Drugs Flashcards

Question

nifedipine

Answer 1

Calcium channel antagonists - Vascular selective vasodilation Headache Flushing - varies with different formulations Dizziness Peripheral oedema ↑ gastro-oesophageal reflux

Answer 2

Angiotensin converting enzyme Inhibitor Hypertension, Heart failure, After MI Particularly beneficial in patients with higher renin levels Inhibits angiotensin II synthesis from angiotensin I and therefore inhibiting vasoconstriction and salt retention Cough Hypotension Reversible renal impairment Hyperkalaemia

Answer 3

Angiotensin converting enzyme Inhibitor Hypertension, Heart failure, After MI Particularly beneficial in patients with higher renin levels Inhibits angiotensin II synthesis from angiotensin I and therefore inhibiting vasoconstriction and salt retention Cough Hypotension Reversible renal impairment Hyperkalaemia

Answer 4

Angiotensin II receptor antagonist Hypertension Heart failure Blocks AT receptors on smooth muscle cells - linked to Gq and then to contraction (inhibits) Hypotension Reversible renal impairment Hyperkalaemia

Answer 5

Angiotensin II receptor antagonist Hypertension Heart failure Blocks AT receptors on smooth muscle cells - linked to Gq and then to contraction (inhibits) Hypotension Reversible renal impairment Hyperkalaemia

Answer 6

Angiotensin II receptor antagonist Hypertension Heart failure Blocks AT receptors on smooth muscle cells - linked to Gq and then to contraction (inhibits) Hypotension Reversible renal impairment Hyperkalaemia

Answer 7

α1-antagonist hypertension, congestive heart failure, benign prostatic hyperplasia α1-receptor activation > activation of Gq, Activation of PLC (phospholipase C) ↑IP3 ↑Ca2+ contraction Antagonists block this > vasodilation First dose effect  postural hypotension and syncope

Answer 8

Loop diuretic Heart failure and oedema Blocks Na/K/Cl transporter in ascending loop of Henle - Large diuresis ↑ loss of H+; metabolic alkalosis ↑ loss of K +; Use with K+ -sparing diuretics (see later) ↑ loss of Ca +, ↑ loss of Mg + ↓ loss of uric acid; gout

Answer 9

Potassium channel opener Severe hypertension, hypertension resistant to other drugs Activation of ATP-dependent potassium channels Hyperpolarisation Closes calcium channels Less calcium influx Less contraction Fluid and salt retention - given with a diuretic to avoid this Baroreceptor-mediated activation of sympathetic nervous system (increased heart rate and contractility) - given with a beta blocker to avoid this Given with an inhibitor of RAAS to prevent remodelling effects on the heart. hypertrichosis (excessive hair growth)

Answer 10

Organic nitrate Anti angina; 30 min duration of action Produce nitric oxide (NO) in endothelial cells NO diffuses into smooth muscle cell, activates guanylyl cyclase (GC) produces cGMP from GTP relaxation of smooth muscle (vascular, biliary and oesophageal). More effect on veins than on resistance arteries  ↓ preload  ↓left and right ventricular chamber size  ↓ wall stress  ↓ oxygen demand – advantage for angina Has marked effect on larger arteries  ↓ afterload ↑ coronary vasodilation  ↑ coronary flow Diverts blood from normal to ischaemic areas of myocardium Tolerance occurs Headache Postural hypotension

Answer 11

Organic nitrate Anti angina; longer duration of action > Twice daily for prophylaxis Produce nitric oxide (NO) in endothelial cells NO diffuses into smooth muscle cell, activates guanylyl cyclase (GC) produces cGMP from GTP relaxation of smooth muscle (vascular, biliary and oesophageal). More effect on veins than on resistance arteries  ↓ preload  ↓left and right ventricular chamber size  ↓ wall stress  ↓ oxygen demand – advantage for angina Has marked effect on larger arteries  ↓ afterload ↑ coronary vasodilation  ↑ coronary flow Diverts blood from normal to ischaemic areas of myocardium Tolerance occurs Headache Postural hypotension

Answer 12

potassium channel opener and NO donor

Answer 13

slows the heart rate by direct action on the pacemaker in the SA node

Answer 14

Bile acid binding resin dyslipidaemia Cholesterol is converted to bile acids in liver then secreted in bile Bile acid binding resins sequester the bile acid and it is excreted in faeces rather than being returned to liver Constipation Reduced absorption of other medicines Fat-soluble vitamin deficiency Increased triglyceride levels Avoid in bowel or biliary obstruction

Answer 15

Bile acid binding resin dyslipidaemia Cholesterol is converted to bile acids in liver then secreted in bile Bile acid binding resins sequester the bile acid and it is excreted in faeces rather than being returned to liver Decrease in cholesterol in hepatocytes > increased LDL receptor > More LDL removed from circulation Constipation Reduced absorption of other medicines Fat-soluble vitamin deficiency Increased triglyceride levels Avoid in bowel or biliary obstruction

Answer 16

Blocks transport protein NPC1L1 in brush border of enterocytes Inhibits transport of both dietary and biliary cholesterol Decrease in cholesterol absorbed > increased LDL receptor > More LDL removed from circulation GI disturbance Headache Hepato-biliary disorders (rare) Increased risk of rhabdomyolysis if used with a statin

Answer 17

Fibrate - Agonists at PPARα receptor Increase expression of lipoprotein lipase in muscle increase fatty acid uptake and oxidation in muscle cells Decrease triglycerides Increase apoAI, apoAII synthesis in hepatocytes  increase plasma HDL GI side-effects most common Myositis-like syndrome Rhabdomyolysis (with statin) Avoid: hepato-biliary disorders

Answer 18

Inhibit HMG-CoA reductase - Responsible for converting HMG-CoA to mevalonate > Inhibits synthesis of cholesterol in liver > increased LDL receptor/decreased lipoprotein synthesis > More LDL removed from circulation ADRs GI disturbances, insomnia, rashes Hepato-biliary effects Monitor LFT’s (baseline, within 3 months and at 12 months) Transaminases Myopathy / rhabdomyolysis Advise patients to seek medical advice if develop muscle pain, tenderness or weakness Contra-indications Active liver disease Pregnancy, breast-feeding CP450 interactions: Avoid - Antibacterials (Clarithromycin, erythromycin) Antifungals (Azoles – ketoconazole, itraconazole) Grapefruit juice Do not exceed simvastatin 20mg/day Amiodarone Anticoagulants Calcium-channel blockers Amlodipine Diltiazem Verapamil 10mg/day Fibrates (bezafibrate or ciprofibrate)

Answer 19

Inhibit HMG-CoA reductase - Responsible for converting HMG-CoA to mevalonate > Inhibits synthesis of cholesterol in liver > increased LDL receptor/decreased lipoprotein synthesis > More LDL removed from circulation ADRs GI disturbances, insomnia, rashes Hepato-biliary effects Monitor LFT’s (baseline, within 3 months and at 12 months) Transaminases Myopathy / rhabdomyolysis Advise patients to seek medical advice if develop muscle pain, tenderness or weakness Contra-indications Active liver disease Pregnancy, breast-feeding

Answer 20

Inhibit HMG-CoA reductase - Responsible for converting HMG-CoA to mevalonate > Inhibits synthesis of cholesterol in liver > increased LDL receptor/decreased lipoprotein synthesis > More LDL removed from circulation ADRs GI disturbances, insomnia, rashes Hepato-biliary effects Monitor LFT’s (baseline, within 3 months and at 12 months) Transaminases Myopathy / rhabdomyolysis Advise patients to seek medical advice if develop muscle pain, tenderness or weakness Contra-indications Active liver disease Pregnancy, breast-feeding

Answer 21

monoclonal antibody for PCSK9 PCSK9 normally decreases LDL receptor number Alirocumab ↑LDL receptors Given s.c. every 2 weeks. Use when statin or statin/ezetimibe are not sufficiently effective

Answer 22

Class III antiarrhythmic Multiple mechanisms – all include prolongation of the action potential and reduction of abnormal automaticity. (poss block of delayed rectifier potassium channel) Both supraventricular and ventricular arrhythmias Hypotension, photosensitivity, pulmonary fibrosis Some ADRs related to its structural similarity to thyroid hormone

Answer 23

Class III antiarrhythmic Multiple mechanisms – all include prolongation of the action potential and reduction of abnormal automaticity. (poss block of delayed rectifier potassium channel) Atrial fibrillation and flutter Fewer ADRs than amiodarone but also less effective Diarrhoea, nausea, vomiting.

Answer 24

Class III antiarrhythmic - also has beta-blocking effects Multiple mechanisms – all include prolongation of the action potential and reduction of abnormal automaticity. (poss block of delayed rectifier potassium channel) Both supraventricular and ventricular arrhythmias Torsades de pointes bronchospasm

Answer 25

Class IB antiarrhythmic Sodium channel blocker fast association and dissociation  prevents premature beat - blocks when cells are depolarised. Ventricular arrhythmias Seizures Nystagmus

Answer 26

Class IC antiarrhythmic Sodium channel blocker slows rate of depolarization Atrial fibrillation, Ventricular arrhythmias, Ventricular tachycardia, Certain congenital ventricular arrhythmias Blurred vision, Exacerbate congestive heart failure, Exacerbate some arrhythmias, Overall mortality increased after MI

Answer 27

Class IA antiarrhythmic Sodium channel blocker slows rate of depolarization

Answer 28

Class IV L-type Calcium channel blockers – cardio selective Slow conduction in SA and AV nodes Shorten plateau of action potential and reduce force of contraction Decreased calcium entry  decrease after-depolarisation. Supraventricular arrhythmias Worsening of heart failure Constipation Sinus bradycardia or AV block (do not use with beta blockers)

Answer 29

Class IV L-type Calcium channel blockers – cardio selective Slow conduction in SA and AV nodes Shorten plateau of action potential and reduce force of contraction Decreased calcium entry  decrease after-depolarisation. Supraventricular arrhythmias Worsening of heart failure Constipation Sinus bradycardia or AV block (do not use with beta blockers)

Answer 30

Unclassified antiarrhythmic Activates A1 adenosine receptors in AV node activate inward rectifier potassium channel hyperpolarisation, slows rate of rise of pacemaker i.v. lasts 20-30s terminates supraventricular tachycardias

Answer 31

The hERG channel was identified in the 1990s and shown to be the channel responsible for one of the repolarising potassium currents IKR. Block of the hERG channel slows repolarisation and leads to “long QT syndrome”.

Answer 32

Inhibits COX-1 irreversibly and hence TxA2 production by platelets Also inhibits prostacyclin synthesis (reversibly) in vascular endothelium Secondary prevention of MI Management of cerebrovascular disease Prevention of vascular events in pts with peripheral vascular disease (PVD) Bleeding – approx 1 in 200 pts GI intolerance Hypersensitivity 0.2% general population 4% of asthmatics Risk of Reyes syndrome in children - avoid

Answer 33

P2Y (ADP) receptor antagonists Irreversibly blocks effect of ADP on platelets

Answer 34

P2Y (ADP) receptor antagonists - anti-platelet Irreversibly blocks effect of ADP on platelets

Answer 35

GPIIb/IIIa inhibitors - anti-platelet Limited to single use Blocks binding of fibrinogen Prevents platelet aggregation given iv; adjunct to aspirin and heparin for coronary artery angioplasty, stenting

Answer 36

Fibrinolytic human recombinant t-PA, activates plasminogen bound to fibrin longer half life Acute ischaemic stroke Arterial thrombosis Life threatening venous thrombosis Acute MI (given within 12 h) ADRs: Bleeding Allergic reactions (streptokinase more antigenic, recombinant are less antigenic) Contraindications: Internal bleeding Pregnancy Trauma (incl CPR) Tranexamic acid inhibits fibrinolysis

Answer 37

Fibrinolytic - directly converts plasminogen to active plasmin Acute ischaemic stroke Arterial thrombosis Life threatening venous thrombosis Acute MI (given within 12 h) ADRs: Bleeding Allergic reactions (streptokinase more antigenic, recombinant are less antigenic) Contraindications: Internal bleeding Pregnancy Trauma (incl CPR) Tranexamic acid inhibits fibrinolysis

Answer 38

Low molecular weight heparins Subcutaneous Preferred over heparin (longer acting, longer half life) Inhibit Xa (but not thrombin) Monitoring not required Not neutralised by protamine Thromboprophylaxis (low doses) DVT and PE – prevents extension of thrombosis Prevent coronary events e.g. in unstable angina MI – prevents extension of thrombosis Haemorrhage Heparin-induced thrombocytopenia Osteoporsis Hyperkalaemia

Answer 39

Low molecular weight heparins Subcutaneous Preferred over heparin (longer acting, longer half life) Inhibit Xa (but not thrombin) Monitoring not required Not neutralised by protamine Thromboprophylaxis (low doses) DVT and PE – prevents extension of thrombosis Prevent coronary events e.g. in unstable angina MI – prevents extension of thrombosis Haemorrhage Heparin-induced thrombocytopenia Osteoporsis Hyperkalaemia

Answer 40

Orally-active Xa inhibitor (DOAC) No reversal agent

Answer 41

Orally-active Xa inhibitor Reversed by andexanet alfa

Answer 42

Given orally Inhibits factors VII, IX, X, II 4-5 days for full effect Reversed by giving vitamin K Vitamin K occurs in green vegetables and green tea Requires monitoring – prothrombin time measured and expressed as INR (International Normalised Ratio) of 2 - 4. Metabolised by CYP2C9 – half life variable

Answer 43

= prostacyclin, PGI2 Bind to prostacyclin IP receptors Increase platelet cAMP Inhibits platelet aggregation and adhesion. Vasodilation. ADRs: flushing headache and hypotension IV, short-lived Used in haemodialysis, severe pulmonary hypertension and circulatory shock associated with meningococcal septicaemia

Answer 44

Phosphodiesterase inhibitor ↑cAMP levels Inhibits cellular reuptake of adenosine: ↑ plasma [adenosine] → activates A2 receptors → ↑ adenylyl cyclase, cAMP → inhibit expression of cell surface GPIIb/IIIa receptors Licensed for prophylaxis of thromboembolism associated with prosthetic heart valves (with warfarin) ADRs: Hypotension, can exacerbate migraine Angina pectoris

Answer 45

Family of sulphated glycosaminoglycans present in mast cells. Activates antithrombin III which inhibits thrombin, factor X and other serine proteases (II, IX, XI, XII) Short-acting, half life depends on dose administered Given by injection Monitoring with APTT test (activated partial thromboplastin time) Antidote = protamine

Answer 46

Neprolysin inhibitors In heart failure, natriuretic peptides (BNP and NT-pro BNP) are elevated and reduce disease progression. Sacubitril inhibits neprilysin which breaks down natriuretic peptides, bradykinin and angiotensin II. It is combined with valsartan (an ARB) to prevent the effects of raised angiotensin II (known as ARNIs).

Answer 47

binds to potassium binding site of Na+/K+ ATPase and inhibits. ↓ sodium gradient. The Na+/Ca2+ exchanger needs this gradient to move Ca2+ out of the cell. ↑ calcium in cell ↑ force of contraction (for heart failure) Digoxin has a very low therapeutic index ectopic beats induce ventricular tachycardia and ventricular fibrillation nausea, vomiting, diarrhoea confusion Digoxin and K+ compete for binding to the Na+/K+ ATPase so if K levels are low as in hypokalaemia, the effect of digoxin is increased – dangerous! It tends to be used when patients have not responded sufficiently to diuretics and ACE-I For arrhythmias, Slowed conduction through AV node Increasing the refractory period of the AV node reduces ventricular rate. Used to slow ventricular rate in rapid persistent atrial fibrillation.

Answer 48

Increased contractility E.g. milrinone Inhibition of phosphodiesterase leads to increased levels of cAMP  increased force of contraction But also increased potential for dysrhythmias

Answer 49

Thrombin inhibitor Pro-drug Rapid onset

Answer 50

analgesic and antipyretic but NOT anti-inflammatory Action likely in CNS few gastric or platelet side effects at therapeutic doses not really a NSAID Overdose  potentially fatal hepatic necrosis through conversion to a toxic metabolite NAPQI and subsequent depletion of glutathione  oxidative stress and damage. Treatment of overdose: Activated charcoal within 4 hours if dose > 7.5 g N-acetylcysteine – acts as glutathione substitute and detoxifies NAPQI Liver failure  transplant

Answer 51

Most common choice of NSAID for mild-moderate pain COX inhibitor inhibition of: Vasodilation, effects of histamine and bradykinin on vascular permeability, hyperalgesia, Regulation of temperature set point ADRs: ↓ mucus and bicarbonate secretion, ↑ acid secretion, Nephrotoxicity, skin rashes, cardovascular effects. Short half-life, Low solubility in water  preparation for iv is difficult, Insoluble in the stomach  slow and erratic absorption, Controlled release formulations using liposomes, polymers or nanoparticles  release in intestine or even colon  plasma concentrations are very low

Answer 52

NSAID: Cox inhibitor inhibition of: Vasodilation, effects of histamine and bradykinin on vascular permeability, hyperalgesia, Regulation of temperature set point ADRs: ↓ mucus and bicarbonate secretion, ↑ acid secretion, Nephrotoxicity, skin rashes, cardovascular effects.

Answer 53

NSAID: Cox 2 inhibitor inhibition of: Vasodilation, effects of histamine and bradykinin on vascular permeability, hyperalgesia, Regulation of temperature set point ADRs: ↓ mucus and bicarbonate secretion, ↑ acid secretion, Nephrotoxicity, skin rashes, cardovascular effects.

Answer 54

NSAID: Cox inhibitor inhibition of: Vasodilation, effects of histamine and bradykinin on vascular permeability, hyperalgesia, Regulation of temperature set point ADRs: ↓ mucus and bicarbonate secretion, ↑ acid secretion, Nephrotoxicity, skin rashes, cardovascular effects.

Answer 55

Analgesic action via µ opioid receptors. Useful for acute pain and “end of life” pain but not neuropathic or chronic pain metabolised to the more potent morphine GPCRs – coupled to Gi decreased cAMP and increased potassium conductance hyperpolarisation decreased neurotransmitter release ADRs: constipation, sedation, nausea etc

Answer 56

Analgesic action via µ opioid receptors. Useful for acute pain and “end of life” pain but not neuropathic or chronic pain GPCRs – coupled to Gi decreased cAMP and increased potassium conductance hyperpolarisation decreased neurotransmitter release ADRs: constipation, sedation, nausea etc

Answer 57

Dual action Opioid receptor agonist Noradrenaline and 5HT reuptake inhibition GPCRs – coupled to Gi decreased cAMP and increased potassium conductance hyperpolarisation decreased neurotransmitter release Only partially reversed by naloxone (opioid antagonist) Metabolised in liver  Active metabolite ? less constipation & respiratory depression Caution in epilepsy, renal/hepatic impairment, & with drugs that can lower the seizure threshold

Answer 58

Analgesic action via µ opioid receptors. Useful for acute pain and “end of life” pain but not neuropathic or chronic pain GPCRs – coupled to Gi decreased cAMP and increased potassium conductance hyperpolarisation decreased neurotransmitter release ADRs: constipation, sedation, nausea etc

Answer 59

Analgesic action via µ opioid receptors. also at delta and kappa opioid receptors Useful for acute pain and “end of life” pain but not neuropathic or chronic pain GPCRs – coupled to Gi decreased cAMP and increased potassium conductance hyperpolarisation decreased neurotransmitter release ADRs: constipation, sedation, nausea etc

Answer 60

Analgesic action via µ opioid receptors. Useful for acute pain and “end of life” pain but not neuropathic or chronic pain GPCRs – coupled to Gi decreased cAMP and increased potassium conductance hyperpolarisation decreased neurotransmitter release ADRs: constipation, sedation, nausea etc

Answer 61

Analgesic action via µ opioid receptors. also at delta and kappa opioid receptors Useful for acute pain and “end of life” pain but not neuropathic or chronic pain GPCRs – coupled to Gi decreased cAMP and increased potassium conductance hyperpolarisation decreased neurotransmitter release ADRs: constipation, sedation, nausea etc

Answer 62

Opioid antagonist reverses effects of opioid overdose

Answer 63

Histamine antagonists in nausea and vomiting Act on H1 histamine receptors in CNS Also have some antimuscarinic actions Used particularly for motion sickness, vestibular disorders, nausea and vomiting associated with surgery Unwanted effects: sedation, drowsiness, dry mouth, constipation, urinary retention, blurred vision

Answer 64

Histamine antagonists in nausea and vomiting Act on H1 histamine receptors in CNS Also have some antimuscarinic actions Used particularly for motion sickness, vestibular disorders, nausea and vomiting associated with surgery Unwanted effects: sedation, drowsiness, dry mouth, constipation, urinary retention, blurred vision

Answer 65

Histamine antagonists in nausea and vomiting Act on H1 histamine receptors in CNS Also have some antimuscarinic actions Used particularly for motion sickness, vestibular disorders, nausea and vomiting associated with surgery Unwanted effects: sedation, drowsiness, dry mouth, constipation, urinary retention, blurred vision

Answer 66

Muscarinic antagonists in nausea and vomiting Used particularly for motion sickness, vestibular disorders, nausea and vomiting associated with surgery Oral or transdermal patch Unwanted effects: constipation; dizziness; drowsiness; dry mouth; dyspepsia; flushing; headache; palpitations; skin reactions; tachycardia; urinary disorders; vision disorders.

Answer 67

Dopamine antagonists in nausea and vomiting SPECIFICALLY ONLY THE PERIPHERY Act as antagonists at D2 dopamine receptors in the chemoreceptor trigger zone (also act on histamine H1 and muscarinic receptors elsewhere). Administration: oral, iv, suppository. Used for severe nausea and vomiting associated with cancer, radiation sickness, cytotoxic drugs, post-operative nausea Unwanted effects: sedative, hypotension, menstrual cycle irregularities, movement disorders, parkinsonism, diarrhoea.

Answer 68

Dopamine antagonists in nausea and vomiting Act as antagonists at D2 dopamine receptors in the chemoreceptor trigger zone (also act on histamine H1 and muscarinic receptors elsewhere). Administration: oral, iv, suppository. Used for severe nausea and vomiting associated with cancer, radiation sickness, cytotoxic drugs, post-operative nausea These are all antipsychotics (except for domperidone)  module 8 Unwanted effects: sedative, hypotension, menstrual cycle irregularities, movement disorders, parkinsonism, diarrhoea.

Answer 69

Dopamine antagonists in nausea and vomiting Act as antagonists at D2 dopamine receptors in the chemoreceptor trigger zone (also act on histamine H1 and muscarinic receptors elsewhere). Administration: oral, iv, suppository. Used for severe nausea and vomiting associated with cancer, radiation sickness, cytotoxic drugs, post-operative nausea These are all antipsychotics (except for domperidone)  module 8 Unwanted effects: sedative, hypotension, menstrual cycle irregularities, movement disorders, parkinsonism, diarrhoea.

Answer 70

Dopamine antagonists in nausea and vomiting Act as antagonists at D2 dopamine receptors in the chemoreceptor trigger zone (also act on histamine H1 and muscarinic receptors elsewhere). Administration: oral, iv, suppository. Used for severe nausea and vomiting associated with cancer, radiation sickness, cytotoxic drugs, post-operative nausea These are all antipsychotics (except for domperidone)  module 8 - High dopamine associated with delusions Unwanted effects: sedative, hypotension, menstrual cycle irregularities, movement disorders, parkinsonism, diarrhoea.

Answer 71

Dopamine antagonists in nausea and vomiting Act as antagonists at D2 dopamine receptors in the chemoreceptor trigger zone (also act on histamine H1 and muscarinic receptors elsewhere). Administration: oral, iv, suppository. Used for severe nausea and vomiting associated with cancer, radiation sickness, cytotoxic drugs, post-operative nausea These are all antipsychotics (except for domperidone)  module 8 Unwanted effects: sedative, hypotension, menstrual cycle irregularities, movement disorders, parkinsonism, diarrhoea.

Answer 72

Dopamine antagonists in nausea and vomiting Act as antagonists at D2 dopamine receptors in the chemoreceptor trigger zone (also act on histamine H1 and muscarinic receptors elsewhere). Administration: oral, iv, suppository. Used for severe nausea and vomiting associated with cancer, radiation sickness, cytotoxic drugs, post-operative nausea These are all antipsychotics (except for domperidone)  module 8 Unwanted effects: sedative, hypotension, menstrual cycle irregularities, movement disorders, parkinsonism, diarrhoea.

Answer 73

Dopamine antagonists in nausea and vomiting Act as antagonists at D2 dopamine receptors in the chemoreceptor trigger zone (also act on histamine H1 and muscarinic receptors elsewhere). Administration: oral, iv, suppository. Used for severe nausea and vomiting associated with cancer, radiation sickness, cytotoxic drugs, post-operative nausea These are all antipsychotics (except for domperidone)  module 8 Unwanted effects: sedative, hypotension, menstrual cycle irregularities, movement disorders, parkinsonism, diarrhoea.

Answer 74

Dopamine antagonists in nausea and vomiting Act as antagonists at D2 dopamine receptors in the chemoreceptor trigger zone (also act on histamine H1 and muscarinic receptors elsewhere). Administration: oral, iv, suppository. Used for severe nausea and vomiting associated with cancer, radiation sickness, cytotoxic drugs, post-operative nausea These are all antipsychotics (except for domperidone)  module 8 Unwanted effects: sedative, hypotension, menstrual cycle irregularities, movement disorders, parkinsonism, diarrhoea.

Answer 75

Serotonin antagonists in nausea and vomiting Antagonists at 5HT3 receptors in gastrointestinal tract and CNS including the chemoreceptor trigger zone. 5HT is released from enterochromaffin cells in the gut then activates 5HT3 receptors on vagal sensory fibres. Irritants can also activate sensory fibres in the gut Used for nausea and vomiting associated with chemotherapy and radiotherapy, post-operative nausea and vomiting. Administration: transdermal, IV, oral Unwanted effects: constipation, feeling hot, headache.

Answer 76

Antagonists at 5HT3 receptors in gastrointestinal tract and CNS including the chemoreceptor trigger zone. 5HT is released from enterochromaffin cells in the gut then activates 5HT3 receptors on vagal sensory fibres. Irritants can also activate sensory fibres in the gut Used for nausea and vomiting associated with chemotherapy and radiotherapy, post-operative nausea and vomiting. Administration: transdermal, IV, oral Unwanted effects: constipation, feeling hot, headache.

Answer 77

Bulk laxative Indigestible polysaccharides Increased volume of intestinal contents stimulates stretch receptors and peristalsis May take several days to work No serious unwanted effects (possibly some bloating)

Answer 78

Osmotic Laxatives Are not absorbed and trap fluid in the lumen Must have sufficient fluid intake Can take 2-3 days to act Unwanted effects: flatulence, cramps, electrolyte disturbance

Answer 79

Osmotic Laxatives Are not absorbed and trap fluid in the lumen Must have sufficient fluid intake Can take 2-3 days to act Unwanted effects: flatulence, cramps, electrolyte disturbance

Answer 80

Faecal Softener Anionic surfactant – lowers surface tension and allows mixing of aqueous and fatty substances to soften the stool. Stimulate intestinal fluid and electrolyte secretion

Answer 81

Stimulant laxative Bisacodyl stimulates sensory nerve endings Senna stimulates myenteric plexus Use lowest dose and shortest time Unwanted effects: flatulence, cramps, electrolyte disturbance

Answer 82

Stimulant laxative Bisacodyl stimulates sensory nerve endings Senna stimulates myenteric plexus Use lowest dose and shortest time Unwanted effects: flatulence, cramps, electrolyte disturbance

Answer 83

Alginates form a viscous gel (‘raft’) that floats on the surface of the stomach contents, reducing acid reflux. Usually combined with antacids.

Answer 84

Ranitidine is a competitive inhibitor of histamine H2-receptors. The reversible inhibition of H2-receptors in gastric parietal cells results in a reduction in both gastric acid volume and concentration.

Answer 85

paracetamol overdose

Answer 86

Unclear but likely involves: • reduced liver glucose production • increased glucose uptake and utilisation in skeletal muscle • Reduced intestinal carbohydrate absorption Most widely prescribed Generally well tolerated and no hypoglycaemia or weight gain

Answer 87

Act on ATP-dependent potassium ion channels in pancreatic beta cells. Block of these channels results in depolarisation of the beta cell and thus release of insulin. Can cause hypoglycaemia, weight gain (these effects less pronounced in the non- sulfonylurea type) Requires beta cells to be functional

Answer 88

Dipeptidylpeptidase 4 (DPP4) is the enzyme that terminates the actions of the incretins GIP and GLP-1 which would normally stimulate insulin secretion, reduce pancreatic glucagon secretion and reduce gastric emptying (so slow rate of nutrient absorption). Not associated with weight gain and little hypoglycaemia than sulfonylureas.

Answer 89

Oestrogen Antagonist SERM Antagonist in hypothalamus and anterior pituitary gland, partial agonist in the ovaries Blocks oestrogen receptors in pituitary  relief of negative feedback inhibition  increased release of GnRH and gonadotropins  ↑ FSH  stimulate follicle growth  oestrogen trigger signal  LH surge  ovulation Induces ovulation

Answer 90

Oestrogen agonists (analogues) less first pass metabolism Replacement therapy: Primary hypogonadism – stimulate development of secondary sexual characteristics At or after menopause  prevent menopausal symptoms (flushing, vaginal dryness, protect against osteoporosis) Contraception Side effects tenderness in breasts endometrial hyperplasia Risk of thromboembolism oedema Migraines, hyperpigmentation, uterine bleeding (postmenopausal)

Answer 91

Inhibitors of the enzyme 5α-reductase prevent the metabolism of testosterone to its active metabolite dihydrotestosterone. Prostate cells are dependent on androgen stimulation for survival → slows the growth of prostate tissue Used in: Benign prostatic hyperplasia Androgenetic alopecia

Answer 92

GnRH Agonist Given in pulses (s.c.) to mimic physiological secretion of GnRH, stimulate gonadotrophin release and induce ovulation It is possible to suppress the hypothalamic-pituitary–gonadal axis either by continuous administration of a GnRH agonist or by administration of a GnRH receptor antagonist Continuous use, by nasal spray or as depot preparations, transiently stimulates then inhibits gonadotrophin release because of downregulation (desensitisation) of GnRH receptors in the pituitary. -> cause gonadal suppression, used in: prostate and breast cancers, endometriosis large uterine fibroids.

Answer 93

Progesterone agonist Active orally GnRH suppression Decreases oestrogen stimulated endometrial proliferation Increased viscosity of cervical mucus Fat and carbohydrate metabolism Decrease Na+ reabsorption Development of breast and endometrium Used in Contraception With oestrogen in combined oral contraceptive pill Progesterone-only pill Injectable or implantable progesterone-only contraception Part of intrauterine contraceptive system HRT – combined with oestrogen Long-term ovarian suppression (resulting in prolonged anovulation and amenorrhea)* Endometriosis Endometrial carcinoma Side effects Weak androgenic actions (see next section) Acne Fluid retention Weight change Depression Change in libido Breast discomfort Irregular menstrual cycles and breakthrough bleeding Increased risk of thromboembolism

Answer 94

Progesterone agonist Active orally GnRH suppression Decreases oestrogen stimulated endometrial proliferation Increased viscosity of cervical mucus Fat and carbohydrate metabolism Decrease Na+ reabsorption Development of breast and endometrium Used in Contraception With oestrogen in combined oral contraceptive pill Progesterone-only pill Injectable or implantable progesterone-only contraception Part of intrauterine contraceptive system HRT – combined with oestrogen Long-term ovarian suppression (resulting in prolonged anovulation and amenorrhea)* Endometriosis Endometrial carcinoma Side effects Weak androgenic actions (see next section) Acne Fluid retention Weight change Depression Change in libido Breast discomfort Irregular menstrual cycles and breakthrough bleeding Increased risk of thromboembolism

Answer 95

Progesterone agonist Active orally GnRH suppression Decreases oestrogen stimulated endometrial proliferation Increased viscosity of cervical mucus Fat and carbohydrate metabolism Decrease Na+ reabsorption Development of breast and endometrium Used in Contraception With oestrogen in combined oral contraceptive pill Progesterone-only pill Injectable or implantable progesterone-only contraception Part of intrauterine contraceptive system HRT – combined with oestrogen Long-term ovarian suppression (resulting in prolonged anovulation and amenorrhea)* Endometriosis Endometrial carcinoma Side effects Weak androgenic actions (see next section) Acne Fluid retention Weight change Depression Change in libido Breast discomfort Irregular menstrual cycles and breakthrough bleeding Increased risk of thromboembolism

Answer 96

Progesterone agonist Active orally GnRH suppression Decreases oestrogen stimulated endometrial proliferation Increased viscosity of cervical mucus Fat and carbohydrate metabolism Decrease Na+ reabsorption Development of breast and endometrium Used in Contraception With oestrogen in combined oral contraceptive pill Progesterone-only pill Injectable or implantable progesterone-only contraception Part of intrauterine contraceptive system HRT – combined with oestrogen Long-term ovarian suppression (resulting in prolonged anovulation and amenorrhea)* Endometriosis Endometrial carcinoma Side effects Weak androgenic actions (see next section) Acne Fluid retention Weight change Depression Change in libido Breast discomfort Irregular menstrual cycles and breakthrough bleeding Increased risk of thromboembolism

Answer 97

SERM: selective oestrogen receptor modulators Antagonist used to ↓ breast cancer Partial agonist - Used for treatment of osteoporosis

Answer 98

SERM: selective oestrogen receptor modulators Antagonist used to ↓ breast cancer Agonist at bone Agonist at endometrium - cancer

Answer 99

Tamsulosin is a type of medicine known as an alpha blocker (or alpha-adrenoreceptor antagonist). If you have an enlarged prostate gland it helps by relaxing the muscle around the bladder and prostate gland, making it easier to pee. In some cases it can also be used to help ease the passing of kidney stones through the urinary tract.

Answer 100

Aromatase inhibitor

Answer 101

* use-dependent block of sodium channels * reduces repetitive firing of action potentials * used for tonic-clonic seizures

Answer 102

* block of sodium channels  reduces repetitive firing of action potentials * and block of T-type calcium channels  decreases rhythmic discharge of thalamic neurons associated with absence seizures * and inhibits GABA transaminase so raises GABA levels  increases levels of inhibition. * Used for absent and tonic clonic seizures

Answer 103

* use-dependent block of sodium channels * reduces repetitive firing of action potentials * used for tonic-clonic seizures and partial seizures. Also used for neuropathic pain and manic-depressive illness.

Answer 104

Calcium channel block Used for absence seizures (may exacerbate tonic-clonic seizures)

Answer 105

Benzodiazepine agonists Act quickly so good for emergency use – buccal, rectal or iv Increases GABA inhibitory effect AE: Tolerance and dependence  withdrawal syndrome which can exacerbate seizures if stopped abruptly. Not good for long-term treatment Sedative

Answer 106

Benzodiazepine agonists Act quickly so good for emergency use – buccal, rectal or iv Increases GABA inhibitory effect AE: Tolerance and dependence  withdrawal syndrome which can exacerbate seizures if stopped abruptly. Not good for long-term treatment Sedative

Answer 107

Benzodiazepine agonists Act quickly so good for emergency use – buccal, rectal or iv Increases GABA inhibitory effect AE: Tolerance and dependence -> withdrawal syndrome which can exacerbate seizures if stopped abruptly. Not good for long-term treatment Sedative

Answer 108

Benzodiazepine agonists Act quickly so good for emergency use – buccal, rectal or iv Increases GABA inhibitory effect AE: Tolerance and dependence  withdrawal syndrome which can exacerbate seizures if stopped abruptly. Not good for long-term treatment Sedative

Answer 109

- inhibits GAT = GABA transporter. used as add-on therapy for partial seizures Drowsiness, confusion, dizziness

Answer 110

Irreversibly inhibit GABA transaminase, ↓ GABA breakdown Designer drug Restricted to patients with resistant epilepsy Irreversible peripheral visual field defects -> systematic screening

Answer 111

Benzodiazepine agonists Act quickly so good for emergency use – buccal, rectal or iv Increases GABA inhibitory effect AE: Tolerance and dependence  withdrawal syndrome which can exacerbate seizures if stopped abruptly. Not good for long-term treatment Sedative

Answer 112

Replaces lost dopamine in parkinson's disease Improves tremor, rigidity, bradykinesia adverse effects: Nausea and anorexia (treat with domperidone* (DA antagonist in periphery) or cyclizine (anti-histamine)) Hypotension Dyskinesias (involuntary movements) Hallucinations, psychosis and confusion (Treat with non-dopaminergic antipsychotics! E.g. clozapine, quetiapine) Also impulse control disorders Increased risk of suicide

Answer 113

Inhibits DOPA decarboxylase so reduces conversion to noradrenaline in peripheral nervous system. When given with L-DOPA: co-careldopa

Answer 114

L-DOPA + Carbidopa Replaces lost dopamine in parkinson's disease Improves tremor, rigidity, bradykinesia Inhibits DOPA decarboxylase so reduces conversion to noradrenaline in peripheral nervous system.

Answer 115

Catechol-O-methyltransferase (COMT) inhibitor Prevents L-DOPA breakdown in periphery so more gets to brain

Answer 116

Monoamine oxidase B inhibitor Prevents dopamine breakdown

Answer 117

Dopamine agonists ADRs: Drowsy, hallucinations, compulsive disorders

Answer 118

Reversible cholinesterase inhibitor Selective (relatively) for CNS First-line for mild-moderate AD and vascular dementia 6-12 month delay in progression Caution: bradycardia Unwanted effects: GI distress – muscle cramping Abnormal dreams

Answer 119

Reversible cholinesterase inhibitor Selective (relatively) for CNS First-line for mild-moderate AD and vascular dementia 6-12 month delay in progression Caution: bradycardia Unwanted effects: GI distress – muscle cramping Abnormal dreams

Answer 120

NMDA antagonist – non-competitive Prevents glutamate-induced excitotoxicity but doesn’t interfere with learning and memory Used in moderate to severe dementia

Answer 121

Tricyclic Antidepressants e.g. amitriptyline, imipramine a.k.a. SNRIs : block both NA and 5HT reuptake Also have antimuscarinic activity and antihistamine activity Dangerous in overdose and when taken with alcohol. Unwanted effects: Dry mouth, constipation, blurred vision, urinary retention, sedation, confusion, postural hypotension, impotence, seizures. Can cause prolonged QT  sudden cardiac death (quinidine-like)

Answer 122

SSRIs e.g. fluoxetine, citalopram, sertraline Unwanted effects: nausea, diarrhoea, insomnia Low risk of overdose Do not use in combination with MAO inhibitors Can inhibit metabolism of other drugs. Not recommended in children Can get prolonged QT  sudden cardiac death

Answer 123

SSRIs e.g. fluoxetine, citalopram, sertraline Unwanted effects: nausea, diarrhoea, insomnia Low risk of overdose Do not use in combination with MAO inhibitors Can inhibit metabolism of other drugs. Not recommended in children Can get prolonged QT  sudden cardiac death

Answer 124

SSRIs e.g. fluoxetine, citalopram, sertraline Unwanted effects: nausea, diarrhoea, insomnia Low risk of overdose Do not use in combination with MAO inhibitors Can inhibit metabolism of other drugs. Not recommended in children Can get prolonged QT  sudden cardiac death

Answer 125

NRIs e.g. lofepramine Unwanted effects: headache, dry mouth, insomnia Used in depression associated with anxiety.

Answer 126

SNRIs e.g. venlafaxine, duloxetine, Unwanted effects: sedation, dizziness Low risk of overdose Do not use in combination with MAO inhibitors Note: St John’s wort Few reported side effects Can inhibit metabolism of other drugs.

Answer 127

Monoamine receptor antagonists. Mirtazepine = α2 and 5HT2c (and histamine) presynaptic inhibitory receptor antagonist => increase NA and 5HT release

Answer 128

Z-drugs, e.g. zopiclone and zolpidem Act at benzodiazepine receptors but do not have a benzodiazepine chemical structure Subtype selective for α1 subunit containing receptors Used for sleep and axiety issues

Answer 129

sedating antipsychotic Reduced aggressiveness, agitation and delusion in schizophrenic patients Produced a characteristic akinesia called “major tranquillizer” or “neuroleptic” Show Show “extra-pyramidal” side-effects = acute dystonia and tardive dyskinesia

Answer 130

Dopamine antagonist Second-generation anti-psychotics a.k.a “atypical” e.g. clozapine, risperidone, olanzepine, quetiapine Fewer extra-pyramidal side effects

Answer 131

Dopamine antagonist Second-generation anti-psychotics a.k.a “atypical” e.g. clozapine, risperidone, olanzepine, quetiapine Fewer extra-pyramidal side effects

Answer 132

Unclear MoA Used for long term bipolar treatment

Answer 133

Alkylating agent chemically reactive and form covalent bonds with guanine or adenine nucleotides. inhibit replication and transcription by binding directly to DNA

Answer 134

forms DNA adduct, inhibits topoisomerase (needed for uncoiling DNA), promotes free radical formation - prevent DNA repair Cardiotoxicity

Answer 135

Methotrexate is an analogue of folic acid Inhibits dihydrofolate reductase (DHFR)

Answer 136

inhibits thymidylate synthase Needed for nucleotide synthesis

Answer 137

forms a complex with the nitrogen atoms in guanines inhibit replication and transcription single- and double-stranded breaks and miscoding  can induce apoptosis.

Answer 138

Inhibit appropriate assembly of microtubules Cells blocked in mitosis

Answer 139

Inhibit appropriate disassembly of microtubules Cells blocked in mitosis

Answer 140

nucleotide analogue