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Pharmacology

Celecoxib

is a highly selective COX-2 inhibitor and primarily inhibits this isoform of cyclooxygenase, whereas traditional NSAIDs inhibit both COX-1 and COX-2. Celecoxib is approximately 10-20 times more selective for COX-2 inhibition over COX-1.

Being a sulphonamide can cause skin rash &  hypersensitivity rxn., occasional oedema& HT.

Indication

Osteoarthritis ( 100‐200mg BID ) , rheumatoid  arthritis, dysmenorrhea, acute gouty attacks,  acute musculoskeletal pain. 

Class IV Calcium Channel Blockers
• Block the movement of calcium into conductile and contractile myocardial cells 
• Treatment: treatment of supraventricular tachycardia 
– Diltiazem 
– Verapamil 

Adverse Effects 
• Adverse effects associated with vasodilation of blood vessels throughout the body. 
• CNS – dizziness, weakness, fatigue, depression and headache, 
• GI upset, nausea, and vomiting. 
• Hypotension CHF, shock arrhythmias, and edema 
 

Cephalosporins

Produced semisynthetically by chemical attachment of side chains to 7-aminocephalosporanic acid. Same mode of action , same resistance mech. 
But tend to be more resistant than penicillins to certain beta –lactamases .


GENERATION BASED ON :
-- BACTERIAL SUSCEPTIBILITY PATTERNS
-- RESISTANCE TO BETA –LACTAMASES
--NOT EFFECTIVE AGAINST -MRSA , L. MONOCYTOGENES , C. DIFFICLE , ENTEROCOCCI

First Generation 

Parentral

- CEPHALOTHIN
- CEFAZOLIN

Oral

- CEPHALEXIN
- CEPHRADINE
- CEFADROXIL

Second Generation

Parentral

CEFUROXIME
CEFOXITIN

Oral

CEFACLOR
CEFUROXIME AXETIL

Third Generation

Parentral

CEFOTAXIME 
CEFTIZOXIME
CEFTRIAXONE 
CEFTAZIDIME
CEFOPERAZONE

Oral 

CEFIXIME 
CEFPODOXIME
CEFDINIR 
CEFTIBUTEN

Fourth Generation

Parentral

CEFEPIME
CEFPIROME

Valproic acid: broad spectrum (for most seizure types)


Mechanism: blocks Ca T currents in thalamic neurons (prevents reverberating activity in absence seizures), ↓ reactivation of Na channels (in tonic/clonic seizures; prolongs refractory periods of neurons, prevents high frequency cell firing)


Side effects: very low toxicity; common = anorexia, N/V; at high doses inhibits platelet function (bruising and gingival bleeding); rarely see idiosyncratic hepatotoxicity


Drug interactions: induces hepatic microsomal enzymes (↓ effectiveness of other drugs), binds tightly to plasma proteins so displaces other drugs

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

Paracetamol

Paracetamol or acetaminophen is analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains.

paracetamol acts by reducing production of prostaglandins, which are involved in the pain and fever processes, by inhibiting the cyclooxygenase (COX)  enzyme.

Metabolism Paracetamol is metabolized primarily in the liver. At usual doses, it is quickly detoxified by combining irreversibly with the sulfhydryl group of glutathione to produce a non-toxic conjugate that is eventually excreted by the kidneys.

Routes of Drug Administration

Intravenous

  • No barriers to absorption since drug is put directly into the blood.
  • There is a very rapid onset for drugs administered intravenously.  This can be advantagous in emergency situations, but can also be very dangerous.
  • This route offers a great deal of control in respect to drug levels in the blood.
  • Irritant drugs can be administer by the IV route without risking tissue injury.
  • IV drug administration is expensive, inconvenient and more difficult than administration by other routes.
  • Other disadvantages include the risk of fluid overload, infection, and embolism.  Some drug formulations are completely unsafe for use intravenously.

Intramuscular:

  • Only the capillary wall separates the drug from the blood, so there is not a significant barrier to the drug's absorption.
  • The rate of absorption varies with the drug's solubility and the blood flow at the site of injection.
  • The IM route is uncomfortable and inconvenient for the patient, and if administered improperly, can lead to tissue or nerve damage.

Subcutaneous

Same characteristics as the IM route.

Oral

  • Two barriers to cross: epithelial cells and capillary wall.  To cross the epithelium, drugs have to pass through the cells.
  • Highly variable drug absorption influenced by many factors:  pH, drug solubility and stability, food intake, other drugs, etc.
  • Easy, convenient, and inexpensive.  Safer than parenteral injection, so that oral administration is generally the preferred route.
  • Some drugs would be inactivated by this route
  • Inappropriate route for some patients.
  • May have some GI discomfort, nausea and vomiting.
  • Types of oral meds = tablets, enteric-coated, sustained-release, etc.
  • Topical, Inhalational agents, Suppositories

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