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Pharmacology - NEETMDS- courses
NEET MDS Lessons
Pharmacology

TRICYCLIC ANTIDEPRESSANTS

e.g. amitriptyline, imipramine, nortriptyline

Belong to first generation antidepressants

ACTION:

Inhibit 5-HT(5-hydroxytryptamine) and norepinephrine reuptake

slow clearance of norepinephrine & 5-HT from the synapse 

enhance norepinephrine & 5-HT neuro-transmission

MODE OF ACTIONMODE OF ACTION

TCAs also block
– muscarinic acetylcholine receptors
– histamine receptors 
– 5-HT receptors
– α1 adrenoceptors

Onset of antidepressant activity takes 2-3 weeks

PHARMACOKINETICS

-  Readily absorbed from the gastro-intestinal tract 
- Bind strongly to plasma albumin
- Has a large volume of distribution(as a result of binding to extravascular tissues)
- Undergo liver CYP metabolism into biologically active metabolites
- These metabolites are inactivated via glucuronidation and excreted in urine

ADVERSE DRUG REACTIONS

Antimuscarinic - dry mouth, blurred vision, constipation and urinary retention
Antihistamine – drowsiness
adrenoceptor blockage(+/- central effect) postural hypotension
Reduce seizure threshold
Testicular enlargement, gynaecomastia, galactorrhoea
AV-conduction blocks and cardiac arrhythmias

TOXICITY

- Fatal in toxicity

- Most important toxic effect is, slowing of depolarisation of the cardiac action potential by blocking fast sodium channels ("quinidine-like" effect) 

- delays propagation of depolarisation through both myocardium and conducting tissue

- prolongation of the QRS complex and the PR/QT intervals

- predisposition to cardiac arrhythmias


DRUG INTERACTIONS

Pharmacodynamic:
– ↑ sedation with antihistamines, alcohol
– ↑ antimuscarinic effects with anticholinergics– ↑ antimuscarinic effects with anticholinergics
– Hypertension and arrhythmias with MAOIs- should be given at least 14 days apart


Pharmacokinetic (via altering CYP metabolism)
– ↓ plasma concentration of TCA by- carbamazepine, rifampicin
– ↑ plasma concentration of TCA by- cimetidine, calcium channel blockers,fluoxetine

OTHER CLINICAL USES OF AMITRIPTYLINE

- Treatment of nocturnal enuresis in children
- Treatment of neuropathic pain
- Migraine prophylaxis

Routes of Drug Administration

Intravenous

  • No barriers to absorption since drug is put directly into the blood.
  • There is a very rapid onset for drugs administered intravenously.  This can be advantagous in emergency situations, but can also be very dangerous.
  • This route offers a great deal of control in respect to drug levels in the blood.
  • Irritant drugs can be administer by the IV route without risking tissue injury.
  • IV drug administration is expensive, inconvenient and more difficult than administration by other routes.
  • Other disadvantages include the risk of fluid overload, infection, and embolism.  Some drug formulations are completely unsafe for use intravenously.

Intramuscular:

  • Only the capillary wall separates the drug from the blood, so there is not a significant barrier to the drug's absorption.
  • The rate of absorption varies with the drug's solubility and the blood flow at the site of injection.
  • The IM route is uncomfortable and inconvenient for the patient, and if administered improperly, can lead to tissue or nerve damage.

Subcutaneous

Same characteristics as the IM route.

Oral

  • Two barriers to cross: epithelial cells and capillary wall.  To cross the epithelium, drugs have to pass through the cells.
  • Highly variable drug absorption influenced by many factors:  pH, drug solubility and stability, food intake, other drugs, etc.
  • Easy, convenient, and inexpensive.  Safer than parenteral injection, so that oral administration is generally the preferred route.
  • Some drugs would be inactivated by this route
  • Inappropriate route for some patients.
  • May have some GI discomfort, nausea and vomiting.
  • Types of oral meds = tablets, enteric-coated, sustained-release, etc.
  • Topical, Inhalational agents, Suppositories

PHARMACOLOGY OF LOCAL ANESTHETICS

 Characteristics

1. Block axon conduction (nerve impulse) when applied locally in appropriate concentrations.

2. Local anesthetic action must be completely reversible; however, the duration of the anesthetic block should be of sufficient length to allow completion of the planned treatment.

3. Produce minimal local toxic effects such as nerve and muscle damage as well as minimal systemic toxic effects of organ systems such as the cardiovascular and central nervous system.

Patient positioning

The most common medical emergency encountered in the dental office setting is syncope. So patients in the supine or semi-supine position to improve venous return and cerebral blood flow provided that the position is tolerated by the patient and is appropriate for their medical condition.

Propofol -Intravenous Anesthetics

- A nonbarbiturate anesthetic
- It is very lipid-soluble, acts rapidly and has a short recovery time.
- It is associated with less nausea and vomiting than some of the other IV anesthetics.
- Propofol is very similar to thiopental in its effects on the cardiorespiratory system.
- It does not have any analgesic properties but lowers the dose of opioid needed when the two agents are used in combination.

- The most significant adverse cardiovascular effect associated with propofol administration is hypotension. It should be used with caution in patients with cardiac disease.

Hydromorphone

  • About 8-10 times more potent than morphine when given intravenously.
  • Slightly shorter duration of action.
  • More soluble than morphine, thus higher concentrations may be injected if necessary.
  • Better oral/parenteral absorption ratio than morphine, but not as good as codeine or oxycodone.
  • It is used for the treatment of moderate to severe pain

Ciprofloxacin : Ciprofloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase

Ciprofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and  Gram-negative bacteria.

Enterobacteriaceae, Vibrio,  Hemophilus influenzae, Neisseria gonorrhoeae

 Neisseria menigitidis,  Moraxella catarrhalis,  Brucella, Campylobacter,

 Mycobacterium intracellulare, Legionella sp., Pseudomonas aeruginosa,

Bacillus anthracis - that causes anthrax

Weak activity against: Streptococcus pneumoniae,

No activity against:  Bacteroides,  Enterococcus faecium, Ureaplasma urealyticum  and others

It is contraindicated in children, pregnancy, and epilepsy.

Ciprofloxacin can cause photosensitivity reactions and can elevate plasma

theophylline levels to toxic values. It can also cause  constipation and sensitivity to caffeine.

Dosage in respiratory infections is 500-1500 mg a day in 2 doses.

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