CENTRAL NERVOUS SYSTEM PHARMACOLOGY

Antipsychotic Drugs

1. Phenothiazines

a. Aliphatic derivatives
(1) Chlorpromaxine
b. Piperidine derivatives
(1) Thioridazine
(2) Mesoridazine
c. Piperazine derivatives
(1) Fluphenazine
(2) Perphenazine
(3) Prochlorperazine
(4) Trifluoperazine

2. Haloperidol resembles the piperazine phenothiazines.

3. Thiothixene resembles the piperazine phenothiazines.

4. Others (e.g., loxapine, pimozide).

5. Newer and more atypical antipsychotic drugs:
a. Clozapine
b. Olanzapine
c. Quetiapine
d. Risperidone
e. Ziprasidone
f. Aripiprazole

Antidepressant Drugs

Drug treatment of depression is based on increasing serotonin (5-HT) or NE (or both) at synapses in selective tracts in the brain. This can be accomplished by different mechanisms.

Treatment takes several weeks to reach full clinical efficacy.

1. Tricyclic antidepressants (TCAs)
a. Amitriptyline
b. Desipramine
c. Doxepin
d. Imipramine
e. Protriptyline

2. Selective serotonin reuptake inhibitors (SSRIs)
a. Fluoxetine
b. Paroxetine
c. Sertraline
d. Fluvoxamine
e. Citalopram

3. Monoamine oxidase inhibitors (MAOIs)
a. Tranylcypromine
b. Phenelzine

4. Miscellaneous antidepressants

a. Bupropion
b. Maprotiline
c. Mirtazapine
d. Trazodone
e. St. John’s Wort

Antimania Drugs

These drugs are used to treat manic-depressive illness.

A. Drugs
1. Lithium
2. Carbamazepine
3. Valproic acid

Sedative Hypnotics

1. Benzodiazepines
2. Barbiturates
3. Zolpidem and zaleplon
4. Chloral hydrate
5. Buspirone
6. Other sedatives (e.g., mephenesin, meprobamate, methocarbamol, carisoprodol, cyclobenzaprine)
7. Baclofen
8. Antihistamines (e.g., diphenhydramine)
9. Ethyl alcohol

Antiepileptic Drugs

Phenytoin
Carbamazepine
Phenobarbital
Primidone
Gabapentin
Valproic acid
Ethosuximide

Anti-Parkinson Drugs

a. L-dopa plus carbidopa (Sinemet).
b. Bromocriptine, pergolide, pramipexole, ropinirole.
c. Benztropine, trihexyphenidyl, biperiden, procyclidine.
d. Diphenhydramine.
e. Amantadine.
f. Tolcapone and entacapone.
g. Selegiline.
 

BradyKinin

An endogenous vasodilator occurring in blood vessel walls. 
At least two distinct receptor types, B1 and B2, appear to exist for BradyKinin

Roles of bradykinin:

1) Mediator of inflammation and pain.
2) Regulation of microcirculation.
3) Their production is interrelated with clotting and fibrinolysin systems.
4) Responsible for circulatory change after birth.
5) Involved in shock and some immune reactions.

Loop (High Ceiling) Diuretics

Loop diuretics are diuretics that act at the ascending limb of the loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or renal insufficiency. While thiazide diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.

Agent: Furosemide

Mechanism(s) of Action

1.    Diuretic effect is produced by inhibit of active 1 Na⁺, 1 K⁺, 2 Cl^-  co-transport (ascending limb - Loop of Henle). 
o    This produces potent diuresis as this is a relatively important Na re-absorption site.

2.    Potassium wasting effect 

a.    Blood volume reduction leads to increased production of aldosterone 
b.    Increased distal Na load secondary to diuretic effect 
c.    a + b = increase Na (to blood) for K (to urine) exchange which produces indirect K wasting (same as thiazides but more likely)

3.    Increased calcium clearance/decreased plasma calcium 

o    secondary to passive decreases in loop Ca++ reabsorption.
o    This is linked to inhibition of Cl^- reabsorption.
o    This is an important clinical effect in patients with ABNORMAL High Ca⁺⁺
 

Procaine penicillin Procaine penicillin is a combination of benzylpenicillin with the local anaesthetic agent procaine. This combination is aimed at reducing the pain and discomfort associated with a large intramuscular injection of penicillin.

Indications

respiratory tract infections where compliance with oral treatment is unlikely ,syphilis, cellulitis

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. 
 

Estimation of the risk of anesthesia (American Society of Anesthesiologists scale)

• ASA 1: healthy patient.

• ASA 2: patient with stable, treated illness like arterial hypertension, diabetes melitus, asthma bronchiale, obesity

• ASA 3: patient with systemic illness decreasing sufficiency like heart illness, late infarct

• ASA 4: patient with serious illness influencing his state like renal insuficiency, unstable hypertension, circulatory insuficiency

• ASA 5: patient in life treatening illness

• ASA 6: brain death- potential organ donor