Mechanism Of Action

Question 1

Adrenaline

Answer 1

Potent agonist of α1, α2, β1, β2

α1 —> vasoconstriction of skin and mucosa vessels
β1 —> increased heart rate and contractility and excitability
β2 —> vasodilatation of coronary vessels and bronchodilatation plus suppression of inflammation mediator release from mast cells

Question 2

Corticosteroids (systemic)

Answer 2

1⃣ Works on glucocorticoid receptors to alter gene transcription. Upregulates anti-inflammatory genes and downregulates pro-inflammatory genes (e.g. cytokines TNF-alpha)

2⃣ Exerts direct effects suppressing circulating monocytes and eosinophils

3⃣ Metabolic - + gluconeogenesis from + circulating amino acids and fatty acids

4⃣ Mineralocorticoid effects - Na+ and H2O retention and K+ excretion

Question 3

Thiazide Like Diuretics

Answer 3

Inhibit the Na+/Cl- cotransporter in the DCT therefore Na+ and H2O are excreted

Some impact on vasodilation - poorly understood

Question 4

Statins

Answer 4

Reduce levels of serum cholesterol

• Inhibit HMG-CoA
• Increase clearance of LDL and TGs
• Increase levels of HDL

Question 5

Clopidogrel

Answer 5

Antiplatelet aggregation by binding to ADP receptors on platelet surface irreversibly.

Independent of COX pathway therefore synergistic with aspirin

Question 6

Antihistamines

Answer 6

H1 receptor antagonists therefore block action of histamine (increased vascular permeability // vasodilation // stimulate sensory nerve endings {itch})

Question 7

Beta-blockers

Answer 7

Beta1-adrenoreceptors = heart,
reduce contraction force and speed of conduction therefore decreasing cardiac work and oxygen demand.
Prolong the refractory period of the AV node
Lower blood pressure by reducing renin secretion from kidney (mediated by Beta1-receptors)

Beta2-adrenoreceptors = vessels and airways

Question 8

5a-reductase inhibitors

Finasteride

Answer 8

Testosterone is not converted to more potent dihydrotestosterone which normally stimulates prostatic growth therefore the drug reduces enlargement and improves urinary flow

Can take several months for clinical effect

Question 9

Alpha blockers

Doxazosin, tamsulosin, alfuzosin

Answer 9

Highly selective for alpha1-adrenoceptor (found mainly on smooth muscle, including blood vessels and urinary tract)

Blocking receptors causes relaxation therefore cause decreased B.P. and resistance to bladder outflow

Question 10

Acetylcholinesterase inhibitors

Donepezil, Rivastigmine

Answer 10

By increasing availability of Ach available for neurotransmission -improves cognition and reduces the rate of cognitive decline

Ach impt for learning and memory

Question 11

Acetylcysteine

Answer 11

1) Paracetamol metabolised normally by conjugations with glucuronic acid & sulfate. Some is converted to NAPQI = liver☠️. It is quickly detoxified through conjugation with glutathione. In overdose the glutathione gets used up leaving toxic NAPQI around. Acetylcysteine replenishes the glutathione.
2) Antioxidant effects to prevent contrast nephropathy
3) Breaks disulfide bonds in mucus, reducing viscosity

Question 12

Activated charcoal

Answer 12

Poisons adsorbed onto surface of activated charcoal to reduce amount absorbed into circulation. Substances that adsorb well are weakly ionic, hydrophobic substances (e.g. benzodiazepines, methotrexate)

Multiple doses are used to maintain a steep concentration gradient of poison to encourage diffusion out of the circulation and help elimination

Question 13

Adenosine

Answer 13

Agonist of C protein coupled adenosine receptors. Effects = reducing frequency of spontaneous depolarisation // increasing resistance to depolarisation –> slows sinus rate // slows conduction velocity // increases AV node refractoriness.
Increasing refractoriness in the AV node breaks the re-entry circuit and allows the SA node to resume control of the heart (cardioversion)

In atrial flutter adenosine will not cadiovert because AV node not involved

Plasma half life is 10 seconds

Question 14

Aldosterone antagonists

spironolactone, eplerenone

Answer 14

Aldosterone = mineralocorticoid (adrenal cortex)

Aldosterone acts on distal tubules of the kidneyto increase activity of luminal epithelial sodium channels (ENaC) therefore increasing the reabsorption of sodium and water.

Therefore aldosterone antagonists competitively bind to receptors causing sodium and water excretion and potassium retention. Greatest effect when circulating aldosterone is high.

Question 15

Alginates and antacids

Gaviscon, Peptac

Answer 15

Antacids: Buffer stomach acids

Alginates: Increase the viscosity of the stomach contents to reduce reflux. Form a floating raft.

Question 16

Allopurinol

Answer 16

Is a xanthine oxidase inhibitor (enzyme which metabolises xanthine (from purines) to uric acid.

Question 17

Aminoglycosides

gentamicin, amikacin, neomycin

Answer 17

Works mainly on Gram -ve aerobic bacteria.
Inhibit the 30s ribosome subunit irreversibly. Enter bacteria through oxygen dependent transport system.
Penicillins weaken cell wall therefore may improve bacterial uptake and therefore enhance activity of aminoglycosides

Question 18

Aminosalicylates

mesalazine, sulfasalizine

Answer 18

In UC: Release 5-ASA which seems to have anti-inflammatory and immunosuppressive effects - act topically on the gut rather than systemically therefore preparations delay release of active ingredient until the colon.

In RA: Sulfapyridine is probably the active component but mechanism unclear (causes s/e in gut therefore replaced by mesalazine)

Question 19

Amiodarone

Answer 19

Blockade of sodium, calcium and potassium channels and antagonism of a- & B- adrenergic receptors –>

Reduce spontaneous depolarisation (automaticity), slow conduction velocity and increase resistance to depolarisation (refractoriness), including in the AV node. By interfering at the AV node, amiodarone reduced the ventricular rate in AF and atrial flutter.

In SVT invloving a re-entry circuit that involves the AV node, amiodarone may break the circuit and restore sinus rhythm.

Amiodarone’s effects in suppressing spontaneous depolarisations make it an option for both treatment and prevention of VT, and for improving the chance of successful defibrillation in refractory VF

Question 20

ACE-inhibitors

ramipril, lisinopril, perindopril

Answer 20

Block ACE therefore stop conversion of angiotensis I to II

Angiotensin II is a vasoconstrictor and stimulates aldosterone secretion therefore with ACE-i get reduced BP. Also get dilation of efferent glomerular arteriolewhich reduces intraglomerular pressure and slows the progression of CKD. Reducing aldosterone also promotes sodium and water excretion

Question 21

Angiotensin Receptor Blockers

losartan, candesartan, irbesartan

Answer 21

ARBs block the action of angiotensin II on the angiotensin type 1 receptor.

Angiotensin = vasoconstrictor, aldosterone secretion, constrict efferent arteriole

ARBs = opposite effect

Question 22

Antidepressants - SSRIs

Citalopram, fluoexetine, sertraline, escitalopram

Answer 22

Inhibit neuronal reuptake of 5-HT from the synaptic cleft therefore increasing availability for neurotransmission.

Do not inhibit noradrenaline uptake like tricyclic antidepressants and cause less blockade of other receptors therefore have fewer side effects

Question 23

Antidepressants - Tricyclics and related

amitriptyline, lofepramine

Answer 23

Inhibit neuronal reuptake of noradrenaline and 5-HT from the synaptic cleft. Also block a wide array of receptors including muscarinic, histamine (H1), a-adrenergic (a1 and a2) and dopamine D2 receptors therefore extensive side effects

Question 24

Antidepressants - Venlafaxine and mirtazapine

Answer 24

ven = SNRI
mir  = antagonist of inhibitory pre-synaptic a2-adrenoceptors

Both drugs increase availability of monoamines for neurotransmission

venlafaxine is a weaker antagonist of muscarinic and histamine receptors than tricyclics but mirtazapine is a potent antagonist of histamine receptors (but not muscarinic) therefore commonly causes sedation

Question 25

Antiemetics - dopamine D2 receptor antagonists

metoclopramide, domperidone

Answer 25

Nausea and vomiting triggered by wide array of stimuli that all converge on a ‘vomiting centre’ in the medulla. This receives input from the chemoreceptor trigger zone, the solitary tract nucleus, the vestibular system and higher neurological centres.

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

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

Question 26

Anti-emetics - histamine H1 receptor antagonists

cyclizine, cinnarizine, promethazine

Answer 26

Nausea and vomiting triggered by wide array of stimuli that all converge on a ‘vomiting centre’ in the medulla. This receives input from the chemoreceptor trigger zone, the solitary tract nucleus, the vestibular system and higher neurological centres.

H1 and ACh (muscarinic) receptors redominate in the vomiting centre and communication with the vestibular system therefore drugs are effective in a wide range of conditions, particularly when associated with motion or vertigo

Question 27

Anti-emetics - serotonin 5-HT3 receptor antagonists

ondansetron, granisetron

Answer 27

Nausea and vomiting triggered by wide array of stimuli that all converge on a ‘vomiting centre’ in the medulla. This receives input from the chemoreceptor trigger zone, the solitary tract nucleus, the vestibular system (5-HT is NOT involved here therefore not good for motion sickness) and higher neurological centres.

There is a high density of 5-HT3 receptors in the CTZ which sense emetogenic substances in the blood.

5-HT is the key neurotransmitter released in the gut in response to emetogenic stimuli - 5HT stimulates 5-HT3 receptors which stimulate the vagus nerve which activates the vomiting centre via the solitary tract nucleus.

Question 28

Antifungal drugs

nystaton, clotrimazole, fluconazole

Answer 28

Fungal cell membranes contain ergosterol - target for drugs. Polyene antifungals (e.g. nystatin) bind to ergosterol forming a polar pore which allows intracellular ions to leak out the cell which kills or slows growth of fungus.

Imidazole and triazole antifungals inhibit ergosterol synthesis which impairs cell membrane synthesis and cell growth and replication.

Resistance is rare but can occur in long-term use in immunosuppressed pts.

Question 29

Antihistamines (H1-receptor antagonists)

cetirizine, loratidine, fexofenadine, chlorphenamine

Answer 29

Histamine is released from storage granules in mast cells in response to antigen binding to IgE on the cell surface. Histamine induces features of immediate type (Type 1) hypersensitivity: increased capillary membrane permeability causing oedema formation (wheal), vasodilatation causing erythema (flare) and itch as a result of sensory nerve stimulation.

Widespread histamine release, as in anaphylaxis causes generalised vasodilatation –> hypotension.

Antihistamines block the effects of excess histamine (NB effect is too slow in anaphylaxis, give adrenaline first line)

Question 30

Antimotility drugs

loperamide, codeine phosphate

Answer 30

Loperamide is opioid similar to pethidine but does not enter CNS. It is an agonist of opioid μ-receptors in the gut. This increases non-propulsive contractions but reduces peristaltic contractions therefore transit of bowel contents is slowed (which also allows increased water resabsorption) and anal sphincter tone increased.

Other opioids have same effect but unless analgesia is required give loperamide.

Question 31

Antimuscarinics, bronchodilators

ipratropium, tiotroprium, glycopyrronium, aclidinium

Answer 31

Act as competitive inhibitor of acetylcholine. Stimulation of the receptor brings about ‘parasympathetic’ effects. Blocking the receptor causes increase in HR and conduction, reduce smooth muscle tone, reduce secretions from glands in resp and GO tracts. In the eye they cause relaxation of the pupillary constrictor and ciliary muscles causing pupillary dilatation and preventing accommodation.

Question 32

Antimuscarinics, cardiovascular and GI uses

atropine, hyoscine butylbromide, glycopyrronium

Answer 32

Stimulation of the receptor brings about ‘parasympathetic’ effects. Blocking the receptor causes increase in HR and conduction, reduce smooth muscle tone, reduce secretions from glands in resp and GO tracts. In the eye they cause relaxation of the pupillary constrictor and ciliary muscles causing pupillary dilatation and preventing accommodation.

Question 33

Antimuscarinics, genitourinary uses

Oxybutynin, tolterodine, solifenacin

Answer 33

Contraction of the smooth muscle of the bladder is under parasympathetic control. Blocking muscarinic receptors therefore promoted bladder relaxation.
Antimuscarinics also help in overactive bladder through antagonism of the M3 receptor which is the main subtype in the bladder (solifenacin is more selective for the M3 receptor)

Question 34

Antipsychotics - first generation (typical)

haloperidol, chlorpromazine, prochlorperazine

Answer 34

Block post-synaptic D2 receptors.
Mesolimbic pathway - main det. of antipsychotic effect
Mesocortical pathway
Nigrostriatal pathway
Tuberohypophyseal pathway = side effects
Also D2 receptors in chemoreceptor trigger zone therefore use in nausea and vomiting
Also sedatory effect

Question 35

Antipsychotics - second generation (atypical)

olanzapine, risperidone, clozapine

Answer 35

Block post-synaptic D2 receptors.
Mesolimbic pathway - main det. of antipsychotic effect
Mesocortical pathway
Nigrostriatal pathway 
Tuberohypophyseal pathway = side effects

More effective against -ve symptoms and fewer EPSE and more effective for tmt-resistant schizophrenia (clozapine) due to higher affinity for other receptors (5-HT2A) and looser binding to D2

Question 36

Antiviral drugs

aciclovir

Answer 36

HS1/HS2/VZV all contain dsDNA which requires a herpes-specific DNA polymerase for the virus to replicate. Aciclovir inhibits this enzyme after entering herpes-infected cells, stopping further DNA synthesis and replication

Question 37

Antiplatelet drugs, ADP-receptor antagonists

clopidogrel, ticagrelor, prasugrel

Answer 37

By preventing platelet aggregation and binding irreversibly to ADP receptors (P2Y12 subtype) on the surface of platelets. This process is independent of COX pathway therefore synergistic with aspirin

Question 38

Antiplatelets

aspirin

Answer 38

Aspirin irreversibly inhibits cyclooxygenase to reduce production of pro-aggregatory factor thromboxane from arachidonic acid, reducing platelet aggregation and the risk of arterial occlusion. This effect occurs at low doses and lasts for the entire lifespan of the platelet

Question 39

Azathioprine

Answer 39

A pro-drug. Metabolised to 6-mercaptopurine which is further metabolised to active substances. These inhibit the synthesis of purines (A and G) and therefore prevent DNA/RNA replication. Most cells can recycle purines but lymphocytes cannot therefore are particularly affected. Metabolism and elimination involves enzymes xanthine oxidase and thiopurine methyltransferase (TPMT) - latter can be reduced or absent in some individuals

Question 40

β-blockers

propanolol, atenolol, bisoprolol, metoprolol, carvedilol

Answer 40

β1-adrenoceptors in heart
β2-adrenoceptors in smooth muscle of blood vessels and airways
Via β1- blockers reduce the force of contraction and speed of conduction in the heart - this relieves myocardial ischaemia by reducing work and O2 demand
Slow ventricular rate in AF by prolonging the refractory period of the AV node - may also terminate a SVT if this is due to a self-perpetuating re-entry circuit
In HTN - many mechs including reducing renin secretion from the kidney (mediated by β1 receptors)

Question 41

β2-agonists

salbutamol, terbutaline, salmeterol, formoterol, indacaterol

Answer 41

β2 receptors found in smooth muscle of bronchi, gut, uterus and blood vessels. Stimulation of G-protein cascade -> smooth muscle relaxation.

β2-agnoists also stimulate Na+/K+ ATPase pumps on cell surface membranes therefore shift K* intracellularly - good for hyperkalaemia esp when IV access is difficult

Short acting (salbutamol, terbutaline) or long acting (salmeterol, formoterol)

Question 42

Benzodiazepines

diazepam, temazepam, lorazepam, chlordiazepoxide, midazolam

Answer 42

Act on the GABA receptor. The GABA-A receptor is a chloride channel that opens in response to GABA (inhibitory neurotransmitter) Opening channel makes cell more resistant to depolarisation.

Benzos enhance binding of GABA to receptor causing widespread depressant effect. Clinically manifests as reduced anxiety, sleepy, anticonvulsice.

Alcohol also acts on GABA-A receptor, in chronic excessive use patient becomes tolerant to its presence. Abrupt cessation provokes excitatory state of alcohol withdrawal which can be treated with benzodiazepine

Question 43

Bisphosphonates

alendronic acid, disodium pamidronate, zolendronic acid

Answer 43

Inhibit osteoclasts

Have similar structure to pyrophosphate therefore gets readily incorporated into bone where they are taken up by osteoclasts in bone resorption and inhibit activity/promote apoptosis therefore get reduced bone loss and increased bone mass.

Question 44

Calcium and Vitamin D

calcium carbonate, calcium gluconate, colecalciferol, alfacalcidol

Answer 44

In osteoporosis - helps prevent bone loss

In CKD impaired phosphate excretion and reduced activation of vitamin D cause hyperphosphataemia and hypocalcaemia -> secondary hyperparathyroidism which causes bone changes. Treat with oral calcium to bind phosphate in the gut and alfacalcidol to provide vit D that doesn’t need renal activation.

In hyperkalaemia calcium raises the myocardial threshold potential, reducing excitability and the risk of arrhythmias - NO EFFECT ON K+ LEVELS

Question 45

Calcium channel blockers

amlodipine, nifedipine, diltiazem, verapamil

Answer 45

Decrease Ca2+ entry into vascular and cardiac cells, reducing intracellular calcium concentration causing relaxation and vasodilation in arterial smooth muscle -> lower arterial pressure

In the heart CCBs reduce myocardial contractility

They suppress cardiac conduction, particularly across the AV node, slowing ventricular rate.

All the actions reduce myocardial oxygen demand preventing angina

Dihydropyridines (amlodipine, nifedipine) rel. selective for the vasculature whereas non-dihydropyridines are more selective for the heart (particularly verapamil)

Question 46

Carbamazepine

Answer 46

Not really understood

Inhibits neuronal sodium channels therefore reducing neuronal excitability

Question 47

Cephalosporins and carbapenems

cefalexin, cefotaxime, meropenem, ertapenem

Answer 47

Broad spectrum of action

Cephalosporin generations have been increasing activity against Gram -ve bacteria including Pseudomonas aeruginosa

Act via β-lactam ring which inhibits enzymes responsible for cross-linking peptidoglycans in bacterial cell walls therefore -> bacterial cell swelling, lysis and death

More resistant to β-lactamase than penicillins.

Question 48

Chloramphenicol

Answer 48

Broad activity

Binds to bacterial ribosomes inhibiting protein synthesis which stops bacterial growth allowing immune system to clear microorganisms.

Bacterial resistance is through production of acetyltransferase enzymes that inactivate the drug. Resistance however remains low.

Question 49

Corticosteroids (glucocoricoids), inhaled

beclometasone, budesonide, fluticasone

Answer 49

Pass through plasma membrane and interact with receptors in the cytoplasm. Activated receptor then passes into nucleus to modify transcription of a large number of genes. Pro-inflammatory interleukins, cytokines and chemokines are downregulated while anti-inflammatory proteins are upregulated.

In the airways this reduces mucosal inflammation, widens airways and reduces mucus secretion.

Question 50

Corticosteroids, topical

hydrocortisone, betamethasone

Answer 50

Immunosuppressive, metabolic and mineralocorticoid effects. Topical effects are limited to site of application but with prolonged or potent use systemic absorption is possible.

Topical corticosteroids can be classified as being mild, moderately potent and very potent, depending on the type and concentration of corticosteroid in the formulation. e.g. hydrocortisone 0.1%-2.5% is mild and betamethasone valerate 0.1% is potent

Question 51

Digoxin

Answer 51

Digoxin is negatively chronotropic (reduces heart rate) and positively inotropic (increased contraction).
In AF and flutter its effect is from increased vagal tone therefore reducing conduction at the AV node and therefore reducing ventricular rate.

In heart failure it inhibits Na+/K+-ATPase pumps, causing Na+ to accumulate in the cell therefore causing Ca2+ to accumulate increasing contractile force.

Question 52

Dipeptidylpeptidase-4 inhibitors

sitagliptin, linagliptin, saxagliptin

Answer 52

Incretins [GLP-1] and glucose-dependent insulinotropic peptide [GIP] are released but the intestine in response to food. They promote insulin secretion and suppress glucagon release, lowering blood glucose. The incretins are inactivated by DPP-4 therefore DPP-ri lower blood glucose by inhibiting incretin degradation. The incretin action is glucose dependent so less likely to cause hypoglycaemia.

Question 53

Direct Oral Anticoagulants

apixaban, dabigatran, edoxaban, rivaroxaban

Answer 53

DOACs act on the final common pathway. Mostly directly inhibit factor Xa, preventing conversion of prothrombin to thrombin.
Dabigatran inhibits thrombin, preventing conversion of fibrinogen to fibrin.
Therefore all inhibit fibrin formation and thus preventing clots forming or extending. Less effective in the arterial circulation - need antiplatelet action instead

Question 54

Diuretics, loop

furosemide, bumetanide

Answer 54

Inhibit Na+/K+/2Cl- cotransporter that normally moves ions into cells from tubular lumen and water follows.
Loop diuretics also cause dilatation of capacitance veins which in heart failure reduces preload and improves contractile function of heart muscle.

Question 55

Diuretics, thiazide and thiazide-like

bendroflumethiazide, indapamide, chlortalidone

Answer 55

Inhibit Na+/Cl- co-transporter in the DCT of the nephron which prevents reabsorption of sodium and therefore water.
Long term antihypertensive effect may be mediated by vasodilatation which is incompletely understood

Question 56

Dopaminergic drugs for Parkinson’s disease

levodopa (As co-careldopa, co-beneldopa), ropinirole, pramipexol

Answer 56

In Parkinson’s deficiency of dopamine in the nigrostriatal pathway that links the substantia nigra in the midbrain to the corpus striatum in the basal ganglia. This causes basal ganglia to inhibit thalamus which in turn reduces input to motor cortex –> bradykinesia and rigidity.
Levodopa is a precursor of dopamine that can cross the BBB.
Ropinirole and pramixerole are selective agonists for the D2 receptor (in striatum mostly)

Question 57

Emollients

aqueous cream, liquid paraffin

Answer 57

Replace water. Soften skin and reduce water loss by protecting against evaporation.

Question 58

Fibrinolytic drugs

alteplase, streptokinase

Answer 58

Catalyse conversion of plasminogen to plasmin which dissolves fibrinous clots and recanalises occluded vessels

Question 59

Gabapentin and pregabalin

Answer 59

Mechanism seems to be mediated therough binding pre-synaptic voltage-sensitive calcium channels (rather than GABA receptors) therefore inhibiting excitatory release of neurotransmitters and reducing neuronal excitability. Central effects along with similar in peripheral nerves may explain mechanism by which they reduce neuropathic pain

Question 60

H2-receptor antagonists

ranitidine

Answer 60

Reduce gastric acid secretion by blocking histamine activation of proton pumps of gastric parietal cells. Don’t have a complete suppressive effect (unlike PPIs)