general principles of pharmacology Flashcards
What is pharmacology?
The effects of drugs on the function of living tissues
What is pharmacodynamics?
study of biochemical and physiologic effects of drugs on the body
How to drugs exert their effect?
What can these targets be?
Drugs exert their effects by binding to specific target molecules
Targets can be:
-classic receptors (e.g., muscarinic receptors)
- enzymes
- transmembrane transport proteins
-ion channels
What is an agonist drug?
What is an antagonist drug?
Drug is an AGONIST= it stimulates its target to produce a desired response. Acts like normal molecule in the body.
Drug is an ANTAGONIST= it blocks the target to prevent binding of the natural agonist (naturally occurring molecule that achieves desired response)
Antagonists can be competitive with naturally occurring agonists.They can be non-competitive as well
what are the sources of drugs?
*Natural e.g., Alkaloids (from plants) example: atropine
*Semi-synthetic drugs. Wanted to alter the chemical structure of naturally occurring compound.
example: cyclopentolate. Altered chemical structure of atropine to shorten its action.
*Synthetic. Prepared by chemical synthesis in pharmaceutical lab
Ophthalmic example: latanoprost in glaucoma treatment.
what is drug specificity?
*A drug should show a high degree of specificity in terms of its binding site
*Absolute specificity is rare
*As you increase dosage of drug, the target receptors are occupied. If drug is present in a high amount, it will start to effect other targets other than the intended one. This leads to side effects
explain the dose-response curve
the curve looks at the relationship of drug and its pharmacologic effect
- No response initially.
Range where there is no effect.
The concentration of the drug is so low, so it doesn’t stimulate enough target receptors to produce a measurable response FLAT LINE
2.As dose increases, therapeutic response increases STEEP LINE
- All of the drug targets are occupied. We have achieved maximal therapeutic effect. FLAT LINE
what is the therapeutic index?
which drug has a narrow TI
*The ratio between the toxic dose of a drug and the therapeutic dose of a drug
*We would want therapeutic dose to be low and toxic dose of drug to be high
*If there is little difference between toxic and therapeutic dose, it will have narrow therapeutic index
*These drugs need to be prescribed with care due to close relationship between therapeutic and toxic dosage.
digoxin
what is pharmacokinetics?
*Describes what the body does to the drug (absorption, distribution, metabolism, and excretion of drugs)
what are the routes of entry of a drug?
enteral-oral
rectal
percutaneous-skin
intravenous-injection into vein
intramuscular-injection into muscle
intrathecal-injection Injection into cerebral spinal fluid
inhalation-used for lung
why do non-polar drugs penetrate more readily?
are most drugs polar or non-polar?
they are lipophilic so can cross cell membranes readily
Most drugs have a mixture of polar and non-polar characteristics as they are weak acids or bases
what state are most drugs in?
what controls their state of equilibrium?
state of equilibrium between ionised and unionised form of drug
surrounding pH and the dissociation constant (pK)
pK: the pH at which the drug is 50% ionised and 50% of the drug is unionised
where in the body are weak acids more readily absorbed and why?
how is the pH of weak acids affected depending on where they are in the body?
in the stomach as its a acid environment
*When an orally administrated drug passes through the stomach (ACID ENVIRONMENT), it will have a low pH
A weak acid in an acid solution will be in its unionised form. Weak acids are well absorbed in an acid
As the drug leaves and passes into small intestine (ALKALINE ENVIRONMENT), it will have a higher pH. More of the drug will be trapped in ionised state due to equilibrium. Drug will have weak absorption in an alkaline environment
where in the body are weak alkalis more readily absorbed?
How is the pH of weak alkalis affected depending on where they are the body?
small intestine
*IN ACID ENVIRONMENT, it will be trapped in ionised state and not readily absorbed. Will be concentrated. No readily absorbed in stomach.
*In ALKALINE ENVIRONMENT, it will be nonionised and have greater ability to cross lipid membranes. More readily absorbed in small intestine.
what is drug absorption in the small intestine depend on ?
what is not readily absorbed in small intestine?
Drug absorption from intestine depends on ionisation and lipid solubility
Strong bases (pK more than 10) and strong acids (pK less than 3) are poorly absorbed as they are fully ionised
what factors effect drug absorption?
*How rapidly drug is moving through the gut
*The level of blood flow in the gut (splanchnic blood flow). High blood flow will take more of the drug away.
*Drug formulation
*Chemical characteristics of drug
when is drug absorption slow?
after a meal means slower absorption as progress to small intestine is delayed
Resistant coatings around tablets/capsules are formulated to delay absorption as these need to be broken down before drug is released.
what are the contraindications of tetracyclines?
People on these drugs are told to limit calcium containing food intake
These drugs are contraindicated in pregnancy and lactation since they affect tooth and bone formation
tetracyclines reduce absorption of oral contraceptives
what is bioavailability of drugs?
The fraction of the dose that proceeds unaltered from the site of administration and becomes available at the site of action
what is first pass metabolism?
what can happens to the drug glyceryl trinitrate to treat angina in this process?
*Happens when drug is administered orally
*The breakdown of the drug after is absorbed by enzymes in gut wall and enzymes in the liver before it reaches plasma compartment
drug becomes altered and is ineffective
