NEET MDS Lessons
Pharmacology
Cells of the Nervous System
1-Neurons (Nerve Cells):function units of the nervous system by conducting nerve impulses, highly specialized and amitotic. Each has a cell body (soma), one or more dendrites, and a single axon.
• Cell Body: it has a nucleus with at least one nucleolus and many of the typical cytoplasmic organelles, but lacks centriolesfor cell division.
• Dendrites:Dendrites and axons are cytoplasmic extensions (or processes), that project from the cell body. They are sometimes referred to as fibers. Dendrites (afferent processes) increase their surface area to receive signals from other neurons, and transmit impulses to the neuron cell body.
• Axon: There is only one axon (efferent process) that projects from each cell body.
It carries impulses away from the cell body.
2-Glial cells: do not conduct nerve impulses, but support, nourish, and protect the neurons. They are mitotic, and far more numerous than neurons.
Astrocyte: A glialcell that provides support for neurons of the CNS, provides nutrients regulates the chemical composition of the extracellularfluid.
• Oligodendrocyte: A type of glialcell in the CNS that forms myelin sheaths.
• Microglia:The smallest glialcells; act as phagocytes (cleaning up debris) and protect the brain from invading microorganisms.
• Schwann cell:A cell in the PNS that is wrapped around a myelinatedaxon, providing one segment of its myelin sheath.
ANTIASTHMATIC AGENTS
Classification for antiasthmatic drugs.
I. Bronchodilators
i. Sympathomimetics (adrenergic receptor agonists)
Adrenaline, ephedrine, isoprenaline, orciprenaline, salbutamol, terbutaline, salmeterol, bambuterol
ii. Methylxanthines (theophylline and its derivatives)
Theophylline
Hydroxyethyl theophylline
Theophylline ethanolate of piperazine
iii. Anticholinergics
Atropine methonitrate
Ipratropium bromide
II. Mast cell stabilizer
Sodium cromoglycate
Ketotifen
III. Corticosteroids
Beclomethasone dipropionate
Beclomethasone (200 µg) with salbutamol
IV. Leukotriene pathway inhibitors
Montelukast
Zafirlukast
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.
ISOPRENALINE
It is beta-receptor stimulant, which stimulates the heart and causes tachycardia.
It relaxes the smooth muscles particularly the bronchial and GIT. It is mainly used in bronchial asthma, in the treatment of shock and as a cardiac stimulant in heart block.
ORCIPRENALINE
Is a potent β-adrenergic agonist.
Receptor sites in the bronchi and bronchioles are more sensitive to the drug than those in the heart and blood vessels.
AMPHETAMINE
increases the systolic and diastolic blood pressure. Amphetamine is a potent CNS stimulant and causes alertness, insomnia, increased concentration, euphoria or dysphoria and increased work capacity.
Amphetamines are drugs of abuse and can produce behavioural abnormalities and can precipitate psychosis.
PHENYLEPHRINE
It is used as a nasal decongestant and mydriatic agent and also in the treatment of paroxysmal supraventricular tachycardia.
UTERINE RELAXANTS (TOCOLYTICS)
ISOXSUPRINE
Isoxsuprine has a potent inhibitory effect on vascular and uterine smooth muscle and has been used in the treatment of dysmenorrhoea, threatened abortion, premature labour and peripheral vascular diseases.
Pharmacodynamics
Pharmacodynamics is the study of what drugs do to the body and how they do it.
Dose-Response Relationships
- Basic Features of the Dose-Response Relationship: The dose-response relationship is graded instead of all-or-nothing (as dose increases, response becomes progressively larger).
- Maximal Efficacy and Relative Potency
- Maximal Efficacy: the largest effects that a drug can produce
- Relative Potency: Potency refers to the amount of drug that must be given to elicit an effect.
- Potency is rarely an important characteristic of a drug.
- Potency of a drug implies nothing about its maximal efficacy.
Antipsychotic Drugs
A. Neuroleptics: antipsychotics; refers to ability of drugs to suppress motor activity and emotional expression (e.g., chlorpromazine shuffle)
Uses: primarily to treat symptoms of schizophrenia (thought disorder); also for psychoses (include drug-induced from amphetamine and cocaine), agitated states
Psychosis: variety of mental disorders (e.g., impaired perceptions, cognition, inappropriate or ↓ affect or mood)
Examples: dementias (Alzheimer’s), bipolar affective disorder (manic-depressive)
B. Schizophrenia: 1% world-wide incidence (independent of time, culture, geography, politics); early onset (adolescence/young adulthood), life-long and progressive; treatment effective in ~ 50% (relieve symptoms but don’t cure)
Symptoms: antipsychotics control positive symptoms better than negative
a. Positive: exaggerated/distorted normal function; commonly have hallucinations (auditory) and delusions (grandeur; paranoid delusions particularly prevalent; the most prevalent delusion is that thoughts are broadcast to world or thoughts/feelings are imposed by an external force)
b. Negative: loss of normal function; see social withdrawal, blunted affect (emotions), ↓ speech and thought, loss of energy, inability to experience pleasure
Etiology: pathogenesis unkown but see biochemical (↑ dopamine receptors), structural (enlarged cerebral ventricles, cortical atrophy, ↓ volume of basal ganglia), functional (↓ cerebral blood flow, ↓ glucose utilization in prefrontal cortex), and genetic abnormalities (genetic predisposition, may involve multiple genes; important)
Dopamine hypothesis: schizo symptoms due to abnormal ↑ in dopamine receptor activity; evidenced by
i. Correlation between potency and dopamine receptor antagonist binding: high correlation between therapeutic potency and their affinity for binding to D2 receptor, low correlation between potency and binding to D1 receptor)
ii. Drugs that ↑ dopamine transmission can enhance schizophrenia or produce schizophrenic symptoms:
A) L-DOPA: ↑ dopamine synthesis
B) Chronic amphetamine use: releases dopamine
C) Apomorphine: dopamine agonist
iii. Dopamine receptors ↑ in brains of schizophrenics: postmortem brains, positron emission tomography
Dopamine pathways: don’t need to know details below; know that overactivity of dopamine neurons in mesolimbic and mesolimbocortical pathways → schizo symptoms
i. Dorsal mesostriatal (nigrostriatal): substantia nigra to striatum; controls motor function
ii. Ventral mesostriatal (mesolimbic): ventral tegmentum to nucleus accumbens; controls behavior/emotion; abnormally active in schizophrenia
iii. Mesolimbocortical: ventral tegmentum to cortex and limbic structures; controls behavior and emotion; activity may be ↑ in schizophrenia
iv. Tuberohypophyseal: hypothalamus to pituitary; inhibits prolactin secretion; important pathway to understand side effects
Antipsychotic drugs: non-compliance is major reason for therapeutic failure
1. Goals: prevent symptoms, improve quality of life, minimize side effects
2. Prototypical drugs: chlorpromazine (phenothiazine derivative) and haloperidol (butyrophenone derivative)
a. Provide symptomatic relief in 70%; delayed onset of action (4-8 weeks) and don’t know why (maybe from ↓ firing of dopamine neurons that project to meso-limbic and cortical regions)
3. Older drugs: equally efficacious in treating schizophrenia; no abuse potential, little physical dependence; dysphoria in normal individuals; high therapeutic indexes (20-1000)
Classification:
i. Phenothiazines: 1st effective antipsychotics; chlorpromazine and thioridazine
ii. Thioxanthines: less potent; thithixene
iii. Butyrophenones: most widely used; haloperidol
Side effects: many (so known as dirty drugs); block several NT receptors (adrenergic, cholindergic, histamine, dopamine, serotonin) and D2 receptors in other pathways
i. Autonomic: block muscarinic receptor (dry mouth, urinary retention, memory impairment), α-adrenoceptor (postural hypotension, reflex tachycardia)
Neuroleptic malignant syndrome: collapse of ANS; fever, diaphoresis, CV instability; incidence 1-2% of patients (fatal in 10%); need immediate treatment (bromocriptine- dopamine agonist)
ii. Central: block DA receptor (striatum; have parkinsonian effects like bradykinesia/tremor/muscle rigidity, dystonias like neck/facial spasms, and akathisia—subject to motor restlessness), dopamine receptor (pituitary; have ↑ prolactin release, breast enlargement, galactorrhea, amenorrhea), histamine receptor (sedation)
DA receptor upregulation (supersensitivity): occurs after several months/years; see tardive dyskinesias (involuntary orofacial movements)
Drug interactions: induces hepatic metabolizing enzymes (↑ drug metabolism), potentiate CNS depressant effects (analgesics, general anesthetics, CNS depressants), D2 antagonists block therapeutic effects of L-DOPA used to treat Parkinson’s
Toxicity: high therapeutic indexes; acute toxicity seen only at very high doses (hypotension, hyper/hypothermia, seizures, coma, ventricular tachycardia)
Mechanism of action: D2 receptor antagonists, efficacy ↑ with ↑ potency at D2 receptor
Newer drugs: include clozapine (dibenzodiazepine; has preferential affinity for D4 receptors, low affinity for D2 receptors), risperidone (benzisoxazole), olanzapine (thienobenzodiazepine)
Advantages over older drugs: low incidence of agranulocytosis (leucopenia; exception is clozapine), very low incidence of motor disturbances (extrapyramidal signs; may be due to low affinity for D2 receptors), no prolactin elevation
Side effects: DA receptor upregulation (supersensitivity) occurs after several months/years; may → tardive diskinesias
Methyl salicylate
also known as oil of wintergreen, betula oil, methyl ester) is a natural product of many species of plants Structurally, it is methylated salicylic acid It is used as an ingredient in deep heating rubs