Mechanisms of Action

Question 1

5α-reductase inhibitors

finasteride

Answer 1

5α-reductase reduces testosterone to active metabolite dihydrotestosterone

Dihydrotestosterone stimulates prostatic growth

So 5α-reductase inhibitors reduce size of prostate gland by inhibiting this

Question 2

α-blockers

doxazosin, tamsulosin, alfuzosin

Answer 2

Drugs in this class are highly selective for α1-adrenoreceptors

α1-adrenoreceptors are found in smooth muscle e.g. vessels + urinary tract

Stimulation of receptors induces constriction
Blockade of receptors induces relaxation

α1-blockers therefore cause vasodilation, ↓ BP and reduced resistance to bladder outflow

Question 3

Acetylcholinesterase inhibitors

donepezil, rivastigmine

Answer 3

Acetylcholine is important CNS neurotransmitter (learning + memory)

These drugs inhibit cholinesterase enzymes which break down acetylcholine in CNS

By increasing availability of acetylcholine, these drugs improve cognitive function + slow rate of decline

Question 4

Acetylcysteine (N-acetylcysteine)

Answer 4

Paracetamol is normally metabolised by conjugation with glucuronic acid and sulfate

Small amount of NAPQI is produced (hepatotoxic) - quickly detoxified by conjugation with glutathione

In poisoning, body’s glutathione is overwhelmed, NAPQI is left free to cause liver damage

Acetylcysteine replenishes body’s supply of glutathione

Question 5

Activated charcoal

Answer 5

Van der Waals forces

Molecules are aDsorbed onto surface of charcoal as they travel through gut, reducing their aBsorption into circulation

Weakly ionic, hydrophobic substances adsorbed best (e.g. benzodiazepines, methotrexate)

Can also increase elimination of certain poisons - multiple doses used to maintain steep conc. gradient of poison to encourage diffusion out of circulation

Question 6

Adenosine

Answer 6

Agonist of adenosine receptors on cell surfaces

In heart, activation of these receptors induces several effects:

• Reducing frequency of spontaneous depolarisation
• Increasing resistance to depolarisation

This transiently slows sinus rate and conduction velocity

Increasing AV node refractoriness

Increased refractoriness in AV node breaks the re-entry circuit, which allows normal depolarisations from SA node to resume control of heart rate (cardioversion)

Question 7

Adrenaline

epinephrine

Answer 7

Potent agonist of α1, α2, β1, β2

α1: vasoconstriction of skin and mucosa vessels

β1: increased heart rate and contractility and excitability

β2: vasodilation of coronary vessels and bronchodilation plus suppression of inflammation mediator release from mast cells

Question 8

Aldosterone antagonists

spironolactone, eplerenone

Answer 8

Mineralocorticoid

Acts on mineralocorticoid receptors in distal tubules of kidney - increases activity of luminal epithelial Na channels (ENaC)

This increases reabsorption of Na and water, elevates BP, increases secretion of K

Aldosterone antagonists competitively bind causing Na and water EXCRETION and K RETENTION

Question 9

Alginates and antacids

gaviscon, peptac

Answer 9

Antacids: buffer stomach acids

Alginates: Increase viscosity of stomach contents to reduce reflux - form “floating raft” separating gastric contents from gastro-oesophageal junction

Question 10

Allopurinol

Answer 10

Xanthine oxidase inhibitor

Xanthine oxidase is enzyme which metabolises xanthine from purines → uric acid

So drug lowers plasma uric acid

Question 11

Aminoglycosides

gentamicin, amikacin, neomycin

Answer 11

Work mainly on Gram -ve aerobic bacteria

Inhibit 30S ribosome subunit irreversibly

Enter bacteria through oxygen dependent transport system

Penicillins weaken cell wall and so may enhance aminoglycoside activity by increasing bacterial uptake

Question 12

Aminosalicylates

mesalazine, sulfasalazine

Answer 12

Ulcerative Colitis:
Release 5-ASA which seems to have anti-inflammatory and immunosuppressive effects
Act topically on gut rather than systemically so preparations delay release of active ingredient until reaching colon

Rheumatoid Arthritis:
Sulfapyridine is probably active component, mechanism unclear

Question 13

Amiodarone

Answer 13

Blockade of Na, Ca, K channels

Antagonism of α- and β-adrenergic receptors

Reduces spontaneous depolarisation, slows conduction velocity and increases resistance to depolarisation, including in AV node

Reduces ventricular rate in AF and atrial flutter (by interfering with AV node)

May break re-entry circuit and restore sinus rhythm in SVT

Options for treatment and prevention in VT

Improves chances of successful defibrillation in refractory VF

Question 14

ACE inhibitors

ramipril, lisinopril, perindopril

Answer 14

Block ACE to prevent conversion of angiotensin I to angiotensin II

Angiotensin II is a vasoconstrictor + stimulates aldosterone secretion

Inhibition therefore causes ↓ BP

Dilates efferent glomerular arteriole so slows progression of CKD

Reducing aldosterone level promotes Na and water excretion so reduces preload

Question 15

Angiotensin receptor blockers

losartan, candesartan, irbesartan

Answer 15

Block action of angiotensin II on angiotensin type 1 receptor

Angiotensin II = vasoconstrictor, stimulates aldosterone secretion, constricts efferent arteriole

ARBs = opposite effect

Question 16

Antidepressants

tricyclics; amitriptyline, lofepramine

Answer 16

Inhibit reuptake of noradrenaline and 5-HT from synaptic cleft, thereby increasing their availability for neurotransmission

Block a wide array of receptors (muscarinic, histamine, α-adrenergic and dopamine) therefore have extensive side effects

Question 17

Antidepressants

venfalaxine, mirtazapine

Answer 17

Venlafaxine = SNRI
Mirtazapine = antagonist of pre-synaptic α2-adrenoreceptors

Both drugs increase availability of monoamines for neurotransmission

Venlafaxine is weaker antagonist of muscarinic and histamine receptors than tricyclics

Mirtazapine is portent agonist of histamine (NOT muscarinic) receptors so commonly causes sedation

Question 18

Antiemetics - dopamine D2-receptor antagonists

metoclopramide, domperidone

Answer 18

Nausea + vomiting triggered by a wide arrange of stimuli that all converge in “vomiting centre” in medulla (this receives input form chemoreceptor trigger zone, solitary tract nucleus, vestibular system and higher centres)

D2 receptor is main receptor in chemoreceptor trigger zone (CTZ) which senses emetogenic substances in blood - therefore D2RAs are good for nausea caused by CTZ stimulation (e.g. drugs)

D2 is important in gut where it promotes relaxation of stomach and LOS , and inhibits gastroduodenal coordination - therefore D2RAs have prokinetic effect → gastric emptying which contributes to antiemetic action in conditions with reduced gut motility (e.g. due to opioids)

Question 19

Antiemetics - histamine H1-receptor antagonists

cyclizine, cinanrizine, promethazine

Answer 19

Nausea + vomiting triggered by a wide arrange of stimuli that all converge in “vomiting centre” in medulla (this receives input form chemoreceptor trigger zone, solitary tract nucleus, vestibular system and higher centres)

Histamine and acetylcholine (muscarinic) receptors predominate in the vomiting centre and its communication with the vestibular system

H1RAs block both receptors and are therefore useful in a wide range of conditions, particularly when associated with motion/vertigo

Question 20

Antiemetics - serotonin 5-HT3-receptor antagonists

ondansetron, granisetron

Answer 20

Nausea + vomiting triggered by a wide arrange of stimuli that all converge in “vomiting centre” in medulla (this receives input form chemoreceptor trigger zone, solitary tract nucleus, vestibular system and higher centres)

High concentration of 5-HT3 receptors in the CTZ responsible for sensing emetogenic substances in the blood (e.g. drugs)

5-HT is key neurotransmitter released by gut in response to emetogenic stimuli

It stimulates the vagus nerve, which in turn stimulates vomiting centre via solitary tract nucleus

Effective against N+V as a result of CTZ stimulation (drugs) and visceral stimuli (gut infection, radiotherapy) but NIOT motion sickness

Question 21

Antifungal drugs

nystatin, clotrimazole, fluconazole

Answer 21

Fungal cell membranes contain ergosterol, human cells do not, therefore it is a target for antifungals

Polyene antifungals (nystatin) bind to ergosterol in cell membrane, creating polar pore which allows intracellular ions to leak out, killing/slowing growth of fungi

Imidazole (clotrimazole) and triazole (fluconazole) fungals inhibit ergosterol synthesis, impairing cell membrane synthesis and cell growth + replication

Question 22

Antihistamines - H1-receptor antagonists)

cetirizine, loratadine, fexofenadine, chlorpgenamine

Answer 22

Antagonism of H1 receptor, which blocks the effects of excess histamine:

Increased capillary permeability causing oedema

Vasodilation causing erythema

Nasal irritation

Sneezing

Rhinorrhoea

Congestion

Conjunctivitis

Itch

Urticaris

Question 23

Antimotility drugs

loperamide, codeine phosphate

Answer 23

Loperamide is an ggonist of opioid receptors in gut

Increases non-propulsive contractions of gut smooth muscle, but reduces propulsive (peristaltic) contractions

Transit of bowel contents is slowed and anal sphincter tone is increased

Question 24

Antimuscarinics - bronchodilators

ipratropium, tiotropoium, glycopyrronium, aclidinium

Answer 24

Bind to muscarinic receptor and competitively inhibit acetylcholine

Stimulation of muscarinic receptor brings about parasympathetic/”rest and digest” effects

In blocking the receptor, antimuscarinics have the opposite effects:

Increase HR and conduction

Reduce smooth muscle tone (inc. resp tract and bladder)

Reduce secretions from gland in resp and GI tracts

Relaxation of pupillary constrictor + ciliary muscles in eye

Question 25

Antimuscarinics - cardiovascular and GI uses | atropine, hyoscine butylbromide, glycopyrronium

Answer 25

Bind to muscarinic receptor and competitively inhibit acetylcholine Stimulation of muscarinic receptor brings about parasympathetic/"rest and digest" effects In blocking the receptor, antimuscarinics have the opposite effects: Increase HR and conduction Reduce smooth muscle tone and peristaltic contraction (including GU tract) Reduce secretions from resp tract and gut Relaxation of pupillary and ciliary muscles in eye

Question 26

Antimuscarinics - GU uses | oxybutynin, tolterodine, solifenacin

Answer 26

Bind to muscarinic receptor and competitively inhibit acetylcholine Promotes bladder relaxation Reduces urinary frequency, urgency and urge incontinence Through antagonism of the M3 receptor

Question 27

Antipsychotics - 1st generation (typical) | haloperidol, chlorpromazine, prochlorperazine

Answer 27

Block post-synaptic dopamine D2 receptors Incompletely understood mechanism

Question 28

Antipsychotics - 2nd generation (atypical) | quetiapine, olanzapine, risperidone, clozapine

Answer 28

Block post-synaptic dopamine D2 receptors Incompletely understood mechanism

Question 29

Antiviral drugs | aciclovir

Answer 29

HSV1 & 2 contain double-stranded DNA This requires herpes-specific DNA polymerase for the virus to replicate Aciclovir enters herpes-infected cells and inhibits the herpes-specific DNA polymerase Inhibiting further viral DNA synthesis & replication

Question 30

Antiplatelet drugs - ADP-receptor antagonists | clopidogrel, ticagrelor, prasugrel

Answer 30

Prevent platelet aggregation Bind irreversibly to adenosine diphosphate (ADP) receptors on surface of platelets

Question 31

Antiplatelet drugs | aspirin

Answer 31

Irreversibly inhibits COX to reduce production of pro-aggregatory factor thromboxane form arachidonic acid Reducing platelet aggregation

Question 32

Azathioprine

Answer 32

Pro-drug Main metabolite is 6-mercaptopurine Metabolites inhibit synthesis of purines and therefore inhibit DNA and RNA replication

Question 33

β-blockers | bisoprolol, atenolol, propanolol, metoprolol, carvedilol

Answer 33

Reduce force of contraction and speed of conduction in the heart Relieves myocardial ischaemia by reducing cardiac work and oxygen demand Slow ventricular rate in AF by prolonging refractory period of the AV node Reduce hypertension through variety of mechanisms including reducing renin secretion from kidneys

Question 34

β2-agonists | salbutamol, terbutaline, salmeterol, formoterol, indacaterol

Answer 34

B2 receptors found in smooth muscle of gut, bronchi, uterus and vessels Stimulation leads to smooth muscle activation Improves airflow in constricted airways Stimulates Na/K/ATPase pumps, causing shift of K from extracellular to intercellular compartment Useful adjunct in hyperkalaemia

Question 35

Benzodiazepines | diazepam, temazepam, lorazepam, chlordiazepoxide, midazolam

Answer 35

Target is the GABAa receptor - a chloride channel that opens in response to binding by GABA Opening channel allows chloride to flood in, making the cell more resistant to depolarisation Benzos facilitate and enhance binding of GABA to GABAa receptor Wide depressant effect - reduced anxiety, sleepiness, sedation, anticonvulsion

Question 36

Bisphosphonates | alendronic acid, disodium pamidronate, zoledronic acid

Answer 36

Reduce bone turnover by inhibiting action of osteoclasts (cells responsible for resorption) Bisphosphonates accumulate in osteoclasts where they inhibit activity and promote apoptosis Reduction in bone loss and improved bone mass

Question 37

Calcium and vitamin D | calcium carbonate, calcium gluconate, colecalciferol, alfacalcidol

Answer 37

Calcium homeostasis is controlled by parathyroid hormone and vitamin D (which increase serum calcium and bone mineralisation) and calcitonin (which reduces serum calcium) In osteoporosis, calcium + vit D may reduce rate of bone loss In CKD there is hyperphosphataemia and hypocalcaemia In hyperkalaemia, calcium raises myocardial threshold potential, reducing excitability and risk of arrhythmias

Question 38

Calcium channel blockers | amlodipine, nifedipine, dilitiazem, verapamil

Answer 38

Decrease calcium entry into vascular and cardiac cells, reducing intracellular calcium concentration Causing relaxation and vasodilation in arterial smooth muscle In heart, CCBs reduce myocardial contractility Suppress cardiac conduction, slowing ventricular rate Reduced cardiac rate, contractility and afterload reduce myocardial oxygen demand, preventing angina

Question 39

Carbamazepine

Answer 39

MoA incompletely understood Appears to inhibit neuronal sodium channels Stabilising resting membrane potentials and reducing neuronal excitability

Question 40

Cephalosporins and carbapenems | cefalexin, cefotazime, meropenem, ertapenem

Answer 40

Bactericidal effect is due to their beta-lactam ring Cephalosporins and carbapenems inhibit enzymes responsible for cross-linking peptidoglycans in bacterial cell walls This weakens cell walls, resulting in bacterial cell swelling, lysis and death

Question 41

Chloramphenicol

Answer 41

Binds to bacterial ribosomes, inhibiting protein synthesis - bacteriostatic Stops bacterial growth, allowing immune system to clear microorganisms

Question 42

Corticosteroids (glucocorticoids) - inhaled | beclometasone, budesonide, fluticasone

Answer 42

Pass through plasma membrane and interact with receptors in the cytoplasm Activated receptor then passes into nucleus to modify transcription of genes Downregulate pro-inflammatory interleukins, cytokines and chemokines Upregulate anti-inflammatory proteins Reducing mucosal inflammation, widening airway and reducing mucus secretion

Question 43

Corticosteroids (glucocorticoids) - systemic | prednisolone, hydrocortisone, dexamethasone

Answer 43

Mainly glucocorticoid effects Bind to cytosolic glucocorticoid receptors which then pass into nucleus and bind to glucocorticoid-response elements which regulate gene expression Modify immune response Upregulate anti-inflammatory proteins Downregulate pro-inflammatory genes (cytokines, TNF alpha)

Question 44

Corticosteroids (glucocorticoids) - topical | hydrocortisone, betamethasone

Answer 44

Immunosuppressive, metabolic and mineralocorticoid effects

Question 45

Digoxin

Answer 45

Negatively chronotropic (reduces heart rate) Positively inotropic (increases force of contraction) In AF and flutter it involves increased vagal (parasympathetic) tone Reduces conduction at AV node, thereby reducing ventricular rate In heart failure, inhibits Na/K/ATPase pumps, causing Na to accumulate in cell - increasing contractile force

Question 46

Dipeptidylpeptidase-4 inhibitors | sitagliptin, linagliptin, saxagliptin

Answer 46

Incretins (GLP-1 and GIP) are released by intestine throughout the day, particularly in response to food They promote insulin secretion and suppress glucagon release, lowering blood glucose Incretins are rapidly inactivated by hydrolysis by DPP-4 DPP-4 inhibitors (gliptins) therefore lower blood glucose by preventing incretin degradation and increasing plasma concentrations of their active forms Actions of incretins are glucose dependent, occurring when blood glucose is elevated

Question 47

Direct oral anticoagulants (DOACs) | apixaban, dabigatran, edoxaban, rivaroxaban

Answer 47

Act on final common pathway of the coagulation cascade - comprising factor X, thrombin and fibrin Apixaban, edoxabab, rivaroxaban directly inhibit activated factor X (Xa), preventing conversion of prothrombin to thrombin Dabigatran directly inhibits thrombin, preventing conversion of fibrinogen to fibrin All DOACs therefore inhibit fibrin formation, prevention clot formation

Question 48

Loop diuretics | furosemide, bumetanide

Answer 48

Act on loop ascending limb of Henle, where they inhibit the Na/K/Cl co-transporter This enzyme is responsible for transporting ions from lumen into epithelium, and water then follows via osmosis Inhibiting this process has a potent diuretic effect Also have a direct effect on vessels, causing dilation of capacitance veins In heart failure this reduces preload and improves contractile function of overstretched heart muscle

Question 49

Thiazide and thiazide-like diuretics | bendroflumethiazide, indapamide, chlortalidone

Answer 49

Inhibit the Na/K/Ca co-transporter in the distal convoluted tubule of the nephron Prevents reabsorption of sodium and its osmotically associated water Resulting diuresis causes an initial fall in extracellular fluid volume

Question 50

Dopaminergic drugs for Parkinson's disease | levodopa as co-careldopa/co-beneldopa, ropinirole, premipexol

Answer 50

In Parkinson's there is a deficiency of dopamine in the nigrostatial pathway Treatment seeks to increased dopaminergic stimulation to the striatum Dopamine does not cross the blood-brain-barrier Levodopa is a precursor of dopamine that can enter via a membrane transporter Ropinirole and pramipexol are relatively selective agonists for the D2 receptor in the striatum

Question 51

Emollients | aqueous cream, liquid paraffin

Answer 51

Help replace water content in dry skin Contain oils/paraffin-based products that help soften skin and reduce water loss by protecting against evaporation from skin surface

Question 52

Fibrinolytic drugs | alteplase, streptokinase

Answer 52

Catalyse conversion of plasminogen to plasmin Which acts to dissolve fibrinous clots and re-canalise occluded vessels

Question 53

Gabapentin and pregablin

Answer 53

Structurally related to GABA, however do not bind with GABA receptors MoA is not completely understood Seems to be mediated through binding with pre-synaptic voltage-sensitive calcium channels This inhibits release of excitatory neurotransmitters Resulting in reduction of neuronal excitability

Question 54

H2-receptor antagonists | ranitidine

Answer 54

Reduce gastric acid secretion Acid normally produced by protein pump which secretes H+ into stomach lumen - regulated by histamine Blocking H2-receptors therefor blocks acid secretion

Question 55

Heparins and fondaparinux | enoxaparin, dalteparin, fondaparinux, unfractioned heparin

Answer 55

Antithrombin inactivates clotting factors, particularly factors IIa (thrombin) and Xa Heparins and fondaparinux act by enhancing the anticoagulation effect of antithrombin

Question 56

Insulin | insulin aspart, insulin glargine, biphasic insulin, soluble insulin

Answer 56

Diabetes: Stimulates glucose uptake from circulation into tissues + increases use of glucose as energy source Hyperkalaemia: Drives potassium into cells (short term)

Question 57

Iron | ferrous fumarate, ferrous sulfate

Answer 57

Aim is to replenish iron stores

Question 58

Lamotrigine

Answer 58

MoA incompletely understood Binds to voltage-sensitive neuronal channels, interfering with Na influx into neuron Impedes repetitive neuronal firing, which is a characteristic of seizure activity

Question 59

Laxatives - osmotic | lactulose, macrogol, phosphate enema

Answer 59

Based on osmotically active substances that are not digested/absorbed Hold water in the stool, maintaining the volume and stimulating peristalsis Lactulose also reduces ammonia absorption

Question 60

Laxatives - stimulant | senna, bisacodyl, glycerol suppositories, docusate sodium

Answer 60

Increase water and electrolyte secretion from colonic mucosa Thereby increasing volume of colonic content and stimulating peristalsis

Question 61

Leukotriene receptor antagonists | montelukast

Answer 61

In asthma, leukotrienes produced by mast cells and eosinophils activate the G-coupled protein receptor CysLT1 This activates a cascade of pathways that result in inflammation and bronchoconstriction LRAs block the CysLT1 receptor, dampening the inflammatory cascade

Question 62

Levetiracetam

Answer 62

Molecular target is SV2A which is expressed throughout the brain presumably through interfering with synaptic vesicle function, levetiracetam modulates neuronal excitability and reduces risk of seizures

Question 63

Lidocaine

Answer 63

Enters cells in uncharged form, then accepts a proton to become charged Enters and blocks voltage-gated Na channels This prevents initiation and propagation of APs in nerves and muscle, inducing local anaesthesia In the heart, it reduces the duration of APs, slows conduction velocity and increases the refractory period

Question 64

Macrolides | clarithromycin, erythromycin, azithromycin

Answer 64

Inhibit bacterial protein synthesis Bind to the 50S subunit of bacterial ribosome and block translocation, a process required for elongation of the polypeptide chain Inhibition of protein synthesis is bacteriostatic (stops bacterial growth), which allows immune system to kill + remove bacteria from the body

Question 65

Metformin

Answer 65

Lowers blood glucose by reducing hepatic glucose output (glycogenolysis and gluconeogenesis) Does not stimulate insulin secretion + therefore does not induce hypoglycaemia Cellular mechanisms involve activation of AMP kinase

Question 66

Methotrexate

Answer 66

Inhibits dihydrofolate reductase, which converts dietary folic acid to tetrahydrofolate (FH4) FH4 is required for DNA and protein synthesis, so lack of it prevents cellular replication Actively dying cells are particularly sensitive to methotrexate, hence its use in cancer Also has anti-inflammatory and immunosuppressive effects

Question 67

Metronidazole

Answer 67

In anaerobic bacteria, reduction of metronidazole generates a nitrosio free radical This binds to DNA, reducing synthesis and causing widespread damage, DNA degradation and cell death

Question 68

Naloxone

Answer 68

Binds to opioid receptors where it acts as a competitive antagonist Little or no effect in the absence of an exogenous opioid If opioid is present, naloxone displaces it from its receptors and in doing so reverses its effects

Question 69

Nitrates | isosorbide mononitrate, glyceryl trinitrate

Answer 69

Nitrates are converted to NO NO increases cGMP synthesis and reduces intracellular Ca in vascular smooth muscle cells, causing them to relax - vasodilation Relaxation of venous capacitance vessels, reduced cardiac preload and left ventricular filling This reduces cardiac work and myocardial oxygen demand, relieving angina and heart failure

Question 70

Nitrofurantoin

Answer 70

Metabolised in bacterial cells by nitrofuran reductase Its active metabolite damages bacterial DNA and causes cell death

Question 71

NSAIDs | naproxen, ibuprofen, etoricoxib

Answer 71

Inhibit prostaglandin synthesis from arachidonic acid by inhibiting COX Therapeutic benefits are principally mediated by COX 2 inhibition E.g. inhibiting prostaglandins that cause inflammation and pain

Question 72

Ocular lubricants - artificial tears | hypromellose, carbomers, liquid and white soft paraffin

Answer 72

Soothing effect Protect eye surface from abrasive damage Electrolyte solutions with high viscosity

Question 73

Oestrogens and progestogens | combined ethinylestradiol products, desogestrel

Answer 73

Suppress LH/FSH release and hence ovulation

Question 74

Opioids - strong | morphine, oxycodone

Answer 74

Activation of opioid receptors in CNS Reduce neuronal excitability and pain transmission In medulla, blunt response to hypoxia and hypercapnoea, reducing respiratory drive Reduce sympathetic nervous system (fight/flight) activity

Question 75

Opioids - weak/moderate | tramadol, codeine, dihydrocodeine

Answer 75

Metabolised in liver to produce relatively small amounts of morphine (from codeine) or dihydromorphine (from dihydrocodeine) These metabolites are stronger agonists of opioid receptors, and account for most of the analgesic effect

Question 76

Oxygen

Answer 76

Increases PO2 in alveolar gas Driving more rapid diffusion of oxygen into blood Increases delivery of oxygen to tissues Accelerates diffusion of nitrogen out of the body In CO poisoning: competes with CO to bind with haemoglobin and thereby shortens half-life of carboxyhaemoglobin

Question 77

Paracetamol

Answer 77

MoA poorly understood Weak inhibitor of COX COX inhibition appears to increase pain threshold and reduce prostaglandin E2 concentrations in thermoregulatory receptors in hypothalamus, controlling fever

Question 78

Penicillins (benzylpenicilin, phenoxymethylpenicillin) (piperacilllin with tazobactam - tazocin) (amoxicillin, co-amoxiclav)

Answer 78

Inhibit enzymes responsible for cross-linking peptidoglycans in bacterial cell walls This weakens cell walls, preventing them from maintaining an osmotic gradient Uncontrolled entry of water into cell causes cell swelling, lysis and death Penicillins contain beta-lactam ring, which is responsible for their bactericidal activity

Question 79

Penicillins - penicillinase-resistant | flucloxacillin

Answer 79

Inhibit enzymes responsible for cross-linking peptidoglycans in bacterial cell walls This weakens cell walls, preventing them from maintaining an osmotic gradient Uncontrolled entry of water into cell causes cell swelling, lysis and death Penicillins contain beta-lactam ring, which is responsible for their bactericidal activity Flucloxacillin has an acyl side chain which protects the beta-lactam ring against beta-lactamases, which are enzymes made by bacteria to deactivate penicillin This makes flucloxacillin effective against beta-lactamase-producing staphylococci

Question 80

Phosphodiesterase (type 5) inhibitors | sildenafil

Answer 80

Phosphodiesterase inhibitor Selective for PDE-5 that is found in smooth muscle of corpus cavernosum of penis and arteries of lung For an erection to occur, stimulation is required - this releases NO which stimulates cGMP production causing arterial smooth muscle relaxation, vasodilation and penile enlargement As PDE-5 is responsible for breakdown of cGMP, inhibition of this by sildenafil increases cGMP concentrations, improving penile blood flow and erection quality Similar mechanisms in pulmonary vasculature

Question 81

Prostaglandin analogue of eye drops | latanoprost, bimatoprost

Answer 81

Glaucoma usually associated with elevated intraocular pressure Lowering intraocular pressure reduces glaucoma progression Prostaglandin analogues reduce intraocular pressure by increasing outflow of aqueous humour via uveoscleral pathway

Question 82

Protein pump inhibitors | lansoprazole, omeprazole, pantoprazole

Answer 82

Reduce gastric acid secretion Irreversibly inhibit H/K-ATPase in gastric parietal cells This is the proton pump responsible for secreting H+ and generating gastric acid

Question 83

Quinine | quinine sulfate

Answer 83

Thought to act by reducing excitability of motor end plate in response to acetylcholine stimulation, reducing frequency of muscle contraction

Question 84

Quinolones | ciprofloxacin, moxifloxacin, levofloxacin

Answer 84

Kill bacteria by inhibiting DNA synthesis

Question 85

Serotonin 5HT1-receptor agonists | sumatriptan

Answer 85

Relieve symptoms of acute migraine Triptans constrict cranial blood vessel and inhibit neurotransmission in peripheral trigeminal nerve and trigeminocervical complex

Question 86

Sex hormone antagonists for breast cancer | tamoxifen, anastrozole, letrozole

Answer 86

2/3s of breast cancers express oestrogen receptors Oestrogen binds to these and stimulates cell proliferation Sex hormone antagonists reduce tumour cell proliferation by blocking effects of oestrogen Tamoxifen is a selective oestrogen receptor modulator which prevents oestrogen binding to its receptor Aromatase inhibitors interfere with synthesis of oestrogens outside the ovary

Question 87

Statins | simvastatin, atorvastatin, pravastatin, rosuvastatin

Answer 87

Reduce serum cholesterol levels Inhibit 3-hydroxy-3-methyl-glytaryl coenzyme A reductase (enzyme involved in making cholesterol) Decrease cholesterol production by the liver and increase clearance of LDL from blood

Question 88

Sulphonylureas | glicazide

Answer 88

Lower blood glucose by stimulating pancreatic insulin secretion Block ATP dependent K channels in pancreatic beta-cell membranes, causing depolarisation of cell membrane and opening Ca channels This increases intracellular Ca concentrations, stimulating insulin secretion

Question 89

Tetracyclines | doxycycline, lymecycline

Answer 89

Inhibit bacterial protein synthesis Bind to ribosomal 30S subunit found specifically in bacteria This prevents binding of transfer RNA to messenger RNA, which prevents addition of new amino acids to growing polypeptide chains Bacteriostatic - stops bacterial growth allowing immune system to kill and remove bacteria

Question 90

Thyroid hormones | levothyroxine, liothyronine

Answer 90

Thyroid produces thyroxine (T4) which is converted to more active triiodothyronine (T3) in target tissues Thyroid hormones regulate metabolism and growth Levothyroxine is synthetic T4 - used for long-term replacement of thyroid hormones Liothyronine is synthetic T3, has a shorter half-life and quicker onset and offset - therefore reserved for emergency treatment of severe/acute hypothyroidism

Question 91

Trimethoprim | trimethoprim, co-trimoxazole

Answer 91

Bacteria are unable to use external sources of folate so need to make their own for essential functions e.g. DNA synthesis Trimethoprim inhibits bacterial folate synthesis, slowing bacterial growth (bacteriostasis)

Question 92

Valproate (valproic acid) | sodium valproate, valproic acid

Answer 92

MoA incompletely understood Appears to be weak inhibitor of neuronal sodium channels, stabilising resting membrane potentials and reducing neuronal excitability Increases brain content of GABA, which regulates neuronal excitability

Question 93

Vancomycin

Answer 93

Inhibits growth and cross-linking of peptidoglycan chains, inhibiting synthesis of the cell wall of Gram-positive bacteria Thus lysing and killing the bacterial (bactericidal)

Question 94

Vitamins | folic acid, thiamine, hydroxocobalamin, phytomenadione

Answer 94

Organic substances required ins mall amounts for normal metabolic processes In pregnancy and preconception period, folic acid reduces risk of congenital neural tube defects

Question 95

Warfarin

Answer 95

Warfarin inhibits hepatic production of vitamin K-dependent coagulation factors (factors II, VII, IX and X, and proteins C and S) It does this by inhibiting vitamin K epoxide reductase, the enzyme responsible for restoring vitamin K to its reduced form

Question 96

Z-drugs | zopiclone, zolpidem

Answer 96

Similar MoA to benzodiazepines Target is the GABAa receptor, a chloride channel that opens in response to binding by GABA Opening the channel allows chloride to flow into the cell, making the cell more resistant to depolarisations Z-drugs facilitate and enhance binding of GABA to the GABAa receptor This has widespread depressant effect on synaptic transmission Resulting in reduced anxiety, sleepiness and sedation