Pharmacodynamics and Pharmacokinetics

Drug

Any chemical substance that affects living processes

Receptor

• Component of tissue where drug can bind

• Normal part ng katawan na kung saan ang gamot is didikit

• Called ligand in some books

Biophse

Establish and maintain for a certain time, an effective concentration of rhe drug in the imediate vicinity.

• dose

• Route of administration

• Degree of ioniztion

• Lipid solubility

• Plasma protein binding

• Biotransformation

• Excretion

To meet the biophase:

• graded-dose relationship

• Quantal dose response relationship

Types of Dose-Response Relationship

Graded dose-response relationship

• as the dose of a drug is increased, the magnitude or intensity of response also increased

• Magnitude/intensity of response is proportional to the effective drug concentration

Graded dose-response relationship

example: anesthetic for an animal that approximately weigh 10kg

• 0.2 ml = sleep for 20 mins

• 0.3 ml = sleep for 40 mins

• 0.4 ml = sleep for 60 mins

• 0.5 ml = sleep for 80 mins

• 0.6 ml = sleep for 100 mins

Quantal dose-response relationship

• As the dose of the drug is increased, the number or proportion of animal exhibiting a response is also increased

• All-or-nothin response

Quantal dose-response relationship

Example: antibiotics for a specific infection

● group 1 with 100 exp’t animal, at 0.1 ml = 10 respond

● group 2 with 100 exp’t animal, at 0.2 ml = 20 respond

● group 3 with 100 exp’t animal, at 0.3 ml = 30 respond

● group 4 with 100 exp’t animal, at 0.4 ml = 40 respond

● group 5 with 100 exp’t animal, at 0.5 ml = 50 respond

ED50 = Median Effective Dose

Dose that will produce response in 50% of the animal population

LD50 = Median Lethal Dose

Dose that will produce death in 50% of the animal population

Agonist

A drug drug that possesses affinity for a particular kind of receptor, and the ability to cause a change in this receptor that give rise to an observable effect.

Antagonist

Any drug that counteracts the effect of an agonist

• pharmacologic antagonism

• Chemical / physiological antagonist

Type of Antagonists

Pharmacologic antagonism

antagonism that interacts with the receptor or any component of the receptor or any component of the effector mechanism to inhibit the action of the agonist.

• competitive antagonist

• non-competitive antagonist

Under pharmacologic antagonism

Competitive antagonist

• antagonists compete for the same receptor with agonist, which noth have affinity.

Spironolactone (aldosterone antagonist)

Competitve antagonist example

Non-competitive antagonist

• prevents the agonist from producing its effect at a given receptif sute, it also inhibit any component of the stimulus

• Glutamic acid

• Glycine

• Serine (dextromethorphan antagonist)

non-competitive antagonist example

Allosteric site

Ability of the receptor to change shape

Chemical / Physiological antagonist

Antagonist does not cause its effect by interaction with tissue receptor sites, but interacts with agonist itself.

• protamine (basic drug)

• Heparin (acidic drug)

chemical / physiological antagonist example

Affinity

Tendency of a drug to combine with a particular kind of receptor

Efficacy (intrinsic activity)

• characterized by the maximal effect the drug can produce

• drug are usually described by their most prominent effect

Selectivity

• Capacity to preferentially produces a particular effectcharacteristic effect of a drug that is produced at a lower dose than those required to elicit other response.

• Ex. Xylazine

  • sedative (efficacy)

  • emetic (selectivity)

Specificity

when all the effects produced by a drug are due to a single mechanics of action.

Anti-muscarinic

Soecificity ng Atropine or AtSO4

• mydrasis -

• Antiperistalsis -

• Decrease salivation -

Dopamine receptor

Non Specificty ng Acepromazine

• sedation - _______

Chemoreceptor Trigger Zone CRTZ

Non Specificty ng Acepromazine

• antiemetic - _________ (causes vomiting)

Anticholinergic

Non Specificty ng Acepromazine

• antispasmodic - _______

Parkinson’s Disease

Disease na nakukuha if dopamine levels are low

Potency

• refers to the dose that must be administered to produce a particular effect of given intensitY

• Compare 2 or more drugs, and a standard must be defined

• iisa lang ang route

• mas kaunti yung dose pero same yung effect kaya mas more potent yung gisang drug

Hydromorphone

pinakapotent is _____?

• morphine - 10 mg - SC - relieves pain

• Hydromorphone - 1.5 mg - SC - relieves pain

• Meperidine - 80 mg - SC - relieves pain

Drug safety

• Paracelsus observed that all substances are poison, for there is nothing without a poisonous quality. It is only the dose which makes a substance poisonous.

• therapeutic index

• Certain safety factor

Drug safety

• margin of index can be assessed through:

Therapeutic Index

• obtained from the ratio of the median lethal dose to the median effective dose

• LD50 / ED50

Certain Safety Factor

• derived from the ratio of the extremes

• LD1 / ED99

• inhalant anaesthetics

• Osmotic diuretics

• Saline cathartics

• Antacids

• Urinary acidifiers

• Urinary alkalinzers

• Antiseptics

Drugs that do not directly need a receptor to produce an effect

• enzyme

• Carriers (membrane transport)

• Ion channels

• Receptors

Drug Targets: (protein molecule)

Allostery

Ability to change its shape

Tolerance

• effect of drug is diminished when given repeatedly

• Gradual decrease in response

Down regulation effect

• chronic stimulation of result in long-term desensitization

• Decrease in the number of population of receptor responding to the drug

Up regulation effect

under stimulation lead to increase number of receptor responding to the drug, leading to super sensitivity

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