1-Pharmacology

2-Pharmacokinetics

3-Pharmacodynamics

1-Pharmacology-study of chemical substances and how it effects the human body.

2-Pharmacokinetics-What the body does to the drug

3-Pharmacodynamics- What the drug does to the body

Trade name- Company name (eg-Viagra)

Generic  name- The name given to the drug by the company that is owned by the Federal govmt. more of a chemical name. (eg-sildenafil)

1- Absorption

2-Distribution

3-Metabolism

4-Excretion

Absorption-definition

(4 things to think about)

Absorption-From the administration site to the blood

1-routes of drug administration

2-Mechanism of transfer (types of transportation of drug from the GI to blood)

3-Factors for transfer

4-Bioavailabilty

1-Enteral-PO

a)oral

b)sublingual

2-Parenteral-not PO

a)IV-intravenous

b)IM-Intramuscular

c)SC-subcutaneous

d)ID-intradermal

e)IH-inhalation

f)IN-intranasal

g)IT-intrathecal-directly into CSF

h)Intraventricular-into the ventricle of he heart or brain

i)topical

j)transdermal-through the skin (eg-morphine patch)

k)Rectal

-PO is most common because it is the safest

-You have about 30-60 minutes before the HCl breaks down the pills in your stomach

-The best way to clear the GI tract is by Vomiting

-Give the pt Ipecac-emesis induction (eg-kid eats a bottle of Zanax)

(never turn the kid upside down and pound on his back, that causes the sphincter to tighten up and u may break bones while pounding)

-Tear at the junction of the stomach  and esophagus and stomach, caused by severe retching during emesis, the esophageal sphinctor is very relaxed and the intercostal muscles contract hard causing the tear

-Possible complication from ipicac

1-Passive Diffusion-pores-(most common) higher concentration to lower concentration

2-Active Diffusion-eg-carrier protiens

3-Endocytosis-of the drug

4-Exocytosis-the drug causes a release of eg-NE

The effect of pH on drug absorption

(the lower the pKa or pH the more acidic)

-The stomach has a low pH, very acidic and as you go further through the GI tract the pH rises, high pH in the large and small bowel

1-(Weak) Acid drugs in an acid media (the stomach) will be unionized or uncharged (will be absorbed through the stomach)

1-(Weak) Basic drugs in an acid media (the stomach) will be ionized or charged (will be absorbed further down the GI tract, wont be absorbed in stomach)

Unionized=can pass through the membrane (be absorbed)

1-If a drug is charged or ionized how is it administered

2-Explain a Neutral drug (Neutral charge)

1-If a drug is charged or ionized it can't be given PO, it must be given Parenteral (eg-IV)

 (a charged drug is always ionized no matter where it is eg-of charged drug-muscle relaxers given in OR, cuare-monkey drug)

2-A neutral drug has no charge so it can be absorbed into the body in the stomach, upper GI, lower GI, these are the most dangerous drugs (eg-ETOH, Hypnotics, Seditives)

3 things for a PO drug to be absorbed

(get through a membrane)

1-Unionized

2-Lipid soluble(highly water soluble drugs won't pass a membrane)

3-small molecular weight (less than 500-1000)

(drug also must be liquified in the stomach or else it will come out in the feces)

1-People with less stomach surface area or upper GI SA, bc they had stomach cancer removed or stomach staple etc. what do we know about them?

2-whats the deal with charcole?

1-they cant absorb acid drugs that well (and same for basic drugs w/ lower GI)

Acid drugs=absorbed in stomach and upper GI

basic drugs=absorbed in lower GI

2-Charcole cannot be liquified by the stomach and it grabs and absorbs everything in the stomach and upper GI. (and in lower GI also)

-The fraction of administered drug that reaches the systemic circulation. (amount of drug that gets absorbed)

-On a graph it would be the AUC-area under curve and IV would be greater than PO obviously

IV=100%

Physical factors influencing absorption

3

1-Blood flow

-(blood flow to the intestine is greater than to the stomach, therefore absorption from intestine is favored over stomach)

-(shock-greatly decreases blood flow to the cutaneous, minimizing SC drug absorption)

2-Surface Area-intestine (microvilli) SA is about 100-fold that of stomach

3-Contact time at absorption surface

(eg-a drug moving quickly trought the GI tract of a pt with diarrhea is not well absorbed)

Distribution

(3 things to think about)

1-Plasma Proteins

2-Drug Interactions

3-Steady State

Plasma Proteins

1-explain distribution of drug here

2-most commom Plasma Protein?

3-give two reasons other than drug interactions tht someone would have a low drug tolerance

1-Drugs bind to plasma proteins and the drug and plasma protein together doesn't effect you, it's too big. The free drug thats left over after all the protein binding spots are full is what effects you

2-The most common plasma protein is albumin

3-Malnourished(geriatrics)-Low albumin level

Alcoholics-Low tolerance bc there liver is damaged

(so lower your dose with these two groups) 

Drug Interactions

1-explain

2-whats drugs are considered interactors

1-If 2 drugs are competeing for the same proteins the one that loses will be free to effect the body more than expected.

(in class he gave the jelo nun example of Phenytoin-epilepsy drug, too much causes near comotose and nystagmus)

2-any drug that binds 90% or greater is considered a drug interactor, pushes other drugs off proteins

Steady State

1-define it

2-when is it reached

1) (is when Absorption of drug=excretion of drug), Steady state is the point when a drug has been given long enough so that the concentration of plasma protein with drug attached will remain the same with each subsequent dose (remember only the free drug fucks you up)

2) 5 x the half life of the drug= steady state (this is where you wanna be)

-the half life is a time period

-take a blood level after approxamatly 5 days

1-Best way to test drug levels

2-the way we test drug levels

?

1-Saliva

2-Blood-gives you total drg level not just free drug level

We change the composition of the drug to make it more H2O soluble then we excrete it out of the kidney

1-Liver-P450 Sysem

2-Blood- Esterases

3-Elimination Half Life (t1/2)

-Liver converts substances to water soluble substances

-57-60 different isoenzymes=reasons for pt's to not be able to metabolize drugs

-drug can induce some isoenzymes while inhibiting others eg-with birth  control, Riampin (antibiotic) could cause a woman to still get prego bc Riampin induces an isoenzyme that excretes estrogen

-drugs

Riampin=hepatitis med., lowers estrogen level, changes the activity of the isoenzyme

Birth control= progesterone and estrogen

-mix em and ur prego

Torrsades=drug enduced A-fib

Elimination half life

(see elimination curve)

The time it takes for a drug level to drop by 50%

-also takes about 5 half lives to get the drug out of the system

Elimination

1-most common route

2-drug level in urin

metabolites-parent compounds

1-the most common elimination route is through the Urine

2-drug level in urin is meaningless bc urine is stagnant in ur body it acumulates over several hours, we test urin just to see if drugs and drug metabolites are present-complience, abuse, peds

Blood gives you the best value of drug in the body

Renal

Biliary

Reectal

Lungs

Saliva

Sweat

others

Pharmacodynamics-def

4 things to think about

what the drug does to the body

1-Receptor

2-Efficacy

3-Agonist

4-Antagonist

1-Receptor

2-Efficacy

1-Receptor=drug goes out into the tissue and meet w/ a receptor site, then you get a DRUG/RECEPTOR COMPLEX=Effect

2-Efficacy=the ability of a drug once compbined w/ the receptor to cause an effect or response

1- Agonist

2-Antagonist

1- Agonist- a drug that produces efficacy or response

2-Antagonist- Blockers, A drug goes to it's receptor but doesn't have any efficacy. (*so there is a complex), most drugs are antagonists or blockers, block receptor sites

*Drugs are either agonists or antagonists

tell me whether this type of drug has affinity and efficacy

1-agonist

2-antagonist

1-agonist- has both affinity and efficacy

2-antagonist-has  affinity but no efficacy

Drug Response

5 things to think about

1-Therapuetic

2-Adverse

3-Hypersensitivity

4-Idiosyncratic

5-Lethal

1-Therapeutic

2-Adverse rxn

1-Therapeutic- Drug + Response= complex

2-Adverse rxn-eg when asprin attaches to receptor site, it can cause pain and irritation

Hypersensitivity

1-definition

2-what can it lead to

3- the number one drug that causes it

4-differene b/w Hypersensitivity rxn to drug vs. rash rxn to  drug

 5-which administrations have a high chance of hypersensitivity

1-Histamine release (coldness breaks down histamine)

2-can lead to anaphylaxis-Rash w/ hives->SOB->BP drop->HR increase->death

the hallmark treatment for anaphylaxis is epinephrine

3-The Penicillins

4-Rash=mast cells->release histamine

Hypersensitivity rxn-Antibody-Antigen=release histamine (drug + antibody=iGG)

IV or IM=much higher chance of H. rxn

1-Idiosyncratic

2-Lethal

1-Idiosyncratic- is an unpredictable rxn, this is the rarest Rx eg-asthma as a Rx to a drug in a pt who doesn't have asthma

2-Lethal- every drug is lethal

ED50=

LD50=

what is the theraputic index?

ED50=(ED-effective dose) the dose which is therapuetic for 50% of subjects

LD50=(LD-lethal dose) Dose at which 50% of people die

The therapuetic index (Ta) is equal to LD50/ED50 the higher Ta the safer the drug bc we are talking about the doses not the number of people dieing for LD50, so you want the lethal dose to be as hi as possible, and vice versa for ED50. (if it is one thats bad) you also want the 2 curves on a graph to be far apart

1-Graded dose response curves

2-Quantal response curve

Graded response- a continous and gradual response

Potency-can be determined from a graded curve

Quantal response- an all or nothing response

Safty (Ta)-can be determined

Time Action

The greater the dose-> (3)

1-the shorter the onset (faster onset)

2-the longer the duration

3-the greater the peak effect

and vice versa

1-ANS-def. and 2 parts

Afferent-in

Efferent-out-this is all we are talking about

ANS is involuntary stuff

1-Sympathetic-  fight or flight (spinal cord and the synapse happens in the chain)

2-Parasympathetic-rest and digest (originate in Brain (CN's) andsynapse in the organ)

1-Conduction

2-Transmission

1-Conduction-moving down a nerve (propogates an impulse)

2-Transmission-crosses a synapse

A cholinergic neuron

1-def.

2-where are they found (2)

1-any neuron that releases Acytylcholine (Ach)

2-All pregangleonic neurons in ANS are cholinergic

2-All postgangleonic neurons of the parasympathetic NS are cholinergic

Adrenergic neuron

1-def.

2-where

3-2 exceptions

1-Any neuron that releases Norepinephron (NE)

2-postgangleonic neurons of sympathetic NS are adrenergic

3-exception-The salivary glans and pilorectal muscles are inervated by the sympathetic, but they have interaction w/ Ach so they are termed cholinergic

Acetate + Choline->and cholinecetalase-> gives you Ach in a vesicle, then it is released

Receptors are

-Muscarinic receptors (on organs)

Nicotinic receptors (only on post ganglionic cells and in somatic NS)

-Acetylcholinesterase is the enzyme that breaks down the Ach and recycles the choline which is put back into the neuron by active transport, through the membrane.

*intracellular CA2+ is increased and causes the release of Ach into the synaptic cleft

tyrosine->dopa->dopamine->norepinephrine vessicle is released (action potential comes down the nerve and triggers Ca influx which allows vesicles to release its contents)

Receptors

Alpha 1, Beta 1, Beta 2,

alpha 2 receptors on dendrites inhibit NE by reuptake

COMT (Extracellular, catechol-O-methyltransferase)

MAO(intracellular)

Tyrosine is taken back in the neuron