Autonomic

Question 1

Pharmacokinetics

Answer 1

Effects of body on drug
Absorption
Distribution
Metabolism
Excretion

Question 2

Pharmacodynamics

Answer 2

Effects of drug on body 
Receptor binding
Drug efficacy
Drug potency
Toxicity

Question 3

a1 receptors

Answer 3

Gq (phospholipase C)

Increase vascular smooth muscle contraction
Increase pupillary dilator muscle contraction (mydriasis)
Increase intestinal and bladder sphincter muscle contraction

Question 4

a2 receptors

Answer 4

Gi (inhibitory; adenylyl cyclase)

Decrease sympathetic outflow
Decrease insulin release
Decrease lipolysis
Increase platelet aggregation

Question 5

B1 receptors

Answer 5

Gs (excitatory; adenylyl cyclase)

Increase HR, contractility, renin release, and lipolysis

Question 6

B2 receptors

Answer 6

Gs (excitatory; adenylyl cyclase)

Vasodilation, bronchodilation
Increase HR, contractility, lypolysis, insulin release, and aqueous humor production
Decrease uterine tone (tocolysis)
Ciliary muscle relaxation

Question 7

M1

Answer 7

Gq (phospholipase C)

CNS
Enteric nervous system

Question 8

M2

Answer 8

Gi (inhibitory; adenylyl cyclase)

Decrease HR and contractility of atria

Question 9

M3

Answer 9

Gq (phopholipase C)

Increase exocrine gland secretions (lacrimal, salivary, gastric acid), gut peristalsis, bladder contraction, pupillary sphincter muscle contraction (miosis)
Bronchoconstriction
Ciliary muscle contraction (accommodation)

Question 10

D1

Answer 10

Gs (adenylyl cyclase)

Relaxes renal vascular smooth muscle

Question 11

D2

Answer 11

Gi (inhibitory; adenylyl cyclase)

Modulates transmitter release, especially in brain

Question 12

H1

Answer 12

Gq (phospholipase C)

Increase nasal and bronchial mucus production
Increase vascular permeability
Contraction of bronchioles
Pruritus
Pain

Question 13

H2

Answer 13

Gs (adenylyl cyclase)

Increase gastric acid secretion

Question 14

V1

Answer 14

Gq (phospholipase C)

Increase vascular smooth muscle contraction

Question 15

V2

Answer 15

Gs (adenylyl cyclase)

Increase H2O permeability and reabsorption in the collecting tubules of the kidney (V2 is found in the 2 kidneys)

Question 16

Phospholipase C pathway (Gq)

Answer 16

Converts PIP2 –> DAG + IP3
DAG –> Protein kinase C
IP3 –> Increased [Ca2+] = smooth muscle contraction

H1, a1, V1
M1, M3
“HaVe 1 M&M”

Question 17

Adenylyl cyclase pathway (Gs)

Answer 17

Converts ATP –> cAMP
cAMP activates protein kinase A = increases [Ca2+] in heart and inhibits myosin light-chain kinase in smooth muscle

B1, B2, D1
H2, V2

Question 18

Adenylyl cyclase pathway (Gi)

Answer 18

INHIBITORY
Blocks conversion of ATP to cAMP, PKA, etc.

M2, a2, D2
“MAD 2’s”

Question 19

Drugs blocking cholinergic synthesis

Answer 19

Hemicholinium
Vesamicol
Botulinum
AChE inhibitors

Question 20

Drugs blocking noradrenergic synthesis

Answer 20

Metyrosine
Reserpine
Bretylium, guanethidine
Amphetamine
Cocaine, TCAs, amphetamines

Question 21

Fraction of administered drug that reaches systemic circulation unchanged

Answer 21

Bioavailability (F)

Question 22

Volume of distribution

Answer 22

Amount of drug in body/plasma drug concentration
Volume occupied by total absorbed drug amount at plasma concentration
Altered by liver and kidney disease

Question 23

Low Vd

Answer 23

Blood (4-8 L)

Large/charged molecules; plasma protein bound

Question 24

Medium Vd

Answer 24

ECF

Small hydrophilic molecules

Question 25

High Vd

Answer 25

All tissues including fat | Small lipophilic molecules, especially if bound to tissue protein

Question 26

Half life

Answer 26

T1/2 = (0.693 x Vd)/Cl Property of first order elimination

Question 27

A drug infused at a constant rate takes how long to reach steady state?

Answer 27

4-5 half lives

Question 28

Clearance

Answer 28

Volume of plasma cleared of drug per unit time ``` Cl = rate of elimination of drug/plasma drug concentration Cl = Vd x Ke (elimination constant) ``` Impaired with cardiac, hepatic, or renal dysfunction

Question 29

Loading dose

Answer 29

Loading dose = (Cp x Vd)/F Cp = target plasma concentration at steady state

Question 30

Maintenance dose

Answer 30

Maintenance dose = (Cp x Cl x dosage interval)/F In renal or liver disease, maintenance dose decreases and loading dose is unchanged

Question 31

Does time to steady state depend on dose and dosing frequency?

Answer 31

NO = time to steady state depends primarily on T1/2 and is independent of dose and dosing frequency

Question 32

Zero order elimination

Answer 32

Rate of elimination constant = constant AMOUNT eliminated per unit time "Capacity-limited" Decreases linearly with time

Question 33

Zero order elimination examples (3)

Answer 33

Phenytoin Ethanol Aspirin (at high or toxic concentrations) "PEA" = round like 0 in zero order

Question 34

First order elimination

Answer 34

Rate of elimination directly proportional to drug concentration = constant FRACTION eliminated per unit time Plasma concentration decreases EXPONENTIALLY with time "Flow dependent"

Question 35

``` Weak acids (3) Overdose treatment? ```

Answer 35

``` Phenobarbital Methotrexate Aspirin Trapped in basic environments Treat overdose with bicarbonte!!! ```

Question 36

``` Weak bases (1) Overdose treatment? ```

Answer 36

Amphetamines Trapped in acidic environment Treat overdose with ammonium chloride

Question 37

Phase I metabolism

Answer 37

Reduction Oxidation Hydrolysis with CYP450 Yields slightly polar/water soluble metabolites (still active) Lost first by geriatric patients

Question 38

Phase II metabolism

Answer 38

Conjugation: Glucuronidation Acetylation Sulfation Yields very polar, inactive metabolites (renal excretion) Retained by geriatric patients Slow acetylators have greater side effects from certain drugs due to decreased rate of metabolism

Question 39

Therapeutic index

Answer 39

TD50/ED50 | Median toxic dose/median effective dose = measures safety of drug

Question 40

Safer drugs have higher/lower TI?

Answer 40

HIGHER!!!

Question 41

Examples of low therapeutic index drugs? (4)

Answer 41

Digoxin Lithium Theophylline Warfarin

Question 42

S/sx of organophosphate/cholinesterase inhibitor poisoning

Answer 42

``` "DUMBBELSS" Diarrhea Urination Miosis Bronchospasm Bradycardia Excitation of skeletal muscle/CNS Lacrimation Sweating Salivation ```

Question 43

Antidote for organophosphate/cholinesterase inhibitor poisoning

Answer 43

Atropine (competitive inhibitor) + pralidoxime (regenerates AChE if given early)