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.
Drugs Used in Diabetes
Goals of diabetes treatment
lower serum glucose to physiologic range
keep insulin levels in physiologic range
eliminate insulin resistance
best initial step in management: weight loss, contractile-based exercise weight loss is more important for insulin sensitivity than is a low-carb diet
Modalities of diabetes treatment
Type I DM
insulin
low-sugar diet
Type II DM
exercise
diet
insulin
6 classes of drugs
Insulin
Sulfonylureas - Glyburide
Meglitinides - Nateglinide
Biguanides Metformin
Glitazones (thiazolidinediones) Pioglitazone
α-glucosidase inhibitors Acarbose
GLP-1 mimetics (incretin mimetics) Exenatide
Amylin analog Pramlintide
TRIMETHOPRIM
It is a diaminopyrimidine. It inhibits bacterial dihydrofolate reductase( DHFRase).
In combination with sulphamethoxzole it is called Co-trimoxazole.
Spectrum of action
S. Typhi. Serratia. Klebsiela and many sulphonamide resistant strains of Staph.aureus. Strep pyogens
Adverse effects
Megaloblastic anemia. i.e.. due to folate defeciency.
Contraindicated in pregnancy.
Diuretics if given with co-trimoxazole cause thrombocytopenia.
Uses
I. UTI. 2. RTI. 3. Typhoid. 5. Septicemias. 5. Whooping cough
DIAGNOSIS
Affective disorders:
I. unipolar depression – depression alone
bipolar affective disorder – alternating II. bipolar affective disorder – alternating depression and mania
Diagnosis is based on
At least five of the following for 2 weeks
I. Depressed mood most of the day
II. Markedly diminished interest or pleasureII. Markedly diminished interest or pleasure
III. Significant weight loss or weight
IV. Insomnia or hypersomnia
V. Psychomotor agitation or retardation
VI. Fatigue or loss of energy
VII. Feelings of worthlessness or excessive guilt
VIII. Diminished ability to think or concentrate,
IX. Recurrent thoughts of death
Underlying biological basis for depression is a deficiency of the monoamine neurotransmitters norepinephrine and/or serotonin in the brain.
Antiemetics
Antiemetic drugs are generally more effective in prophylaxis than treatment. Most antiemetic agents relieve nausea and vomiting by acting on the vomiting centre, dopamine receptors, chemoreceptors trigger zone (CTZ), cerebral cortex, vestibular apparatus, or a combination of these.
Drugs used in the treatment of nausea and vomiting belong to several different groups. These include:
1. Phenothiazines, such as chlorpromazine, act on CTZ and vomiting centre, block dopamine receptors, are effective in preventing or treating nausea and vomiting induced by drugs, radiation therapy, surgery and most other stimuli (e.g. pregnancy).
They are generally ineffective in motion sickness.
Droperidol had been used most often for sedation in endoscopy and surgery, usually in combination with opioids or benzodiazepines
2. Antihistamines such as promethazine and Dimenhyrinate are especially effective in prevention and treatment of motion.
3. Metoclopramide has both central and peripheral antiemetic effects. Centrally, it antagonizes the action of dopamine. Peripherally metoclopramide stimulates the release of acetylcholine, which in turn, increases the rate of gastric. It has similar indications to those of chlorpromazine.
4. Scopolamine, an anticholinergic drug, is very effective in reliving nausea & vomiting associated with motion sickness.
5. Ondansetron, a serotonin antagonist, is effective in controlling chemical-induced vomiting and nausea such those induced by anticancer drugs.
6. Benzodiazepines: The antiemetic potency of lorazepam and alprazolam is low. Their beneficial effects may be due to their sedative, anxiolytic, and amnesic properties
Warfarin (Coumadin):
- The most common oral anticoagulant.
- It is only active in vivo.
- Warfarin is almost completely bound to plasma proteins. -96% to 98% bound.
- Warfarin is metabolized by the liver and excreted in the urine.
- Coumarin anticoagulants pass the placental barrier and are secreted into the maternal milk.
- Newborn infants are more sensitive to oral anticoagulants than are adults because of lower vitamin K levels and lower rates of metabolism.
- Bleeding is the most common side effect and occurs most often from the mucous membranes of the gastrointestinal tract and the genitourinary tract.
Oral anticoagulants are contraindicated in:
• Conditions where active bleeding must be avoided, Vitamin K deficiency and severe
hepatic or renal disease, and where intensive salicylate therapy is required.
Carbamazepine (Tegretol): most common; for generalized tonic-clonic and all partial seizures; especially active in temporal lobe epilepsies
Mechanism: ↓ reactivation of Na channels (↑ refractory period, blocks high frequency cell firing, ↓ seizure spread)
Side effects: induces hepatic microsomal enzymes (can enhance metabolism of other drugs)