Phenobarbital (Luminal): for generalized tonic-clonic and partial seizures (not used for absence seizures)

Mechanism: enhances GABA inhibition (↑ open time of Cl channels in presence of GABA)

Side effects: sedation, ataxia, cognitive impairment, induction of hepatic microsomal enzymes

Mixed Narcotic Agonists/Antagonists

These drugs all produce analgesia, but have a lower potential for abuse and do not produce as much respiratory depression.

A. Pentazocine

• Has a combination of opiate analgesic and antagonist activity.
• Orally, it has about the same analgesic potency as codeine.
• In contrast to morphine, cardiac workload tends to increase due to an increase in pulmonary arterial and cerebrovascular pressure. Blood pressure and heart rate both also tend to increase.
• Adverse reactions to Pentazocine

• Nausea, vomiting, dizziness.

• Psychotomimetic effects, such as dysphoria, nightmares and visual hallucinations.

• Constipation is less marked than with morphine.

B. Nalbuphine

• Has both analgesic and antagonist properties.
• Resembles pentazocine pharmacologically.
• Analgesic potency approximately the same as morphine.
• Appears to be less hypotensive than morphine.
• Respiratory depression similar to morphine, but appears to peak-out at higher doses and to reach a ceiling.
• Like morphine, nalbuphine reduces myocardial oxygen demand. May be of value following acute myocardial infarction due to both its analgesic properties and reduced myocardial oxygen demand.
• Most frequent side effect is sedation.

C. Butorphanol

• Has both opiate agonist and antagonist properties.Resembles pentazocine , pharmacologically., 3.5 to 7 times more potent than morphine., Produces respiratory depression, but this effect peaks out with higher doses. The respiratory depression that does occur lasts longer than that seen following morphine administration.
• Butorphanol, like pentazocine, increases pulmonary arterial pressure and possibly the workload on the heart.
• Adverse reactions include sedation, nausea and sweating.

D. Buprenorphine

• A derivative of eto`rphine. Has both agonist and antagonist activity. 20 to 30 times more potent than morphine.Duration of action only slightly longer than morphine, but respiratory depression and miosis persist well after analgesia has disappeared.
• Respiratory depression reaches a ceiling at relatively low doses.
• Approximately 96% of the circulating drug is bound to plasma proteins.
• Side effects are similar to other opiates:
  • sedation, nausea, vomiting,
  • dizziness, sweating and headache.

Loop (High Ceiling) Diuretics

Loop diuretics are diuretics that act at the ascending limb of the loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or renal insufficiency. While thiazide diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.

Agent: Furosemide

Mechanism(s) of Action

1.    Diuretic effect is produced by inhibit of active 1 Na⁺, 1 K⁺, 2 Cl^-  co-transport (ascending limb - Loop of Henle). 
o    This produces potent diuresis as this is a relatively important Na re-absorption site.

2.    Potassium wasting effect 

a.    Blood volume reduction leads to increased production of aldosterone 
b.    Increased distal Na load secondary to diuretic effect 
c.    a + b = increase Na (to blood) for K (to urine) exchange which produces indirect K wasting (same as thiazides but more likely)

3.    Increased calcium clearance/decreased plasma calcium 

o    secondary to passive decreases in loop Ca++ reabsorption.
o    This is linked to inhibition of Cl^- reabsorption.
o    This is an important clinical effect in patients with ABNORMAL High Ca⁺⁺
 

Megltinides

nateglinide
repaglinide

Mechanism

binds to K+ channels on β-cells → postprandial insulin release

Clinical use
type 2 diabetes mellitus
may be used as monotherapy, or in combination with metformin

Ketamine 
- Causes a dissociative anesthesia.
- Is similar to but less potent than phencyclidine.
- Induces amnesia, analgesia, catalepsy and anesthesia, but does not induce convulsions.
- The principal disadvantage of ketamine is its adverse psychic effects during emergence from anesthesia. These include: hallucinations, changes in mood and body image.
- During anesthesia, many of the protective reflexes are maintained, such as laryngeal, pharyngeal, eyelid and corneal reflexes.
- Muscle relaxation is poor.
- It is not indicated for intracranial operations because it increases cerebrospinal fluid pressure.
- Respiration is well maintained.
- Arterial blood pressure, cardiac output, and heart rate are all elevated.

Glucocorticoids 
Cortisol (hydrocortisone) and its synthetic derivatives 

Mechanism 

↓ the production of leukotrienes and prostaglandins   - inhibits phospholipase A2 , inhibits expression of COX-2 , will also stimulate the bone marrow to produce neutrophils resulting in leukocytosis 

halts inflammatory cascade 

↓ leukocyte migration
↓ capillary permeability
↓ phagocytosis
↓ platelet-activating factor
↓ interleukins (e.g. IL-2)

may trigger apoptosis in dividing and non-dividing cells

used in cancer chemotherapy

Clinical use

anti-inflammatory
immunosuppression
cancer chemotherapy (prednisone most common)
CLL
Hodgkin's lymphomas
part of MOPP regimen
Addison disease
asthma

Toxicity

1) must taper dose to avoid toxicity
2) suppression of ACTH → shock state if abrupt withdrawal - > cortical atrophy, malaise, myalgia, arthralgia, fever
3) iatrogenic Cushing  syndrome ->buffalo hump, moon facies, truncal obesity, muscle weakness and atrophy, thin skin, easy bruising, acne
4) osteoporosis - vertebral fractures, aseptic hip necrosis, ↓ skeletal growth in children 
5) hyperglycemia (diabetes) -due to ↑ gluconeogenesis , glaucoma, cataracts, and other complications can subsequently result
6) ↑ GI acid release -ulcers
7) Na+ retention -> edema, HTN, hypokalemia alkalosis, hypocalcemia
8)↓ wound healing
9) ↑ infections
10) mental status changes
11) cataracts