The strongest bond

Two bonding atoms share electrons

2nd strongest bond

atoms with an excess of electrons (imparting an overall negative charge on the atom) are attracted to atoms with a deficiency of electrons (imparting an overall postive charge on the atom)

3rd strongest bond

Hydrogen atoms bound to nitrogen or oxygen become more positively polarized allowing them to bond to more negatively polarized atoms such as oxygen, nitrogen, or sulfur.

Least strongest bond

shifting electrons density  in areas of a molecule, or in a molecule as a whole, results in the generation of transient positive or negative charges- these areas interact with transient areas of opposite charge on another molecules.

What are the six major types of drug-receptor interactions

What the body does to the drug.

Aging- kidney function decreases, less muscle mass, Liver function decreases, lungs function decreases

Patients with renal disease, cardiac disease

Other medications

Makes more enzymes, the drug is metabolized too quickly/excreted too quickly

Increased transcription or translation

Decreased degradation

Induction by another drug or autoinduction

Highly distributed into non-vascular compartments.  Distribute very well to various sites of action.  

Most of the drug is free and able to be used.

Covalent- electrons are shared equally, usually is not reversible.

Metabolizes drugs.

Approx. greater than 75% go through the CYP 450 system.

If this enzyme is not present they may not respond to the drug you are giving them.

Grapefruit juice interferes with CYP 450.

Water-loving/water soluble

Polar- usually ionized

Renal excretion

Requires transport mechanism to cross cell membranes & BBB

Forms H+ bonds

Fat loving/ water insoluble

Lipophilic

Non-polar, usually not ionized

Passively diffuses across cell membranes and BBB

Antihistimine makes them sleepy - the drug is crossing BBB

If you have an infection in the brain- you need a medication that is going to cross the BBB

Hydrophilic drugs can penetrate the CNS via all of the mechanisms listed below except:

A. active transport

B. Facilitated transport

C. Intrathecal administration

D. Passive Diffusion

Drug binds with Receptor - DR*  (*- illicits a response)

full response

Ex. Morphine

What happens if you keep increasing the dose?  CNS/Respirations become more depressed.  You have a higher risk of going into toxic/lethal dose.

Causes maximal change in cellular activity of target

Stabilizes DR*

DR and DR*

Drug binds with a receptor and illicits a response- it also responds to receptors and doesn't illicit a response.

You will not get a full affect like you do with morphine.  This helps with drug withdrawels.

Ex. Buprenorphine

Activates receptor without maximal efficacy

Stabilizes DR and DR*

Stabilizes DR in the case of R*

If you have a drug that responds to a receptor and you have a low response or no response

Cancer drug- shrink tumor

Inactivates free active receptors.

Competitve-Reversible binding blocks agonist at active or allosteric site

Stabilizes DR, Prevents DR*

Non-Competitive- Irreversible binding blocks agonist at active or allosteric site

Stabilizes DR, Prevents DR*

median toxicity dose in 50%

Ex. Diarrhea

Effective dose: 200mg-800mg

The higher the dose the closer they are going to be to the toxic dose.

Less likely to get adverse affects if you can get them by on the smaller dose.

Which of the following is the most desireable PD for a medication?

Low LD 50

LOW TI

High TI

Low TD 50

PO (oral meds)

First pass effect

Goes through GI tract- liver

First pass effect- going to absorb a little of the drug

Transdermal- bypasses the liver.  Doesnt have a first pass effect.  Lower dose needed.

Oral drugs are higher in dosing.  

Ex. Codeine

It has to be metabolized.  It is not active until it is metabolized to its active form (morphine)

Only give PO because it has to be metabolized (first pass effect)

Irratic absorption

not the same first pass effect as oral.

Nonionized, lipophilic drugs favored for oral absorption

Weak acids are best absorbed in the stomach

Weak bases are best absorbed in the small intestine.

Drugs must be free (non protein bound) in order to reach its site of action and be metabolized and eliminated

Druges with a Low Vd may be highly protein bound and more likely to remain in the plasma compartment.

dilantin occupied the protein and made more free coumadin increasing his INR

phenytoin can decrease or increase the anticoagulant effect of warfarin an decrease is attributed to hepatic enzyme induction, and an increase to displacement of warfarin from protein binding sites.

Vitamin K interferes with warfarin

Dose too high

Chronic activation or inhibition effects

Unintended receptor

Incorrect receptor is activated or inhibited

correct receptor but incorrect tissue

Dose too hight

Chronic activation or inhibition effects

Ex. Benadryl

incorrect receptor is activated or inhibitied

Ex. Beta Blocker

Swelling itchy and has a rash

Drug toxicity?

Drug class?

what type of reaction is seen in a positive tb skin test?

Type 1- anaphylactic

PCN

TB- Type 4 Cell mediated

Tissue: Heart

Action: Increased force and rate of contraction

Antagonist: Beta Blocker- decrease BP and HR

Tissue: Respiratory, uterine, vascular smooth muscle

Actions:  Promotes smooth muscle relaxation

Tissue: Skeletal Muscle

Actions: Promotes potassium uptake

Tissue: Liver

Action:  Activates glycogenolysis

Tissue: Fat Cells

Action: Lypolysis

Tissue: Smooth muscle

Action: Dilates renal blood vessels

Tissue: Nerve endings

Action: Modulates transmitter release

Used in Parkinsons

Low dose- increase renal perfusion

High dose- increases blood pressure

Muscarinic Effects Mnemonic

SLUG BAM

SALIVATION/SECRETIONS/SWEATING

LACRIMATIN

URINATION

GASTROINTESTINAL UPSET

BRADYCARDIA/BROCHOCONSTRICTION//BOWEL MOVEMENT

ABDOMINAL CRAMPS

ANOREXIA

MIOSIS

DIARRHEA

EMESIS

KNOW THE ABCD'S OF ANTI-CHOLINERGIC SIDE EFFECTS

OR CAN'TS

ANOREXIA 

BLURRY VISION

CONSTIPATION/CONFUSION

DRY MOUTH

SEDATION/STASIS OF URINE

CAN'T PEE

CAN'T SEE

CAN'T SPIT

CAN'T SHIT

MIXED ALPHA AND BETA AGONIST

A1=A2

B1=B2

Increased mental activity

Brochiolar Dilation

Increased Resp Rate

Amino acids

Tyrosine and phenylalanine

Non selective sympathomimetic drugs

Epinepherine

Direct Acting

alpha 1= alpha 2

betal 1 = beta 2

Direct acting

alpha 1= alpha 2

Beta 1 >> Beta 2

Direct Acting

Beta 1

Direct Acting

D1/D2, B1, Alpha 1

Indirect Acting

Enhance the release of catecholamines

• BP guidelines

• Normal BP <120 systolic and <80 diastolic
• All persons with BP >120/80 should initiate “Lifestyle Modifications”
• Treatment thresholds/goals
  • <140/90 without DM or kidney disease
  • <130/80 with DM or kidney disease

• First-line therapy is thiazide diuretic unless there is a “compelling indication.”
• Most patients will require at least two medications to reach goal.
• In many cases, it is more effective to add a second agent from a different drug class than to increase the dose of the first agent.

• Heart failure: Thiazide diuretic, β-blocker, ACEI, ARB, aldosterone antagonist
• MI: β-blocker, ACEI, aldosterone antagonist
• High CVD risk: Thiazide, β-blocker, ACEI, CCB
• Diabetes: Thiazide diuretic, β-blocker, ACEI, ARB, CCB
• Chronic kidney disease: ACEI or ARB
• Recurrent stroke prevention: Thiazide diuretic, ACEI
• Isolated systolic hypertension: Thiazide diuretic, CCB

• Diastolic pressure >120 with evidence of progressive end organ damage
• Goal: decrease DBP to 100-105 within 24 hrs
• Clonidine

• Diastolic pressure >120 with evidence of end organ failure
• Goal: decrease DBP 100-105 asap
• Nitroprusside, NTG, Labetalol, Fenoldopam

• β1-blockers
• α1-blockers
• α2-agonists

• Calcium-channel blocker
• Potassium-channel openers

• Diuretics

• ACE Inhibitors
• ARBs

Proceed very carefully.  Patient can get into trouble quickly.

You must monitor these drug levels closely.

Drug interactions can cause this, decreased renal fx, n/v, burn, decreased albumin/protein.

What are your free drug levels? This is the amount of drug that can act

High Volume of Distribution

Low Volume of Distribution

K+ Sparing

lisinopril, catopril, ramipril, enalapril, fosinopric, quinapril, benazepril

MOA: blocks ace from converting angiotensin 1 to angiotensin 2 Clinical Use: Diabetes with proteinuria, HTN, benefits for Heart Failure

AE: Cough (caused by build-up of bradykinin), angioedema, hyper K+

 CI: Pregnancy, Renal artery stenosis Use of ibuprofen can interfere with hypertensive meds...it interferes with bradykinin

Indications: BPH CI: Heart failure

MOA: Inhibitor peripheral vasomotor tone, reducing vasoconstriction, decreasing SVR

Precaution: 1st dose effect- postural hypotension

Na/H20 retention when given without a diuretic

Hepatically metabolized non -CYP