B10 Flashcards
Enalapril,
Lisinopril,
Ramipril,
Captopril
ACE inhibitors
Competitive inhibitor of angiotensin-converting enzyme.
MoA: They prevent conversion of angiotensin I to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS).
How does angiotensin II increase blood pressure?
ATII increases blood pressure using several mechanisms:
♣ Stimulation of secretion of aldosterone from the adrenal cortex
♣ Stimulation of Vasopressin secretion from the posterior pituitary gland
♣ Through direct arterial vasoconstriction
♣ ATII induces the thirst response via stimulation of hypothalamic neurons
ACEis involved in deactivation of bradykinin
Inhibiting deactivation of bradykinin increases bradykinin levels causing what?
Increased vasodilation and decreased blood pressure
Amiloride
Sodium channel blocker (ENaC antagonist)
It is an antihypertensive, potassium-sparing diuretic often used in conjunction with thiazide or loop diuretics.
MoA: Antikaliuretic-diuretic:
o Directly inhibit epithelial Na+ channel (ENaC) in late DCT + CD
o Reduces Na+ reabsorption hyperpolarisation of apical membrane
o Makes luminal potential more positive + inhibits K+ secretion
Use: Due to its potassium-sparing capacities, hyperkalaemia (high blood potassium levels) are occasionally observed.
There are 5 targets of the nephron. List them.
- Carbonic anhydrase inhibitorr - Proximal tubule
- Osmotic diuretics (e.g. Mannitol) - thin descending limb of the loop of henle
- Na-K-Cl co-transporter inhibitor - thick ascending loop of henle
- Na-Cl transport inhibitor - Distal convoluted tubule
- Thiazides, Chlorothiazides, Hydrochlorothiazides - Mineralocorticoid receptor antagonist, ENaC antagonist, ADH antagonist (K-sparing) - Collecting duct
Bendroflumethiazide
Thiazide diuretic
Acts on distal tubule like all thiazide diuretics.
MoA:
• Inhibiting carbonic anhydrases in the smooth muscle
• Activating the large-conductance calcium-activated potassium (KCa) channel, in the smooth muscle
Chlorthalidone
A monosulfonamyl diuretic
It form other thiazide diuretics in that a double ring system is incorporated into its structure
MoA: Chlorthalidone inhibits Na+ transport across the renal tubular epithelium in the ascending limb of LoH. By increasing the delivery of sodium to the distal renal tubule and collecting duct, Chlorthalidone indirectly increases potassium excretion via the sodium-potassium exchange mechanism
Use: Chlorthalidone is used alone or with atenolol in the management of hypertension and edema
Spironolactone
Mineralocorticoid nuclear hormone receptor antagonist
A potassium sparing (weak) diuretic
MoA: Spironolactone inhibits the effect of aldosterone by competitively competing for intracellular aldosterone receptor in the distal convoluted tubule cells.
Spironolactone bind to this mineralocorticoid receptor, blocking the actions of aldosterone on gene expression.
Note: Spironolactone has a slow onset of action, taking several days to develop and similarly the effect diminishes slowly.
Acetazolamide
A reversible carbonic anhydrase inhibitor (proximal tubule) –> Increases Na/H/CO3 excretion
MoA: Acetazolamide inhibits carbonic anhydrase leading to a reduction in the availability of hydrogen ions for active transport in the renal tubule lumen.
This leads to alkaline urine and an increase in the excretion of bicarbonate, sodium, potassium, and water
Doxazosin
A selective alpha-adrenergic inhibitor
MoA: Doxazosin is a selective inhibitor of the alpha1 subtype of alpha adrenergic receptors.
Doxazosin inhibits the postsynaptic alpha (1)-adrenoceptors on vascular smooth muscle. Blocking the vasoconstrictor effect of circulating and locally released catecholamines. In the human prostate, Doxazosin competitively antagonized the pressor effects of phenylephrine (an alpha1 agonist) and the systolic pressor effect of norepinephrine
Use: Therefore is used to treat hypertension and benign prostatic hyperplasia.
Cisplatin
An alkylating agent used to treat cancer
MoA: Alkylating agents are cell cycle-nonspecific (cancer drugs) that can work via 3 mechanisms. These mechanisms affect the ability of DNA to uncoil and separate, preventing DNA replication and therefore cell proliferation, leading to cell death.
Methotrexate
An antineoplastic anti-metabolite
- Antimetabolites are synthetic versions of purine or pyrimidines
MoA: Methotrexate inhibits folic acid reductase which converts folic acid to tetrahydrofolic acid.
Tetrahydrofolic acid is required for both purines and pyrimidine biosynthesis, Thus, DNA synthesis cannot proceed due to a lack of purine and pyrimidines. Given this effect on DNA, Methotrexate affects the most rapidly dividing cells.
Use: The management of severe, active, classical, or definite rheumatoid arthritis
Phenobarbital
A barbiturate which acts on GABA receptors, increasing synaptic inhibition
MoA: Phenobarbital acts on GABA receptors, increasing synaptic inhibition.
This has the effect of elevating seizure threshold and reducing the spread of seizure activity from a seizure focus.
The sedative-hypnotic effects of phenobarbital are likely the result of its effect on the polysynaptic midbrain reticular formation, which controls CNS arousal.
Use: Phenobarbital, the longest-acting barbiturate, is used for its anticonvulsant and sedative-hypnotic properties in the management of all seizure disorders except absence (petit mal)
Meperidine
Use: Meperidine is a synthetic opiate agonist recommended for relief of moderate to severe acute pain.
Note: The onset of action is more rapid than morphine, but has a shorter duration of action.
MoA: Meperidine is a kappa-opiate receptor agonist with local anaesthetic effects.
Mannitol
An osmotic diuretic
Mannitol is a metabolically inert osmotic diuretic which is present naturally in the diet. Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma.
MoA: Mannitol induces diuresis as it is not reabsorbed in the renal tubule, and therefore increases the osmolality of the glomerular filtrate. This aids water excretion.
