Gentamicin

Gentamicin is a aminoglycoside antibiotic, and can treat many different types of bacterial infections, particularly Gram-negative infection.

Gentamicin works by binding to a site on the bacterial ribosome, causing the genetic code to be misread.

Like all aminoglycosides, gentamicin does not pass the gastro-intestinal tract, so it can only be given intravenously or intramuscularly.

Gentamicin can cause deafness or a loss of equilibrioception in genetically susceptible individuals. These individuals have a normally harmless mutation in their DNA, that allows the gentamicin to affect their cells. The cells of the ear are particularly sensitive to this.

Gentamicin can also be highly nephrotoxic, particularly if multiple doses accumulate over a course of treatment. For this reason gentamicin is usually dosed by body weight. Various formulae exist for calculating gentamicin dosage. Also serum levels of gentamicin are monitored during treatment.

E. Coli has shown some resistance to Gentamicin, despite being gram-negative

Valproic acid: broad spectrum (for most seizure types)

Mechanism: blocks Ca T currents in thalamic neurons (prevents reverberating activity in absence seizures), ↓ reactivation of Na channels (in tonic/clonic seizures; prolongs refractory periods of neurons, prevents high frequency cell firing)

Side effects: very low toxicity; common = anorexia, N/V; at high doses inhibits platelet function (bruising and gingival bleeding); rarely see idiosyncratic hepatotoxicity

Drug interactions: induces hepatic microsomal enzymes (↓ effectiveness of other drugs), binds tightly to plasma proteins so displaces other drugs

Sympatholytics (Antiadrenergic Agents)

PHENOXYBENZAMINE
It is a potent alpha-adrenergic blocking agent 

It effectively prevents the responses mediated by alpha receptors and diastolic blood pressure tends to decrease.
It interferes with the reflex adjustment of blood pressure and produces postural hypotension. 
It increases the cardiac output and decreases the total peripheral resistance.

It is used in the management of pheochromocytoma and also to treat peripheral vasospastic conditions e.g. Raynaud’s disease and shock syndrome.

Phentolamine, another alpha blocker is exclusively used for the diagnosis of pheochromocytoma and for the prevention of abrupt rise in blood pressure during surgical removal of adrenal medulla tumors.

ERGOT ALKALOIDS

 Ergotamine is an  important alkaloid that possesses both vasoconstrictor and alpha-receptor blocking activity. Both ergotamine and dihydroergotamine are used in the treatment of migraine.

METHYSERGIDE

It is a 5-hydroxytryptamine antagonist ). It is effective in preventing an attack of migraine. 

SUMATRIPTAN

It is a potent selective 5-HT 1D  receptor agonist used in the treatment of migraine.

PRAZOSIN
It is an piperazinyl quinazoline effective in the management of hypertension. It is highly selective for α1  receptors. It also reduces the venous return and cardiac output. It is used in essential hypertension, benign prostatic hypertrophy and in Raynaud’s syndrome.
Prazosin lowers blood pressure in human beings by relaxing both veins and resistance vessels but it dilates arterioles more than veins.

TERAZOSIN
It is similar to prazosin but has higher bioavailability and longer plasma t½

DOXAZOSIN
It is another potent and selective α1 adrenoceptor antagonist and quinazoline derivative.
It’s antihypertensive effect is produced by a reduction in smooth muscle tone of peripheral vascular beds.

TAMSULOSIN
It is uroselective α1A  blocker and has been found effective in improving BPH symptoms.

Other drugs used for erectile dysfunction

Sildenafil: It is orally active selective inhibitor of phosphodiesterase type 5 useful in treatment of erectile dysfunction.

Example calculations of maximum local anesthetic doses for a 15-kg child

Articaine

5 mg/kg maximum dose × 15 kg = 75 mg

4% articaine = 40 mg/mL

75 mg/(40 mg/mL) = 1.88 mL

1 cartridge = 1.8 mL

Therefore, 1 cartridge is the maximum

Lidocaine

7 mg/kg × 15 kg = 105 mg

2% lidocaine = 20 mg/mL

105 mg/(20 mg/mL) = 5.25 mL

1 cartridge = 1.8 mL

Therefore, 2.9 cartridges is the maximum

Mepivacaine

6.6 mg/kg × 15 kg = 99 mg

3% mepivacaine = 30 mg/mL

99 mg/(30 mg/mL) = 3.3 mL

1 cartridge = 1.8 mL

Therefore, 1.8 cartridges is the maximum.

Prilocaine

8 mg/kg × 15 kg = 120 mg

4% prilocaine = 40 mg/mL

120 mg/(40 mg/mL) = 3 mL

1 cartridge = 1.8 mL

Therefore, 1.67 cartridges is the maximum

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.
 

DIURETICS

The basis for the use of diuretics is to promote sodium depletion (and thereby water) which leads to a decrease in extracellular fluid volume.
An important aspect of diuretic therapy is to prevent the development of tolerance to other antihypertensive drugs.

TYPES OF DIURETICS
A. Thiazide Diuretics examples include     chlorothiazide 
hydrochlorothiazide 
a concern with these drugs is the loss of potassium as well as sodium

B. Loop Diuretics (High Ceiling Diuretics) examples include 
furosemide (Lasix)
bumetanide
these compounds produce a powerful diuresis and are capable of producing severe derangements of electrolyte balance

C. Potassium Sparing Diuretics examples include
triamterene
amiloride 
spironolactone 
unlike the other diuretics, these agents do not cause loss of potassium

Mechanism of Action

Initial effects: through reduction of plasma volume and cardiac output.
Long term effect: through decrease in total peripheral vascular resistance.

Advantages

Documented reduction in cardiovascular morbidity and mortality.
Least expensive antihypertensive drugs.
Best drug for treatment of systolic hypertension and for hypertension in theelderly.
Can be combined with all other antihypertensive drugs to produce synergetic effect.

Side Effects
Metabolic effects (uncommon with small doses): hypokalemia,hypomagnesemia, hyponatremia, hyperuricemia, dyslipidemia (increased total
and LDL cholesterol), impaired glucose tolerance, and hypercalcemia (with thiazides).
Postural hypotension.
Impotence in up to 22% of patients.  

 Considerations
- Moderate salt restriction is the key for effective antihypertensive effect of diuretics and for protection from diuretic - induced hypokalaemia. 
- Thiazides are not effective in patients with renal failure (serum creatinine > 2mg /dl) because of reduced glomerular filtration rate.
- Frusemide needs frequent doses ( 2-3 /day ).Thiazides can be given once daily or every other day.
- Potassium supplements should not be routinely combined with thiazide or loop diuretics. They are indicated with hypokalemia (serum potassium < 3.5 mEq/L) especially with concomitant digitalis therapy or left ventricular hypertrophy.
- Nonsteroidal antiinflammatory drugs can antagonize diuretics effectiveness.

Special Indications

Diuretics should be the primary choice in all hypertensives.

They are indicated in:
- Volume dependent forms of hypertension: blacks, elderly, diabetic, renal and obese hypertensives.
- Hypertension complicated with heart failure.
- Resistant hypertension: loop diuretics in large doses are recommended.
- Renal impairment: loop diuretics