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Pharmacology

Osmotic diuretics

An osmotic diuretic is a type of diuretic that inhibits reabsorption of water and sodium. They are pharmacologically inert substances that are given intravenously. They increase the osmolarity of blood and renal filtrate.

Mechanism(s) of Action

1.    Reduce tissue fluid (edema) 
2.    Reflex cardiovascular effect by osmotic retention of fluid within vascular space which increases blood volume (contraindicated with Congestive heart failure) 
3.    Diuretic effect

o    Makes H2O reabsorption far more difficult for tubular segments insufficient Na & H2O capacity in distal segments
o    Increased intramedullary blood flow (washout)
o    Incomplete sodium recapture (asc. loop). this is indirect inhibition of Na reabsorption (Na stays in tubule because water stays) 
o    Net diuretic effect: 
    Tubular concentration of sodium decreases 
    Total amount of sodium lost amount increases 
    GFR unchanged or slightly increased

Toxicity

Circulatory overload, dilutional hyponatremia,  Hyperkalemia, edema, skin necrosis

Agents
Mannitol

Serotonin or 5-hydroxytryptamine (5-HT)

It is a neurotransmitter, widely distributed in the CNS, beginning in the midbrain and projecting into thalamus, hypothalamus, cerebral cortex, and spinal cord. CNS serotonin is usually an inhibitory neurotransmitter and is associated with mood, the sleep-wake cycle.

Serotonin is thought to produce sleep by inhibiting CNS activity. 

In the blood, 5-HT is present in high concentration in platelets (regulator of platelets function) and also high concentration in intestine

Pharmacological effects:

Smooth muscles. 5-HT stimulates the G.I smooth muscle; it increases the peristaltic movement of intestine.
Serotonin contracts the smooth muscle of bronchi; 

Blood vessels. If serotonin is injected i.v, the blood pressure usually first rises, because of the contraction of large vessels and then falls because of arteriolar dilatation. Serotonin causes aggregation of platelets. 

Specific agonists

- Sumatriptan a selective 5-HT1D used in treatment of acute migraine.
- Buspirone a selective 5-HT1A used in anxiety.
- Ergotamine is a partial agonist used in migraine. It acts on 5-HT1A receptor.

Nonspecific 5-HT receptor agonist

o Dexfenfluramine used as appetite suppressant.

Specific antagonists

o Spiperone (acts on 1A receptor) and
o Methiothepin (acts on 1A, 1B, 1D receptors)

Stimulants: 

Amphetamines: amphetamine is a substrate of serotonin and NE uptake transporters so in cytoplasm, it competes for transport into storage vesicles → ↑ [ ] in cytoplasm then excess amines bind to membrane transporter and are transported out of cell

Drugs: 
a.    Dextroamphetamine: psychomotor stimulant (↓ fatigue), short-term weight loss, prevents narcolepsy
b.    Methylphenidate (Ritalin): prevents narcolepsy, treatment for ADD and ADHD
c.    Methamphetamine: psychomotor stimulant, abused widely (cheap, easy to make)

Side effects: 
a.    CNS: euphoria, anxiety, agitation, delirium, paranoia, panic, suicidal/homicidal impulses, psychoses, tolerance (develops rapidly to most CNS effects), physical dependence (not clinically relevant)
b.    CV: headache, chills, arrhythmias and HTN (may be fatal)

Pramlintide -Amylin mimetics

Mechanism
synthetic analogue of human amylin that acts in conjunction with insulin
↓ release of glucagon
delays gastric emptying

Clinical use

type I and II DM

Operator position

For the right-handed operator, the 8 and 10 o’clock position and for left-handed operators, the corresponding 2 and 4 o’clock position almost always allows for optimal visualization of the injection field.

Classification

I) Esters

 1. Formed from an aromatic acid and an amino alcohol.

 2. Examples of ester type local anesthetics:

 Procaine

Chloroprocaine

Tetracaine

Cocaine

Benzocaine- topical applications only

2) Amides

 1. Formed from an aromatic amine and an amino acid.

 2. Examples of amide type local anesthetics:

Articaine

Mepivacaine

Bupivacaine

Prilocaine

Etidocaine

Ropivacaine

Lidocaine

Ampicillin offered a broader spectrum of activity than either of the original penicillins and allowed doctors to treat a broader range of both Gram-positive and Gram-negative infections. Ampicillin is often used in molecular biology as a test for the uptake of genes (e.g., by plasmids) by bacteria (e.g., E. coli)

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