PHARM: Pharmacokinetics and Pharmacodynamics

drug

any agent used to diagnose, prevent, treat or cure a disease or a condition

what does the drug include

synthetic organic molecules, peptides, proteins, RNA, DNA, vitamins, minerals, etc

pharmacology

the study of drugs and their interaction with living systems.

what is the focus on pharmacology on

the mechanism of action of drugs as the rational basis for the therapeutic use of drug

what does pharmacology include

knowledge of the use of drugs, adverse effects, toxicities, abuse etc.

Pharmacokinetics

what the body does to the drug

Pharmacodynamics

what the drug does to the body

pharmacokinetics: movement of the drug=

changes the drug

the changes in the drug during pharmacokinetics depends on

chemical properties of the drug

the body acts on drugs by what process

ADME process

ADME

– Absorption: drug movement into the body.

– Distribution: drug movement within the body.

– Metabolism (biotransformation): drug is

chemically changed to an inactive molecule.

– Excretion: drug is removed from the body.

pharmacodynamics long def

• Change in body caused by the drug

• Mechanism of action

• Drug activity/ action

• Therapeutic or adverse effe

when will a drug not be absorbed

when administered by IV because the medicine is already in the blood.

pharmacokinetics photes

metabolism= liver excretion= kidney

pharmacodynamics pic

efficacy

how effective is the drug in giving therapeutic affect

what do you need to make the drug for it to be excreted

polar/ hydrophobic

absorption

Movement of drug from outside the body to inside the body

• Process by which a drug moves across cell membranes from its site of administration into the bloodstream

first pass effect

Drugs given orally first pass through the liver before circulating to other tissues and organs

• basically if the drug disappears/ is eliminated before getting to blood stream med cant be given orally.

drug has to be what to be absorbed

lipophillic

what are some factors that affect oral absorption

drug charge and solubility in water and lipids

stability of drugs in acid

GI motility

• foods: some inhibit absorption while some drugs irritate the stomach so they can be taken with food

factors that affect oral absorption: drug charge and solubility in water and lipid

• Drug absorption depends on the chemical nature of the drug itself.

• The drug must dissolve in the aqueous digestive tract and cross lipid cell membranes

• pH affects whether a drug is charged or not

charged drugs are

ionized or polar

charged drugs (polar or ionized ) are

poorly absorbed

non-charged drugs are

neutral or nonpolar

nonchargeable/ neutral or non-polar are

well absorbed

factors that affect oral absorption: stability of drugs in acid

Peptides/proteins and some other drugs are destroyed by acid in stomach.

factors that affect oral absorption: GI motility

Diarrhea and vomiting - fast and poor absorbtion.

Constipation - too slow, risk of toxicity.

drug distribution

After entrance into the blood, the drug is distributed to most regions of the body.

what affects the amount od drug reaching the organs

the local blood flow

what will make the drug easier to be distributed in the body

more fat soluble

Sites of Preferential Drug Accumulation

Fat – Benzodiazepines, cannabinoids (THC): Bone and Teeth – tetracycline

distribution: Plasma protein (Albumin) binding

• Only free drug (drug not bound to plasma proteins etc.) produce effects.

• In addition, only free drug is metabolized or excreted.

distribution: drug-drug interactions

Plasma protein binding can cause drug-drug interactions – one drug can displace another drug from plasma protein to increase free (active) drug concentration in the blood (changes equlibrium)

what is the goal of the body when dealing with meds

make meds more/ polar/waterloving/hydrophillic

primarily organ involoved in drug metabolism/ biotransformation

LIVER

what may you need to do in hepatic dysfucntion/failure

reduce dose of drug eliminated by liver metabolism

liver drug metabolism is a…

chemical change of the drug

liver drug metabolism process

• Hepatocytes (liver cells) contain enzymes (cytochrome P450 [CYP450] enzymes) that metabolize drugs. CYP3A4, CYP2D6, etc. > 50.

• Usually, results in metabolites that are inactive

• Infants and elderly have reduced liver enzymes

CREATES ACTIVE DRUG TO INACTIVE DRUG (inactive= more polar)

drug metabolism: inhibition of metabolism

Competition of one drug with another drug for the same metabolic enzymes reduces the drugs metabolism and plasma levels increase.

• one drug inhibiting another drug in cyp450 class

what is a major cause of drug-drug interactions

inhibition of metabolism

prodrug

The administered drug is inactive and is metabolized to an active drug

which organ is the primary route of drug excretion

kidney

decreased GFR (Glomerular Filtration Rate (GFR)=

GFR is decreased when renal blood flow is decreased. Decreased GFR means less drug is filtered into the kidney

drugs- reabsorption vs excretion

Some drugs can be reabsorbed from renal tubules by passive diffusion. Some drugs remain in the urine and are excreted.

what will happens with renal dsyfunction/faoilure

For drugs eliminated by the kidney, the dose given should be reduced

more hydrophilic=

greater the extent of excretion= less likely to be reabsorbed

plasma half lite

time needed for the plasma concentration of a drug to fall to 50% (or one-half) of its previous concentration

what is plasma half lite determined by

drug elimination

what is there no effect on in half life

no effect of the route of administration or absorption

how long does it take to remove the drug from blood or body

4-5 half lives

what does half life deterine

duration of action of a drug and how often the drug is given.

when is the next dose usually given when dealing with halflife

once the previouse dose reaches it half life

most drugs produce their effects by interacting with

receptors (drug targets)

what do receptors interact with

drug to produce its affects

what are receptors and where are they usally located

Receptors are often cellular proteins and are often located on the cell surface membrane

what does the specific shape of the receptor determine

what specific drug molecules interact with it (like a lock and key)

what are receptors named according to

the type of neurotransmitter, hormone or drug with which it interacts,

for a drug to fit a chiral…

it has to have to right sterochemistry

agonist are

Drugs that bind to a receptor and activate some biologic process to produce an effect, or response

where are agonist found

either naturally within the body or made synthetically by chemists

antagonists

Drugs that bind with the cell receptors but do not cause a response.

what do antagonists block

endogenous molecules in the body from interacting with the receptor.

most agonist and antagonist bind to receptor

in the same location so they compete with each other for the receptor (competitive).

second messengers

molecules that relay signals from receptors to targets inside cell to cause a response

dose response curve

For all drugs, as the dose increases, the response (effect) also increases until a maximum response is reached. The dose which causes 1/2 maximal response is called the ED50

ED 50

effective dose of 50% of the effect

potency

The dose of drug needed to cause a certain level of response. The smaller the ED50, the more potent is the drug.

Efficacy (Effectiveness)

Provides information about the magnitude, intensity or size of the response.

• basicaaly tells us what it did

what is more important potency or efficacy

Often, efficacy is more important than potency.

side effect

A secondary drug effect seen at therapeutic doses.

adverse reaction

An undesirable or harmful effect of a drug.

toxicity

An adverse reaction seen at excessive drug doses or any very severe adverse drug reaction

what is the goal of drug treatment

optimize therapeutic effectiveness and minimize adverse reactions.

therapeutic index/ margin of safety

an indicator of how safe a drug is.

therapeutic index

the ratio of the Toxic Dose (TD50) compared to the Effective Dose (ED50) of a drug

the wider/ bigger number in the therapeutic index

the safer the drug

drugs with a narrow/small number on the therapeutic index

the less safe the drug is and it requires attention

some meds that help with life threntening condition

have a narrow ti

the 5 rights to medication

plasma drug concentrations over time

absorption characteristics of oral med administration

Variable absorption depending on many factors:

• Chemistry of drug

• Gut pH and motility

• Timing of dose with respect to meals

• possible first pass effect

oral administration route advantages

• Convenient

• Economical

• Good for self-administration

oral administration route disadvantage

Self-administration requires good patient compliance

• Unsuitable for drugs that are insoluble or with poor oral absorbed

• Usually unsuitable for infants and may be unsuitable for children or adults unable to swallow - unconscious patients or patients with frequent vomiting

intravenous absorption characterisitics

absorption is immediate

IV administration advantages

• Ideal for emergency use since desired effects usually appear quickly

• Useful for large volumes of drug, or irritating drugs if suitably diluted

IV aminstration disadvantages

Adverse effects appear rapidly (unable to make adjustments quickyly to medication)

• Effects may be of short duration, requiring frequent administration - infusion

• Insoluble substances (eg. suspensions) cannot be given

• Risk of infection, pain, vasculitis, extravasation

• Not suitable for self-administration.

Subcutaneous, Intramuscular absorption characterisitcs

• Rapid if aqueous solutions are used

• Slow and prolonged if oily or other depot preparation or suspension is used

• Absorption speed depends on local blood flow

Subcutaneous, Intramuscular absorption advantages

• Requires administration by nursing or other medical personnel or training of patient for self- administration;

• Small to moderate drug volumes

Subcutaneous, Intramuscular absorption disadvantages

• May be painful

• IM - Chance of muscle damage, increase bleeding risk during anticoagulant therapy

• Risk of infection

inhalation administration absorption characterisitcs

Rapid absorption unless drug is specifically formulated for local effects in respiratory tract (eg. steroids used for asthma)

inhalation administration absorption advantages

• Common route for bronchodilators to relax airways

• Route for some general anesthetics to give a gaseous or volatile liquid drug that cannot be given in another form

inhalation administration absorption disadvantages

• Drugs for self-administration require training, and dexterity for optimal effect

• Some inhaled drugs may cause coughing/wheezing

• Inhalational drugs given by professional personnel (i.e. anesthetics) may require advanced training, special equipment

sublingual administration absorption characterisitcs

Absorption is usually rapid, complete (same with nasal insuflation)

sublingual/ nasal insufflation administration absorption advantages

A preferred route for drugs that are inactivated by first-pass metabolism in the liver when they are given orally because they arent going in the GI tract

sublingual/ nasal insufflation administration absorption disadvantages

• Efficacy, speed, duration of effects depend on retaining tablet at administration site

• Eating or drinking may interfere with absorption