Mechanism of Action Flashcards
MOA Paroxetine
SSRI: Paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake. Paroxetine likely inhibits the reuptake of serotonin at the neuronal membrane, prolonging its activity at synaptic receptor sites and potentiating 5-HT in the CNS
MOA Ibuprofen
- Ibuprofen is a non-selective inhibitor of cyclooxygenase, an enzyme invovled in prostaglandin synthesis. Inhibition of cylooxygenase-2 (COX-2) decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever and swelling.
- Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.
- Inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration.
MOA Carvedilol
Carvedilol is nonselective beta-adrenoreceptor blocker. Carvedilol’s beta-adrenergic receptor blocking ability decreases the heart rate, myocardial contractility, and myocardial oxygen demand. Carvedilol also decreases systemic vascular resistance via its alpha adrenergic receptor blocking properties.
MOA Cefuroxime
Cefuroxime, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefuroxime interferes with an autolysin inhibitor.
MOA Erythromycin
Erythromycin acts by penetrating the bacterial cell membrane and reversibly binding to the 50 S subunit of bacterial ribosomes or near the “P” or donor site so that binding of tRNA (transfer RNA) to the donor site is blocked. Translocation of peptides from the “A” or acceptor site to the “P” or donor site is prevented, and subsequent protein synthesis is inhibited. Erythromycin is effective only against actively dividing organisms.
MOA Atorvastatin
Atorvastatin selectively and competitively inhibits the hepatic enzyme HMG-CoA reductase. As HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate in the cholesterol biosynthesis pathway, this results in a subsequent decrease in hepatic cholesterol levels. Decreased hepatic cholesterol levels stimulates upregulation of hepatic LDL-C receptors which increases hepatic uptake of LDL-C and reduces serum LDL-C concentrations.
MOA Glyceryl Trinitrate
Similar to other nitrites and organic nitrates, nitroglycerin is converted to nitric oxide (NO), an active intermediate compound which activates the enzyme guanylate cyclase. This stimulates the synthesis of cyclic guanosine 3’,5’-monophosphate (cGMP) which then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells, eventually resulting in the dephosphorylation of the myosin light chain of the smooth muscle fiber. The subsequent release of calcium ions results in the relaxation of the smooth muscle cells and vasodilation.
MOA Aspirin - its anti inflammatory, antipyretic and analgesic roles
- 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. This makes acetylsalicylic acid different from other NSAIDS (such as diclofenac and ibuprofen) which are reversible inhibitors.
- Salicylate may competitively inhibit prostaglandin formation.
MOA Aspirin - its anticoagulation role
- The platelet aggregation-inhibiting effect of acetylsalicylic acid specifically involves the compound’s ability to act as an acetyl donor to cyclooxygenase.
- Irreversible acetylation renders cyclooxygenase inactive, thereby preventing the formation of the aggregating agent thromboxane A2 in platelets.
- Since platelets lack the ability to synthesize new proteins, the effects persist for the life of the exposed platelets (7-10 days).
MOA Diamorphine
- Heroin is a mu-opioid agonist. It acts on endogenous mu-opioid receptors that are spread in discrete packets throughout the brain, spinal cord and gut in almost all mammals.
- Heroin, along with other opioids, are similar to four natural neurotransmitters. They are beta-endorphin, dynorphin, leu-enkephalin, and met-enkephalin. The body responds to heroin in the brain by reducing (and sometimes stopping) production of the endogenous opioids when heroin is present.
- Endorphins are regularly released in the brain and nerves, attenuating pain. Their other functions are still obscure, but are probably related to the effects produced by heroin besides analgesia (anti-coughing, anti-diarrheal).
MOA Clopidogrel
The active metabolite of clopidogrel prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. The drug specifically and irreversibly inhibits the P2Y12 subtype of ADP receptor. As the glycoprotein GPIIb/IIIa complex is the major receptor for fibrinogen, its impaired activation prevents fibrinogen binding to platelets and inhibits platelet aggregation.
tPA MOA
tPA: a Clot Dissolver: binds to fibrin rich clots via the fibronectin finger-like domain and the Kringle 2 domain. The protease domain then cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.
MOA Ramipril: it inhibits ACE, but what does ACE do?
- What is ramipril converted to?
- How is ATII production stimulated?
- What are the 4 effects of ATII?
- How else does ACE cause decrease in BP?
Ramipril is an ACE inhibitor: inactive prodrug is converted to ramiprilat in the liver. Ramiprilat confers blood pressure lowing effects by antagonizing the effect of the RAAS.
During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ACE inhibitors inhibit the rapid conversion of ATI to ATII.
ATII increases blood pressure using a number of mechanisms.
- Aldosterone secretion from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes.
- Vasopressin secretion: (also known as antidiuretic hormone, ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules.
- Vasoconstriction: ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction.
- Thirst: ATII induces the thirst response via stimulation of hypothalamic neurons.
ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain the effects of ramiprilat by causing increased vasodilation and decreased blood pressure.
MOA Bendroflumethazide (2)
- As a diuretic, bendroflumethiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like bendroflumethiazide also inhibit 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.
- The antihypertensive mechanism of bendroflumethiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.
MOA Amlodipine
- Amlodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. The vasodilatory effects of amlodipine result in an overall decrease in blood pressure.
- Another possible mechanism is that amlodipine inhibits vascular smooth muscle carbonic anhydrase I activity causing cellular pH increases which may be involved in regulating intracelluar calcium influx through calcium channels.
