NEET MDS Lessons
Pharmacology
Anticonvulsant Drugs
A. Anticonvulsants: drugs to control seizures or convulsions in susceptible people
B. Seizures: abnormal neuronal discharges in the nervous system produced by focal or generalized brain disturbances
Manifestations: depend on location of seizure activity (motor cortex → motor convulsions, sensory cortex → abnormal sensations, temporal cortex → emotional disturbances)
Causes: many brain disorders such as head injury (glial scars, pH changes), anoxia (changes in pH or CSF pressure), infections (tissue damage, high T), drug withdrawal (barbiturates, ethanol, etc.), epilepsy (chronic state with repeated seizures)
C. Epilepsy: most common chronic seizure disorder, characterized by recurrent seizures of a particular pattern, many types (depending on location of dysfunction)
Characteristics: chronic CNS disorders (years to decades), involve sudden and transitory seizures (abnormal motor, autonomic, sensory, emotional, or cognitive function and abnormal EEG activity)
Etiology: hyperexcitable neurons; often originate at a site of damage (epileptogenic focus), often found at scar tissue from tumors, strokes, or trauma; abnormal discharge spreads to normal brain regions = seizure
Idiopathic (70%; may have genetic abnormalities) and symptomatic epilepsy (30%; obvious CNS trauma, neoplasm, infection, developmental abnormalities or drugs)
Neuropathophysiology: anticonvulsants act at each stage but most drugs not effective for all types of epilepsy (need specific drugs for specific types)
Seizure mechanism: enhanced excitation (glutamate) or ↓ inhibition (GABA) of epileptic focus → fire more quickly → ↑ release of K and glutamate → ↑ depolarization of surrounding neurons (=neuronal synchronization) → propagation (normal neurons activated)
ANTIDEPRESSANTS
Monoamine uptake inhibitors
1. Tricyclic antidepressants (TCAs)
2. Selective serotonin reuptake inhibitors (SSRIs)
3. Serotonin-norepinephrine reuptake inhibitors(SNRIs)
4. Norepinephrine reuptake inhibitor
Monoamine oxidase inhibitors (MAOIs)
Monoamine receptor antagonists
Ethosuximide (Zarontin): use in absence seizures (may exacerbate tonic-clonic seizures)
Mechanism: ↓ T-type Ca currents in thalamic neurons, inhibits bursts of APs, ↓ synchronous neuronal firing
i. Thalamo-cortical reverberating circuits: during absence type seizures, have reverberating circuits between cerebral cortex and thalamus at 3 Hz maintained by T-type Ca channels (since blocking these channels blocks the reverberating circuit)
Side effects: quite non-toxic; common= N/V and anorexia; less common = headache, sedation, photophobia
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
Fifth Generation:
These are extended spectrum antibiotics.
Ceftaroline, Ceftobiprole
Drug-Receptor Interactions
Drug Receptor: any functional macromolecule in a cell to which a drug binds to produce its effects. at receptors, drugs mimic or block the action of the body's own regulatory molecules.
Receptors and Selectivity of Drug Action : If a drug interacts with only one kind of receptor, and if that receptor regulates just a few processes, then the effects of the drug will be limited.
Even though a drug is selective for one type of receptor, it can still produce a variety of effects.
Selectivity does not guarantee safety.
Theories of Drug-Receptor Interaction
- Simple Occupancy Theory: Two factors - The intensity of the response to a drug is proportional to the number of receptors occupied by that drug, and the maximal response will occur when all available receptors have been occupied.
- Modified Occupancy Theory: Assumes that all drugs acting at a particular receptor are identical with respect to the ability to bind to the receptor and the ability to influence receptor function once binding has taken place.
• Affinity: The strength of the attraction between a drug and its receptor. Affinity is reflected in potency. (Drugs with high affinity are very potent).
• Intrinsic Activity: The ability of a drug to activate a receptor following binding. Reflected in the maximal efficacy (drugs with high intrinsic activity have high maximal efficacy).
Distal (Potassium Sparing) Diuretics
Agents:
spironolactone
triamterene
Mechanism of action
Inhibition of Na/K exchange at aldosterone dependent distal tubular site
Spironolactone - competes with aldosterone for regulatory site
Triamterene - decreases activity of pump directly
• Either mechanism decreases potassium wasting
• Either mechanism produces poor diuresis (when used alone)
o relatively unimportant Na recovery site
Diurectic activity increased if:
• sodium load (body) is high
• aldosterone concentrations are high
• sodium load (tubule) is high - secondary to diuresis
Other electrolytes unaffected
Toxicity
• spironolactone may produce adrenal and sex hormone effects with LONG-TERM use
• Both drugs may produce electrolyte imbalance