Excretion
Routes of drug excretion
The most important route of drug elimination from the body is via the kidney

Renal Drug Excretion

- Glomerular Filtration

- Passive Tubular Reabsorption: drugs that are lipid soluble undergo passive reabsorption from the tubule back into the blood.

- Active Tubular Secretion

Factors that Modify Renal Drug Excretion

- pH Dependent Ionization:  manipulating urinary pH to promote the ionization of a drug can decrease passive reabsorption and hasten excretion.

- Competition for Active Tubular Transport

- Age:  Infants have a limited capscity to excrete drugs.

Nonrenal Routes of Drug Excretion
Breast Milk
Bile, Lungs, Sweat and Saliva

The kidney is the major organ of excretion. The lungs become very important for volatile substances or volatile metabolites.

Drugs which are eliminated by the kidney are eliminated by:

a) Filtration - no drug is reabsorbed or secreted.

b) Filtration and some of the drug is reabsorbed.

c) Filtration and some secretion.

d) Secretion

By use of the technique of clearance studies, one can determine the process by which the  kidney handles the drug.

Renal plasma clearance = U x V ml/min U  / Cp = conc. of drug in urine

Cp = conc. of drug in plasma

V = urine flow in ml/min

Renal clearance ratio = renal plasma clearance of drug (ml/min) / GFR (ml/min)

Total Body Clearance = renal + non-renal

Dextromethorphan  
O-methylated dextrorphan,  Excellent oral antitussive,  No analgesic effect,  No GI effects,  No respiratory depression

Classification

1. Natural Alkaloids of Opium

Phenanthrenes -> morphine, codeine, thebaine

Benzylisoquinolines -> papaverine, noscapine

2. Semi-synthetic Derivatives

diacetylmorphine (heroin) hydromorphone, oxymorphone hydrocodone, oxycodone

3. Synthetic Derivatives

phenylpiperidines pethidine, fentanyl, alfentanyl, sufentnyl

benzmorphans pentazocine, phenazocine, cyclazocine

propionanilides methadone

morphinans levorphanol

Antiemetics

 Antiemetic drugs are generally more effective in prophylaxis than treatment. Most antiemetic agents relieve nausea and vomiting by acting on the vomiting centre, dopamine receptors, chemoreceptors trigger zone (CTZ), cerebral cortex, vestibular apparatus, or a combination of these.
 
 Drugs used in the treatment of nausea and vomiting belong to several different groups. These include:
 
1. Phenothiazines, such as chlorpromazine, act on CTZ and vomiting centre, block dopamine receptors, are effective in preventing or treating nausea and vomiting induced by drugs, radiation therapy, surgery and most other stimuli (e.g. pregnancy).
They are generally ineffective in motion sickness.
Droperidol had been used most often for sedation in endoscopy and surgery, usually in combination with opioids or benzodiazepines

2. Antihistamines such as promethazine and Dimenhyrinate are especially effective in prevention and treatment of motion.

3. Metoclopramide has both central and peripheral antiemetic effects. Centrally, it antagonizes the action of dopamine. Peripherally metoclopramide stimulates the release of acetylcholine, which in turn, increases the rate of gastric. It has similar indications to those of chlorpromazine.

4. Scopolamine, an anticholinergic drug, is very effective in reliving nausea & vomiting associated with motion sickness.

5. Ondansetron, a serotonin antagonist, is effective in controlling chemical-induced vomiting and nausea such those induced by anticancer drugs. 

6. Benzodiazepines: The antiemetic potency of lorazepam and alprazolam is low. Their beneficial effects may be due to their sedative, anxiolytic, and amnesic properties

Ketorolac

Mechanism of action

primary action responsible for its anti-inflammatory/antipyretic/analgesic effects is inhibition of prostaglandin synthesis through inhibition of the enzyme cyclooxygenase (COX). Ketorolac is not a selective inhibitor of COX enzymes

Indications: short-term management of pain

Contraindications

hypersensitivity to ketorolac, and against patients with the complete or partial syndrome of nasal polyps, angioedema, bronchospastic reactivity or other allergic manifestations to aspirin or other non-steroidal anti-inflammatory drugs (due to possibility of severe anaphylaxis).

Warfarin (Coumadin):

• The most common oral anticoagulant.
• It is only active in vivo.
• Warfarin is almost completely bound to plasma proteins. -96% to 98% bound.
• Warfarin is metabolized by the liver and excreted in the urine.
• Coumarin anticoagulants pass the placental barrier and are secreted into the maternal milk.
• Newborn infants are more sensitive to oral anticoagulants than are adults because of lower vitamin K levels and lower rates of metabolism.

• Bleeding is the most common side effect and occurs most often from the mucous membranes of the gastrointestinal tract and the genitourinary tract.

Oral anticoagulants are contraindicated in:

• Conditions where active bleeding must be avoided, Vitamin K deficiency and severe

hepatic or renal disease, and where intensive salicylate therapy is required.