1. Pharmacology
Pharmacology consists of pharmacodynamics and pharmacokinetics
Pharmacodynamics describes how a drug acts in the body
Pharmacokinetics describes how the body acts on the drug

2. Drugs and mechanisms of action
A drug’s mechanism of action is how a drug acts in the body specifically and this is the term used in drug monographs packaged with the drugs and used in references
Typically a drug has a pharmacological target. A pharmacological target is a target in a cell of the body that the drug acts on to produce its effect. Its called sometimes as the drug’s “site of action”
Pharmacological targets
Cell membrane receptors
Cellular enzymes
Cell ion channels

3. Drug Receptor Interaction
Drug that produces its effect on a receptor is often called an agonist or antagonist
A receptor is a molecule, usually on the surface of a cell, that binds to a hormone, neurotransmitter, or a drug. The receptor once it binds its ligand triggers a series of chemical reactions in the cell that produces a response.
For example, a beta receptor is a receptor that is present on the heart and lungs. When the beta receptor binds to norepinephrine or adrenalin, it signals to the heart to begin contracting stronger and at a faster rate.

4. Ligand and Receptor Interaction
Example is the heart
Cell= cardiac myocyte
Ligand= norepinephrine
Receptor= Beta Receptor
Cellular response is the opening of Na+ and Ca++ channels to produce a faster and more forceful contraction
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5. Examples of Receptors in the Body
Alpha receptors in the arteries of the body
Beta receptors in the lungs and the heart
Insulin receptors on fat cells and muscle
Muscarinic receptors on the eyes, GI tract, and many other organs including the heart
Nicotinic receptors on skeletal muscles
Histamine receptors in the skin and brain
Vasopressin receptors in the kidney and arteries
LH, FSH receptors on testes/ovaries

6. An agonist is a drug that binds to a receptor and triggers the receptor.
An antagonist is a drug that binds to a receptor and blocks its activation.

7. Drugs that target enzymes
An enzyme is a protein in the cell that catalysts and enables a chemical reaction to take place in the cell.
Examples
Glucokinase= enzyme that initiates metabolism of glucose
DNA polymerase= enzyme that allow the replication of DNA

8. Drug Enzyme Interaction
E= HMG CoA reductase (a enzyme that allows the liver to make cholesterol)
S= HydroxymethylGlutaryl CoA
Reaction= Cholesterol formation after a long reaction
I= Statin drugs
Some Enzyme Inhibitors are POISONS
E= Cytochrome C oxidase
S= oxygen and cytochrome C
I= cyanide ion
No reaction= complete inhibition of cellular respiration and death of the organism
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9. Examples of Enzyme Inhibitors
The drug Oristat or Xenical ® is a drug that blocks the enzyme pancreatic lipase from working. This will cause the fats to not be broken down and not absorbed. Xenical ® was marketed as an anti obesity drug.
The class of drugs called statins (lipitor® and Zocor®) are inhibitors of the enzyme, HMG CoA reductase in the liver, which is required to make cholesterol.
Viagra® is a cGMP phosphodiesterase inhibitor. The enzyme causes the sexual organs to lose blood. If it is blocked, erections are prolonged and sustained
Reverse transcriptase (aka RNA dependent DNA polymerase) is an enzyme that is critical in HIV reproduction. Block this enzyme with reverse transcriptase inhibitors block HIV reproduction
Retrovir® (Zidovudine) first drug to be approved for HIV (aka AZT)
Videx® (Didanosine) second drug to be approved for HIV
Epivir® (Lamivudine) first drug to be approved for HIV and HBV

10. Examples of Enzyme Inhibitors
Chronic myeloid Leukemia is a cancer of white blood cells. An enzyme called BCR-ABL tyrosine kinase is critical in the growth of these cancer cells. A group of drugs called tyrosine kinase inhibitors block this enzyme and cause this cancer to go into remission.
Imitinab mesylate (Gleevac®) was introduced in 2001 and has revolutionize cancer therapy
Erlotinib (Tarceva®
Gefinitib (Iressa®)

11. Drug that bind to Ion channels
Ion channels are protein channels that span a cellular membrane that provides a pathway for the flow of ions
Ions important for human physiology are Na, K, Ca, Cl and Mg
Clinically the important ones are the channels for Na, K and Ca.
Under normal conditions some channels are open or closed. When the cell is stimulated by a chemical trigger (neurotransmitter, hormone, or a drug agonist) the state of the channel either opens or closes

12. Sodium Ion Channel Blockers
These drugs can be used to treat cardiac arrhythmias, seizures, and to induce localized anesthesia
Sodium channels are open in responds to hormones and other electrical triggers. The flow of sodium begins nerve impulse conduction in neurons.
Sodium Blockers include:
Lidocaine (Xylocaine®) used to block sensory neurons for anesthesia purposes and the treat ventricular tachycardias.
Procainamide (Pronestyl®) used to treat cardiac arrhythmias
Quinidine is an older drug used before procainamide
Phenytoin (Dilantin®) is a drug used to treat epileptic seizures

13. Calcium Channel Blockers
Drugs that block calcium ion channels
Clinically a very important group of drugs
Blocking calcium flow into the heart as two effects
Lowers the heart rate
Decrease the force of contraction
Blocking calcium flow in the smooth muscles of arteries relaxes them.

14. Calcium Channel Blockers
Dihydropyridine type : used to treat HTN
Amlodipine (Norvasc®)
Felodipine (Plendil®)
Isradipine (Dynacirc®)
Nicardipine (Cardene®)
Nifedipine (Procardia®)
Non dihydropyridine: used to slow rapid heart rates
The two to remember are:
Verapamil (Calan® and others)
Diltiazem (Cardizem®)

15. Drug Interactions
Drug Interactions typically involve pharmacodynamic interactions in which the way the two drugs work on the body can produce synergistic effects or antagonistic effects.
Synergistic drug interactions:
Agonists are the same receptor: epinephrine and norepinephrine
Drugs with different mechanisms of action producing same effect: epinephrine (agonist at the beta receptor) and atropine (antagonist at the muscarinic receptor) both receptor in the heart
True case in point: IV Metoprolol ( beta blocker)+ IV Diltiazem (Calcium channel blocker) + IV lidocaine (sodium channel blocker) to produce severe bradycardia and cardiac arrest

16. Antagonistic drug interactions
Two drugs that work on a receptor one as an agonist and one as an antagonist. For example, albuterol (agonist on beta receptor) and metoprolol (beta blocker). Effect is variable but both drug cancel the others effect.
Two drugs with different mechanisms of action to produce opposite effects. Example. Insulin NPH 25 units at bedtime and prednisone 20 mg bid. One drug lowers blood glucose and the other raises it

17. Pharmacokinetic Drug Interaction
Some drug interactions involve pharmacokinetics in that one drug effects the way the body handles or metabolize the other drug. One drug may block the metabolism of the other or it can accelerate the metabolism of another
The body primary detoxifier is the liver. The liver has a series of enzymes the job of which is to metabolize drugs or chemicals to inactive forms. The system is called the cytochrome P450 system or CYP450 for short.
Some drugs block the activity of this system.
HIV protease inhibitors (ritonovir also known as Norvir ®)
Grapefruit juice (real juice) contains a chemical called naringin that blocks this system
Some drugs activate or induce the system
Rifampin
Phenytoin
Barbiturates (Phenobarbital)
St. John’s wort (flowering weed of the Hypericum family) is a herb used around the world for depression. A chemical called amentoflavone is an enzyme inducer

18. Dose Response Curve

19. In a dose response curve , as the dose increases the response increase slowly at first, then dramatically and then the response levels off, this is called a ceiling effect
The ceiling effect is sometimes called pharmacological tolerance and notably occurs with opiate analgesics
ED50 is the dose of drug that produces 50% of the maximal drug effect

20. Pharmacokinetics The study of the way that body handles the drug
The pharmacokinetics of a drug involves its absorption, distribution, metabolism and the elimination of the drug or the “ADME” of a drug
Pharmacokinetics most often involve the time course of a drug. Time course include its “onset of action”, “duration of action” and its “elimination” or wearing off.
Absorption and distribution constitute the “onset of action” of a drug and its “duration of action”.
The metabolism and elimination are involved in the “wearing off” effect.

21. Absorption
It could be in the stomach, the small intestine, or the skin.
Not all of the drug that is given is actually absorbed. Some of the drug passes into the feces.
In addition, once a drug is absorbed in the GI tract. Its travel through the hepatic portal vein into the liver where the drug is partially metabolized by the CYP450 system. Thus the fraction of the drug that makes it into the body is called the bioavailability.
The passing of an oral dose through the liver is called the “first pass effect”
The first pass effect is why IV administration of a drug is more potent that the oral route

22. Distribution
Distribution involves the flow of the drug through the body via the blood. Once the drug reaches its target cell, the following is important to consider
Passive Diffusion: Drug passes through the membrane intact
Facilitated Diffusion: Drug passes through the membrane with assistance by membrane carrier proteins
Active Transport: Drug passes through the membrane with the help of a carrier against a concentration gradient

23. Metabolism
The liver and the kidney and sometimes other organs are involved in the metabolism of drugs to inactive metabolites. Mostly the liver does this for the body

24. Elimination
When drugs are converted to inactive metabolites they are then transported into the blood to the kidneys
The kidney then filters out the drug metabolites into the urine.
At times the metabolites that the liver produces are not completely inactive. Thus in elderly patients and in people with renal disease that have bad renal function are at high risk for drug metabolite accumulation and severe side effects
A commonly used measure of renal function is the creatinine clearance. A clearance of 30 ml/min is considered renally impaired
When taken together the metabolism and elimination of a drug is called its clearance.