General Pharmacology, part 2

Pharmaco-dynamics &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 lipid-soluble 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 paths2) Nerve moves the response: depolarization3) Depolarization stimulates norepinephrine sacks

• Sacks move to the end of the nerve and dump out their contents

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4) Norepinephrine travels across the synapse• Attaches to a receptor on the organ, organ responds

to the signal5) Norepineprhine detaches and is deactivated

• 2 options: destroy it or move it back into its sack

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• 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