Intro & Pharm Basis.

pptx
Basic Principles of Pharmacology
 Pharmacodynamics: The effect of drugs on the body
o Drug-receptor interaction

o Drug-receptor activity (i.e. inhibits activity)

o Dose-response relationship (therapeutic, toxic)

o Drug potency and efficacy

 Pharmacokinetics: The movement of drug within the body

o Absorption

o Distribution

o Metabolism

o Elimination

Drug receptors are usually proteins that interact with and mediate the action of a drug
Drug-Dose Relationship

● Dose-response curve: depicts the relation between drug dose and magnitude of
effect

● Doses below the curve do not produce a pharmacological response

● Doses above the curve do not produce much additional pharmacological

response

○ May have unwanted effects → toxicity

Dose-Response Curve
Minimum Effective and Minimum Toxic Concentration

● Minimum effective concentration (MEC): level below which therapeutic effects will
not occur

● Minimum toxic concentration (MTC): level above which toxic effects begin

● Therapeutic index or range: MTC to MEC

Drug-Receptor Interactions

● Most drugs work by binding to receptors

● Receptors are located on the cell surface

● The drug molecule must “fit” into the receptor

○ Like a lock and key mechanism

Note >Exceptions being general anesthesia

Drug-Receptor Binding

● Drug-receptor binding is reversible

● Drug-receptor binding is selective

 ● Drug-receptor binding is graded

○ The more receptors filled, the greater the pharmacological response

● Drugs that bind to receptors may be agonists, partial agonists, or antagonistic

○ Agonists: drugs that produce change every time they bind

○ Antagonists: drugs that occupy a receptor without stimulating it (they

prevent other molecules from producing a response)

○ Partial Agonists: when they bind to receptor site they stimulate only some
of the receptors
NOTE : Very few irreversibly bind (i.e botox – effect exists until new receptors can be
reproduced by the motor nerve terminal cells) The receptors do not have to be
completely occupied to produce effect.

Pharmacokinetics

● Absorption: the way a med is presented to the body

○ Oral, Parenteral (IM, IV, SC), Topical

● Distribution: the way a med moves through the body

● Metabolism: changing one chemical into another

● Excretion: moving a med from inside to outside the body

Drug Bioavailability

● Percentage of drug that is absorbed and available to reach the target tissues

● By definition, when a medication is administered IV, its bioavailability is 100%

● When a medication is administered via other routes (i.e. PO), its bioavailability
decreases due to incomplete absorption and first-pass metabolism

● In general, drug actions occur through free, unbound drugs in the circulation
NOTE: PO meds bioavailability range from 10% - 90% and this effects dosing as more
of a drug may be needed to occupy the appropriate receptors.
Protein Binding

● Drug binds to proteins in the blood (plasma proteins)

● This has several advantages:

○ Helps drug freely circulate in bloodstream

○ Helps normalize concentration of drug throughout body

○ Drug is protected from liver metabolism and kidney excretion

● It has some disadvantages:

○ Drug actions occur mostly through free, unbound states

○ Drugs bound to proteins cannot interact with their receptor site

■ Drugs can unbind

○ When other drugs bind to proteins it can affect the amount of the other
drug in circulation

■ Can cause more Warfarin to be active, leading to prolonged

bleeding
NOTE:

● Albumin is a plasma protein

● Chronic disease (liver disease with low albumin, malnutrition, CKD) negatively
impacts use of medications that largely bind to plasma proteins
Drug Metabolism
 ● The liver is the major organ for drug metabolism

○ Has large number of metabolizing enzymes

○ Is the 1st organ encountered by drugs after being absorbed by GI tract

● There is a group of enzymes called Cytochrome P450

○ Many drugs are metabolized through these

○ Variation in CYPs can result in differences in drug metabolism among

patients

○ Drugs can compete for the same enzyme, thus extending the half-life of
one.
NOTE:
● Concern when multiple medications prescribed are metabolized similarly
● Remember half-life is the time it takes for the drug concentration to decrease by
half
● Some drugs are prodrugs – they are pharmacologically inactive until metabolized
(i.e. codeine into morphine)
Factors That Influence Metabolism
 Age
 Genetically determined differences
 Drug interactions
 Pregnancy
 Liver disease
 Time of day
 Environment
 Diet
 Alcohol
Excretion

● Definition: removal of the drug from the body by organs of elimination

● Most drugs are eliminated by the kidneys

● Drugs are also eliminated by

 ○ Lungs

○ Gastrointestinal (GI) tract

○ Sweat and saliva

○ Mammary glands (breast milk)

Rational Drug Selection
World Health Organization (WHO) definition of rational drug selection:
” Patients receive medications appropriate to their clinical needs, in doses that meet
their own individual requirements, for an adequate period of time, and at the lowest cost
to them and their community.”

● Examples of irrational drug selection (from WHO):

○ Polypharmacy

○ Inappropriate prescribing of antibiotics (for viral vs. bacterial infections)

○ Overuse of injections vs. oral preparations

○ Failure to follow guidelines when prescribing

6 Steps of Rational Drug Selection

NOTE: Passive (educate pt on treatment and instruct patient when to f/u) and active
monitoring (scheduling a f/u appt to re-evaluate)
Example of passive being strep pharyngitis, active being cellulitis
The ‘I Can PresCribE A Drug’ Mnemonic

● Indication

○ Antibiotics are indicated for UTIs

● Contraindications

○ Amoxicillin is contraindicated in pts with PCN allergy

● Precautions

○ Prozac is pregnancy cat C. Use caution in pregnant women

● Cost/Compliance

○ Meijer has free abx. Use/suggest generic when possible

● Efficacy

○ Penicillin is effective in treating strep throat and preventing ARF

● Adverse effects

○ Lisinopril can cause a cough in up to 10% of pts

● Dose/Duration/Direction

○ Dose: 100mg BID; Duration: for 7 days; Direction: PO on empty stomach

Barriers to Adherence
NOTE:
● Asymptomatic conditions (HTN, Lipids)
● Cognitive impairment and psychiatric illness
● Communication difficulties
● Multiple providers, multiple medications=confusion
Medication Compliance

● Ways to improve medication compliance:

○ Make sure patient is part of decision making

○ Patient education! Encourage teach back

○ Handouts (include name and how to take, also include why they are taking
each med)

○ Pill box, home delivery

○ Have patients bring medication bottles to each appointment (“brown bag

medication reconciliation”)

○ Once-daily dosing when possible

○ Schedule follow-up appointments before they leave

Adverse Drug Reactions(ADR)

● An undesirable or unintended effect following administration of a medical product

● In the US, there are over 2 million ADRs annually

● There are 120,000 deaths from ADRs per year

● Adult dosing is based on average weight of 150 lbs

Type A ADRs

● Type A reactions are predictable from a drug’s known pharmacological properties

● May be exaggeration of pharmacological effect of drug

○ Hypoglycemia from insulin

○ Hypotension from antihypertensives

● May be a drug’s secondary effect

○ Diarrhea from antibiotics

○ Anticholinergic effects with antidepressants

NOTE: Pharmacologic ADR

Type B ADRs: Allergic Response

● Drug allergy or hypersensitivity

● A drug allergy occurs when a patient’s immune system identifies a drug, a drug
metabolite, or a drug contaminate as a foreign substance

● The body mounts an immune response

● Type I, II, III, IV allergic responses

NOTE: Idiosyncratic