Hypothalamic - Pituitary Drugs

Somatropin

Growth hormone (GH) mimetic

Mechanism

agonist at GH receptors
increases production of insulin growth factor-1 (IGF-1)

Clinical use

GH deficiency
increase adult height for children with conditions associated with short stature 
Turner syndrome
wasting in HIV infection
short bowel syndrome

Toxicity

scoliosis
edema
gynecomastia
increased CYP450 activity

Octreotide

Somatostatin mimetic

Mechanism

agonist at somatostatin receptors

Clinical use

acromegaly
carcinoid
gastrinoma
glucagonoma
acute esophageal variceal bleed

Toxicity

GI upset
gallstones
bradycardia
Oxytocin

Mechanism

agonist at oxytocin receptor

Clinical use

stimulation of labor
uterine contractions
control of uterine hemorrhage after delivery
stimulate milk letdown

Toxicity

fetal distress 
abruptio placentae 
uterine rupture
Desmopressin
ADH (vasopressin) mimetic

Mechanism

agonist at vasopressin V2 receptors

Clinical use

central (pituitary) diabetes insipidus
hemophilia A (factor VIII deficiency)
increases availability of factor VIII
von Willebrand disease
increases release of von Willebrand factor from endothelial cells

Toxicity

GI upset
headache
hyponatremia
allergic reaction

Seizure classification:

based on degree of CNS involvement, involves simple ( Jacksonian; sensory or motor cortex) or complex symptoms (involves temporal lobe)

1.    Generalized (whole brain involved): 

a.    Tonic-clonic:

Grand Mal; ~30% incidence; unconsiousness, tonic contractions (sustained contraction of muscle groups) followed by clonic contractions (alternating contraction/relaxation); happens for ~ 2-3 minutes and people don’t breathe during this time

Drugs: phenytoin, carbamazepine, Phenobarbital, lamotrigine, valproic acid

Status epilepticus: continuous seizures; use diazepam (short duration) or diazepam + phenytoin

b.    Absence:

Petit Mal; common in children; frequent, brief lapses of consciousness with or without clonic motor activity; see spike and wave EEg at 3 Hz (probably relates to thalamocorticoreverburating circuit)

Drugs: ethosuximide, lamotrigine, valproic acid

c.    Myoclonic: uncommon; isolated clinic jerks associated with bursts of EEG spikes; 

Drugs: lamotrigine, valproic acid

d.    Atonic/akinetic: drop seizures; uncommon; sudden, brief loss of postural muscle tone
Drugs: valproic acid and lamotrigine

2.    Partial:  focal

a.    Simple:  Jacksonian; remain conscious; involves motor or sensory seizures (hot, cold, tingling common)

Drugs: carbamazepine, phenytoin, Phenobarbital, lamotrigine, valproic acid, gabapentin

b.    Complex: temporal lobe or psychomotor; produced by abnormal electrical activity in temporal lobe (involves emotional functions)

Symptoms: abnormal psychic, cognitive, and behavioral function; seizures consist of confused/altered behavior with impaired consciousness (may be confused with psychoses like schizophrenia or dementia)

Drugs: carbamazepine, phenytoin, laotrigine, valproic acid, gabapentin

Generalizations: most seizures can’t be cured but can be controlled by regular administration of anticonvulsants (many types require treatment for years to decades); drug treatment can effectively control seizures in ~ 80% of patients

Pharmacodynamics

Pharmacodynamics is the study of what drugs do to the body and how they do it.

Dose-Response Relationships

- Basic Features of the Dose-Response Relationship:  The dose-response relationship is graded instead of all-or-nothing (as dose increases, response becomes progressively larger).

- Maximal Efficacy and Relative Potency

- Maximal Efficacy: the largest effects that a drug can produce

- Relative Potency:  Potency refers to the amount of drug that must be given to elicit an effect.

- Potency is rarely an important characteristic of a drug.

- Potency of a drug implies nothing about its maximal efficacy.
 

Propofol -Intravenous Anesthetics

- A nonbarbiturate anesthetic
- It is very lipid-soluble, acts rapidly and has a short recovery time.
- It is associated with less nausea and vomiting than some of the other IV anesthetics.
- Propofol is very similar to thiopental in its effects on the cardiorespiratory system.
- It does not have any analgesic properties but lowers the dose of opioid needed when the two agents are used in combination.

- The most significant adverse cardiovascular effect associated with propofol administration is hypotension. It should be used with caution in patients with cardiac disease.

ANTIBIOTICS

Chemotherapy: Drugs which inhibit or kill the infecting organism and have no/minimum effect on the recipient.

Antibiotic these are substances produced by microorganisms which suppress the growth of or kill other micro-organisms at very low concentrations.

Anti-microbial Agents: synthetic as well as naturally obtained drugs that attenuate micro-organism.

SYNTHETIC ORGANIC ANTIMICROBIAL DRUGS

Sulfonamides

Trimethoprim-sulfamethoxazole

Quinolones – Ciprofloxacin

ANTIBIOTICS THAT ACT ON THE BACTERIAL CELL WALL

Penicillins

Cephalosporins

Vancomycin

INHIBITORS OF BACTERIAL PROTEIN SYNTHESIS

Aminoglycosides - Gentamicin

Antitubercular Drugs: Isoniazid & Rifampin

Tetracyclines

Chloramphenicol

Macrolides – Erythromycin, Azithromycin

Clindamycin

Mupirocin

Linezolid

 ANTIFUNGAL DRUGS

Polyene Antibiotics (Amphotericin B, Nystatin and Candicidin)

Imidazole and Triazole Antifungal Drugs

Flucytosine

Griseofulvin

ANTIPROTOZOAL DRUGS

Antimalarial Drugs – Quinine, Chloroquine, Primaquine

Other Antiprotozoal Drugs – Metronidazole, Diloxanide, Iodoquinol

 ANTIHELMINTHIC DRUGS

Praziquantel

Mebendazole

Ivermectin

ANTIVIRAL DRUGS

Acyclovir

Ribavirin

Dideoxynucleosides

Protease inhibitors

A. Sympathetic Nervous System Depressants

1. Antagonists

Both α-adrenoceptor antagonists and β-adrenoceptor antagonists are useful  antihypertensives.

• α-blocker                     Prazosin, phentolamine, phenoxybenzamine
• β-blocker                     Propranolol ,Metoprolol, atenolol
• α/β-blocker                  labetalol

2. Sympathetic depressants

a. Examples of peripherally acting agents include

• reserpine This agent interferes with the storage of norepinephrine
• quanethidine This agent interferes with the release of norepinephrine
• trimethaphan This agent blocks transmission through autonomic ganglia.

b. Examples of Centrally acting agents include

• alphamethyldopa
• clonidine. These agents act by decreasing the number of impresses along sympathetic nerves.

Adverse Effect

include nasal congestion, postural hypotension, diarrhea, sexual dysfunction, dry mouth. sedation and drowsiness.

B. Directly Acting Vasodilators

Act on vascular smooth muscle cells independently of adrenergic nerves and adrenergic receptors.

Relaxation of vascular smooth muscle which leads to a decrease in peripheral vascular resistance.

Sites of action of vasodilators are many. For example

 Calcium Channel Blocker’s  MOA

. Decrease automaticity & conduction thru SA & AV nodes

. Decreased myocardial contractility

. Decreased peripheral & coronary 

smooth muscle tone = decrease SVR

Potassium channels activators

minoxidil, cause vasodilation by activating potassium channels in vascular smooth muscle.

An increase in potassium conductance results in hyperpolarization of the cell membrane which is associated with relaxation of smooth muscle.

Nitrovasodilators, such as sodium nitroprusside,

Increase in intracellular cGMP. cGMP in turn activates a protein kinase. Directly-Acting Vasodilators are on occasion used alone but more frequently are used in combination with antihypertensive agents from other classes (esp. a β-blocker and a diuretic.)