Transcript 100908 Gen Pharm (pt 2).

General
Pharmacology,
part 2
Pharmacodynamics &
Medication
Administration
• F ‘08
• P. Andrews
Pharmacodynamics
• Most drugs bind to a receptor
– Protein molecules
– Can be stimulated/inhibited by chemicals
– Each receptor’s name generally corresponds to
the drug that stimulates it
• Affinity
– Force of attraction between a drug and a receptor
– Different drugs may bond to same receptor site,
but strength of bond may vary – binding site’s
shape determines receptivity to chemicals
• Drug’s pharmacodynamics involves its efficacy
• Generally, drugs either stimulate or inhibit the
cell’s normal actions.
• Efficacy and affinity not directly related
– Drug A causes a stronger response than drug B
– Drug B binds to the receptor site more strongly
than drug A
• When drug binds to receptor,
chemical change occurs
• Drugs
– Interact with receptor and result
in desired effect
– Interact with receptor and cause
release/production of a second
compound
Giving medications safely
• Know:
– Indications
– Contraindications
– Precautions
• Practice proper technique
• Observe & document
• Take careful drug histories
Remember the 6 rights of medication
administration!
• Right
– Person
– Drug
– Dose
– Time
– Route
– Documentation
– And - refusal
So…. What happens anyway?
Cells talk to each other
• Three distinct languages
– Nervous system
• neurotransmitters
– Endocrine system
• hormones
– Immune system
• cytokines
In disease, all systems are affected
• The three systems can’t exist without
each other
• The actions of one impact the actions of
the others
– I.e., stress (nervous system) disrupts
endocrine system which may respond with
glucocorticoid production = suppressed
immune response
Drugs have class
Drug Class Examples
• Nitroglycerin
– Body system: “Cardiac drug”
– Action of the agent: “Anti-anginal”
– Mechanism of action: “Vasodilator”
• Indications for nitroglycerin
– Cardiac chest pain
– Pulmonary edema
– Hypertensive crisis
• Which drug class best describes this drug?
Another way to classify drugs
• Mechanism of Action
– Drugs in each category work on similar sites in the
body and will have similar specific effects/side effects
•
•
•
•
Beta blockers: metoprolol
ACE inhibitors: lisinopril
Alpha blockers: prazosin
Calcium-channel blockers: verapamil
• Example: beta blocker actions and impacts
– Suppress the actions of the sympathetic nervous
system
– Prehospital administration of epinephrine may not
produce as dramatic effects with a patient taking a
drug in this class
Prehospital example:
Hyperglycemics
• Dextrose 50% and glucagon
– Both will raise blood glucose
• Mechanism of action
– Glucagon: hormone that works in the liver to convert
stored chains of carbohydrate to glucose
– Dextrose 50%: ready-made simple sugar that is ready
to enter into the cell
• Which drug is considered first-line for
hypoglycemia? Why?
• What are some limitations for glucagon in the
presence of severe hypoglycemia?
Distribution
• Some drugs bind to proteins in blood and
remain for prolonged period
• Therapeutic effects due to unbound portion of
drug in blood
• Drug bound to plasma proteins can’t cross
membranes
• Changing blood pH can affect protein-binding
action of drug.
• TCA’s are strongly bound to plasma proteins.
Drugs bind to proteins
• Albumen is one of the chief proteins in the
blood available for binding with drugs.
• When a pt. Is malnourished, albumen is low.
• What significance does this have re; drug
therapy?
The blood – brain barrier
• Tight junctions of capillary
endothelieal cells in CNS form a
barrier
• Only non-protein-bound, highly lipidsoluble drugs can enter CNS
• Placental barrier similar
Other deposits
• Fatty tissue serves as drug reservoir
• Bones and teeth can accumulate drugs that
bind to calcium
– Ie., tetracycline
Ok, you’ve given the drug – now what?
Biotransformation
• Drugs are metabolized – broken
down into metabolites
• Transforms drug into more or less
active metabolite
• Make drug more water soluble to
facilitate elimination
• Protein-bound drugs are not
available for biotransformation
Biotransformation, cont.
• Occurs in liver primarily
• Also occurs in kidney, lung, GI
tract
• First-pass effect
– Some drugs can’t be given orally
What alters drug response?
•
•
•
•
•
•
•
•
Age
Body mass
Sex
Environmental
Time of administration
Pathologic state
Genetic factors
Psychological factors
• Drugs that change physical properties
– Osmotrol
• Drugs that chemically bind with other
substances
– Isopropyl alcohol – denatures proteins on surface
of bacterial cells
• Drugs alter a normal metabolic pathway
– Anticancer, antiviral drugs
Response to drug
administration
• We must carefully weight risk vs benefit!
• Allergic reaction
– Hypersensitivity
• Idiosyncrasy
– Effect unique to person; not expected
• Tolerence
– Decreased response to drug after repeated administration
It’s all about the cell….
1) Brain sends out the response via nerve paths
2) Nerve moves the response: depolarization
3) Depolarization stimulates norepinephrine sacks
• Sacks move to the end of the nerve and dump
out their contents
2
3
4)
Norepinephrine travels across the synapse
• Attaches to a receptor on the organ, organ responds
to the signal
5) Norepineprhine detaches and is deactivated
• 2 options: destroy it or move it back into its sack
5
2
3
4
• Now, how do we
get rid of the
drug?
Elimination
• Most drugs excreted in urine
– Some in feces or air
• Glomerular filtration
– A function of glomerular filtration pressure (BP
and kidney blood flow)
– Active transport system; requires ATP
• Tubular secretion
– Urine pH affects reabsorption in renal tubules
Elimination, cont.
• Some drugs and metabolites are eliminated in
expired air
– Breathalyzer
• Feces, sweat, saliva, breast milk
Ok, so how do they get in our system?
Drug Routes
• Enteral
– Oral (PO)
– Orogastric/Nasogastric
(OG/NG)
– Sublingual (SL)
– Buccal
– Rectal (PR)
Drug routes, cont. Parenteral
– Intravenous (IV)
– Endotracheal
(ET)
– Intraosseous
(IO)
– Umbilical
– Intramuscular
(IM)
– Subcutaneous
(SC, SQ, SubQ)
– Inhalation/
Nebulized
– Topical
– Transdermal
– Nasal
– Instillation
– Intradermal
Drug forms
– Liquid: (solute - solvent) - Solution
– Tinctures: drug extracted
chemically with alcohol.
– Suspensions - liquid preparations
don’t remain mixed
– Spirits: Volatile chemicals dissolved
in alcohol
– Gaseous – Oxygen, Nitrous Oxide
– Emulsions: oily substance mixed with a
solvent that won’t dissolve it. (oil and
vinegar).
– Elixirs: Drug in an alcohol solvent. (Nyquil)
– Syrups: Drug dissolved in sugar and water
(cough syrup).
– Solids: capsule, tablet, lozenge, powder
– Topical use: ointment, paste, cream, aerosol
Other stuff you should know
Drug storage
• Properties may be altered by environment.
– Temperature
– Light
– Moisture
– Shelf-life
Drug response
relationship
• Plasma level profiles
– Length of onset, duration, termination of action, minimum
effective concentration and toxic levels
• Onset of action
– A medication reaches it’s minimum effective concentration
• Minimum effective concentration
– Level of drug needed to cause a given effect
• Duration of action
– How long the drug remains above it’s minimum effective
concentration
• Termination of action
– Time from when a drug drops below minimum effective
concentration until it’s eliminated
• Therapeutic index
– Ratio of a drug’s lethal dose for 50% of population to its
effective dose for 50% of population
• Half-life
– Time the body takes to clear one half of the drug
• Cross tolerence
– Tolerence for a drug that develops after administration of a
different drug
• Tachyphylaxis
– Rapidly occuring tolerance to a drug
• Decongestants, bronchodilators
• Cumulative effect
– Increased effectiveness when a drug is given in several
doses
• Drug dependence
– Pt becomes accustomed to drug; will suffer withdrawal
symptoms
• Drug interaction
– Effects of one drug alters response to another drug
• Drug antagonism
– Effects of one drug blocks response to another drug
• Summation
– Additive effect; two drugs that both have same effect are
given together
Second messenger
• Calcium or cyclic adenosine monophosphate
(cAMP)
– Most common second messenger
– Activates other enzymes; cascading
• Number of receptor sites on target cell
constantly changes
– Receptor proteins destroyed during function
– Reactivated or remanufactured
• Down regulation
– Binding of a drug or hormone that causes number of
receptors to decrease
• Synergism
– Two drugs that have the same effect are given together
and produce a response greater than the sum of their
individual responses
• Potentiation
– One drug enhances the effect of another
• Interference
– One drug affects the pharmacology of another drug
Summary