MOA Flashcards
Ramipril
Lisinopril
Limits conversion of Angiotensin I to Angiotensin II by inhibiting circulating and tissue ACE
-> reduction in Angiotensin II activity ->
- vasodilation (reduces peripheral resistance & afterload
- reduced aldosterone release (increased Na & water excretion)
- reduced vasopressin (ADH) release (increased water excretion)
- reduced cell growth and proliferation
Losartan
Candesartan
Selective inhibition of angiotensin II by competitive antagonism of the angiotensin II receptors
Directly targets AT1 receptors which is more effective at inhibiting Angiotensin II mediated vasoconstriction than ACEi
AT1 receptors are important in CVS regulation but also antagonises AT2 receptors
No effect on bradykinin, dry cough and angioedema much less likely than with ACEi
Amlodipine
Nifedipine
Nimodipine
Dihydropyridine Ca Channel Blockers are selective for peripheral vasculature with little chronotropic or ionotropic effects - Acts primarily on vascular smooth muscle
CCBs are often 1st choice antihypertensive in pts with low renin
Amlodipine has a long half life
Cerebral vs peripheral selectivity
Nimodipine is selective for cerebral vasculature - useful for ischaemic effects of SAH
Verapamil
Prolongs AP/effective refractory period
Less peripheral vasodilation, -ve chronotropic and ionotropic effects
Diltiazem
Inhibits the inflow of calcium ions into the cardiac muscle during depolarization. Reduced intracellular calcium concentrations increase smooth muscle relaxation, resulting in arterial vasodilation and decreased blood pressure.
Action in between phenylalkamines and dihydropyridine CCBs
Bendroflumethiazide
Indapamide
Inhibits Na+/Cl- co-transporter in distal convoluted tubule -> decreases Na+ and water reabsorption (RAAS compensates with time)
Spironolactone
Eplerenone
Aldosterone antagonist -> reduced ENaC (and Na/K/ATPase) expression in late DCT and collecting duct -> decreased Na+ uptake and therefore water
K sparing
Bisoprolol
Labetalol
Metoprolol
Decrease sympathetic tone by blocking NA and reducing myocardial contraction
resulting in reduced cardiac output
Suppresses renin secretion (β1 on JG cells) -> antihypertensive
Cardiac effects:
- Increases AP duration and refractory period in AV node to slow AP conduction velocity
- Reduce phase 4 depolariasation
- Lowers BP
Effects on ECG:
- Increase PR interval
- Reduce HR - less automacitity
Doxazosin
Selective antagonism of α-1 adrenoceptors
Reduces peripheral vascular resistance
Tamsulosin
Highly selective antagonism of the urinary tract α-1 adrenoceptors
Furosemide
Bumetanide
Inhibits the N+/K+/2Cl- co-transporter
Reduces N+/K+/2Cl- into epithelium -> water follows
Direct dilation of capacitance veins - reduces preload (likely primary benefit in HF)
Amiloride
Blocks ENaC channels
Reduces Na+ reabsorption in DTC and reduces K+ excretion
Mannitol
Remains in tubular lumen, increases osmotic pull -> water follows in proximal tubule and descending limb and excreted in urine
Can lead to hyperNa
Sacubitril
Inhibits natriuretic inactivating enzyme -> potentiates effects of ANP/BNP -> natriuresis (Na loss)
Stops breakdown of bradykinin -> vasodilation
Atorvastatin
Simvastatin
Competitive inhibition of HMG-CoA reductase (rate controlling enzyme in HMG-CoA to mevalonate pathway)
- contributes to upregulation of LDL receptors
-> increased clearance of circulating LDL
Undergo Phase I metabolism by the CYP3A4 isoenzyme (substrate) - not all statins are the same CYP
Fenofibrate
Activation of nuclear transcription factor - PPARalpha
regulates expression of genes that control lipoprotein metabolism - increases production of lipoprotein lipase
Main effects:
- increased removal of triglycerides from lipoprotein in plasma
- increased fatty acid uptake by liver
Other effects:
- increased levels of HDL
- increased LDL affinity for receptor
Rarely used alone, co-prescribed with statins in mixed hyperlipidaemias
Ezetimibe
Inhibits NPC1L1 transporter at brush border of small intestine
Reduces cholesterol absorption in the gut by ~50%
Hepatic LDL receptor expression increases
Reduction in total cholesterol by ~15% and LDL by ~20%
Prodrug - hepatic metabolism -> enterohepatic circulation which limits systemic exposure
Alirocumab
Evolocumab
Inhibits action of PCSK9 (normally binds to LDL-R directing it for degredation) which significantly reduces LDL cholesterol level in primary hyperlipidemia
Not routinely used as still very expensive and must be injected sub-cut
Inclisiran
siRNA - inhibits hepatic translation of PCSK9 (normally binds to LDL-R directing it for degredation) so less is produced
Lidocaine
Mexiletine
IV Lidocaine
PO Mexiletine - swap to this after multiple lidocaine doses -> preventative
Effects on cardiac activity:
- Fast binding offset kinetics so need to keep giving frequently
- No change in phase 0 in normal tissue (no tonic block)
- AP duration slightly decreased in normal tissue
- increase threshold for Na+
- AP decreased in phase 0 conduction in fast beating (VT) or ischaemic tissue
Effects on ECG:
- None in normal heart
- Increased QRS in fast beating (VT) or ischaemic
Flecainide
Propafenone
Propafenone less used
Effects on cardiac activity:
- Substantially decreases phase 0 by blocking Na+ channels in normal
- reduces automaticity by increasing threshold
- increases AP duration (K+) and refractory period esp. in rapidly depolarising atrial tissue e.g. in A fib or Atrial flutter
Effects on ECG:
- prolonged PR, QRS and QT interval
Amiodarone
Prolong repolarization
Cardiac effects:
- increases refractory period and AP duration by affecting K+ channels
- reduces phase 0 and conduction through Na+ channels
- increase AP threshold
- decreases phase 4
- decreases speed of AV conduction
Effects on ECG:
- increases PR, QRS, QT intervals
- reduces HR
Verapamil
Diltiazem
Calcium channel blockers
Cardiac effects:
- slows conduction through AV by affecting Ca2+ intake
- increases refractory period in AV node
- increases slope of phase 4 in SA node to slow HR
Effects on ECG:
- Increase RP interval
- Mainly reduce HR but can increase depending on BP response and baroreflex
Adenosine
Rapid IV bolus, T1-2 seconds
Cardiac effects:
- decreased HR
- decreased Ca2+ currents -> increased refractory period in AV node
- stops heart for ~10s
Impending doom
Digoxin
Enhances vagal activity - increasing refractory period
Slows AV conduction and HR
Reduces ventricular rates in A fib and A flutter
Rarely used as dependant on renal function - if low can lead to bradycardia and death
Atropine
Selective muscarinic antagonist
Blocks vagal activity to speed up AV conduction and increase HR
Treats vagal bradycardia (helps with fainting)
Ivabradine
Blocks funny current in SAN
Slows SAN but does not affect BP
Tiotropium
Blocks muscarinic ACh R in airway smooth muscle
Prevents vaguely mediated contraction
Side effects: anticholinergic effects e.g. dry mouth/eyes, urinary retention
Sotalol
Prolong repolarization
Cardiac effects:
- Increased AP duration and refractory period in both atrial and ventricular tissue
- Slow phase 4 (beta blocker action too)
- Slows AV conduction
Effects on ECG:
- prolongs QT interval
- reduce HR
Alteplase
Converts plasminogen to the proteolytic enzyme plasmin, which lyses fibrin as well as fibrinogen
Anaesthetics
Can be local or general
General anaesthetic is normally inhaled or IV
- Anaesthetic drugs bind to the GABA receptor to potentiate the action of GABAA. GABAA is a major inhibitory neurotransmitter. This leads to the anaesthetic state of unconsciousness, muscle relaxation and analgesia.
- Anaesthetic drugs also work by opening K+ channels that modulate neuro-excitability. Opening these channels reduce membrane excitability. (Remember your action potential curve where Na+ goes in and K+ goes out. Opening K+ channels will lead to more negative resting potential, making it more difficult to start an action potential).
- Anaesthetic drugs inhibit opening of ligand-gated ion channels that allow Na+ to enter the cell.
Propofol
Propofol is a general anaesthetic given intravenously. It is often used as an induction agent and in intensive care for ventilated patients. Propofol decreases the rate of dissociation of GABA from its receptor, which increases the duration of the GABA-activated opening of the chloride channel leading to hyperpolarization of cell membranes. This leads to increased inhibitory tone in the central nervous system. There is pain on injection (due to activation of the pain receptor transient receptor potential ankyrin 1 - TRPA1).
Thiopental
Thiopental is a general anaesthetic given intravenously. It is a type of barbiturate that works by decreasing neuronal activity which decreases cerebral metabolic rate of oxygen consumption and decreases the cerebrovascular response to carbon dioxide, which will decrease intracranial pressure. It is very lipid-soluble so affects the brain quickly but can also cause laryngospasm.
Halothane
Halothane is an inhaled general anaesthetic which works by activating Gamma-aminobutyric acid (GABA) and glycine receptors, antagonising N-methyl-D-aspartate (NMDA) receptors and inhibiting voltage gates sodium channels and twin pore potassium channels. This leads to depressed nerve conduction, breathing and cardiac contractility. Adverse effects include hepatotoxicity, myocardial depression and malignant hyperthermia.
Atypical anti-psychotics e.g.
Clozapine
Risperidone
Olanzapine
Quetiapine
Aripiprazole
5HT2 and D2 receptor antagonists
Antagonising dopamine D2 receptors in the mesolimbic pathway blocks dopamine from acting at post-synaptic receptors. The binding is dissociable so some dopamine neurotransmission still takes place. Action on the serotonin 5HT2A receptors in the frontal cortex decreases adverse effects (compared to typical antipsychotics).
Carbamazepine
Carbamazepine is chemically similar to the tricyclic antidepressants. It binds to voltage-dependent sodium channels and increases their refractory period, thus preventing the action potential. It is used in epilepsy and bipolar disorder.
Can cause hyponatraemia. Carbamazepine acts on voltage-dependent sodium channels which carry inward membrane current. This reduces the likelihood of the delopment of an action potential
P450 enzyme inducer
Amitriptyline
Tricyclic antidepressants (TCAs) inhibit a membrane pump mechanism responsible for the re-uptake of transmitter amines (e.g noradrenaline/serotonin) into the presynaptic cleft. Thus, their concentration at the synaptic clefts is increased, and they restimulate post-synaptic receptors. Noradrenaline and serotonin are important in regulating mood, and their increased concentration in the synaptic cleft helps to reduce depressive symptoms.
Bleomycin
Teicoplanin
Vancomycin
Glycopeptides target the bacterial cell wall by binding to acyl-D-alanyl-D-alanine in peptidoglycan. This prevents the addition of new units to the peptidoglycan in the cell wall.
Tamoxifen
Tamoxifen is a selective oestrogen receptor modulator (SERM) which acts partially as an oestrogen receptor antagonist, blocking oestrogen from binding to breast cancer cells causing them to grow and divide, and a partial agonist in tissues such as the uterus and bones.
Metformin
Reduces hepatic glucose production by inhibiting gluconeogenesis
Limited weight gain - supresses appetite
Gliclazide
Stimulates beta cell pancreatic insulin secretion
(needs residual pancreatic function)
Risk of hypoglycaemia
Weight gain - anabolic effects of insulin
Dapagliflozin
Reduces glucose absorption from tubular filtrate
Increases urinary glucose excretion
Modest weight loss
Low risk of hypoglycaemia
Increases risk of uti
Semaglutide
GLP-1 receptor agonist
Increases glucose dependent synthesis of insulin secretion from beta cells
Activates GLP-1 receptor
Resistant to degradation by DPP-4
Subcut injection
Promotes satiety - GLP-1 reduces peristalsis in the gut
Aspirin
COX-1 inhibitor
Prevents COX-1 mediated production of TXA2 and irreversibly reduces platelet aggregation
Platelet lifespan is 7-10 days
Avoid in children <16 years old due to Reye’s syndrome and pregnancy 3rd trimester due to premature closure of ductus arteriosus
High dose inhibits endothelial prostacyclin (PGI2)
Clopidogrel
Acts independently of COX pathway
Inhibits binding of ADP to P2Y12 receptor
-> inhibits activation of GPIIb/IIIa receptors
Irreversible inhibitor of P2Y12
Prodrug -> CYP inhibitors e.g. omeprazole reduce efficacy
Hepatic metabolism
Ticagreglor
Acts independently of COX pathway
Reversible inhibitor of P2Y12
Rapid onset of action compared to clopidogrel
Alteplase
Fibrinolytic (clot buster)
Dissolve the fibrin meshwork of thrombus
Activate plasmin (plasminogen -> plasmin -> increased fibrinolysis)
Streptokinase
Fibrinolytic (clot buster)
Dissolve the fibrin meshwork of thrombus
Activate plasmin (plasminogen -> plasmin -> increased fibrinolysis)
Can only be used once as antibodies develop
Transexamic acid (TXA)
Inhibits fibrinolysis
Stops bleeding
Celecoxib
Selective COX-2 inhibitor
No antiplatelet action but inhibits PGI2
Less analgesic affect but useful in sever osteo/RA long term
All NSAIDs increase risk of MI including in low risk people (reduced PGI2 protective function)
NSAIDs displace other bound drugs -> increase free drug conc e.g. supfonurea -> hypoglycaemia, methotrexate -> hepatotoxicity, warfarin -> increased risk of bleeding
Paracetamol
MOA is unknown
non-NSAID, non-opiate analgesic and antipyretic
Risk of overdose
Paracetamol -> NAPQI (conjugated by glutathione -> harmless metabolite
Treat OD with N-acetylcysteine (glutatione replacement)
Opiates:
Codeine
Fentanyl
Morphine
Tramadol
CNS depressant
Binds to opioid receptor Gai (AC cAMP)
Decreased Ca2+ influx in presynaptic terminal in response to incoming AP
Decreases release of excitatory neurotransmitters e.g. glutamate
Also dampens response to excitatory neurotransmitters at post-synaptic neuron (increases K+ efflux)
In OD use naloxone
Gaviscon
Antacid - buffers stomach acid
Alginic acid - increases stomach content viscosity and reduces reflux
Magnesium salts -> diarrhoea
Aluminium salts -> constipation
Balanced
Omeprazole
PPI
Irreversibly inhibits the H+/K+ ATPase in gastric parietal cells
Significantly reduces acid secretion
Ranitidine
H2 receptor antagonist - competitive inhibition in gastric parietal cells
Lactulose
Osmotic laxative
Draws fluid into bowel
Macrogols
Osmotic laxative
Limits loss of fluid from stool
Metaclopramide
Anti-emetic, D2 receptor antag
Increases intestinal motility (prokinetic)
Hyoscine hydrobromide
Muscularinic receptor antag
Competitive inhibition of muscularinic ACh receptors
Some action through central trigger zone (via CN8)
Sedative effect
Meropenem
Inhibits bacterial cell wall synthesis (stops building and repairing)
Very broad spectrum
Generally safe in penicillin allergy
Vancomysin
Inhibits bacterial cell wall synthesis
Generally gram +ve
Flucloxacillin
Inhibits bacterial cell wall synthesis
Metronidazole
Antibiotic, MOA not fully understood but affects bacterial nucleic acid synthesis
Can’t take with alcohol
Gentamycin
Inhibits bacterial protein synthesis - acts on ribosomes
Profound activity against gram -ve
Nephrotoxic, ototoxic
Ceftriaxone
Inhibits bacterial cell wall synthesis
Aciclovir
Inhibits viral DNA polymerase
Oseltamivir
Viral neuraminidase enzyme inhibitor
- Prevents budding from the host cell, viral replication, and infectivity
Amoxicillin
Inhibits bacterial cell wall synthesis
Trimethoprim
Dihydrofolate inhibitor
Interferes with folate synthesis -> inhibits bacterial DNA synthesis
Avoid in pregnancy (1st trimester) -> neural tube defects
Nitrofurantoin
Own class
Converted by bacterial nitroreductases to electrophilic intermediates which inhibit the citric acid cycle as well as synthesis of DNA, RNA, and protein.
Doxycycline
Inhibits bacterial protein synthesis - acts on ribosomes
Co-amoxiclav
Beta-lactam antibiotic (inhibits cell wall synthesis) +
Clavulanic acid - beta-lactamase inhibitor, stops bacteria inhibiting antibiotic
Clarythromycin
Inhibits bacterial protein synthesis - acts on ribosomes
Erythromycin
Inhibits bacterial protein synthesis - acts on ribosomes
Azithromycin
Inhibits bacterial protein synthesis - acts on ribosomes
Ofloxacin
Inhibiting two enzymes involved in bacterial DNA synthesis (DNA topoisomerase)
