NEET MDS Lessons
Pharmacology
Anti-Parkinson Drugs
The disease involves degeneration of dopaminergic neurons in the nigral-striatal pathway in the basal ganglia. The cause is usually unknown. Sometimes it is associated with hypoxia, toxic chemicals, or cerebral infections.
Strategy
1. Increase dopamine in basal ganglia.
2. Block muscarinic receptors in the basal ganglia, since cholinergic function opposes the action of dopamine in the basal ganglia.
3. Newer therapies, such as the use of β-adrenergic receptor blockers.
Drugs
a. L-dopa plus carbidopa (Sinemet).
b. Bromocriptine, pergolide, pramipexole, ropinirole.
c. Benztropine, trihexyphenidyl, biperiden, procyclidine.
d. Diphenhydramine.
e. Amantadine.
f. Tolcapone and entacapone.
g. Selegiline.
Mechanisms of action of three drugs affecting DOPA
1. L-dopa plus carbidopa:
L-dopa is able to penetrate the blood–brain barrier and is then converted into dopamine. Carbidopa inhibits dopa decarboxylase, which catalyzes the formation of dopamine.
Carbidopa does not penetrate the blood–brain barrier; it therefore prevents the conversion of L-dopa to dopamine outside the CNS but allows
the conversion of L-dopa to dopamine inside the CNS.
2. Bromocriptine, pergolide, pramipexole, and ropinirole are direct dopamine receptor agonists.
3. Benztropine, trihexyphenidyl, biperiden, and procyclidine are antimuscarinic drugs.
4. Diphenhydramine is an antihistamine that has antimuscarinic action.
5. Amantadine releases dopamine and inhibits neuronal uptake of dopamine.
6. Selegiline is an irreversible inhibitor of monoamine oxidase B (MAO-B), which metabolizes dopamine. Selegiline therefore increases the level of dopamine.
7. Tolcapone is an inhibitor of catechol-O-methyl transferase (COMT), another enzyme that metabolizes dopamine.
8. Entacapone is another COMT inhibitor.
Dopamine and acetylcholine.
Loss of dopaminergic neurons in Parkinsonism leads to unopposed action by cholinergic neurons. Inhibiting muscarinic receptors can help alleviate symptoms of Parkinsonism
Adverse effects
1. L-dopa
- The therapeutic effects of the drug decrease with time.
- Oscillating levels of clinical efficacy of the drug (“on-off” effect).
- Mental changes—psychosis.
- Tachycardia and orthostatic hypotension.
- Nausea.
- Abnormal muscle movements (dyskinesias).
2. Tolcapone, entacapone (similar to L-dopa).
3. Direct dopamine receptor agonists (similar to L-dopa).
4. Antimuscarinic drugs
- Typical antimuscarinic adverse effects such as dry mouth.
b. Sedation.
5. Diphenhydramine (see antimuscarinic drugs).
6. Amantadine
- Nausea.
- Dizziness.
- Edema.
- Sweating.
7. Selegiline
- Nausea.
- Dry mouth.
- Dizziness.
- Insomnia.
- Although selegiline is selective for MAO-B, it still can cause excessive toxicity in the presence of tricyclic antidepressants, SSRIs, and meperidine.
Indications
Parkinson’s disease is the obvious major use of the above drugs. Parkinson-like symptoms can occur with many antipsychotic drugs. These symptoms are often treated with antimuscarinic drugs or diphenhydramine.
Dental implications of anti-Parkinson drugs
1. Dyskinesia caused by drugs can present a challenge for dental treatment.
2. Orthostatic hypotension poses a risk when changing from a reclining to a standing position.
3. The dentist should schedule appointments at a time of day at which the best control of the disease occurs.
4. Dry mouth occurs with several of the drugs.
Oxyphenbutazone: one of the metabolites of phenylbutazone. Apazone. Similar to phenylbutazone, but less likely to cause agranulocytosis
Tetracycline
Tetracycline is an antibiotic produced by the streptomyces bacterium
Mechanism and Resistance Tetracycline inhibits cell growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. This prevents the addition of amino acids to the elongating peptide chain, preventing synthesis of proteins. The binding is reversible in nature.
Example: Chlortetracycline, oxytetracycline, demethylchlortetracycline, rolitetracycline, limecycline, clomocycline, methacycline, doxycycline, minocycline
Source: Streptomyces spp.; some are also semi-synthetic
Spectrum of activity: Broad-spectrum. Exhibits activity against a wide range of Gram-positive, Gram-negative bacteria, atypical organisms such as chlamydiae, mycoplasmas, rickettsiae and protozoan parasites.
Effect on bacteria: Bacteriostatic
Cells become resistant to tetracyline by at least two mechanisms: efflux and ribosomal protection.
Contraindications Tetracycline use should be avoided during pregnancy and in the very young (less than 6 years) because it will result in permanent staining of teeth causing an unsightly cosmetic result.
Tetracyclines also become dangerous past their expiration dates. While most prescription drugs lose potency after their expiration dates, tetracyclines are known to become toxic over time; expired tetracyclines can cause serious damage to the kidneys.
Miscellaneous: Tetracyclines have also been used for non-antibacterial purposes, having shown properties such as anti-inflammatory activity, immunosuppresion, inhibition of lipase and collagenase activity, and wound healing.
Valdecoxib
used in the treatment of osteoarthritis, acute pain conditions, and dysmenorrhoea
Etoricoxib new COX-2 selective inhibitor
Drugs used to induce vomiting
In case of poisoning with noncorrosive agents, and assuming incomplete absorption of the poison has taken place, induction of vomiting can be carried out. One of the drugs used for this purpose is emetine which causes irritation of the upper gut and, on absorption, it also acts on CTZ.
Chemotherapeutic agents (or their metabolites) can directly activate the medullary chemoreceptor trigger zone or vomiting center; several neuroreceptors, including dopamine receptor Type 2 and serotonin Type 3 (5-HT3) from cell damage(GIT and pharynx) play roles in vomiting.
Methods of general anesthesia
CIRCLE SYSTEM
*HIGH-FLOW
FRESH GAS FLOW > 3 l/min.
*LOW-FLOW
FGF ok. 1l/min.
*MINIMAL-FLOW
FGF ok. 0,5 l/min.
Beta - Adrenergic Blocking Agents
Mechanisms of Action
- Initial decrease in cardiac output, followed by reduction in peripheral vascular resistance.
- Other actions include decrease plasma renin activity, resetting of baroreceptors, release of vasodilator prostaglandins, and blockade of prejunctional beta-receptors.
Advantages
- Documented reduction in cardiovascular morbidity and mortality.
- Cardioprotection: primary and secondary prevention against coronary artery events (i.e. ischemia, infarction, arrhythmias, death).
- Relatively not expensive.
Considerations
- Beta blockers are used with caution in patients with bronchospasm.
- Contraindicated in more than grade I AV, heart block.
- Do not discontinue abruptly.
Side Effects
- Bronchospasm and obstructive airway disease.
- Bradycardia
- Metabolic effects (raise triglyerides levels and decrease HDL cholesterol; may worsen insulin sensitivity and cause glucose intolerance). Increased incidence of diabetes mellitus.
- Coldness of extremities.
- Fatigue.
- Mask symptoms of hypoglycemia.
- Impotence.
Indications
- First line treatment for hypertension as an alternative to diuretics.
- Hypertension associated with coronary artery disease.
- Hyperkinetic circulation and high cardiac output hypertension (e.g., young hypertensives).
- Hypertension associated with supraventricular tachycardia, migraine, essential tremors, or hypertrophic cardiomyopathy.
Beta adrenergic blocker Drugs
Atenolol 25-100
Metoprolol 50-200
Bisoprolol 2.5-10