Lithium carbonate: 1st choice (controls mania in bipolar disorders); delay before onset of therapeutic benefit; no psychotropic effects in normal humans

i. Mechanism: blocks enzymes in inositol phosphate signaling pathway; no consistent effects of lithium on NE, 5-HT, and DA
ii. Side effects: severe CNS (ataxia, delirium, coma, convulsions) and CV (cardiac dysrhythmias)

GLP-1 analogs

Exenatide

Mechanism

GLP-1 is an incretin released from the small intestine that aids glucose-dependent insulin secretion
basis for drug mechanism is the observation that more insulin secreted with oral glucose load compared to IV 

Exenatide is a GLP-1 agonist

↑ insulin
↓ glucagon release
the class of dipeptidyl peptidase inhibitors ↓ degradation of endogenous GLP-1
e.g.) sitagliptin, -gliptins 
 

Clinical use
type II DM
 

Toxicity
nausea, vomiting
pancreatitis
hypoglycemia
if given with sulfonylureas

Metabolism

Hepatic Drug-Metabolizing Enzymes:  most drug metabolism in the liverperformed by the hepatic microsomal enzyme system.

Therapeutic Consequences of Drug Metabolism
- Accelerated Renal Drug Excretion:  The most important consequence of drug metabolism is the promotion of renal drug excretion.  Metabolism makes it possible for the kidney to excrete many drugs that it otherwise could not.

- Drug Inactivation
- Increased Therapeutic Action: Metabolism may increase the effectiveness of some drugs.
- Activation of Prodrugs:  A prodrug is a compound that is inactive when administered and made active by conversion in the body.

- Increased or Decreased Toxicity

Factors that influence rate of metabolism:  

- Age:  Hepatic maturation doesn't occur until about a year old.

- Induction of Drug-Metabolizing Enzymes:  Some drugs can cause the rate of metabolism to increase, leading to the need for an increased dosage.  May also influence the rate of metabolism for other drugs taken at the same time, leading to a need for increased dosages of those drugs as well.

- First-Pass Effect:  Hepatic inactivation of certain oral drugs.  Avoided by parentaral administration of drugs that undergo rapid hepatic metabolism.

- Nutritional Status

- Competition between Drugs

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

Hydromorphone

• About 8-10 times more potent than morphine when given intravenously.
• Slightly shorter duration of action.
• More soluble than morphine, thus higher concentrations may be injected if necessary.
• Better oral/parenteral absorption ratio than morphine, but not as good as codeine or oxycodone.

• It is used for the treatment of moderate to severe pain

Benzylpenicillin (penicillin G)

Benzylpenicillin, commonly known as penicillin G, is the gold standard penicillin. Penicillin G is typically given by a parenteral route of administration because it is unstable to the hydrochloric acid of the stomach.

Indications :

bacterial endocarditis, meningitis, aspiration pneumonia, lung abscess,community-acquired pneumonia, syphilis, septicaemia in children