Drug Mechanism of action

Insulin binds to insulin receptors leading to activation of tyrosine kinase

leading to phosphorylation of intracellular proteins lead to increase
Insulin
glucose transporters which fuse with cell membrane of muscles and
adipose tissue leads to increase glucose uptake.
1. Increase insulin release from -cells of pancreas: Sulfonylurea bind to
Sulphonylurea and block ATP-sensitive K+ channels→ Reduced K+ efflux causes
membrane depolarization, which activates voltage-sensitive
Ca2+channels→ Influx of Ca2+causes insulin release by exocytosis.
2. Extra-pancreatic effect: increase the number and sensitivity of insulin
Meglitinides receptors on target tissues, so potentiate peripheral actions of insulin
e.g., lipogenesis in adipose tissue and suppress hepatic gluconeogenesis
and glycogenolysis.
It inhibits the enzyme DDP-4 which is responsible of inactivation of
gastrointestinal hormones, glucagon like peptide-1 (GLP-1) and Glucose
Dipeptidyl- dependent insulinotropic peptide (GIP) that are called incretin.
peptidase IV Inhibition of DPP-4 enzyme results in increase the levels of the two
inhibitors peptides and prolongation of their activity to inhibit glucagon release,
increase insulin secretion, decrease gastric emptying and decrease blood
glucose levels
1. Metformin increases peripheral glucose uptake and utilization
(glycolysis) in skeletal muscle.
Biguanides 2. It reduces hepatic glucose production and gluconeogenesis.
3. It reduces intestinal glucose absorption.
4. Increased sensitivity of insulin receptors.
They bind to specific nuclear receptor (Peroxisome-Proliferator-
Activator-Receptor-Gamma= PPAR-γ) in insulin-sensitive tissues e.g.,
Thiazolidinediones
adipose, skeletal muscle & liver to activate gene expression, for
(TZDs) or
synthesis of cellular molecules important for insulin signaling, in fat
Glitazones
synthesis and carbohydrate metabolism resulting in increased insulin
sensitivity.
Alpha glucosidase Reversibly inhibit α glucosidase in the intestinal brush border leading
inhibitors to decrease absorption of carbohydrates. So, decrease postprandial
(Acarbose and hyperglycemia
miglitol)
They combine with penicillin-binding proteins (PBPs) and inactivate
transpeptidase enzymes which are responsible for cross-linkage
β-lactam formation between peptidoglycan layers. This results in loss of cell wall
antibiotics rigidity. They activate autolysins produced by some bacteria leading to
cell wall degradation.
Vancomycin Inhibits 2ndstep in cell wall synthesis in Gm-positive organisms.
Bind to 30S ribosomal bacterial subunit → inhibit binding of tRNA and
Tetracyclines
inhibit protein synthesis.
 Bactericidal. Irreversibly bind with 30S ribosomal bacterial subunits
Aminoglycosides
leading to inhibition of protein synthesis.
Binds to 50S ribosomal subunit preventing translocation → inhibition of
Macrolides
protein synthesis.
Clindamycin Similar to macrolides (bacteriostatic).
It binds with 50S ribosomal subunits inhibiting transpeptidation leading
Chloramphenicol
to inhibition of protein synthesis.
Inhibit DNA gyrase enzyme, which is responsible for supercoiling and
Quinolones
replication of DNA.
Rifampicin Inhibits DNA-dependent RNA polymerase resulting in inhibition of RNA
(Rifampin) synthesis.
They compete with it for the enzyme DHPS resulting in inhibition of
Sulphonamides
folate synthesis followed by inhibition of DNA & RNA synthesis.
Inhibition of DHFR enzyme, which converts folic acid to tetrahydro folic
Trimethoprim
acid (folinic acid) which is essential for DNA synthesis.
-Prodrug activated in anaerobic bacteria and sensitive protozoa by
reduction of
its nitro group →reactive reduction products →disruption of DNA
Metronidazole
structure
(Flagyl)
& function and cell death.
-Affect trophozoites not cysts due to decrease luminal concentration as
it is completely absorbed.
Binds to ergosterol of cell membrane → formation of artificial pores →
Amphotericin B
cell death.
Flucytosine transformed to 5-flurouracil (5-FU) → inhibits nucleic acid synthesis.
Azoles Inhibition of ergosterol synthesis
Concentrated in newly formed keratin preventing its infection by:
1- Interfering with microtubular function → interfere with mitosis.
Griseofulvin
2- Inhibiting nucleic acid synthesis.
When infected keratin is shed it is replaced by uninfected one.
Inhibition of squalene epoxidase enzyme which is essential for
Terbinefine
ergosterol synthesis of cell membrane.
Binds to ergosterol of fungal cell membrane → formation of artificial
Nystatin pores—» damage of membrane → leakage of important cell
constituents → cell death.
Heparin Binds antithrombin to increase its activity (1000 times).
Low molecular Inhibit activated factor Xa only.
weight heparin
(LMWH)
Bivalirudin bivalent thrombin inhibitor.
Vit. K antagonist Warfarin inhibits hepatic synthesis of vit. K-dependent activated clotting
(Warfarin) factors (II, VII, IX, X), so anticoagulants in vivo only.
Acetyl salicylic acid Inhibits thromboxane A2 synthetase enzyme
(Aspirin)
Ticlopidine& Irreversibly block ADP receptors on platelet membrane.
Clopidogrel
Abciximab, Block GPIIb/IIIa receptor, so prevent binding of fibrinogen.
Eptifibatide and
Tirofiban
• Inhibit Na+/ K+/2Cl-co transport system in the thick ascending loop of
Henle
Loop Diuretics
• ↓K efflux decreases luminal +ve potential so inhibit reabsorption of
(LDs)
Ca+2 & Mg+2.
• Increase PG synthesis that induce V.D. and increase renal blood blow.
• Inhibit NaCl reabsorption from of DCT, increasing excretion of NaCl
and water.
• Thiazides increase Ca2+ reabsorption from the DCT, increasing Ca2+
Thiazide Diuretics
level in blood.
Activates ATP-dependent K+ channels → Hyperpolarization→ VD.
Release of vasodilator PGs.
Weak diuretics, inhibit of NaCl reabsorption and K+ and H+ secretion
A] Spironolactone: aldosterone antagonist, so has delayed onset of
K+-sparing
action (3-4 days).
diuretics
B] Amiloride and triamterene: direct acting, so have rapid onset of
action.
Nitrates release nitric oxide→ V.D.
Organic Nitrates
Useful in all types of angina Pectoris: acute attack and prophylaxis.
Dihydropyridines V.D. > ↓ Heart
dihydropyridines ↓Heart > V.D.
Decrease myocardial oxygen demand
β-Blockers Aldosterone System (RAAS)Antagonists Drugs ↓ Release of Renin: beta
blockers.
Ivabradine produces dose dependent reduction in heart rate.
Alteplase Thrombolytic
Inhibit Angiotensin Converting Enzyme →↓ Synthesis of
Angiotensin
angiotensin II:
Converting Enzyme
↓VC, ↓ Aldosterone & ↓ Sympathetic activity.
Inhibitors (ACEIs)
↓Inactivation of Bradykinin →↑Bradykinin → VD
Angiotensin II (AT1) Compete with Angiotensin II for AT1-receptors.
Receptor Blockers
Proglumide Gastrin antagonists
• Protonated at pH 3 or below (canaliculus).
Proton-pump
• Irreversibly inhibits H+-K+ ATPase (proton pump). At least 18hrs.are
inhibitors
required for synthesis of new H+/K+ ATPase pump molecules.
 • Competitively inhibit the interaction of histamine with H2 receptors.
• ↓ Gastric acid secretion (reduce both volume and H+ concentration).
H2 Histamine • H2 antagonists are especially effective at inhibiting nocturnal acid
receptor secretion (which depends largely on histamine) but have a modest
antagonists impaction meal-stimulated acid secretion (which is stimulated by gastrin
and acetylcholine as well as histamine). Thus, they block more than 90%
of nocturnal acid but only 60-80% of day time acid secretion.
• ↓ Basal secretion (40-50%).
Selective • ↓ Volume not concentration of acid.
muscarinic • ↑ Gastric mucosal blood flow.
antagonists (M1) • ↑ Motility → ↑ LESP “lower esophageal sphincter pressure” (M1
receptors have a role in inhibitory motility pathway).
1. Both acid inhibition & mucosal protection:
Inhibits acid secretion (inhibits adenyl cyclase & gastrin release).
Prostaglandin Stimulates mucus and bicarbonate secretion.
analogue, Increases blood flow.
misoprostol 2. Other actions:
(cytotec) Stimulates intestinal electrolyte &fluid secretion.
Stimulates intestinal motility.
Stimulates uterine contraction.
• Dopamine antagonist.
Dopamine
• Antipsychotic.
antagonist
• Antiemetic.
(Sulpiride)
• Prokinetic (↑ gastric motility).
Dogmatil
• Inhibits gastrin release → ↓ gastric acid secretion.
Carbenoxolone ↑production, secretion & viscosity of intestinal mucus.
(Biogastrone)
Bismuth 1. Coats ulcer.
compound: 2. Lysis of Helicobacter pylori.
colloidal bismuth
sub citrate (Denol)
1. At acid pH (below 4) → polymerization → gel → selective binding to
Sucralfate: necrotic ulcer tissues for up to 6hrs. Sucrose sulfate (negatively charged)
(Sucrose octa binds to proteins (positively charged) in the base of ulcers or erosion,
sulfate + Al+3 forming a physical barrier.
hydroxide) 2. Absorbs bile salts & pepsin.
3. Stimulates PG & bicarbonate secretion.
Sympathetic control: There is no sympathetic innervation, but there is
Sympathomimetics plenty of β2 adrenoceptors producing bronchodilatation (due to
accumulation of cAMP).
 1-Theophylline is phosphodiesterase inhibitor, increases intracellular
cAMP which causes redistribution of intracellular Ca⁺⁺ ion.
2-It improves diaphragmatic contraction, and ventilatory response to
Methylxanthines hypoxia (improves dyspnea).
3-It blocks adenosine receptor (centrally and peripherally) producing
bronchodilatation.
4-It stabilizes the mast cell membrane and inhibits release of mediators.
Selective PDE-4 inhibitor → selective action on airways and
Roflumilast:
inflammatory cells with fewer adverse effects.
Muscarinic Atropine blocks the muscarinic receptors in bronchial muscle, but it is
Receptor not effective in bronchial asthma because:
Antagonists
Corticosteroids → synthesis of lipocortin which ↓↓ phospholipase A₂
activity with ↓↓ of arachidonic acid, PGs and leukotrienes.
Corticosteroids decrease antibody formation (immunosuppressive).
Stabilize mast cell membrane, reduce capillary permeability, reduce
Corticosteroids
mucosal oedema and inhibit antigen antibody reaction.
Corticosteroids enhance catecholamine effects because they block
reuptake, stimulate methylation of noradrenaline to adrenaline and
stimulate adenyl cyclase increasing cAMP concentration.
They do not prevent antigen-antibody reactions but if given before
exposure to the antigen, they stabilize the mast cell membrane possibly
Mast cell by blocking calcium flow into the mast cell thus preventing the release
stabilizers: These of allergic mediators, e.g., histamine and leukotrienes.
include These drugs also inhibit phosphodiesterase enzyme thus increasing
intracellular cAMP.
Ketotifen has additional an antihistaminic effect on H1 receptors.
Selectively binds to human IGE → inhibits IGE binding to its receptor on
Omalizumab surface of mast cells and basophils → inhibits release of inflammatory
mediators.
Montelukast and Cysteinyl leukotriene receptors antagonists
zafirlukast (orally).
5-lipoxygenase inhibitors
zileuton (orally)
that acts by decreasing leukotriene synthesis.