NEET MDS Lessons
Pharmacology
Sedative-Hypnotic Drugs
Sedative drug is the drug that reduce anxiety (anxiolytic) and produce sedation and referred to as minor tranquillisers.
Hypnotic drug is the drug that induce sleep
Effects: make you sleepy; general CNS depressants
Uses: sedative-hypnotic (insomnia ), anxiolytic (anxiety, panic, obsessive compulsive, phobias), muscle relaxant (spasticity, dystonias), anticonvulsant (absence, status epilepticus, generalized seizures—rapid tolerance develops), others (pre-operative medication and endoscopic procedures, withdrawal from chronic use of ethanol or other CNS depressants)
1- For panic disorder alprazolam is effective.
2- muscle disorder: (reduction of muscle tone and coordination) diazepam is useful in treatment of skeletal muscle spasm e.g. muscle strain and spasticity of degenerative muscle diseases.
3-epilepsy: by increasing seizure threshold.
Clonazepam is useful in chronic treatment of epilepsy while diazepam is drug of choice in status epilepticus.
4-sleep disorder: Three BDZs are effective hypnotic agents; long acting flurazepam, intermediate acting temazepam and short
acting triazolam. They decrease the time taken to get to sleep They increase the total duration of sleep
5-control of alcohol withdrawals symptoms include diazepam, chlordiazepoxide, clorazepate and oxazepam.
6-in anesthesia: as preanesthetic amnesic agent (also in cardioversion) and as a component of balanced anesthesia
Flurazepam significantly reduce both sleep induction time and numbers of awakenings and increase duration of sleep and little rebound insomnia. It may cause daytime sedation.
Temazepam useful in patients who experience frequent awakening, peak sedative effect occur 2-3 hr. after an oral dose.
Triazolam used to induce sleep in recurring insomnia and in individuals have difficulty in going to sleep, tolerance develop within few days and withdrawals result in rebound insomnia therefore the drug used intermittently.
Drugs and their actions
1. Benzodiazepines: enhance the effect of gamma aminobutyric acid (GABA) at GABA receptors on chloride channels. This increases chloride channel conductance in the brain (GABA A A receptors are ion channel receptors).
2. Barbiturates: enhance the effect of GABA on the chloride channel but also increase chloride channel conductance independently of GABA, especially at high doses
3. Zolpidem and zaleplon: work in a similar manner to benzodiazepines but do so only at the benzodiazepine (BZ1) receptor type. (Both BZ1and BZ2 are located on chloride channels.)
4. Chloral hydrate: probably similar action to barbiturates.
5. Buspirone: partial agonist at a specific serotonin receptor (5-HT1A).
6. Other sedatives (e.g., mephenesin, meprobamate, methocarbamol, carisoprodol, cyclobenzaprine):
mechanisms not well-described. Several mechanisms may be involved.
7. Baclofen: stimulates GABA linked to the G protein, Gi , resulting in an increase in K + conductance and a decrease in Ca2+ conductance. (Other drugs mentioned above do not bind to the GABA B receptor.)
8. Antihistamines (e.g., diphenhydramine): block H1 histamine receptors. Doing so in the CNS leads to sedation.
9. Ethyl alcohol: its several actions include a likely effect on the chloride channel.
Anesthesia agents
1. Inhalation anesthetics (volatile anesthetics)
- gases : N2O, xenon
- Fluids (vaporisers)
2. Intravenous anesthetics
- Barbiturans : thiopental
- Others : propofol, etomidat
3. Pain killers
- Opioids: fentanyl, sufentanil, alfentanil, remifentanil, morphine
- Non Steroid Anti Inflamatory Drugs: ketonal, paracetamol
4. Relaxants
- Depolarising : succinilcholine
- Non depolarising : atracurium, cisatracurium, vecuronium, rocuronium
5. adiuvants
-benzodiazepins: midasolam, diazepam
Neuron Basic Structure (How brain cells communicate)
• Synapse:A junction between the terminal button of an axon and the membrane of another neuron
• Terminal button(orbouton):The bud at the end of a branch of an axon; forms synapses with another neuron; sends information to that neuron.
• Neurotransmitter:A chemical that is released by a terminal button; has an excitatory or inhibitory effect on another neuron.
Different types of Synapses
1-Axo-denrdritic
2-Axo-axonal
3-Axo-somatic
Chemical transmission in the CNS
The CNS controls the main functions of the body through the action endogenous chemical substances known as “neurotransmitters”.
These neurotransmitters are stored in and secreted by neurons to “transmit”information to the postsynaptic sites producing either excitatoryor inhibitory responses.
Most centrally acting drugs exert their actions at the synaptic junctions by either affecting neurotransmitter synthesis, release, uptake, or by exerting direct agonistor antagonistaction on postsynaptic sites.
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)
Insulin
Insulin is only given parenterally (subcutaneous or IV) Various preparations have different durations of action
|
Preparation |
Onset (hrs) |
Peak (hrs) |
Duration (hrs) |
| Lispro (rapid-acting) | 15 min | 0.5-1.5 | 3-4 |
| Regular (short-acting) | 0.5-1 | 2-4 | 5-7 |
| NPH (intermediate) | 1-2 | 6-12 | 18-24 |
| Glargine (long-acting) | 1 | None | >24 |
Mechanism
bind transmembrane insulin receptor
activate tyrosine kinase
phosphorylate specific substrates in each tissue type
liver
↑ glycogenesis
store glucose as glycogen
muscle
↑ glycogen and protein synthesis
↑ K+ uptake
fat
increase triglyceride storage
Clinical use
type I DM
type II DM
life-threatening hyperkalemia
increases intracellular K+
stress-induced hyperglycemia
Toxicity
hypoglycemia
hypersensitivity reaction (very rare)
Insulin Synthesis
first generated as preproinsulin with an A chain and B chain connected by a C peptide.
c-peptide is cleaved from proinsulin after packaging into vesicles leaving behind the A and B chains
Propoxyphene
- A methadone analog.Used orally to relieve mild to moderate pain.
- A typical opiate, it does not possess anti-inflammatory or antipyretic actions, but has little or no antitussive activity.
- Cannot be used parenterally because of irritant properties.
- Has a low addiction potential primarily due to its lack of potency as an opiate.
- The most common adverse side effects are:• dizziness, drowsiness, and nausea and vomiting. • these effects are more prominent in ambulatory patients.
- Withdrawal symptoms have occurred in both adults and in neonates following use of the drug by the mother during pregnancy.
- CNS depression is additive with other CNS depressants.
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.