All Pharmacology Flashcards
Explain the mechanism of action of Atropine
Atropoine is a muscarinic receptor antagonist.
Atropine binds to and inhibits the muscarinic acetylcholine receptor. Adequate doses of atropine abolish various types of reflex vagal cardic slowing or asystole.
The drug also prevents or abolishes bradycardia or asystole produced by injection of choline esters, anticholinesterase agents or other parasympathomimetic drugs, and cardiac arrest produced by stimulation of the vagus.
Atropine may lessen the degree of partial heart block when vagal activity is an etiological factor.
Explain the mechanism of action of Betamethasone.
Betamethasone is a glucocorticoid receptor agonist. Binding of betamethasone to the glucocorticoid receptor forms a complex which moves to the nucleus, binds DNA causing alteration in gene transcription.
This altered gene transcription causes the production of lipocortins, which inhibits transcription. This altered gene transcription causes the production of lipocortins, which inhibits phospholipase A2 and therefore reduces the biosynthesis of prostaglandins and leukotrienes.
In addition, corticoid steroid reduces the gene expression of interleuken-1, which is an important inflammatory cytokine.
The overall effect of both action drives the anti-inflammatory immunosupressive and anti-mitogenic effects of steroids.
In the plasmna, it binds to transcortin, and it becomes active when it is not bound to transcortin.
If prescribed to be taken orally it is best to use in combination with beclomethasone. If prescribed as a glucocorticoid, then better with hydrocortisone or prednisolone.
Explain the mechanism of action of Digoxin
Digoxin is a cardiac glycoside (A sodium potassium ATPase inhibitor).
Digoxin is used to treat congestive heart failure, and supraventricular arrythmias.
It’s mode of action is via inhibition of the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium.
This causes in turn the sodium calcium exchanger (NCX) to extrude the sodium and pump in more calcium.
This alteration in calcium concentration is thought to promote activation of contractile proteins (e.g. actin, myosin). Digoxin also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarisation, shorterning the action potential duration, and decreasing the maximal diastolic potential.
Explain the mechanism of action of Edrophonium
Edrophonium is a rapid-onset, short-acting cholinesterase inhibitor used in cardiac arrhythmias and in the diagnosis of myasthenia gravis.
Edrophonium’s mode of action is to prolong the action of acetylcholine, via inhibiting acetylcholinesterase at sites of cholinergic transmission. Its effect is present within 60 seconds after injection and lasts for an average of 10 minutes.
Nicotinic acetylcholine receptors are found throughout the body, especially on muscle. Stimulation of these receptors causes muscle contraction.
In myasthenia gravis the body’s immune system destroys many of the nicotinic acetylcholine receptors, so the muscle is less responsive to nervous stimulation.
Edrophonium increases the amount of acetylcholine at the nerve endings, therefore allowing the remaining receptors to function more efficiently.
Still used as part of tensilon test. Otherwise more likely to be used: pyridostigmine.
Explain the mechanism of action of Ethanol.
Ethanol has multiple effects. It
1) Binds to receptors for acetylcholine, serotonin, GABA and NMDA receptors. The sedative effects of ethanol are mediated through binding to GABA receptors and glycine receptors (alpha 1 and alpha 2 subunits). It also inhibits NMDA receptor functioning.
2) Ethanol has an anti-infective role as it acts as a dehydrating agent that disrupts osmotic balance across cell membranes.
Fomepizole has replaced first line treatment for methanol/ethylene glycol poisoning.
Explain the mechanism of action of Ethinylestradiol.
Ethinylestradiol is a synthetic derivative of natural estrogen testradiol.
It interacts with estrogen receptor (alpha or beta) present on female organs, breasts, the hypothalamus and pituitary gland.
Upon ligand binding, the estrogen receptor enters the nucleus and regulates gene transcription. This leads to an increase in the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid binding globulin (TBG) and other seum proteins, and suppresses FSH from the anterior pituitary.
During mensturation, increasing oestradiol levels causes the maturation and release of the egg; as well as thickening of the uterus lining to allow a fertilised egg to implant.
The hormone is made primarily in the ovaries, so levels reduce as women age and decrease significantly during menopause. Too much oestradiol has been linked to acne, constipation, loss of sex drive and depression. Conversely, too little oestradiol retards bone growth and development.
In men, proper oestradiol levels help with bone maintenance, nitric oxide production and brain function. Used within the combined oral contraceptive pill.
Explain the mechanism of action of Ketaconazole.
Ketaconazole is a broad-spectrum anti-fungal agent (A Lanosine demethylase inhibitor). It inhibits 14-alpha-demethylase, a cytochrome p450 enzyme which converts lanosterol to ergosterol.
The inhibition of ergosterol causes increased fungal cellular permeability. However, there are also other possible mechanisms of its action.
1) Inhibition of endogenous respiration.
2) Interaction with membrane phospholipids.
3) Inhibition of yeast transformation to mycelial forms.
4) Inhibition of purine uptake.
5) Impairment of triglycerice and/or phospholipid biosynthesis.
Explain the mechanism of action of Morphine.
Morphine is an analgesic (an opiate agonist).
The precise mechanism is unknown. However, it binds to certain other receptors including:
1) The mu-opiod receptors. The mechanism of respiratory depression involves a reduction in the brain stem respiratory centres to increases in carbon dioxide tension and electrical stimulation.
2) The GABA inhibitory interneurons. Morphine inhibits the activity of these and therefore limits the descending pain inhibition pathway. Therefore, without the inhibitory signals, pain modulation can proceed downstream.
Explain the mechanism of action of Naloxone.
Naloxone is an opiate antagonist that prevents or reverses the effects of opioids such as respiratory depression, sedation and hypotension. As such it is described as a pure narcotic antagonist (and therefore does not induce respiratory depression).
Its mechanism of action is not clear but it is though to be able to antagonise all three opioid receptors (Mu, Kappa, and Gamma), although it has the strongest binding to the Mu receptor. It onset of action is dependent on how it is given but intravenously, the onset of action is within 2 minutes, whilst its effects are slower if given subcutaneously or intramuscularly’
Naloxone can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine.
Explain the mechanism of action of Rifampicin
Rifampicin is a broad spectrum antibiotic (targets both gram positive and gram negative bacteria). It is easily absorbed and distributed throughout the body.
Its mode of action is via the inhibition of DNA-dependent RNA polymerase, leading to a supression of RNA synthesis and cell death.
Importantly, Rifampicin can target bacterial but not mammalian versions of the enzyme. Due to the emergence of resistant bacteria, the use of Rifampicin is restricted to Tuberculosis.
Rifampicin is metabolised in the liver and eliminated mainly in the bile, and, to a limited extent, in urine.
Explain the mechanism of action of Suxamethonium
Suxamethonium’s mode of action is to mimic acetylcholine at the neuromuscular junction. However, Suxamethonium is hydrolysed much slower than acetylcholine, causing prolonged depolarisation and therefore desensitisation and muscle relaxation.
Unlike the non-depolarising neuromuscular blocking drugs, Suxamethonium cannot be reversed and recovery is spontaneous.
Suxamethonium is given after a general anaesthetic as muscle relaxation can be preceded by painful muscular fasciculations.
Anticholinesterases such as neostigmine is given alongside Suxamethonium to potentiate the neuromuscular block.
Explain the mechanism of action of Tamoxifen
Tamoxifen is a selective estrogen receptor modulator (SERM).
It can have both estogenic and antiestrogenic effects.
The mode of action of Tamoxifen is via binding to the estrogen receptor, leading to a conformational change in the receptor and therefore altering the expression of estrogen dependent genes.
Prolonged binding of Tamoxifen to the nuclear chromatin reduces DNA polymerase activity, impairs thymidine utilization, blocks estradiol uptake, and decreases estrogen response. Tamoxifen can bind either the ER-a or Erb receptors, and most likely will interact with multiple co-repressors, or co-activators leading to its ability to have either estrogenic or antiestrogenic effects.
Explain the mechanism of action of Tubocurarine.
Tubocurarine binds stereo-selectively to nicotinic-cholinergic receptors at the autonomic ganglia, the adrenal medulla, neuromuscular junctions, and in the brain.
Tubocurarine has two main effects: stimulation and reward.
Te stimulatory effect occurs mainly in the cortex via the locus cerulus, whilst the reward effect is exerted in the limbic system. At low doses, the stimulant effects predominate whilst at higher doses the reward effects predominate.
Tubocurarine has been superceded by Suxamethonium as the clinically used depolarising neuromuscular blocker.
Explain the mechanism of action of Paracetemol
Paracetemol is an analgesic and antipyretic compound (a COX inhibitor).
Paracetamol is used when NSAIDs cannot be. An example is a patient with peptic ulcer. It has analgesic and antipyretic effects, but lacks ant platelet, anti-inflammatory, and gastric ulcerative effects. The mechanism of action is complex and not well understood. There are three possible mechanisms
1) It indirectly inhibits COX, which is ineffective in the presence of peroxides. This could explain why it does not work well within platelets.
2) It inhibits COX-3. This enzyme is not well understood.
3) Its antipyretic effects are due to effects on the hypothalamus, resulting in peripheral vasodilation and sweating.
Explain the mechanism of action of Diamorphine (Heroin)
Diamorphine/Heroin is an opiate receptor agonist (analgesic).
Heroin is a mu-opioid agonist. Heroin, targets four endogenous neurotransmitters (beta-endorphin, dynorphin, leu-enkephalin, and met-enkephalin). Heroin reduces (and sometimes stops) production of the endogenous opioids. Endorphins are regularly released in the brain and nerves, attenuating pain.
The onset of heroin’s effects is dependent on the method of administration. Taken orally, heroin is totally metabolized in vivo into morphine before crossing the blood-brain barrier; so the effects are the same as oral morphine. Taken by injection, heroin crosses into the brain, where it is rapidly metabolized into morphine by removal of the acetyl groups. It is the morphine molecule that then binds with opioid receptors and produces the subjective effects of the heroin high.
Still used clinically, but probably morphine more common in clinical practice.
Explain the use of oxygen in clinical settings.
Oxygen levels, or oxygen saturation is a key clinical diagnostic. Healthy individuals should have an Oxygen SAT of greater than 96%. However, patients with lung diseases, such as pneumonia, can have reduced ability to breathe in or transport oxygen effectively, identified in a reduced Oxygen SAT (less than 88%). Therefore, patients with low blood oxygen levels can be treated with additional pure oxygen or air/oxygen mixtures via a mask, nasal cannula, or tracheal intubation. This increased delivery of oxygen should alleviate the symptoms caused by low oxygen levels in the tissues.
What are B-Adrenergic antagonists?
(Atenolol, Propanolol etc).
b-adrenergic antagonists competes with sympathomimetic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart and vascular smooth muscle. This results in a reduction in resting heart rate, cardiac output, systolic and diastolic blood pressure, and reflex orthostatic hypotension.
Explain the mechanism of action of Atenolol
Atenolol has similar properties to propranolol, but does not have a negative inotropic effect. Higher doses of Atenolol also competitively block beta(2)-adrenergic responses in the bronchial and vascular smooth muscles.
Atenolol is not commonly used today, much more likely to be bisoprolol.
Explain the mechanism of action of Propanolol
A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety.
Rarely used other than in migraine, cirrhosis of the liver with portal hypertension, and in thyrotoxicosis
Explain the use of Bendroflumethiazide.
Bendroflumethiazide is a thiazide diuretic.
Bendroflumethiazide, as a diuretic increases urinary excretion of water, and can cause blood vessel dilatation. It has two mechanisms of action,
1) It inhibits the Na-Cl cotransporter, blocking active chloride reabsorption in the early distal tubule. This results in an increase in the excretion of sodium, chloride, and water.
2) It inhibits sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism.
Both of these mechanism apply to its role as a diuretic. However its antihypertensive mechanism is less well understood. It may act although it may be mediated
1) inhibiting carbonic anhydrases in the smooth muscle
2) activating the large-conductance calcium-activated potassium (KCa) channel, in the smooth muscle.
Explain the mechanism of action of Digoxin.
Digoxin is a cardiac glycoside (a sodium postassium ATPase inhibitor)
Digoxin is used to treat congestive heart failure, and supraventricular arrhythmias. Its mode of action is via inhibition of the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium. This causes in turn the sodium calcium exchanger (NCX) to extrude the sodium and pump in more calcium. This alteration in calcium concentration is thought to promote activation of contractile proteins (e.g., actin, myosin). Digoxin also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.
Still used in Atrial Fibrillation, but now very much third line treatment option. Rarely used in heart failure as much better drugs available
Explain the mechanism of action of Amiodarone.
Amiodarone is an antianginal and antirhythmic agent.
Amiodarone is a Vaughan-Williams Class III antiarrhythmic agent. The antiarrhythmic effect of amiodarone may be due to at least two major actions.
1) Prolonging the myocardial cell-action potential (phase 3) duration and refractory period and
2) Acts as a noncompetitive a- and b-adrenergic inhibitor.
It can also have
1) b-blocker activity and calcium channel blocker-like actions on the SA and AV nodes
2) increases the refractory period via sodium- and potassium-channel effects
3) slows intra-cardiac conduction of the cardiac action potential, via sodium-channel effects.
Still used but much less common as defibrillators are now inserted.
Explain the mechanism of action of Warfarin.
Warfarin is an anticoagulant (a Vitamin K antagonist).
Warfarin is used in the prevention and treatment of thromboembolic disease including venous thrombosis, thromboembolism, and pulmonary embolism as well as for the prevention of ischemic stroke in patients with atrial fibrillation (AF). Warfarin can cross the placental barrier during pregnancy resulting in foetal bleeding, spontaneous abortion, and neonatal death.
Warfarin inhibits vitamin K reductase, reducing levels of the reduced form of vitamin K. As vitamin K is required for the production of coagulation factors II, VII, IX, and X and anticoagulant proteins C and S, these levels also drop. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decreased prothrombin levels, decreased thrombin generation and reduced ability to form a clot.
Warfarin is declining in use with the advent of non-vitamin K antagonist oral anticoagulants.
Explain the mechanism of action of Ramipril, Lisinopril, Enalapril and Captopril.
They are competative inhibitors of angiotensin converting enzyme (ACE).
ACE converts angiotensin I to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). ATII increases blood pressure using a number of mechanisms.
1)Stimulation of secretion of aldosterone from the adrenal cortex
2)Stimulation of Vasopression secretion from the posterior pituitary gland.
3)Through direct arterial vasoconstriction.
In addition ATII induces the thirst response via stimulation of hypothalamic neurons. There are two isoforms of ACE, a somatic isoform, and a testicular isoform. Somatic ACE has two functionally active domains, N and C. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain.
Captopril inhibits the conversion of ATI to ATII and therefore inhibits increases in blood pressure. Captopril’s affinity for ACE is approximately 30,000 times greater than that of ATI. ACE is also involved in the deactivation of bradykinin. Inhibiting the deactivation of bradykinin increases bradykinin levels causing increased vasodilation and decreased blood pressure.
Ramipril is the drug of choice, followed by Lisinopril, and rarely Enalapril. Captopril is hardly prescribed.
Explain the mechanism of action of Noradrenaline.
Norepinephrine is a precurser of epinephrine secreted by the adrenal medulla. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. Norepinephrine functions as a peripheral vasoconstrictor by acting on both alpha-1 and a-2 adrenergic receptors. It is also an inotropic stimulator of the heart and dilator of coronary arteries as a result of it’s activity at the beta-adrenergic receptors.
Explain the mechanism of action of Verapamil
Verapamil is a Class IV anti-arrythmia agent (a calcium channel blocker).
Verapamil inhibits voltage-dependent calcium channels. In the heart it blocks the L-type calcium channels causing a reduction in ionotropy and chronotropy, reducing heart rate and blood pressure. There are two enantiomers of Verapamil. The R-enantiomer is more effective at reducing blood pressure compared to the S-enantiomer. However, the S-enantiomer is 20 times more potent than the R-enantiomer at prolonging the PR interval in treating arrhythmias.
Verapamil is still used (not commonly) but it can only be given via IV. Diltiazem more common as a non-dihydropyridine Calcium Channel Blocker, but this is not available via IV (although it is in the USA).
Explain the mechanism of action of Chlorpromazine
Chlorpromazine is a phenothiazine based antipsychotic.
Chlorpromazine is an antagonist on dopaminergic-receptors (subtypes D1, D2, D3 and D4), serotonergic-receptors (5-HT1 and 5-HT2), histaminergic-receptors (H1-receptors), alpha1/alpha2-receptors and muscarinic (cholinergic) M1/M2-receptors. Chlorpromazine’s antipsychotic actions are due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup
Chlorpromazine is now used less due to longterm side effects. Prochlorperazine is preferentially used. It is from the same class of drug.
Explain the mechanism of action of Domperidone
Domperidone inhibits the dopamine receptor (D2 and D3) in the chemoreceptor trigger zone, located just outside the blood brain barrier. Domperidone also acts as a gastrointestinal emptying (delayed) adjunct and peristaltic stimulant.
Explain the mechanism of action of Metoclopramide.
Metoclopramide is a dopamine receptor antagonist. Therefore it raises the threshold of activity in the chemoreceptor trigger zone and decreases the input from afferent visceral nerves.
In addition high doses of metoclopramide can antagonize 5-hydroxytryptamine (5-HT) receptors in the peripheral nervous system.
Metoclopramide can also inhibit gastric smooth muscle relaxation produced by dopamine, therefore increasing cholinergic response of the gastrointestinal smooth muscle. Furthermore it can decrease reflux into the oesophagus by increasing the resting pressure of the lower oesophageal sphincter and improves acid clearance from the oesophagus by increasing amplitude of oesophageal peristaltic contractions.
Explain the mechanism of action of Perhpenazine
Perhpenazine is a phenothiazine.
Perphenazine is 10 to 15 times as potent as chlorpromazine. Perphenazine inhibits the dopamine D1 and dopamine D2 receptors.
The mechanism of the anti-emetic effect is due predominantly to blockage of the dopamine D2 neurotransmitter receptors in the chemoreceptor trigger zone and vomiting centre.
Perphenazine also binds the alpha andrenergic receptor that activate a phosphatidylinositol-calcium second messenger system. Perphenazine is a piperazinyl phenothiazine, and has a greater behavioural potency than other phenothiazine derivatives.
Explain how histamine (H1) antagonists are used in anti-emetic therapy.
Vomiting is a protective mechanism for removing irritant/harmful substances from the upper GI tract. It is controlled by the vomiting centre in the medulla region of the brain, which includes the chemotrigger zone (CTZ). The vomiting centre possesses neurons rich in muscarinic cholinergic and histamine containing synapses. The histamine receptors are especially important in transmission of vomiting signals from the vestibular apparatus, induced by motion sickness to CTZ and then the vomiting centre. Competitive antagonists at histamine H1 receptors may be divided into sedating or non-sedating agents.
Explain the mechanism of action of Cyclizine
Cyclizine is antiemetic agent used in the prevention and treatment of nausea, associated with motion sickness. Additionally, it has been used in the management of vertigo in diseases affecting the vestibular apparatus. Its mechanism of action is not understood, but it possesses anticholinergic, antihistaminic, central nervous system depressant, and local anaesthetic effects.
Explain the mechanism of action of Cinnarizine
Cinnarizine inhibits dopamine D2 receptors, histamine H1 receptors, muscarinic acetylcholine receptors, and also vascular smooth muscle contraction via by blockage of L-type and T-type voltage gated calcium channels.
Explain the mechanism of action of Promethazine
Promethazine is a H1-antagonist with anticholinergic, sedative, and antiemetic effects and some local anaesthetic properties.
Explain the mechanism of action of Hyocine
Hyoscine is a muscarinic antagonist.
Scopolamine is a muscarinic antagonist that blocks the muscarinic acetylcholine receptors. It is used to prevent motion sickness. It is thought Ach plays an important role in communication between the vestibular system and the vomiting centre. Therefore by blocking this communication there is a reduction in the activity of the vomiting centre and a reduction in nausea. However, as Scopolamine also may work directly on the vomiting centre its precise mechanism of action is unclear. Scopolamine works best before the onset of motion sickness.
Explain the mechanism of action of Ondansetron
Ondansetron is a selective serotonin 5-HT3 receptor antagonist with low affinity for dopamine receptors. The serotonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the CTZ. The antiemetic activity of the drug is via inhibition of 5-HT3 receptors present both centrally (CTZ) and peripherally (GI tract). This inhibition of 5-HT3 receptors in turn inhibits the visceral afferent stimulation of the vomiting center, and serotonin activity in the CTZ.
The drug of choice for the 5-HT3 pathway is now Granisetron rather than Ondansetron
Explain the mechanism of action of Aspirin
The analgesic, antipyretic, and anti-inflammatory effects of acetylsalicylic acid are due to actions by both the acetyl and the salicylate portions of the intact molecule as well as by the active salicylate metabolite.
Acetylsalicylic acid directly and irreversibly inhibits the activity of both types of cyclooxygenase (COX-1 and COX-2) to decrease the formation of precursors of prostaglandins and thromboxanes from arachidonic acid.
Acetylsalicylic acid’s antirheumatic actions are a result of its analgesic and anti-inflammatory mechanisms. Irreversible inhibition of COX prevents the formation of the aggregating agent thromboxane A2 in platelets. Platelets cannot produce more COX enzyme and thus, the effects of aspirin persist for the life of the exposed platelets (7-10 days).
Explain the mechanism of action of Ibuprofen.
Ibuprofen is a reversible inhibitor of the COX enzyme. Its pharmacological effects are believed to be due to inhibition cylooxygenase-2 (COX-2) which decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever and swelling. The antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.
Explain the mechanism of action of Naproxen
The mechanism of action of naproxen, like that of other NSAIDs, is believed to be associated with the inhibition of cyclooxygenase activity. Naproxen has analgesic and antipyretic properties.
Explain the mechanism of action of Esomeprazole
Proton pump inhibitors target gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. This inhibition block transport of H+ ions into the stomach lumen and therefore increases the pH of the stomach contents.
Inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), and H. pylori eradication to reduce the risk of duodenal ulcer recurrence. Esomeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that target specifically the H+/K+ ATPase in the gastric parietal cell. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.
Explain the mechanism of action of Omeprazole
Proton pump inhibitors target gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. This inhibition block transport of H+ ions into the stomach lumen and therefore increases the pH of the stomach contents.
The anti-secretory effect of omeprazole occurs within one hour of oral dosing with a maximal effect within two hours. However the effect is long lasting with an approximate 50% inhibition of acid secretion and duration of inhibition lasting upto 72 hours. This is due to prolonged irreversible binding to the parietal H+/K+ ATPase enzyme. When the drug has been discontinued, secretory activity will return to baseline over 3-5 days. Systemic effects of omeprazole in the CNS, cardiovascular and respiratory systems have not been found to date.
Explain the mechanism of action of Ranitidine
Histamine H2 antagonists: Ranitidine is a competitive inhibitor of histamine on parietal cells in the stomach, decreasing acid production. It is an example of an inverse agonists rather than a true receptor antagonists. Rantidine reduces stomach acid by blocking histamine binding.
Reduce the effect of other substances that promote acid secretion (such as gastrin and acetylcholine) on parietal cells.
These drugs are used in the treatment of dyspepsia, however their use has waned since the advent of the more effective proton pump inhibitors.
Explain the mechanism of action of Magnesium trisilicate (an Antacid).
Antacids can neutralize gastric acid and reduce acid delivery to the duodenum. They might be useful for treatment against peptic ulcers (although PPIs are much more likely to be used). There are different mechanisms by which they could aide healing of peptic ulcers,
1) Aluminum hydroxide binds growth factors, possibly serving to deliver growth factors to injured mucosa.
2) Antacids promote angiogenesis in injured mucosa
3) Antacids bind bile acids and also inhibit peptic activity.
4) Heavy metals suppress, but generally do not eradicate, H. pylori.
Explain the mechanism of action of Misoprostol
Misoprostol is used for the treatment and prevention of stomach ulcers induced by NSAIDs. Misoprostol inhibits gastric acid secretion by binding to the prostaglandin receptor on the parietal cell. This receptor inhibits the activity of adenylate cyclase, reducing cAMP levels, and the downstream protein kinase activity. This reduces the availability of the proton pump at the surface reducing acid secretion. In addition Misoprostol can also
1) Increased secretion of bicarbonate.
2) Reduce the volume and pepsin content of the gastric secretions.
3) Prevent harmful agents from disrupting the tight junctions between the epithelial cells which stops the subsequent back diffusion of H+ ions into the gastric mucosa.
4) Increase the thickness of mucus layer.
5) Enhanced mucosal blood flow as a result of direct vasodilatation.
6) Stabilization of tissue lysozymes/vascular endothelium.
7) Improvement of mucosal regeneration capacity
8) Replacement of prostaglandins that have been depleted.
Explain the mechanism of action of Amoxicillin
Amoxicillin is a beta-lactam antibiotic.
Amoxicillin is active against a wide range of Gram-positive, and a limited range of Gram-negative organisms. Amoxicillin binds to penicillin-binding protein 1A (PBP-1A) located inside the bacterial cell well. This inactivation of PBP-1A prevents the cross-linking of two linear peptidoglycan strands, inhibiting bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. Amoxicillin is susceptible to degradation by β-lactamase-producing bacteria, and so may be given with clavulanic acid to increase its susceptibility. Amoxicillin can be combined with clavulanic acid, a β-lactamase inhibitor, to overcome bacterial antibiotic resistance mediated through β-lactamase production.
Explain the mechanism of action of Clarithryomycin
Clarithromycin is a macrolide antibiotic.
Clarithromycin activity includes many (Staphylococcus aureus, S. pneumoniae, and S. pyogenes) aerobic (Gram-negative and gram positive) bacteria (Haemophilus influenzae, H. parainfluenzae, and Moraxella catarrhalis), many anaerobic bacteria, and some mycobacteria. Clarithromycin penetrates the bacteria cell wall and reversibly binds to domain V of the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome, blocking translocation of aminoacyl transfer-RNA and polypeptide synthesis. Clarithromycin also inhibits the hepatic microsomal CYP3A4 isoenzyme and P-glycoprotein, an energy-dependent drug efflux pump.
Explain the mechanism of action of Metronidazole
A nitroimidazole antibacterial and antiprotozoal.
Metronidazole, is used against protozoa such as Trichomonas vaginalis, amebiasis, and giardiasis. Metronidazole is extremely effective against anaerobic bacterial infections and is also used to treat Crohn’s disease, antibiotic-associated diarrhea, and rosacea. Metronidazole is a prodrug. Unionized metronidazole is taken up by anaerobic bacteria, and is then reduced to its active form. This reduced metronidazole then covalently binds to DNA, disrupting its helical structure, inhibiting bacterial nucleic acid synthesis and resulting in bacterial cell death.
Explain the mechanism of action of Thalidomide
Thalidomide is an immunomodulatory agent can also have anti-angiogenic effects. Its mechanism of action is not well understood, but it is thought that its immune modulation is due to changes in the concentration of TNFa, whilst it can also affect VEGF leading to its effects on the blood vessels. It has teratogenic effects on humans.
Explain the mechanism of action of Orlistat
Orlistat is a lipase inhibitor.
Orlistat is a reversible inhibitor of gastric and pancreatic lipases. The inactivated enzymes cannot hydrolyze triglycerides into absorbable free fatty acids and monoglycerides. Therefore as fat absorption is reduced this can have a positive effect on weight control. At the recommended therapeutic dose, orlistat inhibits dietary fat absorption by approximately 30%. As some vitamins are fat soluble, there absorption can be affected and as such orlistat should be taken with fatty meals, and a multivitamin tablet containing these vitamins (D E K and beta-carotene).
