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.

DOPAMINE

It is an immediate metabolic precursor of noradrenaline. It activates D1 receptors in several vascular beds, which causes vasodilatation. It acts on dopaminergic and other adrenergic receptors (α & β1).

Adverse effects of dopamine include nausea, vomiting, ectopic beats, anginal pain, tachycardia, palpitation and widened QRS.
Contraindications are atrial or ventricular tachyarrhythmias, hyperthyroidism and pheochromocytoma.

Pramlintide -Amylin mimetics

Mechanism
synthetic analogue of human amylin that acts in conjunction with insulin
↓ release of glucagon
delays gastric emptying

Clinical use

type I and II DM

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.
 

Pharmacology is the study of drugs and the way they interact with living systems.  Clinical pharmacology is the study of drugs in humans.

A drug is any chemical that can effect living processes.

Therapeutics: the medical use of drugs.

An ideal drug has several important properties.  Three of these properties are of utmost importance: effectiveness, safety and selectivity. 

Effectiveness: This is the most important quality that a drug can have.  Effectiveness refers to the drug's ability to do what it is supposed to do.

Safety:  Although no drug can be totally safe, proper usage can lessen the risks of adverse effects.

Selectivity:  A truly selective drug would have no side effects, and would effect only the body process' for which it is designed and given.  Therefore, there is no such thing as a selective drug.

Pharmacokinetics: The way the body deals with a drug.  Pharmacokinetics is concerned with the processes of absorption, distribution, metabolism and excretion.

Pharmacodynamics:  What a drug does to the body.

Pharmacokinetics and pharmacodynamics are two of the processes that determine how a person will respond to a drug.  Other factors include how a drug is administered (dose, route, and timing of administration), interactions with other drugs, and individual physiological variables (weight, age, function of body systems).

Lithium carbonate: 1st choice (controls mania in bipolar disorders); delay before onset of therapeutic benefit; no psychotropic effects in normal humans

i. Mechanism: blocks enzymes in inositol phosphate signaling pathway; no consistent effects of lithium on NE, 5-HT, and DA
ii. Side effects: severe CNS (ataxia, delirium, coma, convulsions) and CV (cardiac dysrhythmias)