SGLT-2 Inhibitors

canagliflozin
empagliflozin

Mechanism

glucose is reabsorbed in the proximal tubule of the nephron by the sodium-glucose cotransporter 2 (SGLT2)
SGLT2-inhibitors lower serum glucose by increasing urinary glucose excretion
the mechanism of action is independent of insulin secretion or action

Clinical use

type II DM

FUNDAMENTALS OF INJECTION TECHNIQUE

There are 6 basic techniques for achieving local anesthesia of the structures of the oral cavity:

 1. Nerve block

 2. Field block

 3. Infiltration/Supraperiosteal

 4. Topical

 5. Periodontal ligament (PDL)

 6. Intraosseous

 Nerve block- Nerve block anesthesia requires local anesthetic to be deposited in close proximity to a nerve trunk. This results in the blockade of nerve impulses distal to this point. It is also important to note that arteries and veins accompany these nerves and can be damaged. To be effective, the local anesthetic needs to pass only through the nerve membrane to block nerve conduction Field block/Infiltration/Supraperiosteal - Field block, infiltration and supraperiosteal injection techniques, rely on the ability of local anesthetics to diffuse through numerous structures to reach the nerve or nerves to be anesthetized:

  - Periosteum

 - Cortical bone

 - Cancellous bone

 - Nerve membrane

Topical - Topical anesthetic to be effective requires diffusion through mucous membranes and nerve membrane of the nerve endings near the tissue surface

PDL/Intraosseous - The PDL and intraosseous injection techniques require diffusion of local anesthetic solution through the cancellous bone (spongy) to reach the dental plexus of nerves innervating the tooth or teeth in the immediate area of the injection. The local anesthetic then diffuses through the nerve membrane

SULPHONAMIDES

Derivative of  sulphonilamide (Para-amino Benzene (PABA ) sulphonamide).

Anti-bacterial spectrum

Bacteriostatic to gram + and gram - bacteria. but bactericidal concentrations arce attained in urine. S pyogencs. H influenzae.E coli, few- Staph aureus. gonococci. pneumococci, proteus, shigella and Lymphogranuloma venereum.

Mechanism of action

Inhibits bacterial folate synthetase as they compete with PABA

Less soluble in acid urine and may precipitate to cause crystalluria.

Accumulate in patients with renal failure and can cause toxicity

Classification

Shart Acting (4-8 Hrs) sulphadiazine, sulphamethizole.

Intermediate acting(8-16 Hrs): sulphamethoxazole , sulphaphenazole

Long Acting(l-7days): sulphamethoxypyridazine.

Ultralong Acting(3-8days): sulfaline

Adverse effects

I. nausea, vomiting and epigastric pain

2. crystalluria

3. hypersensitivity-like polyarthritis nodosa. Steven-Johnson Syndrome. photosenstivity

4.hemolysis in G-6PD deficiency

5. kernicterus

They inhibit metabolism of phenytoin. tolbutamide. methotrexate

Therapeutic Use

UTI Meningitis, Streptococcal pharyngitis, Bacillary Dysentery

Needle selection

Nerve blocks:

Inferior alveolar- 25 G short (LLU technique)

PSA- 25 G short

Mental/Incisive- 25 G short

Palatal- 27/30 G short/ultrashort

Gow-Gates/Akinosi- 25 G long

Infraorbital- 25 G long

Field Block:

ASA 25/27 short

Infiltration:

Infiltration/SP 25/27 short

PDL/Intraosseous

PDL 27/30 short

Intraosseous 30 short/ultrashort

Class II Beta Blockers 

Block SNS stimulation of beta receptors in the heart and decreasing risks of ventricular fibrillation
– Blockage of SA and ectopic pacemakers: decreases automaticity 
– Blockage of AV increases the refractory period
- Increase AV nodal conduction ´ 
- Increase PR interval
- Reduce adrenergic activity

Treatment: Supraventricular tachycardia (AF, flutter, paroxysmal supraventricular tachycardia 
– Acebutolol 
– Esmolol 
– Propanolol 

Contraindications and Cautions 

• Contraindicated in sinus bradycardia P < 45
• Cardiogenic shock,  asthma or respiratory depression which could be made worse by the blocking of Beta receptors. 
• Use cautiously in patients with diabetes and thyroid dysfunction, which could be altered by the blockade of Beta receptors 
• Renal and hepatic dysfunction could alter the metabolism and excretion of these drugs.
 

Drug-Receptor Interactions

Drug Receptor:  any functional macromolecule in a cell to which a drug binds to produce its effects.  at receptors, drugs mimic or block the action of the body's own regulatory molecules.  

Receptors and Selectivity of Drug Action : If a drug interacts with only one kind of receptor, and if that receptor regulates just a few processes, then the effects of the drug will be limited.

Even though a drug is selective for one type of receptor, it can still produce a variety of effects.

Selectivity does not guarantee safety.

Theories of Drug-Receptor Interaction

- Simple Occupancy Theory:  Two factors - The intensity of the response to a drug is proportional to the number of receptors occupied by that drug, and the maximal response will occur when all available receptors have been occupied.

- Modified Occupancy Theory:  Assumes that all drugs acting at a particular receptor are identical with respect to the ability to bind to the receptor and the ability to influence receptor function once binding has taken place.

•    Affinity:  The strength of the attraction between a drug and its receptor.  Affinity is reflected in potency.  (Drugs with high affinity are very potent).

•    Intrinsic Activity:  The ability of a drug to activate a receptor following binding.  Reflected in the maximal efficacy (drugs with high intrinsic activity have high maximal efficacy).