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.
 

Glucocorticoids 
Cortisol (hydrocortisone) and its synthetic derivatives 

Mechanism 

↓ the production of leukotrienes and prostaglandins   - inhibits phospholipase A2 , inhibits expression of COX-2 , will also stimulate the bone marrow to produce neutrophils resulting in leukocytosis 

halts inflammatory cascade 

↓ leukocyte migration
↓ capillary permeability
↓ phagocytosis
↓ platelet-activating factor
↓ interleukins (e.g. IL-2)

may trigger apoptosis in dividing and non-dividing cells

used in cancer chemotherapy

Clinical use

anti-inflammatory
immunosuppression
cancer chemotherapy (prednisone most common)
CLL
Hodgkin's lymphomas
part of MOPP regimen
Addison disease
asthma

Toxicity

1) must taper dose to avoid toxicity
2) suppression of ACTH → shock state if abrupt withdrawal - > cortical atrophy, malaise, myalgia, arthralgia, fever
3) iatrogenic Cushing  syndrome ->buffalo hump, moon facies, truncal obesity, muscle weakness and atrophy, thin skin, easy bruising, acne
4) osteoporosis - vertebral fractures, aseptic hip necrosis, ↓ skeletal growth in children 
5) hyperglycemia (diabetes) -due to ↑ gluconeogenesis , glaucoma, cataracts, and other complications can subsequently result
6) ↑ GI acid release -ulcers
7) Na+ retention -> edema, HTN, hypokalemia alkalosis, hypocalcemia
8)↓ wound healing
9) ↑ infections
10) mental status changes
11) cataracts

Piroxicam:

Half‐life of 45 hrs. Once‐daily dosing. Delay onset of  action.

High doses inhibits PMN migration, decrease oxygen  radical production, inhibits lymphocyte function. 

used to relieve the symptoms of  arthritis, primary dysmenorrhoea, pyrexia; and as an analgesic,non-selective  cyclooxygenase (COX) inhibitor

The risk of adverse side efects is nearly ten times higher than with other NSAIDs. Peptic ulcer (9.5 higher)

Amoxicillin

a moderate-spectrum

β-lactam antibiotic used to treat bacterial infections caused by susceptible

Mode of action Amoxicillin acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell wall of Gram-positive bacteria. microorganisms. It is usually the drug of choice within the class because it is better absorbed, following oral administration, than other beta-lactam antibiotics. Amoxicillin is susceptible to degradation by  β-lactamase-producing bacteria, and so is often given clavulanic acid.

Microbiology Amoxicillin is a moderate-spectrum antibiotic active against a wide range of Gram-positive, and a limited range of Gram-negative organisms

Susceptible Gram-positive organisms : Streptococcus spp., Diplococcus pneumoniae, non β-lactamase-producing Staphylococcus spp., and Streptococcus faecalis.

Susceptible Gram-negative organisms  Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis, Escherichia coli, Proteus mirabilis and Salmonella spp.

Resistant organisms Penicillinase producing organisms, particularly penicillinase producing Staphylococcus spp. Penicillinase-producing N. gonorrhoeae and H. influenzae are also resistant

All strains of Pseudomonas spp., Klebsiella spp., Enterobacter spp., indole-positive

Proteus spp., Serratia marcescens, and Citrobacter spp. are resistant.

The incidence of β-lactamase-producing resistant organisms, including E. coli, appears to be increasing.

Amoxicillin and Clavulanic acid Amoxicillin is sometimes combined with clavulanic acid, a β-lactamase inhibitor, to increase the spectrum of action against

Gram-negative organisms, and to overcome bacterial antibiotic resistance mediated through β-lactamase production.

Loperamide

• Similar chemically and pharmacologically to Diphenoxylate.
• Slows gastrointestinal motility by effects on the circular and longitudinal muscles of the intestine.
• Not well absorbed following oral administration.
• Useful in the treatment of diarrhea.

Ofloxacin : It is a quinolone antibiotic and similar in structure to  levofloxacin. It is an alternative treatment to ciprofloxacin for anthrax.