treated with corticosteroids (prednisolone) DMARDs, NSAIDs

Answer 72

Autoimmune attack on blood vessels primarily caused by leukocyte migration. Signs/symptoms: * Fever * Headache * Weight loss * Visual loss * Purpura on skin * Hypertension * Myalgia/arthralgia Treat with corticosteroids (predisone) cyclophosphamide

Answer 73

* Symptomatic relief * Prevention of organ damage * Reduction in mortality * Reduction in morbidity by drugs

Answer 74

* DMARDS * Methotrexate * Sulfasalazine (sulfapyridine) * Azathioprine * Cyclosporine * Calcineurin inhibitors (ciclosporin/tacrolimus) * Anti-TNF * Infliximab / rituximab * Immunosuppressants * Corticosteroids

Answer 75

* Prevents production of interleukin-1 and 6 by macrophages * Inhibits all stages of T-cell activation by inhibiting gene expression in the nucleus * Anti-inflammatory

Answer 76

* Weight gain * Striae * Osteoporosis * Hypoglycaemia * Risk of infection * Cataracts * Delayed wound healing * Drug-induced Cushing's Syndrome

Answer 77

* Used as maintenance therapy in SLE and vasculitis, IBD, dermatitis, RA, leukaemia, transplants * Cleaved to 6-MP and functions as an anti-metabolite to decrease RNA/DNA synthesis * Adverse effects: * Myelosuppression * Risk of infection * Malignancy * Hepatitis

Answer 78

* Ciclosporin - binds to cyclophilin * Tacrolimus - binds to tacrolimus-binding protein * Complex binds to calcineurin to stop phosphatase activity in activated T cells and prevents IL-2 forming

Answer 79

* Used in transplants, atopic dermatitis, psoriasis * Used in rheumatology for cytopenic patients * Adverse effects: * Nephrotoxicity * Hypertension * Hyperlipidaemia * Gingival hyperplasia * Hyperuricaemia in gout * Drug interactions with P450 agents

Answer 80

* Inhibits inosine monophosphate dehydrogenase required for guanine synthesis * Impairs B and T cell proliferation (highly selective) * Adverse effects: * Myelosuppression * GI disturbance * Metallic taste * Used in transplants and lupus nephritis * Contraindicated by renal and hepatic disease

Answer 81

* Cross links DNA by alkylation to stop replication * Suppresses B and T cell activity * Used in lymphoma, leukaemia, lupus nephritis * Interacts with P450 enzymes * Excreted by the kidney * Adverse effects: * Bladder cancer * Lymphoma * Leukaemia * Infertility

Answer 82

* Inhibits dihydrofolate reductase to inhibit DNA and RNA synthesis during S phase of cell cycle * Used in RA, malignancy, psoriasis, Crohn's * Requires monthly toxicity monitoring * Taken orally, IM or SC - WEEKLY DOSING ONLY * Adverse effects: * Myelosuppression * Hepatitis / cirrhosis * Risk of infection * Dry cough / lung problems * Teratogenic * Interacts with other immunosuppressants, ant-cancer drugs, NSAIDs, penicillin, renal drugs

Answer 83

* Inhibits T-cell proliferation and IL-2 production * Used for RA and IBD * Poorly absorbed in the gut * Adverse effects: * Myelosuppression * Hepatitis * Rash * Nausea * Safe in pregnancy due to little drug interactions and not carcinogenic

Answer 84

* Decreases inflammation, angiogenesis and joint destruction * Only prescribed after methotrexate and other DMARDS due to expense * Adverse effects: * Skin/soft

Answer 85

* TH2 driven inflammation → Mucosal oedema, bronchoconstriction, mucus plugging * Airway remodelling leads to wall thickening, mucous gland hyperplasia and increased smooth muscle * Immediate phase = inital response to allergen * IgE causes release of histamine - bronchospasm * Late phase = release of mediators/chemotaxis to bring leucocytes to area * Epithelial damage * Thickened basement membrane * Oedema * Mucous production

Answer 86

* Sympathetic - B2 adrenoceptors * Bronchodilation * Decreased histamine * Increased mucociliary clearance * Parasympathetic - M3 * Maintains smooth muscle tone

Answer 87

1. Mild intermittent asthma = short acting B2 agonist * Salbutamol / terbutaline for symptom relief 2. Regular preventor = inhaled corticosteroids * Budesonide 3. Add on therapy - long acting B2 agonists in combination with corticosteroids * Formoterol / salmeterol 4. If persistent poor control * Leukotriene receptor antagonists * Methylxanthines (theophylline) * Long acting anticholinergics (triotropium) 5. Oral steroids or anti-IgE

Answer 88

* Acts on airway smooth muscle via Gs * Increase adenyl cyclase, cAMP, PKA * Bronchodilation by decreasing calcium * Adverse effects: * Skeletal muscle termor * Tachycardia / dysrhythmia * Interacts with beta blockers

Answer 89

* Suppresses gene transcription in pro-inflammatory cells (mainly eosinophils) * Increases B2 receptor expression * Decreases number of mast cells in respiratory mucosa * Usually inhaled but can be oral - first pass metabolism * Adverse effects * Sore throat * Thrush * Immunosuppression * Weight gain * Delayed wound healing

Answer 90

* Ease of use * Increase in compliance * Decrease in number of prescriptions Also reduces exacerbations, improves symptoms and lung function

Answer 91

* Blocks LTC4 release * Decrease bronchoconstriction * Decrease mucus secretion * Decrease mucosal oedema * Adverse effects: * Angio-oedema * Anaphylaxis * Fever * Arthralgia

Answer 92

* Inhibits phosphodiesterase to increase cAMP * Antagonises adenosine receptors * Adverse effects: * Fits * Arrhythmias * Nausea * Headaches * Cytochrome P450 inhibitors

Answer 93

* Binds to M3 in smooth muscle to block constriction from acetylcholine * Used when unresponsive to B2 agonists and in COPD * Adverse effects: * Dry mouth * Urinary retention * Glaucoma

Answer 94

1. High flow oxygen 2. Nebulised salbutamol 3. Oral prednisolone 4. Add nebulised ipatropium bromide 5. Conider IV aminophylline if no improvement

Answer 95

* Eliminated by the enzyme TPMT * Genetic polymorphism can create variations in number of TPMT enzymes in different individuals * Increased TPMT = undertreatment * Decreased TPMT = toxicity

Answer 96

* Analgesia * Anti-inflammatory * Anti-pyresis

Answer 97

Cell membrane phospholipids (Phospholipase A2) Arachidonic acid (COX-1/COX-2) PG G (COX-1/COX-20 PG E / F / G / I

Answer 98

The response to injurious stimuli to reduce risk of further damage to the organism. It alerts the body to the injury via signalling through the pain pathway * Molecular mediators (autacoids) = bradykinin, histamine, neuropeptides, NO, leukotrienes, cytokines * Prostaglandins (eicosanoids) * Localised release * Short half lives

Answer 99

* COX-1 = constitutively (all the time) expressed * Cytoprotection in gastric mucosa, myocardium, renal parenchyma * Short T1/2 - requires constant synthesis * Most ADRs by NSAIDs due to COX-1 inhibition * COX-2 = induced by inflammatory mediators (bradykinin) * Main therapeutic effects of NSAIDs * Larger 'tunnel' allows inhibition by larger drugs

Answer 100

PGE2 (released from tissue/neurons following trauma) binds to EP1 (Gq) on C fibre 1. Increases neuronal sensitivity to bradykinin 2. Inhibition of K+ channels 3. Increase in Na+ channel sensitivity 4. Increase intracellular calcium to increase neurotransmitter release = INCREASE C FIBRE ACTIVITY

Answer 101

1. Sustained nociception peripherally increases release of cytokines in dorsal horn cell body * Increases COX-2 to increase production of PGE2 2. PGE2 binds to EP2 (Gs) to increase sensitivity of secondary interneurones * Removal of glycinergic inhibition * Increase cAMP to increase PKA 3. Increased pain perception

Answer 102

* GI - pain, nausea, heartburn, bleeding, ulceration * Decrease in cytoprotective mucus * Increase in acid secretion * Renal - reduced renal bloodflow = decreased GFR * Ion and water retention = hypertension * HRH compromisation * Vascular = increase in bleeding time and bruising due to effect on thromboxane * Hypersensitivity * Bronchial asthma

Answer 103

* Other NSAIDs - competition for protein binding sites * Sulphonylurea - hypoglycaemia * Warfarin - bleeding * Methotrexate - toxicity

Answer 104

* Phase 2 conjugation with glucoronide/sulphate becomes saturated * Phase 1 oxidation using glutathione also becomes saturated due to depletion of glutathione * Zero order kinetics * Accumulation of toxic NAPQI * Necrotic hepatic cell death

Answer 105

* Activated charcoal orally if * N-acetylcysteine if 0-36 hours

Answer 106

* Analgesic and anti-pyresis * No anti-inflammatory action * 1st agent for mild to moderate pain and fever * 1st pass metabolism * T1/2 2-4 hours * Caution in alcoholics or liver disease

Answer 107

* Irreversibly inhibits COX-1 by acetylation * Inhibits platelet generation of thromboxane A2 * Antithrombotic effect * Also inhbits COX pathways to block production of prostaglandins * Analgesic and anti-pyretic effect * T1/2

Answer 108

* Nociceptor → Dorsal root of spinal cord (via A deta/C fibres) * Dorsal root → Thalamus/primary sensory cortex * Inhibited by interneurones in substantia gelatinosa * Also inhibited by descending inhibition from cortex * Mimicked by opioiods to reduce pain Opioids inhibit the release of Substance P from nerve terminals to mimic inhibitory descending pathways

Answer 109

* Endogenous = peptides distributed in CNS and PNS that play roles in processing pain signals * Endorphins * Enkephalins * Dynorphins * Exogenous = natural and synthetic agents with actions on endogenous opioid receptors * Eg: morphine

Answer 110

* Mu (MOP) * Supraspinal * Delta (DOP) * Spinal cord * Kappa (KOP * Everywhere (enkephalins)

Answer 111

* Increases efflux of potassium to decrease excitability * Decreases influx of calcium via channels * Decreases cAMP synthesis * Via Gi Overall decreases intracellular calcium to decrease neurotransmitter release and block transmission of pain signals

Answer 112

* Nausea/vomiting * Constipation * Drowsiness * Miosis * Respiratory depression * Increased risk with pulmonary deficit, sleep or other depressant drugs * Hypotension (relaxes smooth muscle) * Dependence / tolerance * Dysphoria

Answer 113

* Full agonists - morphine, codeine, methadone * Higher affinity for mu * Partial agonists/antagonists - nalbuphine * Analgesia without euphoria * Full antagonists - naloxone * Mainly mu * Reversal of fatal agonist effect

Answer 114

* ALL - analgesic for moderate to severe pain * Morphine - terminal illness, diarrhoea * Diamorphine (heroin) = terminal illness * Methadone = maintenance in dependence * Codeine = mild to moderate pain * Fentanyl / alfentanil = anaesthetic * Naloxone = reverse opioid toxicity and dependence

Answer 115

* Other CNS drugs - increase analgesic effect * Naloxone (IV) is highly competitive with opiates to reverse overdose/toxicity * Important to monitor closely

Answer 116

* Given enterally and parenterally * IV for rapid response * Intrathecal for severe pain * Hepatic and renal failure increases T1/2 to up to 50 hours * Consider with palliative care treatment * Varying oral bioavailability due to hepatic first pass metabolism and protein binding * Dose adjustment is necessary * CODEINE - CYP2D6 interactions

Answer 117

* Misuse of Drugs Act 1971 / Misuse of Drugs Regulation 2001 * Some opiiod analgesics are controlled drugs * Diamorphine (heroin) * Morphine * Remifentanil * Pathidine

Answer 118

Virchow's triad: * Hypercoagulability * Genetic * Acquired - smoking, OCP, cancer * Endothelial damage * Athermoma - MI, CVA * Hypertension * Toxins - smoking, homocysteine * Stasis * Immobility - post-op, health, social class * Cardiac abnormalities - AF, congestive heart failure, MI, mitral valve

Answer 119

Plaque build up and rupture * Aggregation of platelets * Tissue factor activated * Cleaves prothrombin into thrombin * Cleaves fibrinogen into fibrin * Thrombin increases aggregation of platelets

Answer 120

* Inhibits production of vitamin K dependent clotting factors * Competitive inhibition of Vitamin K reductase * Stops conversion of Vitamin K to active form

Answer 121

* Given PO due to good GI absorption * Slow onset of action due to slow turnover of clotting factors * Use heparin at beginning of treatment * Stop 3 days before surgery to allow synthesis of new clotting factors * Heavily protein bound * Metabolised by P450 system in liver

Answer 122

* Extrinsic pathway clotting factors * Prothrombin time * International Normalised Ratio - measure of clotting * Should be between 2 and 3 if on blood thinners * If \> 6 stop warfarin until

Answer 123

* Potentiating warfarin (increases concentration and INR) * Inhibit hepatic metabolism - amiodarone, quinolone, cimetidine, alcohol * Inhibit platelet function - aspirin * Decrease vitamin K from gut bacteria - cephalosporin * Inhibit warfarin (induce hepatic enzymes to decrease concentration and INR) * Antiepileptics * Rifampicin * St John's Wort

Answer 124

* DVT (3-6 months) * PE (6 months) * AF (until risk \> benefit) * Mechanical prosthetic valves * Recurrent thromboses * CVA * Thrombophilia * Cardiomyopathy

Answer 125

* Bleeding/bruising * Intracranial * GI loss * Epistaxis * Teratogenic - crosses placenta * Can cause brain haemorrhage in foetus in later stages

Answer 126

If INR \> 6 * IV Vitamin K * Prothrombin Complex Concentrate - active clotting factors * Fresh frozen plasma - active clotting factors

Answer 127

* Unfractionated - binds to anti-thrombin III to increase activity * Inactivates thrombin (IIa) and vrious other clotting factors * Large enough to bind simultaneously to IIa and ATIII to catalyse inhibition of IIa * Low Molecular Weight Heparins - binds to anti-thrombin III but does not inactivate thrombin * Only inactivates factor Xa (due to smaller molecules)

Answer 128

* Unfractionated = IV * LMWH = subcutaneous * Poor GI absorption so given parenterally * Rapid onset and offset * LMWH more predictable dose-response and bioavailability * No monitoring required * Cleared by kidneys

Answer 129

* Prevention of thrombo-embolism * Peri-operative (low dose) * Immobility (frail/unwell patient) * DVT/PE/AF prior to warfarin * Rapid onset compared to warfarin * Acute Coronary Syndromes * Reduces recurrence of coronary artery thrombosis * Pregancy * Not teratogenic

Answer 130

* Bruising/bleeding * Thrombocytopenia (autoimmune) * Osteoporosis

Answer 131

Protamine sulphate - dissociates heparin from anti-thrombin III

Answer 132

Inhibit platelet adhesion, activation and aggregation * Aspirin - COX-1 inhibition by covalent acetylation of serine * Dipyridamole - phosphodiesterase inhibitor * Positive ionotrope and vasodilator * Secondary prevention of stroke * Clopidogrel - ADP antagonist * Blocks P2Y12 receptor (Gi) * ACS, PCI * Glycoprotein IIb/IIIa inhibitors - decreases platelet aggregation/cross linking by fibrinogen * Used in ACS/post PCI

Answer 133

* Alteplase - generates plasmin (via recombinant tPA) * Cleaves fibrin and other coagulation factors * Streptokinase - binds to and activates endogenous plasminogen * Plasminogen is converted to plasmin by plasminogen activators (tPA/uPA) * Works preferentially in presence of fibrin (clot specific)

Answer 134

* Bacterial protein - antigenic * Can cause allergic reaction * Generation of blocking antibodies

Answer 135

* Acute MI ( * Pulmonary embolism * Major venous thrombosis

Answer 136

* Haemorrhage - brain / GI * Transfusion of blood / volume expanders * Tranexamic acid / clotting factors to prevent further fibrinolysis * Anaphylaxis * Adrenaline, oxygen. IV fluids, antihistamine * Hypotension when being infused (streptokinase) * Slowly/stopping infusion

Answer 137

* Peptic ulcer / other potential bleeding source * Recent trauma or surgery * Previous cerebral haemorrhage or stroke * Uncontrolled hypertension * Coagulation defect

Answer 138

* General * Inhalational - fluranes, NO * IV - propofol, thiopental * Local * Regional - lidocaine

Answer 139

* GABA activated chloride channels (IV/inhalational) * Increases sensitivity to GABA = increases chloride currents = hyperpolarisation = decreases excitability * Glycine activated chloride channels (IV/inhalational) * Increase sensitivity to glycine = increases chloride currents = hyperpolarisation = decreases excitability * Important in spinal cord and brainstem

Answer 140

* Neuronal nicotinic Ach receptors (N2O, NO, ketamine) * Decreases excitatory Na+ currents to cause analgesia and amnesia * NMDA receptors (glutamate) * Decreases calcium current to decrease modulation of synaptic response

Answer 141

* Minimum Alveolar Concentration = concentration of inhaled anaesthetic that abolishes response to surgical stimuli in 50% of patients * Lower MAC = higher potency * Increased by pregnancy, alcoholism, hyperthermia * Decreased by other anaesthetics, opioids * Controlled by spinal cord

Answer 142

* Minimum Alveolar Concentration affected by lipid solubility * Blood:Gas coefficient = volume of gas (L) that can dissolve in 1L of blood * 1.4 = 1.4L of gas in 1L blood * If coefficient is increased, more gas readily enters blood * Tissue:Blood coefficient = how readily anaethetic moves from blood to tissue * If brain is 1.6 and muscle is 3.2, muscle takes up 2x more anaesthetic * Anaethetic REDISTRIBUTES into tissue compartments depending on solubility

Answer 143

* NOT metabolised * Source is removed so blood concentration drops causing anaethetic to move out of the cell membranes and into the venous system * Back to alveoli to be eliminated unchanged * Followed by brain/kidney/liver, then muscle, then fat stores * Can cause long recovery due to large capacitance in different tissues

Answer 144

* Two stage distribution profile: * Rapid distribution to CNS (5 mins) * Redistribution via circulation into muscle/fat * Further dosing required * Propofol - hepatic and extrahepatic conjugation * T1/2 = 2 hours

Answer 145

* Benzodiazepine - anxiolysis and amnesia * Propofol (IV) - sedation * Nitrous oxide - analgesia * Also reduces MAC of fluranes * Opioids - analgesia * Neuromuscular blocking agents - muscle relaxant * Competitive NAChR antagonists (tubocurarine) * NAChR depolarising agents (succinylcholine) * Abolish normal muscular reflexes

Answer 146

* Fluranes - cardiovascular/respiratory depression via decreased neuronal activity in medullary control centres * Arrythmias / hypotension / increased ICP * Bronchodilation / coughing / laryngospasm * NO = diffusion hypoxia = decreases alveolar oxygen concentrations when diffusing out of blood * Expansion of airway cavities * Propofol = CV/respiratory depression * Benzodiazepines/opioids = respiratory depression

Answer 147

* Patient assessment - age, BMI, medical/surgical history, medication, airways * Monitoring (anaesthetic and adjuvant delivery) * Monitor % partial pressures of O2, fluranes, N2O, N2 * Rate of mechanical ventilation * Physiological monitoring * CV and thermoregulatory function * ECG, BP, pulse oximetry, expired CO2, EEG

Answer 148

* Induction - administer propofol and start inhalational agent delivery / adjuvants * Maintenance - keep adjuvants in balance by regular adjustment to maintain anaesthetic depth * Recovery - agents withdrawn and physiological function monitored closely * With/without antidotes

Answer 149

1. Analgesia 2. Excitement (delirium/aggression) * Usually bypassed due to fast onset 3. CNS depression and muscles relaxed * MAC 1.2-2.2 4. Medullary depression - respiratory/cardiac arrest

Answer 150

Drugs that have few pharmaceutical effects on their own but increase the efficacy or potency of other drugs when given in combination * Eg: decreases MAC of fluranes

Answer 151

* Regulatory - fluid/acid-base/electrolyte balance * Excretory - waste products/drug elimination * By glomerular filtration or tubular secretion * Endocrine * RAAS * Erythropoeitin * Prostaglandins * Metabolism * Vitamin D * Polypeptides (insulin, PTH)

Answer 152

* Renin is produced by the kidney is response to low BP/volume/Na+ at macula densa * Renin cleaves angiotensinogen (from liver) into angiotensin I * Further cleaved to angiotensin II by ACE * Increases aldosterone * Increases H20 and Na+ retention * Vasoconstriction * Increases BP

Answer 153

* Acetazolamide * Inhibits carbonic anhydrase on PCT epithelium to stop conversion of H2O+CO2⇔HCO3- + H+ * Inhibits reabsorption of HCO3- which inhibits NHE and therefore Na+ reabsorption * Indicated in glaucoma and cystinuria * ADR - electrolyte imbalance (Cl-) renal stones, allergic reaction

Answer 154

* Mannitol * Increases osmolarity of tubular fluid to prevent water reabsorption * Indicated in acute renal failure (increase urine volume) and reduce increased intracranial and intraocular pressure * ADR - dehydration, hypernatraemia, pulmonary oedema in heart failure patients

Answer 155

* Furosemide, bumetamide * Inhibits NKCL2 channel in thick ascending limb of Loop of Henle, which inhibits reabsorption of NaCL * Also decreases reabsorption of Ca2+ and Mg2+ due to positive lumen potential inhibition * Indicated in pulmonary oedema, congestive heart failure, hypertension, hyperkalamia/calcaemia, acute renal failure * ADR - hypokalaemia, ototoxicity, hypomagnesaemia, allergy

Answer 156

* Chlorothiazide * Inhibit Na+-Cl- channel in DCT which inhibitd NaCl reabsorption * Also increases Ca2+ reabsorption by enhancing activity of NCX * Indicated in hypertension, oedema, nephrogenic diabetes insipidus * ADRs - hypokalaemia/natraemia/chloraemia /magnesaemia, hypercalcaemia/glycaemia/ lipidaemia, hypotension, gout, erectile dysfunction

Answer 157

1. Na+ channel inhibitors (amiloride) - inhibits ENaC in collecting duct * Indicated in pseudo-hyperaldosteronism, CF * ADRs - hyperkalaemia, CNS symptoms 2. Aldosterone antagonists (spironolactone) - inhibits aldosterone to decrease expression and function fo ENaC * Indicated in hyperaldosteronism, hepatic cirrhosis and prevention of hypokalaemia * ADRs - hyperkalaemia, metabolic acidosis in cirrhosis, impotence, hirsutism, CNS

Answer 158

* Heart failure - loop + thiazide * Hypertension - thiazide + spironolactone * Decompensated liver disease - loop + spionolactone

Answer 159

* ACE-i + K+-sparing = hyperkalaemia = cardiac issues * Aminoglycosides + loop diuretics = oto/nephrotoxicity * Digoxin + thiazide/loop = hypokalaemia * Beta blockers + thiazide = hyperglycaemia/ lipidaemia / uricaemia

Answer 160

* ACE-inhibitors - decreases GFR in renovascular disease by dilating efferent arteriole * Aminoglycosides * Penicillins * Metformin * NSAIDs * Cyclosporin

Answer 161

* Avoid nephrotoxins * Reduce dosage in line with GFR if handled by kidneys * Increased risk of hyperkalaemia - monitor bloods and ECG * Monitor function and drug levels

Answer 162

* Tall T waves * Elongated QRS * Lack of P waves Treatment: * Calcium gluconate * Insulin / dextrose * Sodium bicarbonate

Answer 163

* Stimulates arterial thickening * Smooth muscle hypertrophy * Accumulation of vascular matrix * Loss of arterial compliance * Target organ damage * Heart * Brain * Kidneys * Eyes

Answer 164

* Primary (essential) = no single evident cause * Secondary * Chronic kidney disease * Adrenal tumour * Coarction of the Aorta * Pregnancy * Drugs (OCP) * Alcoholism

Answer 165

* Treat underlying cause * Address underlying cadiovascular risk factors * Lifestyle advice * BMI 20-25 * Salt intake * Alcohol * Pharmacological therapy * ACE inhibitors * Angiotensin Receptor Blockers * Calcium channel blockers * Thiazide diuretics

Answer 166

* Ramipril / lisonipril * Reduce formation of angiotensin II by inhibiting Angiotensin-converting enzyme * Arterial vasodilation * Reduces stimulation of aldosterone * Potentiates action of bradykinin * ADRs: * Dry cough * Angio-oedema * Renal faiilure * Hyperkalaemia

Answer 167

* Losartan * Binds to angiotensin I receptor to stop conversion into angiotensin II * Stops vasoconstriction and aldosterone stimulation * ADRs: more tolerable than ACE-i but still: * Renal failure * Hyperkalaemia

Answer 168

* Amplodipine / verapamil * Binds to L-type calcium channels to reduce calcium entry * Causes vasodilation to peripheral, coronary and pulmonary arteries * ADRs: * Amlodipine = tachycardia, flushing, oedema (sympathetic NS) * Verapamil = constipation, bradycardia, -ve inotrope * Benzothiazepine = bradycardia

Answer 169

* Bendroflumethiazide * Decreases Na+ reabsorption in DCT to decrease blood volume and TPR * ADRs: * Hypokalamia * Increase in urea/uric acid * Increase in cholesterol/TGs * RAAS activation

Answer 170

* * \>55 or black = Calcium channel blocker / thiazide * If not responsive to those treatments = ACE-i + CCB OR thiazide * If not responsive to those treatments = ACE-i + CCB + thiazide * If not reponseive = consider other hypertensive therapies

Answer 171

* Alpha blockers (doxazosin) = antagonise contraction from NA on a-1 adrenoceptors = decrease TPR * Postural hypotension, dizziness, oedema * Beta blockers (bioprolol) = Decrease heart rate, cardiac output and renin stimulation * Lethargy, bradycardia, decreased exercise tol. * Contraindicated in asthma * Direct renin inhibitor (aliskiren) = blocks cleavage of angiotensinogen to AT1 = vasodilation * Contraindicated in pregnancy

Answer 172

* Thiazides - Heart failure, elderly * Contraindicated in gout * Beta blockers - MI / angina * Contraindicated in astham, COPD, heart block * CCB - elderly * ACE-i - heart failure, MI, diabetes * Contraindicated in pregnancy, renovascular disease

Answer 173

* Ischaemic heart disease * Hypertension * Cardiomyopathy * Alcohol / chemotherapy / iron * Valve disease

Answer 174

* Lifestyle advice - smoking, exercise * Pharmacology 1st line * ACE-inhibitors * Beta blockers * Pharmacology 2nd line * Aldosterone antagonists * Angiotensin receptor blocker * Digoxin

Answer 175

* Reduce heart rate via B1 adrenoceptor * Reduce blood pressure via reduced cardiac output * Reduces myocardial oxygen demand * Reduces mobilisation of glycogen * Negate unwanted effects of catecholamines (Adrenaline, DA)

Answer 176

Initiate at low dose and titrate slowly as failing myocardium is still dependent on heart rate

Answer 177

Either disturbance in pacemaker impulse formation orcontraction impulse conduction. Causes rate/timing of muscle contraction that is insufficient to maintain normal cardiac output

Answer 178

1. Automatic rhythms * Enhanced normal automaticity = Increae AP from SAN * Ectopic focus = AP not from SAN 2. Triggered rhythms due to abnormal Na+ and K+ channels * Delayed afterdepolarisation * Early Afterdepolarisations

Answer 179

1. Conduction block = impulse not conducted from atria to ventricles * 1st degree - slowed conduction * 2nd degree - some impulses do not reach ventricles * 3rd degree - complete block 2. Re-entry * Circus movement * Reflection 3. Abnormal anatomic conduction = accessory Bundle of Kent pathway causes re-entry and re-excitation (Wolf-Parkinson-White Syndrome)

Answer 180

* Class I = Na+ channel blockers * 1A = quinidine * 1B = lidocaine / phenytoin * 1C = felcainide * Class II = beta blockers (propanolol / bisoprolol) * Class III = K+ channel blockers (amiodarone) * Class IV = Calcium channel blockers (verapamil)

Answer 181

* 1A - decreases conduction velocity (phase 0) and increases threshold and refractory period * Uses = AF and supra/ventricular tachycardia * ADR = hypotension, decreased cardiac output, arrhythmia, CNS symptoms * 1B - decreases conduction velocity in ischaemic tissue and increases threshold * Uses = only ventricular tachycardia * ADR = CNS but less proarrhythmic * 1C = decreases conduction velocity and automaticity, increases AP duration * Uses = supraventricular, WPW syndrome * ADR = sudden death (proarrhythmia), CNS

Answer 182

* Beta blockers - increase refractory period in AVN and decrease phase 4 depolarisation * Uses: * Re-entrant tachycardia * Sinus tachy arrhythmias * ADR: * Bronchospasm * Hypotension * Decreases BP in heart failure

Answer 183

* K+ channel blockers = increases refractory period and threshold, decreases phase 0 conduction and phase 4 depolarisation * Uses = wide spectrum * ADR: * Pulmonary fibrosis * Hepatic injury * Increases LDLs * Thyroid disease * DDIs - digoxin and warfarin

Answer 184

* Calcium channel blockers = slows AV conduction, increases refractory period and phase 4 slope to slow HR * Uses = Supraventricular tachycardia * ADRs: * Damage with AV block (asystole) * Hypotension * GI disturbance

Answer 185

* Adenosine = binds to A1 to activate K+ currents in SAN/AVN to decrease AP duration, AV conduction and calcium currents * Uses - re-entrant supraventricular arrhythmia * Digoxin (cardiac glycoside) = enhances vagal activity to increase refractory period and decrease AV conduction * Uses = atrial fibrillation / flutter

Answer 186

* Proto-oncogenes mutate to active oncogenes * Usually control cell division and apoptosis * Tumour supressor gene - inactivation

Answer 187

* A - dividing cells reveiving adequate nutrient and vascular supply * Most susceptible to chemotherapy (targets the cell cycle) * B - resting cells in G0 phase but able to rejoin cycle * Less susceptible as no actively dividing cells * Medication to push cells back into cycle? * C - cells can no longer divide * Only treatment in surgical removal

Answer 188

The proportionate killing of cells in a tumour * EG: 10^9 - 10^4 cells killed = 10^5 remaining * 4 log kill ratio * Not all cells available for attack * Kill rate for cancer cells must be compared to healthy cells * Ensure rate of regrowth of healthy tissues \> cancer

Answer 189

* DNA intercalators / topoisomerase II inhibitors * Alkylating agents (cyclophosphamide) * Antimetabolites * Methotrexate * 5-FU * Microtubule inhibitors * Vinca alkaloids (vincristine) * Taxanes

Answer 190

* DNA intercalators / topoisomerase inhibitors = intercalate between base pairs to interfere with transcription * Stops breaking, rotation and re-ligation of DNA * DNA scisson (bleomycin) = binds with NH2 group on DNA, chelates with Fe2+ and produces ROS which attacks phosphodiester bonds * Alkylating agents = covalently bonds to 2 DNA strands to prevent uncoiling and replication * Bonds via Cl- or platinum * Mainly targets S and G1 (enzymes) phase

Answer 191

Interfere with nucleotide production by acting as a direct competitive analogue * Methotrexate = inhibits DHFR enzyme to interfere with folate metabolism * Folate vital for nucleotide production * 5-FU = irreversibly inhibits thymidylate synthase to stop production of thymidine * Both specific to S phase only

Answer 192

* Vinca alkaloids (vincristine) = binds to beta-tubulin subunit to prevent microtubule formation * No mitotic spindle formation * Taxanes = bind to beta-tubulin to promote/stabilise microtubules and inhibit dissassembly * Cell stuck in metaphase → apoptosis * Only target mitosis phase of cell cycle

Answer 193

* Decreased entry or increased exit of agent * Inactivation of agent in cell * Enhanced repair of DNA lesion Overcome by using high dose, short term intermittent therapy

Answer 194

* Mainly IV bolus * PO - based on oral bioavailability * Sub cutaneous * Into cavity * Bladder/pleural effusion * Intrathecal * Intralesional - directly into tumour

Answer 195

* Acute renal failure (hyperuricaemia due to tumour lysis) * GI perforation at site of tumour * DIC for acute myeloid leukaemia * Alopecia * Skin toxicity - extravasation at site of entry * Mucositis - sore throat, diarrhoea, GI bleed * Vomiting

Answer 196

* Doxorubicin (intercalator) - cardiomyopathy * Cyclophosphamide (alkylating agent) - arrhythmia * Bleomycin (DNA scisson) - lung fibrosis

Answer 197

* Absorption - decreased in GI cancer * Distribution * Weight loss * Ascites (ovarian cancer) - increased toxicity * Elimination - renal/liver/bladder cancer * Other drugs * Protein binding - low albumin in liver cancer

Answer 198

* Narrow therapeutic indices * Significant side effects * Dose altered based on: * Surface area/ BMI * Renal/liver function * General wellbeing

Answer 199

* Vincristine + itraconazole (anti fungal) = increased neuropathy * 5-FU + warfarin/St John's Wort/grapefruit = increased drug levels * Methotrexate + penicillin/NSAIDs = increased drug levels

Answer 200

* Response of cancer: * Imaging * Tumour marker blood tests * Bone marrow * Drug levels * Organ damage * Creatinine (GFR) * ECG

Answer 201

Episodic discharge of abnormal high frequency electrical activity in the brain leading to seizures. * Diagnosis requires evidence of recurrent suizures unprovoked by other identifiable causes

Answer 202

* Partial (focal) seizures = affects only one area of the brain * Simple = fully conscious during seizure * Complex = unresponsive/unconscious * Secondary generalised = seizure begins as partial but spreads to all areas of the brain * Generalised = centrally generated and spreads through both hemispheres with loss of consciousness * Tonic-clonic = stiffness followed by limb jerk * Absence = 'switching off' * Atonic = loss of all muscle tone

Answer 203

* Primary = idiopathic * Secondary * Vascular * Tumour * Infection * Head injury

Answer 204

* Sensory stimuli * Brain disease/trauma * Metabolic (hypoglycaemia/calcaemia/natraemia) * Infection * Febrile convulsants in infants * Drugs

Answer 205

* Physical injury during seizures * Status epilepticus = prolonged seizure length * Medical emergency - if untreated can cause brain damage or death * SUDEP (sudden death in epilepsy) * Hypoxia * Brain dysfunction * Cognitive impairment * Adverse effects of medication

Answer 206

* Voltage-gated sodium channel blockers = reduce probability of high abnormal spiking activity by binding to Na+ channels in the inactive state and prolonging this period. It detaches when membrane potential is back to normal so doesn't interfere with physiological function * Carbamazepine, phenytoin, lamotrigine * GABA-mediated inhibitors = Agonists to GABA(A) receptor - increases chloride current into to neuron to increase action potential threshold. Makes membrane potential more negative. * Sodium valproate, benzodiazepines

Answer 207

* V-G sodium channel blocker * Treats generalised tonic-clonic and all partial * ADRs = CNS (dizziness, ataxia, motor disturbance) GI disturbance, BP variation, rashes, hyponatraemia * Strong inducer of CYP450 * Decreases concentration of phenytoin, warfarin, corticosteroids, OCP * Interacts with other antidepressants * Needs monitoring and dose adjusting as half life decreases over time

Answer 208

* V-G Na+ channel blocker * Treats generalised tonic-clonic and all partial * ADRs = CNS, gingival hyperplasia, rashes * Strong inducer of CYP450 * Non liner pharmacokinetics = variable half life * Dose is specific to patient * Monitoring of free plasma concentration * Competitive binding with valproate and NSAIDs * Interactions with OCP (decreases) and cimetidine (increases)

Answer 209

* V-G Na+ channel blocker and Ca2+ channel blocker * Treats generalised tonic-clonic, all partial and absence * ADRs - CNS (less) nausea, rashes * Decreases with OCP and increases with valproate * Safer in pregnancy * Linear pharmacokinetics with no CYP450 induction * Less monitoring required

Answer 210

* Pleiotropic - GABA agonist, VGSC blocker, CCB * Treats generalised tonic-clonic, all partial and absence * ADRs (less severe) - CNS, liver damage (increases transaminases) * Interactions - antidepressants (D VP) antipsychotics (D threshold) and aspirin (I VP) * Close monitoring of free plasma concentration essential * Blood, metabolic and hepatic disorders

Answer 211

* Positive allosteric effector on GABA * Used in status epilepticus (lorazepam) and short-term for absence * ADRs = sedation, tolerance, confusion, aggression, respiratory/CNS depression * Overdose treated with flumazenil

Answer 212

* Choice based on individual patients/condition * Aim for monotherapy * Start on low dose and increase gradually * Monitor plasma levels - polypharmacy is common * Monitor liver function - enzyme inducer or inhibitors * Cessation should be gradual to avoid withdrawal * Could trigger seizures

Answer 213

* AEDs increase failure of conception rate * Dangers to foetus * Congenital malformations * Facial/digital hypoplasia * Learning difficulties * Neural tube defects (valproate) * Balance between teratogenic risk and trauma risk of seizures * Lamotrigine safest, valproate worst * Consider giving folate (neural tube) and Vitamin K (coagulopathy) supplements

Answer 214

1. ABC 2. High flow oxygen 3. Bloods - exclude hypoglycaemia 4. IV lorazepam (benzodiazepine) * Phenytoin if unresponsive

Answer 215

* Generalised - valproate sodium * Partial - carbamazepine * Women of child bearing age - lamotrigine * Status Epilepticus - lorazepam

Answer 216

Clinical syndrome characterised by TRAP symptoms: * Tremor * Rigidity * A/bradykinesia * Postural instability Causes: * Drugs (antipsychotics) * Vascular * Multiple systems atrophy * Infections - AIDs, CJD, encephalitis lethargica

Answer 217

* Structural neuroimaging - MRI shows no abnormalities in Parkinson's * Response to treatment * Functional neuroimaging * DaTSCAN - shows loss of dpoaminergic neurons

Answer 218

* Loss of dopaminergic neurons in Substantia Nigra * Reduced inhibition in neostriatum * Decreased motor planning, reward-seeking and learning * Increased production of aceylcholine (excitatory) * Abnormal signalling = impaired mobility

Answer 219

* Levodopa (L-DOPA) = precursor to dopamine that can cross the BBB * Dopamine receptor agonists * MAO inhibitors = Prevents breakdown of dopamine by monoamine oxidase * Smooths out motor response * COMT inhibitors = reduces peripheral breakdown of L-DOPA to 3-O-methyldopa * Used with L-DOPA to reduce 'wearing off' * Anticholinergics (tremor treatment) = inhibits the antagonistic effect of acetylcholine on dopamine

Answer 220

* Precursor to dopamine that can cross the BBB * Given with DOPA decarboxylase to prevent conversion to dopamine in peripheral tissues * ADRs - nausea, anorexia, hypotension, psychosis, tachycardia * Motor = dyskinesia, dystonia, freezing * Interacts wtih pyridone (D LD) antipsychotics (block receptors) and MAOIs (hypertension) * Loss of efficacy long term - not given in young patients

Answer 221

* De novo/add on therapy * Non-ergot (ropinirole) doesn't cause fibrosis of heart valves and other tissues * Ergot does * ADRs = less motor, more psychiatric (hallucinations) sedation * Impulse control disorders - gambling, hypersexuality, shopping * Direct acting but less efficacious than L-DOPA

Answer 222

Surgery - if significant side effects with L-DOPA and no psychiatric illness * Lesion in thalamus for tremor * Lesion in Globus Pallidus Interna for dyskinesias * Deep brain stimulation * Subthalamic nucleus

Answer 223

* Mood and cognitive changes * Loss of bladder control * Swallowing problems * Sleep disorders * Constipation * Orthostatic hypotension * Smell dysfunction (olfactory bulb affected first)

Answer 224

A neuromuscular disease caused by autoimmune attack on acetylcholine receptors on the post-synaptic membrane. Symptoms: * Muscle weakness * Ptosis * Dysphagia * Facial expression * Respiratory * Fatiguability

Answer 225

Acetylcholinesterase inhibitors = decreases breakdown of acetylcholine in neuromuscular junction * Enhances neuromuscular transmission in skeletal and smooth muscle * ADRs: * Bradycardia * Hypotension * Bronchoconstriction * SLUDGE (sweating, lacrimation, urinary incontinence, diarrhoea, GI upset, emesis)

Answer 226

* Acute exacerbation = myasthenic crisis * Beta blockers * Aminoglycosides * ACE-inhibitors * Overtreatment = cholinergic crisis (depolarising block)

Answer 227

1. Deficiency of monoamine neurotransmitters (noradrenaline/serotonin) * Treat with MAO inhibitors to block MAO from destroying neurotransmitters 2. Abnormality in monoamine receptors 3. Deficiency in molecular functioning

Answer 228

* Core (need at least 2): * Low mood * Anhedonia (decreases pleasure in activities) * Decreased energy * Secondary * Decreased appetite * Self harm/suicide * Hopelessness * Sleep disturbance * Psychosis

Answer 229

* Selective serotonin uptake inhibitor (fluoxetine) = prevents reuptake of serotonin into neuron so increases synaptic concentration * First line for moderate to severe depression * Tricyclic antidepressants (antitryptillin) * Inhibits NA uptake * Muscarinic cholinoceptor block * Alpha1 adrenoceptor blockade * Non-selective monoamine uptake inhibitors (duloxetine) = prevents reuptake of monoamines * Second/third line

Answer 230

* Long half life = once daily dosage * Takes weeks to be 100% effective * Metabolised by liver * ADRs: * Common = anorexia, nausea, diarrhoea * Rare = mania, suicidal ideation, tremor, extrapyramidal (dystonia, tardive dyskinesia etc) * Safe in overdose

Answer 231

* Long half lives * Metabolised by liver * ADRs: * CNS = sedation, lower seizure threshold * CVS = tachycardia, postural hypotension, decreased contracility * Constipation * Decreased glandular secretions * Overdose causes arrhythmia * Cardiac monitor

Answer 232

* Short half life * Withdrawal syndrome if suddenly stopped * Side effects same as SSRIs * Increased BP * Hyponatraemia * Dry mouth

Answer 233

Psychosis - lack of contact with reality * Caused by drugs, depression, dementia * Symptoms: * Hallucination = perception in absence of external stimulus * Delusion = fixed false belief that is out of keeping with someone's culture/beliefs * Behavioural changes, disturbances in thinking, apathy, self neglect

Answer 234

* Drugs are antipsychotic, sedatives and tranquilisers * Eg: Haloperidol (emergencies) = blocks DA, ACh, alpha-adrenergic and antihistamine * Side effects: * Extra-pyramidal = Parkinsonism, tardive dyskinesia (horse mouth) * Neuroleptic malignant syndrome = rigidity, hyperthermia * Postural hypotension, weight gain, prolactinaemia * Toxicity = CNS depression, cardiac toxicity

Answer 235

* 1st line treatment (olanzapine, risperidone) * Side effects * Less extrapyramidal so more tolerable * Sedation * Weight gain * Prolactinaemia

Answer 236

Fear out of proportion to a situation * Symptoms = light headedness, dyspnoea, hot/cold flushes, nausea, palpitations, numbness * Treatment: * Non pharmacological = CBT (exposure-response prevention) * Treat coexisting disorder * Drugs - antidepressants, anxiolytics, antipsychotics * Benzodiazepines short term * Neurotransmitters = GABA, 5-HT, NA

Answer 237

* Short term management of anxiety (+ status) * Diazepam/lorazepam * Full GABA agonists = increase enhancement of GABA (inhibitory effects) * Highliy lipid soluble so rapid CNS diffusion * Renal excretion * Side effects: * Common = drowsiness, dizziness, psychomotor impairment * Occasional = blurred vision, ataxia, hypotension * NB: tolerance and dependence!! * Toxic to foetus - cleft lip/palate * Overdose = respiratory depression * Treat with flumazenil (many doses as shorter half life)

Answer 238

Episodes of depression and mania * Mania symptoms: * Unusually excited/happy * Overactive * Poor sleep * Poor concentration * Psychosis * Treatment = lithium, antipsychotics (atypical), antiepileptics (valproate sodium, carbamazepine) * Avoid anti depressants due to increased manic episodes

Answer 239

* Theories: * Compete with Mg2+ and Ca2+ ions * Increases 5-HT / decreases 5-HT receptor sites * Attenuates effects of certain neurotransmitters * Renal excretion BUT nephrotoxic so check eGFR * Narrow therapeutic window - tailor dose to patient * Side effects = memory problems, thirst/polyuria, tremor, weight gain, rashes, hypothyroid * Treat toxicity (renal/thyroid) with IV fluids and anticonvulsants * Haemodialysis may be necessary

Answer 240

A chronic brain degeneration marked by memory disorders, mood changes and impaired reasoning * Acetcholinesterase inhibitors - increases ACh in synapse * Side effects = GI upset, fatigue insomnia, bradycardia, worsens COPD, gastric ulcers * NMDA receptor antagonist (memantine) * Side effects = hypertension, dyspnoea, headache, drowsiness

Answer 241

Defensive: * Epithelial integrity * Cell replication/restitution * Mucous barrier Aggressive: * Acid * Helicobacter pylori * Drugs (NSAIDs)

Answer 242

* Gastrin → CCK-B * Histamine → H2 receptor * Acetylcholine → M3 receptor All increase activity of H+/K+ exchanger to increase secretion of H+

Answer 243

Rennies / Gaviscon (bicarbonates) * Neutralise gastric acid to stop irritation of stomach mucosa and heal ulceration * Used in combination with an alginate to protect inflamed mucosa * Indicated in GORD, oesophagitis, ulcers

Answer 244

Cimetidine / ranitidine * Blocks histamine receptor to decrease acid production * Short half life - taken as required / twice a day * Cimetidine side effects = CYP interaction, gynecomastia, diarrhoea, hypotension, headache, fatigue * Less potent than PPIs = less severe side effects * Used in ulcers, GORD, dyspepsia

Answer 245

Omeprazole / lansoprazole * Inhibits K+/H+ ATPase to completely block acid secretion * Only binds to active pump so patients need to eat for it to be effective * Side effects - diarrhoea, increased infections (C. diff) headache, flatulence, pain, fatigue * Indicated in GORD, dyspepsia, ulcers, H. pylori eradication

Answer 246

* Lifestyle changes - alcohol, smoking, losing weight * Antacids + alginates * H2 receptor antagonists * PPI * Surgery (fundoplication) = reinforcement of the lower oesophageal sphincter

Answer 247

* Releases ammonia and other chemicals that are toxic to epithelial cells * Causes inflammation which allows stomach acid to overwhelm the mucous barrier Treated with PPI + clarithromycin + amoxycillin

Answer 248

* Myogenic - slow waves of depolarisation through smooth muscle causing rhythmic contraction * Pacemaker = Interstital cells of Cajal * Neural: * Post-ganglionic cholinergic enteric nerves increases contraction * Non-adrenergic inhibitory nerves decreases contraction * Hormonal = gastrin, secretin, CCK etc

Answer 249

1. Stimulus (pregnancy, toxins, pain, sensory) activates the vomiting centre = chemoreceptor trigger zone 2. Preliminary signs = nausea, salivation, sweating, pallor 3. Vomiting * Pyloric sphincter closes which cardia and oesophagus relax * Contraction of abdominal wall and diaphragm propels gastric contents up oesophagus * Glottis closes and soft palate elevates to prevent any entry of vomit into trachea and nasopharynx

Answer 250

Area of the medulla oblongata that initiates vomiting in response to triggers * Located within postrema (floor of 4th ventricle) * Neurotransmitters = ACh, histamine, 5-HT, dopamine

Answer 251

* Gastric emptying scintigraphy = ingesting a radiolabelled food with gamma camera images taken to measure emptying * Nondigestible wireless capsules - measure pH changes, pressure and temperature throughout GI tract

Answer 252

* Dopamine D2 receptor antagonists (domperidone) = acts on postrema and stomach to increase rate of gastric emptying * Indicated in nausea/vomiting by L-DOPA * ADRs - prolactin release, dystonia (rarely) * 5-HT receptor antagonist (ondansteron) = stops vagal stimulation when 5-HT released into gut * Indicated in radiation sickness and chemotherapy * ADRs = headaches, constipation, flushing * Metoclopramide = D2 antagonist, anti-cholinergic and blocker of vagal 5-HT stimulation * Indicated in GI causes, migraine, post-op * ADRs = extra-pyramidal, galactorrhoea

Answer 253

* Treat underlying medical cause - diabetes, Parkinson's, cancer etc * Lifestyle - increase fluid and fibre intake, exercise * Laxatives * Bulk * Faecal softeners * Osmotically active * Irritant/stimulant (soft faeces)

Answer 254

* Bulk = insoluble substances which distend the gut to activate stretch receptors and contraction * Used in IBS, pregnancy * Contraindicated in other adhesion/ulcerations due to obstruction * Faecal softeners = lubricate and soften stool * Indicated in adhesions/haemorrhoids * Osmotically active (Mg/Na salts) cause water retention to increase peristalsis * Used in 'resistant' constipation * Lactulose in liver failure (DC ammonia) * Irritant/stimulant (senna) = excites sensory nerves endings to cause water and electrolyte retention * Used in faecal impaction or before surgery

Answer 255

* Dehydration - lightheadedness, headaches, dark urine * Hypokalaemia * Flatulence * Bloating * Nausea * Diarrhoea

Answer 256

* Anti-motility (increases time for fluid absorption, increases anal tone, decreases sensory defaecation reflex) * Opiate analgesics (codeine) * Opiate analogue (imodium) * Contraindicated in IBD * Bulk forming (ispaghula) via water absorption * Indicated in IBS and ileostomy * Fluid absorbents (kaolin) = produces more formed stool

Answer 257

Symptoms based diagnosis based on chronic abdominal pain, discomfort, bloating, alteration of bowel habits (diarrhoea/constipation) weight loss, bloody stools * Treat with mebeverine = relieves spasm of intestinal muscle * Increase fibre intake

Answer 258

Understanding how individual genotypes influence the metabolic pathways of a drug which can determine therapeutic and adverse effects of the drug

Answer 259

* Pharmacokinetics - differences in ADME * Pharmacodynamics * Receptors * Enzymes (CYP etc)

Answer 260

* Drug-drug interactions * Age * Renal/liver function * Co-morbidity * Lifestyle - smoking/alcohol/diet/exercise * Genetic variation - metabolism * Younger and caucasions have higher RAS activity = more effective response to ACE-inhibitor

Answer 261

* A = metabolism * Increased expression of CYP2D6 = rapid metabolism and decreased effiacy * Absent CYP2D6 = ADRs by reduction in first pass metabolism, drug accumulation or metabolic re-routing * B: * Hepatic porphyrias = enzyme deficiency in liver (sedatives, antipsychotics) * Haemolytic anaemia = G6PD deficiency causes loss of oxidative damage protection

Answer 262

* Glomerulosa - mineralocorticoid (aldosterone) * Fasciculata - glucocorticoid (cortisol) * Reticularis - sex steroids

Answer 263

* Increase glucose concentrations * Glycogenolysis * Gluconeogenesis * Proteinolysis

Answer 264

Deficiency = Addison's * Hypoglycaemia * Weight loss * Nausea * Hypotension Excess = Cushing's * Hyperglycaemia * Weight gain * Increased appetite * Hypertension

Answer 265

Deficiency: * Hyponatraemia * Hyperkalaemia * Dehydration * Hypotension Excess: * Hypernatraemia * Hypokalaemia * Hypertension

Answer 266

* Very lipid soluble = increase bioavailability * Renal and hepatic clearance * Decreases with age * Many different routes of administration * Topical to avoid systemic (Cushing's) side effects

Answer 267

* Anti-inflammatory - asthma, IBD, eczema, RA * Decreases B/T cell response, phagocytic function and cytokine transcription * Immunosuppression * Malignancy * Adrenal insufficiency

Answer 268

Mineralocorticoid: * Fluid retention → hypertension * Hypokalaemia Glucocorticoids: * Osteoporosis (inhibits osteoblasts) * Hypertension * Diabetes * Impaired growth * Skin atrophy * Increased infections * Cushingoid (central obesity and dorso-cervical fat pad)

Answer 269

Risk of hypoadrenal crisis: * Hypotension * Hyperkalaemia * Hypoglycaemia * Dehydration * Hyponatraemia