NEET MDS Lessons
Pharmacology
Local Anesthetics
1. Procaine (Novocaine)
a) Classic Ester type agent, first synthetic injectable local anesthetic.
b) Slow onset and short duration of action
2. Tetracaine (Pontocaine)
a) Ester type agent--ten times as potent and toxic as procaine.
b) Slow onset but long duration of action.
c) Available in injectable and topical applications.
3. Propoxycaine (Ravocaine)
a) Ester type agent–five times as potent and toxic as procaine.
b) Often combined with procaine to increase duration of action.
4. Lidocaine (Xylocaine)
a) Versatile widely used amide type agent.
b) Two - three times as potent and toxic as procaine.
c) Rapid onset and relatively long duration of action.
d) Good agent for topical application.
5. Mepivacaine (Carbocaine)
a) Amide type agent similar to lidocaine.
b) Without vasoconstrictor has only short duration of action.
6. Prilocaine (Citanest)
a) Amide type agent — less potent than lidocaine.
b) Without vasoconstrictor has only short duration of action.
c) Metabolized to o-toluidine which can cause methemoglobinemia — significant only with large doses of prilocaine.
d) Higher incidences of paresthesia reported with 4 % preparation
7. Bupivacaine (Marcaine)
a) Amide type agent of high potency and toxicity.
b) Rapid onset and very long duration of action even without vasoconstrictor.
8. Articaine (Septocaine)
a) Amide type agent
b) Only amide-type local anesthetic that contains an ester group, therefore metabolized both in the liver and plasma.
c) Approved by the FDA in 2000
d) Evidence points to improved diffusion through hard and soft tissues as compared to other local anesthetics.
e) Reports of a higher incidence of paresthesia, presumably due to the 4% concentration
f) Not recommended for use in children under 4 years of age
Estimation of the risk of anesthesia (American Society of Anesthesiologists scale)
• ASA 1: healthy patient.
• ASA 2: patient with stable, treated illness like arterial hypertension, diabetes melitus, asthma bronchiale, obesity
• ASA 3: patient with systemic illness decreasing sufficiency like heart illness, late infarct
• ASA 4: patient with serious illness influencing his state like renal insuficiency, unstable hypertension, circulatory insuficiency
• ASA 5: patient in life treatening illness
• ASA 6: brain death- potential organ donor
Aspirin
Mechanism of Action
ASA covalently and irreversibly modifies both COX-1 and COX-2 by acetylating serine-530 in the active site Acetylation results in a steric block, preventing arachidonic acid from binding
Uses of Aspirin
Dose-Dependent Effects:
Low: < 300mg blocks platelet aggregation
Intermediate: 300-2400mg/day antipyretic and analgesic effects
High: 2400-4000mg/day anti-inflammatory effects
Often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. It has also an anticoagulant (blood thinning) effect and is used in long-term low-doses to prevent heart attacks
Low-dose long-term aspirin irreversibly blocks formation of thromboxane A2 in platelets, producing an inhibitory affect on platelet aggregation, and this blood thinning property makes it useful for reducing the incidence of heart attacks
Its primary undesirable side effects, especially in stronger doses, are gastrointestinal distress (including ulcers and stomach bleeding) and tinnitus. Another side effect, due to its anticoagulant properties, is increased bleeding in menstruating women.
Rofecoxib
Inhibit prostacyclin(PGI2) in vascular endothelium , letting TXA2 act freely and promote platelet aggregation.
used in the treatment of osteoarthritis, acute pain conditions, and dysmenorrhea
Higher incidence of cardiovascular thrombotic events.
Not used due to increase risk of heart attack, stroke
Erythromycin
used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma. It is also used to treat outbreaks of chlamydia, syphilis, and gonorrhea.
Erythromycin is produced from a strain of the actinomyces Saccaropolyspora erythraea, formerly known as Streptomyces erythraeus.
GENERAL ANESTHETICS
General anesthesia often involves more than one drug to get different, favourable effects.
Premedication is often used to:
1. Treat anxiety - Benzodiazapenes
2. Reduce pain - Opiod anaglesics such as morphine
3. Produce muscle paralysis -E.g. Tubocurare
4. Reduce secretions
Induction of anesthesia is often done via intravenous anesthetics, which are quick and easy to administer.
Maintenance of anesthesia involves inhalation agents.
Prototype Agents:
Volatile Anesthetics:
• Nitrous Oxide
• Ether
• Halothane
• Enflurane
• Isoflurane
Injectable Anesthetics:
• Thiopental
• Ketamine
• Etomidate
• Propofol
• Midazolam
Insulin
Insulin is only given parenterally (subcutaneous or IV) Various preparations have different durations of action
|
Preparation |
Onset (hrs) |
Peak (hrs) |
Duration (hrs) |
| Lispro (rapid-acting) | 15 min | 0.5-1.5 | 3-4 |
| Regular (short-acting) | 0.5-1 | 2-4 | 5-7 |
| NPH (intermediate) | 1-2 | 6-12 | 18-24 |
| Glargine (long-acting) | 1 | None | >24 |
Mechanism
bind transmembrane insulin receptor
activate tyrosine kinase
phosphorylate specific substrates in each tissue type
liver
↑ glycogenesis
store glucose as glycogen
muscle
↑ glycogen and protein synthesis
↑ K+ uptake
fat
increase triglyceride storage
Clinical use
type I DM
type II DM
life-threatening hyperkalemia
increases intracellular K+
stress-induced hyperglycemia
Toxicity
hypoglycemia
hypersensitivity reaction (very rare)
Insulin Synthesis
first generated as preproinsulin with an A chain and B chain connected by a C peptide.
c-peptide is cleaved from proinsulin after packaging into vesicles leaving behind the A and B chains