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Pharmacology - NEETMDS- courses
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Pharmacology

Different Systems of the CNS & their functions

These systems are pathways formed of specific parts of the brain and the neurons connecting them. 

They include:
1.The pyramidal system 
2.The extrapyramidal system 
3.The limbic system 
4.The reticular formation 
5.The tuberohypophyseal system

The pyramidal system: 

It originates from the motor area of the cerebral cortex and passes through the spinal cord, therefore it is also known as the “corticospinaltract”. 
It is responsible for the regulation of the fine voluntary movements.

The extrapyramidal system: 

It also controls the motor functionbut involves areas other than the corticospinal tract. 
It is involved in the regulation of gross voluntary movements, thus it complements the function of the pyramidal system. 


The “basal ganglia” constitute an essential part of this system. 

Degenerative changes in the pathway running from the “substantianigra”to the “corpus striatum”(or nigrostriatal pathway) may cause tremors and muscle rigidity characteristic of “Parkinson’s disease”.


The limbic system: 

The major parts of this system are: the hypothalamus, the basal ganglia, the hippocampus(responsible for short term memory), and some cortical areas. 

The limbic system is involved in the control of “behavior”& “emotions”.


The reticular formation:

It is composed of interlacing fibers and nerve cells that run in all directions beginning from the upper part of the spinal cord and extending upwards. 
It is important in the control of “consciousness” and “wakefulness”.


The tuberohypophyseal system: 

It is a group of short neurons running from the hypothalamusto the hypophysis(pituitary gland) regulating its secretions.
 

Ciclopirox:Ciclopirox is a synthetic antifungal agent for topical dermatologic use.

Benzodiazepines
All metabolites are active sedatives except the final glucuronide product. Elimination half-life varies a great deal from drug to drug.

?-Hydroxylation is a rapid route of metabolism that is unique to triazolam, midazolam, and alprazolam.
This accounts for the very rapid metabolism and short sedative actions of these drugs.

Pharmacological effects of benzodiazepines

- Antianxiety.
- Sedation.
- Anticonvulsant (including drug-induced convulsions).
- Amnesia, especially drugs like triazolam.
- Relax skeletal muscle (act on CNS polysynaptic pathways).

Indications

- IV sedation, (e.g., midazolam, diazepam, lorazepam).
- Antianxiety.
- Sleep induction.
- Anticonvulsant (e.g., diazepam, clonazepam).
- Panic disorders.
- Muscle relaxation.


Adverse effects

- Ataxia, confusion.
- Excessive sedation.
- Amnesia (not a desired effect with daytime sedation).
- Altered sleep patterns (increase stage 2 and decrease stage 4 sleep).

TCI -Target Controlled Infusion

TCI is an infusion system which allows the anaesthetist to select the target blood concentration required for a particular effect and then to control depth of anaesthesia by adjusting the requested target concentration

Mechanism

Instead of setting ml/h or a dose rate (mg/kg/h), the pump can be programmed to target a required blood concentration.

• Effect site concentration targeting is now included for certain pharmacokinetic models.

• The pump will automatically calculate how much is needed as induction and maintenance to maintain that concentration.

Thiopental 

- A barbiturate that is generally used to induce anesthesia.
- The temporal course of effects from induction to recovery depends almost entirely upon progressive redistribution.
- Metabolic degradation or excretion during anesthesia is negligible, except in the case of methohexital.
- The barbiturates produce minimal analgesia.
- Respiratory depression may be pronounced.
- Cardiac output is reduced while total peripheral resistance is increased.
- It does not sensitize the heart to catecholamines.
- It may cause bronchiospasm, especially in asthmatics.
- It is contraindicated in acute intermittent porphyria.

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

Beta - Adrenoceptor blocking Agents

These are the agents which block the action of sympathetic nerve stimulation and circulating sympathomimetic amines on the beta adrenergic receptors. 

At the cellular level, they inhibit the activity of the membrane cAMP. The main effect is to reduce cardiac activity by diminishing β1 receptor stimulation in the heart. This decreases the rate and force of myocardial contraction of the heart, and decreases the rate of conduction of impulses through the conduction system.

Beta blockers may further be classified on basis of their site of action into following two main classes namely 

cardioselective beta blockers (selective beta 1 blockers) 

non selective beta 1 + beta 2 blockers 

Classification for beta adrenergic blocking agents.

A. Non-selective (β1+β2)

Propranolol  Sotalol  Nadolol Timolol  Alprenolol Pindolol 

With additional alpha blocking activity

Labetalol  Carvedilol  

B. β1 Selective (cardioselective)

Metoprolol  Atenolol  Bisoprolol  Celiprolol  

C. β2  Selective

Butoxamine 


Mechanisms of Action of beta blocker

Beta adrenoceptor Blockers competitively antagonize the responses to catecholamines that are mediated by beta-receptors and other
adrenomimetics at β-receptors 

Because the β-receptors of the heart are primarily of the β1 type and those in the pulmonary and vascular smooth muscle are β2 receptors, β1-selective antagonists are frequently referred to as cardioselective blockers. 


β-adrenergic receptor blockers (β blockers)
1. Used more often than α blockers.
2. Some are partial agonists (have intrinsic sympathomimetic activity).
3. Propranolol is the prototype of nonselective β blockers.
4. β blocker effects: lower blood pressure, reduce angina, reduce risk after myocardial infarction, reduce heart rate and force, have antiarrhythmic effect, cause hypoglycemia in diabetics, lower intraocular pressure.
5. Carvedilol: a nonselective β blocker that also blocks α receptors; used for heart failure.
 

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