Fentanyl (Sublimaze)

• Related chemically to meperidine.
• Approximately 80 times more potent than morphine.
• Duration of action very short (t1/2 20 min).
• Used mainly following general anesthesia.
• Neurolept analgesia: Fentanyl & Droperidol (Innovar)
• fentanyl in analgesic (2-10 µg/kg), or anaesthetic (30-100 µg/kg) doses seldom causes significant decreases in blood pressure when given alone, even in patients with poor LV function
• hypotension following fentanyl is mostly due to bradycardia and can be prevented by the use of anticholinergics, sympathomimetics or agents such as pancuronium this is more likely to occur in patients with high pre-existing sympathetic tone
• hypertension is the commonest disturbance with high dose fentanyl anaesthesia, usually accompanying intubation, sternotomy, or aortic root dissection

Clarithromycin Used to treat  pharyngitis, tonsillitis, acute maxillary

sinusitis, acute bacterial exacerbation of chronic  bronchitis,  pneumonia (especially atypical pneumonias associated with Chlamydia pneumoniae or TWAR), skin and skin structure infections, and, in HIV and AIDS patients to prevent, and to treat, disseminated Mycobacterium avium complex or MAC.

Unlike erythromycin, clarithromycin is acid-stable and can therefore be taken orally without being protected from gastric acids. It is readily absorbed, and diffused into most tissues and phagocytes.

Clarithromycin has a fairly rapid first-pass hepatic metabolism, i.e it is metabolised by the liver. However, this metabolite, 14-hydroxy clarithromycin is almost twice as active as clarithromycin.

Contraindications Clarithromycin should be used with caution if the patient has liver or kidney disease, certain heart problems (e.g., QTc prolongation or bradycardia), or a mineral imbalance (e.g., low potassium or magnesium levels).

NSAIDs: Classification by Plasma Elimination Half Lives

Short Half Life (< 6 hours):

more rapid effect and clearance

• Aspirin (0.25-0.33 hrs),

• Diclofenac (1.1 ± 0.2 hrs)

• Ketoprofen (1.8± 0.4 hrs),

• Ibuprofen (2.1 ± 0.3 hrs)

• Indomethacin (4.6 ± 0.7 hrs)

Long Half Life (> 10 hours):

slower onset of effect and slower clearance

• Naproxen (14 ± 2 hrs)

• Sulindac (14 ± 8 hrs),

• Piroxicam (57 ± 22 hrs)

Example calculations of maximum local anesthetic doses for a 15-kg child

Articaine

5 mg/kg maximum dose × 15 kg = 75 mg

4% articaine = 40 mg/mL

75 mg/(40 mg/mL) = 1.88 mL

1 cartridge = 1.8 mL

Therefore, 1 cartridge is the maximum

Lidocaine

7 mg/kg × 15 kg = 105 mg

2% lidocaine = 20 mg/mL

105 mg/(20 mg/mL) = 5.25 mL

1 cartridge = 1.8 mL

Therefore, 2.9 cartridges is the maximum

Mepivacaine

6.6 mg/kg × 15 kg = 99 mg

3% mepivacaine = 30 mg/mL

99 mg/(30 mg/mL) = 3.3 mL

1 cartridge = 1.8 mL

Therefore, 1.8 cartridges is the maximum.

Prilocaine

8 mg/kg × 15 kg = 120 mg

4% prilocaine = 40 mg/mL

120 mg/(40 mg/mL) = 3 mL

1 cartridge = 1.8 mL

Therefore, 1.67 cartridges is the maximum

Properties of inhalation anesthetics

The lower the solubility, the faster the onset and the faster the recoverability.

All general anesthetics:

1. inhibit the brain from responding to sensory stimulation.

2. block the sensory impulses from being recorded in memory.

3. prevent the sensory impulses from evoking “affect”.

Most general anesthetic agents act in part by interacting with the neuronal membranes to affect ion channels and membrane excitability.

· If the concentration given is too low:

1. Movement may occur

2. Reflex activity present (laryngeal spasm)

3. Hypertension

4. Awareness

Premedication of analgesic drugs and muscle relaxants are designed to minimise these effects

· If the concentration given is too high:

1. Myocardial depression

2. Respiratory depression

3. Delayed recovery

Benzodiazepines (BZ): 

newer; depress CNS, selective anxiolytic effect (no sedative effect); are not general anesthetics (but does produce sedation, stupor) or analgesics 

BZ effects: 

1.  Central: BZs bind GABA_A receptors in limbic system (amygdala, septum, hippocampus; involved in emotions) and enhance inhibition of neurons in limbic system (this may produce anxiolytic effects of BZs)

a. GABA receptor: pentameric (α, β, δ, γ subunits)
i.  Binding sites: GABA (↑ conductance (G) of Cl-, hyperpolarization, inhibition), barbiturate (↑ GABA effect), benzodiazepine (↑ GABA effect), picrotoxin (block Cl channel)

b. GABA agonists: GABA (binds GABA → Cl influx; have ↑ frequency of Cl channel opening; BZs alone- without GABA don’t affect Cl channel function)

c.  Antagonists: bicuculline (competitively blocks GABA binding; ↓ inhibition,→ convulsions; no clinical use), picrotoxin (non-competitively blocks GABA actions,  Cl channel → ↓ inhibition → convulsions)

2.  Other agents at BZ receptor: 

a.    Agonists: zolpidem (acts at BZ receptor to produce pharmacological actions)

b.    Inverse agonists: β-carbolines (produce opposite effects at BZ binding site-- ↓ Cl conductance; no therapeutic uses since → anxiety, irritability, agitation, delirium, convulsions)

3. Antagonists: flumazenil (block agonists and inverse agonists, have no biological effects themselves; can precipitate withdrawal in dependent people)

Metabolism: many BZs have very long action (since metabolism is slow); drugs have active metabolites

2 major reactions: demethylation and hydroxylation (both very slow reactions)

Fast reaction: glucuronidation and urinary excretion

Plasma half life: long (for treating anxiety, withdrawal, muscle relaxants), intermediate (insomnia, anxiety), short (insomnia), ultra-short (<2hrs; pre-anesthetic medication)

Acute toxicity: very high therapeutic index and OD usually not life threatening (rarely see coma or death)

Treatment: support respiration, BP, gastric lavage, give antagonist (e.g., glumazenil; quickly reverses BD-induced respiratory depression)

Tolerance: types include pharmacodynamic (down-regulation of CNS response due to presence of drug; this is probably the mechanism by which tolerance develops), cross-tolerance (with other BZ and CNS depressants like EtOH and BARBS), acquisition of tolerance (tolerance develops fastest in anticonvulsant > sedation >> muscle relaxant > antianxiety; means people can take BZs for long time for antianxiety without → tolerance)

Physical dependence: low abuse potential (no buz) but physical/psychological dependence may occur; physical dependence present when withdrawal symptoms occur (mild = anxiety, insomnia, irritability, bad dreams, tremors, anorexia; severe = agitation, depression, panic, paranoia, muscle twitches, convulsions)

Drug interactions: minimally induce liver enzymes so few interactions; see additive CNS depressant effects (can be severe and → coma and death if BZs taken with other CNS depressants like ethanol)