Potentiative response:

One drug may intensify the effects of the other

Can increase therapeutic effects (beneficial) OR can increase adverse effects (detrimental/unsafe) Coumadin and asprin

Inhibitory responses

One drug may reduce the effects of the other
Reduce adverse OR reduce therapeutic effects (bronchodialator & propanolol

The combination may produce a new response not seen with either drug alone

mechanisms of drug-drug interactions

1.    Direct chemical or physical - Ex: precipitates in IV

2.    Pharmacokinetic

a.     Altered absorption, distribution, metabolism, excretion

b.     Ex: antacid changing pH in the stomach to effect absorption

3.  Pharmacodynamic

a.     Drug can trigger down/up regulate # of receptors available OR change affinity

4.    Combined toxicity - Enhanced (ex: alcohol & Tylenol)

drug-food interaction: 

What are the 2 types

-       grapefruit juice effect     

o   inhibits drug metabolism

o   strong interaction w/ an enzyme family that inhibits metabolism (more left in blood)

o   Dosing will need to be decresed!

-       MAO inhibitors

o   Monoamine oxidase  breaks down catecholimines

o   tyramine (AA precursor to DA, NE, E) found in dairy products

o   tyramine combined w/MAOIs, catecholimines don’t get broken down

o   Dramatic increase in BP that could be fatal 

 immune response. happens frequently with penicillins

idiosyncratic effect

precaution vs. contraindication

-       precaution is lesser than a contraindication, use vigilance

-       contraindication is against indication and you should do it, don’t want to use

-       absolute = never (ie pregnancy)

-       relative = benefits of drug outweigh side effects

physical dependence

-       Altered state produced by repeated drug administration

-       Tolerance and dependence may occur together (not always)

-       Need continued drug admin to prevent a w/drawal syndrome (i.e., physiologic or psychologic)

-        Related to the abuse of drugs with action on the CNS -- e.g., ETOH

-        May develop after only hours or days of repeated drug administration, or may take months.

-        Variable withdrawal: dependent on patient characteristics and drug

*be concerned with history of abuse and potential for abuse

ways to minimize adverse drug reactions

-       Minimize # of drugs taken

-       Get a thorough drug history

-       Vigilant when patient is taking med w/narrow therapeutic range

-       Anticipate ADR that may occur

-       Monitor organ systems that may be at risk

-       Nurse must evaluate pts for ADRs and educate patients in ways to avoid or minimize harm.

-       If mistake, do the right thing and tell someone, try to reverse what you did if necessary

factors that influence individual variation in drug response

-       Body weight and composition (excess fat can hold onto a drug)

-       Age (particularly elderly and children d/t fragile renal clearance)

-       Gender (women have different enzymes)

-       Race (genetic difference in enzymes we have to break down)

-       Pathophysiology (kidney or liver disease, pt may have multiple disease)

Patient related Factors that affect drug response

-       individual physiology

-       behavioral variability: stress (how can we get them to be compliant)

-       food/ETOH intake: pH changes

-       smoking: increases metabolism (increases breakdown of drug)

-       substance abuse: Hx will effect what drug is used

-       preexisting disease

-       genetically-determined enzyme differences

-       interactions of prescribed drugs with OTC drugs

-       poor medication adherance

drug tolerance

(Definition)

•       decreased responsiveness to a drug due to repeated drug administration, Always need a higher dose with tolerance, must be higher to get an effect

categories of drug tolerance (3)

•       Pharmacodynamic tolerance

•       R/t Long-term administration

•       (MEC abnormally high)

•       Drug down regulated receptor production make it harder for drug to get in

•       Metabolic tolerance

•       D/t accelerated drug metabolism

•       Induce liver enzymes to metabolize the drug

•       Tachyphylaxis

•       Repeat dosing over a short time

•       Not common.  Ex: transdermal meds need to be put in different spots

impact and ways to enhance medication adherence

-       Patient education

-       Attitude towards taking meds

-       Self-care capacity

-       Finances (prescribe something they can afford)

Process of conducting an action potential down the axon of the neuron

Drug that affects axonal conduction will affect conduction of all nerves it has access to. Ex: anethesia

Information carried across  gap between neuron & the post synaptic cell

most drugs usually target synaptic transmission b/c drugs that alter synaptic transmission can produce effects much more selective than those produced by drugs that alter axonal conduction.

Steps in synaptic transmission and effect of drugs on these steps

1.     Synthesis

a.     Increase transmitter synthesis (drug cause receptor activation to increase)

b.     Decrease transmitter synthesis (drug cause decreased receptor activation)

c.     Enhance the effect of the transmitter

2.    Storage (storage inhibited by drug and depleted)

3.    Release (drug can inhibit or promote release)

4.    Receptor binding - NT cross syn gap & undergo reversible binding to receptors, Drugs can:

ü  Cause activation (Morphene)

ü  Block receptor activation by other agents (Naloxone)

ü  Enhance receptor activation by the natural transmitter site. (indirect)

5.    Termination of transmission

a.     Drugs can block Reuptake or inhibit degredation

The divisions of nervous system

(CP SAPS)

•       Central nervous system - Brain and spinal cord

•       Peripheral nervous system

–      Somatic motor (Voluntary muscle movement)

–      Autonomic (Involuntary Muscle movement) Heart, secretions, smooth muscle

–      Parasympathetic (rest and digest)

Parasympathetic Nervous System (PSNS): REST & DIGEST

The regulatory functions of PNS affect these sites

•       Heart rate: decrease

•       Gastric secretions: increase

•       Bladder and bowel: allow emptying

•       Vision: constrict pupil, clarity for near objects

•       Bronchial smooth muscle: constriction

Sympathetic Nervous System (SNS): FLIGHT OR FIGHT

3 main things it  regulates

•       Regulation of cardiovascular system

•       Regulating body temp

•       Implementing flight/fight response

regulatory & innervation patterns of PSNS and SNS to various organs / blood vessels

•       Often dual innervations (oppose each other), basaltone (1 sys wins). PSNS tends to win out Except in Blood vessels capillaries innervated ONLY by sympathetic,

•       Sometimes effects are complimentary (as with ejaculation) 

Principal NTs of the peripheral nervous systems &

what junctions each neurotransmitter functions

-       Acetylcholine

o   ParaNS: All preganglionic AND postganglionic neurons

o   SymNS: All preganglionic AND postganglionic neurons of SWEAT GLANDS

o   all motor neurons to skeletal muscles

-       Norepinephrine

o   SymNS: Released by postganglionic, EXCEPT those of sweat glands

-       Epinephrine

o   Released by adrenal medulla

-       Dopamine

 Receptor Cholinergic (mediate responses re: ACh)

What are the receptor subtypes

•       Nicotinic n

–      Activation promotes ganglionic transmission at all ganglia of SNS & para NS.

–      Activation promotes release of epinephrine from the adrenal medulla

•       Nicotinic m - Cause contraction of skeletal muscles

•       Muscarinic  - Located on target organ of para NS

–      Activation causes

•       increased glandular (pulmonary, gastric, intestinal, sweat) secretions, contraction of smooth muscle in bronchi and GI tract,  slow heart rate, contraction of sphincter muscles or iris (constriction & near vision), dilation of blood ves - No nerve terminals at vascular muscarinic recept

•       voiding of bladder

Receptor specificity - What receptors can they activate

Epi

NE

Dopamine

Acetylcholine

-       Epinephrine can activate all alpha and beta receptors, but not dopamine receptors

-       Norepinephrine can activeat alpha1, alpha2, beta1 receptors

-       Dopamine can activate alpha1, beta1, dopamine receptors

-       Acetylcholine can activate all subtypes of cholinergic receptors. (Nn, Nm, Muscarinic)

Muscarinic Agonist (Stimulate Rest & Digest)

Benthacol - Therapuetic Uses

ü  direct acting and stimulates the muscarinic receptor used for

ü  Uriniary Retention (promotes voiding)

ü  GERD (increase gastric emptying – decreases acid reflux)

ü  Ileus (increases bowel motility – paralytic ileus)

ü  Post-operative abdominal distension (increase smooth muscle to move it out)

• when you stimulate muscarinic agonist (Benthacol) you stimulate all muscarinic receptors on all organs and everything goes into rest and digest mode
• Clinical usefulness of Benthacol is low d/t SE

Muscarinic Agonist (Stimulate Rest & Digest)

3 types of poisoning

ü  Direct-acting muscarinic agonist drugs (overdose, or synergistic overdose)

ü  Cholinesterase inhibitors

ü  Mushrooms 

Muscarinic Antagonist (Stimulate Flight or Fight)

Atropeine - Effects on organs

ü  Competitively blocks muscarinic receptors, no effect on its own, preventing receptor activation from ACth

ü  Heart Rate (increase)

ü  Secretions – Salivary/Gastric (decrease)

ü  Bronchi (dilates)

ü  Bladder tone (decreased tone of bladder, no void)

ü  Smooth muscle (decreases)

ü  Pupil (dilates)

ü  Disorders of the eye (dialates the eye - mydriasis)

ü  Bradycardia (increases heart rate)

ü  Intestinal hypermotility (slow down motility)

ü  Muscarinic agonist poisoning (be a competitive blocker)

ü  Asthma (bronchiodialater)

ü  Peptic ulcer disease (refractory symptoms)

ü  Overactive bladder (so you cant pee)

ü  Dry mouth (xerostomia) blocks secretion

ü  Blurred vision (cannot see close)

ü  Photophobia (b/c pupils are large)

ü  Increased intraocular pressure

ü  Urinary retention (decrease voiding)

ü  Constipation

ü  Tachycardia