Meperidine (Demerol)

Meperidine is a phenylpiperidine and has a number of congeners. It is mostly effective in the CNS and bowel

• Produces analgesia, sedation, euphoria and respiratory depression.
• Less potent than morphine, 80-100 mg meperidine equals 10 mg morphine.
• Shorter duration of action than morphine (2-4 hrs).
• Meperidine has greater excitatory activity than does morphine and toxicity may lead to convulsions.
• Meperidine appears to have some atropine-like activity.
• Does not constrict the pupils to the same extent as morphine.
• Does not cause as much constipation as morphine.
• Spasmogenic effect on GI and biliary tract smooth muscle is less pronounced than that produced by morphine.
• Not an effective antitussive agent.
• In contrast to morphine, meperidine increases the force of oxytocin-induced contractions of the uterus.
• Often the drug of choice during delivery due to its lack of inhibitory effect on uterine contractions and its relatively short duration of action.
• It has serotonergic activity when combined with monoamine oxidase inhibitors, which can produce serotonin toxicity (clonus, hyperreflexia, hyperthermia, and agitation)

 Adverse reactions to Meperidine

• Generally resemble a combination of opiate and atropine-like effects.

- respiratory depression, - tremors, - delirium and possible convulsions, - dry mouth

• The presentation of mixed symptoms (stupor and convulsions) is quite common in addicts taking large doses of meperidine.

Amphotericin B

Main use is in systemic fungal infections (e.g. in immunocompromised patients), and in visceral leishmaniasis. Aspergillosis, cryptococcus infections (e.g. meningitis) and candidiasis are treated with amphotericin B. It is also used empirically in febrile immunocompromised patients who do not respond to broad-spectrum antibiotics.

MOA:

As with other polyene antifungals, amphotericin B associates with ergosterol, a membrane chemical of fungi, forming a pore that leads to K+ leakage and fungal cell death

Side effects: nephrotoxicity (kidney damage) , headache, vomiting, convulsions and fever

The side-effects are much milder when amphotericin B is delivered in liposomes

Warfarin (Coumadin):

• The most common oral anticoagulant.
• It is only active in vivo.
• Warfarin is almost completely bound to plasma proteins. -96% to 98% bound.
• Warfarin is metabolized by the liver and excreted in the urine.
• Coumarin anticoagulants pass the placental barrier and are secreted into the maternal milk.
• Newborn infants are more sensitive to oral anticoagulants than are adults because of lower vitamin K levels and lower rates of metabolism.

• Bleeding is the most common side effect and occurs most often from the mucous membranes of the gastrointestinal tract and the genitourinary tract.

Oral anticoagulants are contraindicated in:

• Conditions where active bleeding must be avoided, Vitamin K deficiency and severe

hepatic or renal disease, and where intensive salicylate therapy is required.

CLASSICATION OF ANTICOAGULANT DRUGS

1. Direct Acting Anticoagulants

a) Calcium Chelators (sodium citrate, EDTA)

b) Heparin

2. Indirect Acting Anticoagulant Drugs

a) Warfarin

Second Generation Cephalosporins

Prototype drug is CEFUROXIME (IV) and CEFUROXIME AXETIL (oral). CEFOXITIN has good activity vs. anaerobes.

1. Expanded activity against gram negative bacilli. Still have excellent activity against gram positive (Staph. and Strep.) bacteria.

Activity for Gram negative bacteria

Neisseria sp. (some gonococci resistant)
H. influenzae (including some ampicillin-resistant strains)
Moraxella catarrhalis (some resistance esp. to cefaclor)
E. coli
Proteus mirabilis
Indole + Proteus (some strains resistant)
Morganella morganii (some strains resistant)
Klebsiella pneumoniae
Serratia sp. (many strains resistant)

2. Anaerobic infections - CEFOXITIN & CEFOTETAN only

Moderate activity against Bacteroides fragilis group.

Good activity for other Bacteroides sp., Peptostreptococcus, Fusobacterium, Clostridium sp

Uses
1. Community-acquired pneumonia - Cefuroxime is widely used for empiric therapy. Has activity vs. many ampicillin-resistant H. influenzae strains.
2. Skin and soft tissue infection
3. Urinary tract infections
4. Upper respiratory tract infections (otitis media, sinusitis). Some resistance to H.influenzae to cefaclor (20-30%).
5. Mixed aerobic & anaerobic infections - Cefoxitin & Cefotetan. Resistance to B.fragilis is increasing.
6. Surgical prophylaxis - Cefoxitin or cefotetan are widely used in cases where mixed aerobic & anaerobic infections may occur, esp. intra-abdominal, colorectal, and gynecologic operations. For cardiovascular and orthopedic procedures, cefuroxime and others may be used, but cefazolin is cheaper and appears to work well.

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