Mechanisms of Action Flashcards
5α-reductase inhibitors
finasteride
5α-reductase reduces testosterone to active metabolite dihydrotestosterone
Dihydrotestosterone stimulates prostatic growth
So 5α-reductase inhibitors reduce size of prostate gland by inhibiting this
α-blockers
doxazosin, tamsulosin, alfuzosin
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
Acetylcholinesterase inhibitors
donepezil, rivastigmine
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
Acetylcysteine (N-acetylcysteine)
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
Activated charcoal
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
Adenosine
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)
Adrenaline
epinephrine
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
Aldosterone antagonists
spironolactone, eplerenone
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
Alginates and antacids
gaviscon, peptac
Antacids: buffer stomach acids
Alginates: Increase viscosity of stomach contents to reduce reflux - form “floating raft” separating gastric contents from gastro-oesophageal junction
Allopurinol
Xanthine oxidase inhibitor
Xanthine oxidase is enzyme which metabolises xanthine from purines → uric acid
So drug lowers plasma uric acid
Aminoglycosides
gentamicin, amikacin, neomycin
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
Aminosalicylates
mesalazine, sulfasalazine
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
Amiodarone
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
ACE inhibitors
ramipril, lisinopril, perindopril
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
Angiotensin receptor blockers
losartan, candesartan, irbesartan
Block action of angiotensin II on angiotensin type 1 receptor
Angiotensin II = vasoconstrictor, stimulates aldosterone secretion, constricts efferent arteriole
ARBs = opposite effect
Antidepressants
tricyclics; amitriptyline, lofepramine
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
Antidepressants
venfalaxine, mirtazapine
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
Antiemetics - dopamine D2-receptor antagonists
metoclopramide, domperidone
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)
Antiemetics - histamine H1-receptor antagonists
cyclizine, cinanrizine, promethazine
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
Antiemetics - serotonin 5-HT3-receptor antagonists
ondansetron, granisetron
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
Antifungal drugs
nystatin, clotrimazole, fluconazole
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
Antihistamines - H1-receptor antagonists)
cetirizine, loratadine, fexofenadine, chlorpgenamine
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
Antimotility drugs
loperamide, codeine phosphate
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
Antimuscarinics - bronchodilators
ipratropium, tiotropoium, glycopyrronium, aclidinium
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
Antimuscarinics - cardiovascular and GI uses
atropine, hyoscine butylbromide, glycopyrronium
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
Antimuscarinics - GU uses
oxybutynin, tolterodine, solifenacin
Bind to muscarinic receptor and competitively inhibit acetylcholine
Promotes bladder relaxation
Reduces urinary frequency, urgency and urge incontinence
Through antagonism of the M3 receptor
Antipsychotics - 1st generation (typical)
haloperidol, chlorpromazine, prochlorperazine
Block post-synaptic dopamine D2 receptors
Incompletely understood mechanism
Antipsychotics - 2nd generation (atypical)
quetiapine, olanzapine, risperidone, clozapine
Block post-synaptic dopamine D2 receptors
Incompletely understood mechanism
Antiviral drugs
aciclovir
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
Antiplatelet drugs - ADP-receptor antagonists
clopidogrel, ticagrelor, prasugrel
Prevent platelet aggregation
Bind irreversibly to adenosine diphosphate (ADP) receptors on surface of platelets
Antiplatelet drugs
aspirin
Irreversibly inhibits COX to reduce production of pro-aggregatory factor thromboxane form arachidonic acid
Reducing platelet aggregation
Azathioprine
Pro-drug
Main metabolite is 6-mercaptopurine
Metabolites inhibit synthesis of purines and therefore inhibit DNA and RNA replication
β-blockers
bisoprolol, atenolol, propanolol, metoprolol, carvedilol
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
β2-agonists
salbutamol, terbutaline, salmeterol, formoterol, indacaterol
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
Benzodiazepines
diazepam, temazepam, lorazepam, chlordiazepoxide, midazolam
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
Bisphosphonates
alendronic acid, disodium pamidronate, zoledronic acid
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
Calcium and vitamin D
calcium carbonate, calcium gluconate, colecalciferol, alfacalcidol
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
Calcium channel blockers
amlodipine, nifedipine, dilitiazem, verapamil
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
Carbamazepine
MoA incompletely understood
Appears to inhibit neuronal sodium channels
Stabilising resting membrane potentials and reducing neuronal excitability
Cephalosporins and carbapenems
cefalexin, cefotazime, meropenem, ertapenem
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
Chloramphenicol
Binds to bacterial ribosomes, inhibiting protein synthesis - bacteriostatic
Stops bacterial growth, allowing immune system to clear microorganisms
Corticosteroids (glucocorticoids) - inhaled
beclometasone, budesonide, fluticasone
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
Corticosteroids (glucocorticoids) - systemic
prednisolone, hydrocortisone, dexamethasone
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)
Corticosteroids (glucocorticoids) - topical
hydrocortisone, betamethasone
Immunosuppressive, metabolic and mineralocorticoid effects
Digoxin
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
Dipeptidylpeptidase-4 inhibitors
sitagliptin, linagliptin, saxagliptin
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
Direct oral anticoagulants (DOACs)
apixaban, dabigatran, edoxaban, rivaroxaban
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
Loop diuretics
furosemide, bumetanide
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
Thiazide and thiazide-like diuretics
bendroflumethiazide, indapamide, chlortalidone
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
Dopaminergic drugs for Parkinson’s disease
levodopa as co-careldopa/co-beneldopa, ropinirole, premipexol
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
Emollients
aqueous cream, liquid paraffin
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
Fibrinolytic drugs
alteplase, streptokinase
Catalyse conversion of plasminogen to plasmin
Which acts to dissolve fibrinous clots and re-canalise occluded vessels
Gabapentin and pregablin
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
H2-receptor antagonists
ranitidine
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
Heparins and fondaparinux
enoxaparin, dalteparin, fondaparinux, unfractioned heparin
Antithrombin inactivates clotting factors, particularly factors IIa (thrombin) and Xa
Heparins and fondaparinux act by enhancing the anticoagulation effect of antithrombin
Insulin
insulin aspart, insulin glargine, biphasic insulin, soluble insulin
Diabetes:
Stimulates glucose uptake from circulation into tissues + increases use of glucose as energy source
Hyperkalaemia:
Drives potassium into cells (short term)
Iron
ferrous fumarate, ferrous sulfate
Aim is to replenish iron stores
Lamotrigine
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
Laxatives - osmotic
lactulose, macrogol, phosphate enema
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
Laxatives - stimulant
senna, bisacodyl, glycerol suppositories, docusate sodium
Increase water and electrolyte secretion from colonic mucosa
Thereby increasing volume of colonic content and stimulating peristalsis
Leukotriene receptor antagonists
montelukast
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
Levetiracetam
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
Lidocaine
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
Macrolides
clarithromycin, erythromycin, azithromycin
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
Metformin
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
Methotrexate
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
Metronidazole
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
Naloxone
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
Nitrates
isosorbide mononitrate, glyceryl trinitrate
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
Nitrofurantoin
Metabolised in bacterial cells by nitrofuran reductase
Its active metabolite damages bacterial DNA and causes cell death
NSAIDs
naproxen, ibuprofen, etoricoxib
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
Ocular lubricants - artificial tears
hypromellose, carbomers, liquid and white soft paraffin
Soothing effect
Protect eye surface from abrasive damage
Electrolyte solutions with high viscosity
Oestrogens and progestogens
combined ethinylestradiol products, desogestrel
Suppress LH/FSH release and hence ovulation
Opioids - strong
morphine, oxycodone
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
Opioids - weak/moderate
tramadol, codeine, dihydrocodeine
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
Oxygen
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
Paracetamol
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
Penicillins
(benzylpenicilin, phenoxymethylpenicillin)
(piperacilllin with tazobactam - tazocin)
(amoxicillin, co-amoxiclav)
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
Penicillins - penicillinase-resistant
flucloxacillin
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
Phosphodiesterase (type 5) inhibitors
sildenafil
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
Prostaglandin analogue of eye drops
latanoprost, bimatoprost
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
Protein pump inhibitors
lansoprazole, omeprazole, pantoprazole
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
Quinine
quinine sulfate
Thought to act by reducing excitability of motor end plate in response to acetylcholine stimulation, reducing frequency of muscle contraction
Quinolones
ciprofloxacin, moxifloxacin, levofloxacin
Kill bacteria by inhibiting DNA synthesis
Serotonin 5HT1-receptor agonists
sumatriptan
Relieve symptoms of acute migraine
Triptans constrict cranial blood vessel and inhibit neurotransmission in peripheral trigeminal nerve and trigeminocervical complex
Sex hormone antagonists for breast cancer
tamoxifen, anastrozole, letrozole
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
Statins
simvastatin, atorvastatin, pravastatin, rosuvastatin
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
Sulphonylureas
glicazide
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
Tetracyclines
doxycycline, lymecycline
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
Thyroid hormones
levothyroxine, liothyronine
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
Trimethoprim
trimethoprim, co-trimoxazole
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)
Valproate (valproic acid)
sodium valproate, valproic acid
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
Vancomycin
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)
Vitamins
folic acid, thiamine, hydroxocobalamin, phytomenadione
Organic substances required ins mall amounts for normal metabolic processes
In pregnancy and preconception period, folic acid reduces risk of congenital neural tube defects
Warfarin
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
Z-drugs
zopiclone, zolpidem
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
